Lymphocytes, Tumor-Infiltrating: Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.Melanoma: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Galectins: A class of animal lectins that bind specifically to beta-galactoside in a calcium-independent manner. Members of this class are distiguished from other lectins by the presence of a conserved carbohydrate recognition domain. The majority of proteins in this class bind to sugar molecules in a sulfhydryl-dependent manner and are often referred to as S-type lectins, however this property is not required for membership in this class.CD8-Positive T-Lymphocytes: A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.Mucins: High molecular weight mucoproteins that protect the surface of EPITHELIAL CELLS by providing a barrier to particulate matter and microorganisms. Membrane-anchored mucins may have additional roles concerned with protein interactions at the cell surface.Histiocytic Disorders, Malignant: Distinctive neoplastic disorders of histiocytes. Included are malignant neoplasms of MACROPHAGES and DENDRITIC CELLS.Peer Group: Group composed of associates of same species, approximately the same age, and usually of similar rank or social status.Video Games: A form of interactive entertainment in which the player controls electronically generated images that appear on a video display screen. This includes video games played in the home on special machines or home computers, and those played in arcades.Videotape Recording: Recording of visual and sometimes sound signals on magnetic tape.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Peer Review, Research: The evaluation by experts of the quality and pertinence of research or research proposals of other experts in the same field. Peer review is used by editors in deciding which submissions warrant publication, by granting agencies to determine which proposals should be funded, and by academic institutions in tenure decisions.Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It is applied also in evaluating the quality of health care provided to patients.Nobel PrizeAwards and PrizesAcetobacter: A species of gram-negative bacteria of the family ACETOBACTERACEAE found in FLOWERS and FRUIT. Cells are ellipsoidal to rod-shaped and straight or slightly curved.IsraelNewspapers: Publications printed and distributed daily, weekly, or at some other regular and usually short interval, containing news, articles of opinion (as editorials and letters), features, advertising, and announcements of current interest. (Webster's 3d ed)Helianthus: A genus herbs of the Asteraceae family. The SEEDS yield oil and are used as food and animal feed; the roots of Helianthus tuberosus (Jerusalem artichoke) are edible.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Sulfonylurea CompoundsEndoplasmic Reticulum Stress: Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.Unfolded Protein Response: A cellular response to environmental insults that cause disruptions in PROTEIN FOLDING and/or accumulation of defectively folded protein in the ENDOPLASMIC RETICULUM. It consists of a group of regulatory cascades that are triggered as a response to altered levels of calcium and/or the redox state of the endoplasmic reticulum. Persistent activation of the unfolded protein response leads to the induction of APOPTOSIS.Transcription Factor CHOP: A CCAAT-enhancer binding protein that is induced by DNA DAMAGE and growth arrest. It serves as a dominant negative inhibitor of other CCAAT-enhancer binding proteins.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.Insulin Infusion Systems: Portable or implantable devices for infusion of insulin. Includes open-loop systems which may be patient-operated or controlled by a pre-set program and are designed for constant delivery of small quantities of insulin, increased during food ingestion, and closed-loop systems which deliver quantities of insulin automatically based on an electronic glucose sensor.Equipment and Supplies: Expendable and nonexpendable equipment, supplies, apparatus, and instruments that are used in diagnostic, surgical, therapeutic, scientific, and experimental procedures.Pancreas, Artificial: Devices for simulating the activity of the pancreas. They can be either electromechanical, consisting of a glucose sensor, computer, and insulin pump or bioartificial, consisting of isolated islets of Langerhans in an artificial membrane.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Device Approval: Process that is gone through in order for a device to receive approval by a government regulatory agency. This includes any required preclinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance. It is not restricted to FDA.Defibrillators, Implantable: Implantable devices which continuously monitor the electrical activity of the heart and automatically detect and terminate ventricular tachycardia (TACHYCARDIA, VENTRICULAR) and VENTRICULAR FIBRILLATION. They consist of an impulse generator, batteries, and electrodes.Diabetes Mellitus, Type 1: A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.Rosette Formation: The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.Islets of Langerhans: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.Diabetic Nephropathies: KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.Dictionaries, MedicalDictionaries as Topic: Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.Dictionaries, ChemicalInsulin-Secreting Cells: A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.Terminology as Topic: The terms, expressions, designations, or symbols used in a particular science, discipline, or specialized subject area.Diabetes Mellitus: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.Cell- and Tissue-Based Therapy: Therapies that involve the TRANSPLANTATION of CELLS or TISSUES developed for the purpose of restoring the function of diseased or dysfunctional cells or tissues.Capital Financing: Institutional funding for facilities and for equipment which becomes a part of the assets of the institution.Pleural Neoplasms: Neoplasms of the thin serous membrane that envelopes the lungs and lines the thoracic cavity. Pleural neoplasms are exceedingly rare and are usually not diagnosed until they are advanced because in the early stages they produce no symptoms.Stem Cell Transplantation: The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.

*ALOX12

1 diabetes or type 2 diabetes as well as in the fat cells of white adipose tissue of morbidly obese type 2 diabetic patients. ... cause excessive production of reactive oxygen species and inflammation which lead to losses in insulin-secreting beta cells and ... The PP cells (i.e. gamma cells) of the pancreas islets appear to be the major if not only site where ALOX12 is expressed in ... HETE in the response of human lens epithelial cells to epidermal growth factor and insulin". Investigative Ophthalmology & ...

*Sulfatide

... and as the β cells in the pancreas secrete insulin, sulfatide aids in the monomerization of insulin, which is the breakdown of ... Additionally, HIV-1-infected patients often suffer from myelin degeneration in the central nervous system. These patients have ... Research has shown that in the pancreases of type II diabetic mouse models, there is a deficiency of C16:0. Additional research ... macrophages dendritic cells Hepatocytes B cells tumor cells thymocytes Each of these different cell types are expressed in ...

*Artificial pancreas

... or stem cells that could differentiate into such cells, which would secrete the amount of insulin, amylin, and glucagon needed ... of a diabetic person by a genetically engineered virus which causes a DNA change of intestinal cells to become insulin- ... Hurley, Dan (24 December 2014) [1] WIRED Magazine, Diabetes Patients Are Hacking Their Way Toward a Bionic Pancreas Knutson, ... either ex vivo to drive stem cells to become beta cells, or used directly to cause cells that do not normally produce insulin ...

*Brockmann body

The islet tissues are in turn composed of endocrine cells which are the principal sites of insulin synthesis. They are ... Both islet groups contain insulin, glucagon, peptide YY and somatostatin, but these proteins are secreted only in the pyloric ... The transplantation of tilapia Brockmann bodies into a diabetic mice model has been shown to promote long-term normal blood ... The Brockmann body of the tilapia (Oreochromis nilotica) is investigated as a potential xenograft tissue for patients with type ...

*Hyperinsulinemia

With a reduced response to insulin, the beta cells of the pancreas secrete increasing amounts of insulin in response to the ... although metformin may be used to reduce insulin levels in some patients (typically where obesity is present). A referral to a ... If the mother of the infant is a diabetic, and does not properly control her blood glucose levels, the hyperglycemic maternal ... The rapid division of beta cells results in increased levels of insulin being secreted to compensate for the high blood glucose ...

*Epigenetics of diabetes Type 2

... in diabetic patients there was less PPARGC1A expressed and also less insulin secreted. This data supports the idea that ... When IRX3 was knocked out, there was a drop in the number of β-cells that produce insulin and the α-cells that produce glucagon ... Metabolic memory is the phenomenon of diabetic vascular stresses persisting after glucose normalization in diabetic patients ... in DNA methylation of the PPARGC1A promoter of human islet cells from diabetics as compared to non-diabetic human islet cells. ...

*Blood sugar level

... cells, Delta (D) cells and F cells. Glucagon is secreted from alpha cells, while insulin is secreted by beta cells. Together ... and symptomatic hypoglycemia is generally found only in diabetics using insulin or other pharmacological treatment, and in ... From the perspective the majority of patients, treatment with an old, well-understood diabetes drug such as metformin will be ... Red blood cells, for instance, do not require insulin to intake glucose from the blood. Higher than normal amounts of white or ...

*C-peptide

In the insulin synthesis pathway, first preproinsulin is translocated into the endoplasmic reticulum of beta cells of the ... Measuring C-peptide levels will help differentiate a healthy patient from a diabetic one. C-peptide may be used for determining ... determine how much of their own natural insulin a person is producing as C-peptide is secreted in equimolar amounts to insulin ... C-peptide also has been reported to have anti-inflammatory effects as well as aid repair of smooth muscle cells. ii Patients ...

*Dulaglutide

... which is known to be inappropriate in the diabetic patient. GLP-1 is normally secreted by L cells of the gastrointestinal ... or patients with diabetic ketoacidosis because these problems are the result of the islet cells being unable to produce insulin ... slowing gastric emptying and increases insulin secretion by pancreatic Beta cells. Simultaneously the compound reduces the ... and one of the actions of Dulaglutide is to stimulate functioning islet cell to produce more insulin. Dulaglutide can be used ...

*Pancreas

... β beta cells secrete insulin (decrease glucose in blood), δ delta cells secrete somatostatin (regulates/stops α and β cells) ... of pancreatic islet cells from a donor into the patient's liver so that the cells can produce the deficient insulin. Diabetes ... It was only in 1889 when Oskar Minkowski discovered that removing the pancreas from a dog caused it to become diabetic (insulin ... The second line, influenced by Pax-6, produces beta cells (β-) and delta cells (δ-), which secrete insulin and somatostatin, ...

*Chronic wound

Another way is to spread onto the wound a gel of the patient's own blood platelets, which then secrete growth factors such as ... Since more oxygen in the wound environment allows white blood cells to produce ROS to kill bacteria, patients with inadequate ... Underlying ischemia may also be treated surgically by arterial revascularization, for example in diabetic ulcers, and patients ... vascular endothelial growth factor (VEGF), insulin-like growth factor 1-2 (IGF), PDGF, transforming growth factor-β (TGF-β), ...

*Insulin resistance

... implies that the body's cells (primarily muscle) lose sensitivity to insulin, a hormone secreted by the ... of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients". The ... Certain cell types such as fat and muscle cells require insulin to absorb glucose. When these cells fail to respond adequately ... When the body produces insulin under conditions of insulin resistance, the cells are resistant to the insulin and are unable to ...

*Lixisenatide

GLP-1 is a hormone that helps pancreatic beta cells to secrete insulin in response to high blood sugar. Because it works like ... by which time Sanofi had lost the lead in the field of anti-diabetic drugs to Novo Nordisk. Lixisenatide received FDA approval ... "Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis". BMJ (Clinical ... insulin is only secreted when blood sugar is high. Like GLP-1, it also slows gastric emptying. Lixisenatixe is a peptide made ...

*Mark Mattson

It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose and food ... Levels of TLR4 are decreased in inferior parietal cortex tissue specimens from end-stage AD patients compared to aged-matched ... His work also revealed a physiological role for the secreted form of amyloid precursor protein generated by alpha-secretase ... or the combination of the two treatments increased levels of BDNF in the hippocampus of diabetic mice. Enhancement of ...

*Adiponectin

... in combination with leptin has been shown to completely reverse insulin resistance in mice. Adiponectin is secreted ... and are reduced in diabetics compared to non-diabetics. Weight reduction significantly increases circulating concentrations. ... The first is a short signal sequence that targets the hormone for secretion outside the cell; next is a short region that ... Rizza S, Gigli F, Galli A, Micchelini B, Lauro D, Lauro R, Federici M (April 2010). "Adiponectin isoforms in elderly patients ...

*Triple test

A positive screen indicates an increased risk of chromosomal abnormalities (and neural tube defects), and such patients are ... if she's diabetic; if she's having twins or other multiples, and the gestational age of the fetus. Weight and ethnicity may ... increases MSAFP because each fetus secretes its own AFP Incorrect estimation of gestational age is the most common cause of ... higher than those of Caucasian women for unknown reasons Women with insulin-dependent diabetes mellitus have MSAFP levels that ...

*Abdominal obesity

... fat cells produce hormones that can affect health (e.g. increased insulin resistance and/or breast cancer risk). The risk ... A study has stated that 75% of patients treated for asthma in the emergency room were either overweight or obese. Based on ... But adiponectin which is found in lower concentration in obese and diabetic individuals has shown to be beneficial and ... Abdominal fat is especially active hormonally, secreting a group of hormones called adipokines that may possibly impair glucose ...

*Anti-diabetic medication

Insulin must be used in Type I, which must be injected. Diabetes mellitus type 2 is a disease of insulin resistance by cells. ... The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional ... Treatments include (1) agents that increase the amount of insulin secreted by the pancreas, (2) agents that increase the ... Insulin zinc (Lente) Examples of long acting insulins include Extended insulin zinc insulin (Ultralente) Insulin glargine ( ...

*Insulin

... the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited. Their ... Children dying from diabetic ketoacidosis were kept in large wards, often with 50 or more patients in a ward, mostly comatose. ... resulting in absolute insulin deficiency Type 2 - either inadequate insulin production by the β-cells or insulin resistance or ... making it more likely for patients to achieve an insulin profile that mimics that of the body´s own insulin release. Insulin is ...

*Exosome (vesicle)

Exosomes secreted from tumour cells can deliver signals to surrounding cells and have been shown to regulate myofibroblast ... Patient blood samples stored in biorepositories can be used for biomarker analysis as colorectal cancer cell-derived exosomes ... activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound ... They induce the expression of a number of growth factors (hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF1), ...

*Gastric inhibitory polypeptide

The amount of insulin secreted is greater when glucose is administered orally than intravenously. GIP recently appeared as a ... in obese and type 2 diabetic patients". Physiological Research. 59 (5): 749-55. PMID 20406045. Yamada Y, Seino Y (2004). " ... It is synthesized by K cells, which are found in the mucosa of the duodenum and the jejunum of the gastrointestinal tract. Like ... It has been found that Type 2 diabetics are not responsive to GIP and have lower levels of GIP secretion after a meal when ...

*Insulin (medication)

Insulin is often measured in serum, plasma or blood in order to monitor therapy in diabetic patients, confirm a diagnosis of ... some researchers have explored the possibility of transplanting genetically engineered non-beta cells to secrete insulin. ... Patients with insulin-dependent diabetes typically require some base level of insulin (basal insulin), as well as short-acting ... Pulsatile insulin uses microjets to pulse insulin into the patient, mimicking the physiological secretions of insulin by the ...

*Cell encapsulation

... microcapsules could prevent the need for the insulin injections needed several times a day by type 1 diabetic patients. The ... The effect of implanting microcapsules loaded with xenogenic cells genetically modified to secrete endostatin, an ... The cells put into the capsules can be from the patient (autologous cells), from another donor (allogeneic cells) or from other ... the islet cells from immune rejection as well as allow the use of animal cells or genetically modified insulin-producing cells ...

*Somatic cell nuclear transfer

These insulin producing cells could be used for replacement therapy in diabetics, demonstrating real SCNT stem cell therapeutic ... One vision for successful stem cell therapies is to create custom stem cell lines for patients. Each custom stem cell line ... The most significant of these cells, were those who expressed insulin and were capable of secreting the hormone. ... 1], Nature Stem Cell Blog. [2], The Scientist 19 June 2007 Human Somatic Cell Nuclear Transfer Using Adult Cells Cell Stem Cell ...

*Jeffrey Scott Flier

Moller, David E.; Flier, Jeffrey S. (1988). "Detection of an Alteration in the Insulin-Receptor Gene in a Patient with Insulin ... "Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance". Science. 190 ( ... Among his work has been the discovery with Bruce Spiegelman, PhD, of altered production of adipocyte secreted factors in ... Flier, JS (1995). "The adipocyte: storage depot or node on the energy information superhighway?". Cell. 80 (1): 15-8. doi: ...
Looking for online definition of radial growth phase melanoma in the Medical Dictionary? radial growth phase melanoma explanation free. What is radial growth phase melanoma? Meaning of radial growth phase melanoma medical term. What does radial growth phase melanoma mean?
Even though the ideal method of diagnosis of melanoma should be complete excisional biopsy,[14] the location of the melanoma may require alternatives. Dermatoscopy of acral pigmented lesions is very difficult but can be accomplished with diligent attention. Initial confirmation of the suspicion can be done with a small wedge biopsy or small punch biopsy.[4] Thin deep wedge biopsies can heal very well on acral skin, and small punch biopsies can give enough clue to the malignant nature of the lesion. Once this confirmatory biopsy is done, a second complete excisional skin biopsy can be performed with a narrow surgical margin (1 mm). This second biopsy will determine the depth and invasiveness of the melanoma,[15] and will help to define what the final treatment will be. If the melanoma involves the nail fold and the nail bed, complete excision of the nail unit might be required. Final treatment might require wider excision (margins of 0.5 cm or more), digital amputation, lymphangiogram with lymph ...
OBJECTIVES To evaluate melanoma biopsy specimens for human papilloma virus (HPV) and determine the relation between the presence of HPV, in vitro growth, and clinical progression of melanoma in the patients from whom the biopsy specimens were derived. SUMMARY BACKGROUND DATA Ultraviolet radiation from sun exposure appears to be the primary causal agent in the development of cutaneous melanoma. However, other agents, including HPV, as observed in different epithelial carcinomas, may also play a role in melanoma development and progression. METHODS Twelve melanoma biopsy specimens obtained from 12 patients with AJCC stage III and IV melanoma were stained with antibodies against gp-100 (HMB-45) and S-100 protein to confirm melanoma diagnosis and with a polyclonal HPV antibody. After mechanical dissociation, the melanoma specimen cells ability to grow in vitro was assessed. Patients were evaluated for melanoma progression ...
In this article, we report the derivation of highly metastatic human melanoma cell lines from poorly metastatic parental lines using an animal metastasis model. We subsequently identified a "metastasis aggressiveness gene signature" by comparing the gene expression patterns of tumor samples from the highly metastatic derivatives with those from their parental lines. By comparisons with gene expression data from human clinical samples, we found that expression of this metastasis gene signature in human melanoma metastases correlates with poor survival of the corresponding patients. The signature is able to segregate melanoma-bearing patients into three groups, one of which has a significantly lower survival probability. This suggests that the signature provides an indication of "aggressiveness" of the melanoma metastases rather than of metastasis per se, similar to the lung metastasis signature reported by Minn et al. (10). This result has been confirmed by alternative ...
Purpose : The effects of zeaxanthin on uveal melanoma in experimental animal models remain unknown. We found that zeaxanthin inhibited the growth and induced apoptosis of human uveal melanoma cells in vitro. We hypothesize that zeaxanthin may also have effects on uveal melanoma in vivo. The present study investigated the in vivo effects of zeaxanthin on human uveal melanoma in a nude mouse model. Methods : Cultured human uveal melanoma cells from an immortal cell line were inoculated into the choroid of nude mice. Mice were randomly divided into control group (without treatment of zeaxanthin), zeaxanthin low group and zeaxanthin high group (treated with intra-choroidal injection of zeaxanthin at 0.171 mg and 0.684 mg, respectively). After 21 days, mice were sacrificed and the eyes enucleated. Gross appearances and tumor mass was determined. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma ...
1. Topalian SL, Solomon D, Rosenberg SA. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol. 1989;142(10):3714-25 2. Baxevanis CN, Dedoussis GV. Papadopoulos NG, Missitzis I,Stathopoulos GP, Papamichail M. Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer. Cancer. 1994;74:1275-82 3. Chen LJ, Zheng X, Shen YP. et al. Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer. Cancer Immunol Immunother. 2012 [Epub ahead of print] 4. Milne K, Alexander C, Webb JR. et al. Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes. J Transl Med. 2012Feb27;10:33 5. Gannot G, Gannot I, Vered H, Buchner A, Keisaris Y. Increase in immune cell infiltration with progression of oral epithelium from hyperkeratiosis to dysplasia and carcinoma. Br J Cancer. 2002;86:1444-8 6. MacLennan GT, Eisenberg R, Fleshman RL. et al. The ...
PurposeUveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial.Methods: The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial (ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m(2) intravenously on day 1 of every 21-day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by blinded independent central radiologic review. Secondary end points included overall survival and objective ...
Tumor-infiltrating lymphocytes, also tumour infiltrating lymphocytes, are white blood cells that have left the bloodstream and migrated into a tumor. They include T cells and B cells and are part of the larger category of tumor-infiltrating immune cells which consist of both mononuclear and polymorphonuclear immune cells, (i.e., T cells, B cells, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, eosinophils, basophils, etc.) in variable proportions. Their abundance varies about tumor type and stage and in some cases relate to disease prognosis Tumor-infiltrating immune cells can often be found in the stroma and ...
Central nervous system imaging is needed during programmed death 1 (PD-1) inhibitor therapy to monitor incidence, patterns of progression, and outcomes of melanoma brain metastases, according to research presented at the 2017 ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).. -----. Related Content. Ipilimumab Combination Significantly Improves Melanoma Outcomes. Skip whole-brain radiation in patients with limited brain metastases. -----. Metastases in the brain is a common occurrence for patients with metastatic melanoma. Currently available therapies are often unable to treat metastatic melanoma tumors in the brain. Limited data exists concerning the incidence, patterns of progression, and outcomes of patients with melanoma brain metastasis treated with PD-1 inhibitors, particularly in conjunction with central nervous system-focused therapy.. Gustavo Schvartsman, MD, MD Anderson Cancer Center (Houston, TX), and colleagues retrospectively reviewed the ...
Tumor-infiltrating immune cells are a hallmark of most solid tumors, and the presence of varied immune populations significantly affects clinical outcomes for patients with cancer (1, 2). Historically, tumor-infiltrating immune cells have been viewed as restraining tumor progression (3), but in recent years, it has become more widely appreciated that chronic immune responses play critical roles in promoting tumor progression, metastasis, and resistance to cytotoxic therapies (1). Therefore, understanding the molecular mechanisms by which malignant cells derail antitumor immune responses to favor disease progression is critical to identify potential therapeutic targets. Recently, we reported that selective depletion of tumor-infiltrating macrophages (TAM) by neutralizing colony-stimulating factor-1 (CSF1) or inhibiting CSF1 receptor (CSF1R) activity improves the efficacy of chemotherapy in ...
Histologically, the tumour has a radial growth phase and is characterized by lentiginous and some nesting proliferation of large atypical melanocytes. Focally, pagetoid spread is present, however this is not as prominent as in superficial spreading melanoma. The melanocytes may be surrounded by a halo giving a lacunar appearance.. Some of the melanocytes may have dendritic processes. The invasive dermal component may be composed of spindle or epithelioid cells or nevus like cells. Diagnosis of Acral lentiginous melanoma during the radial growth phase is often difficult, and it may not be recognized initially, but treatment in this phase offers an excellent prognosis. There is a high incidence of regressive changes and desmoplasia in Acral lentiginous melanoma.. These changes, together with the anatomic peculiarities of nail beds, palms, and soles as compared with other skin areas, make it difficult to determine the Clarks level and to ...
Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node ...
Background: Tumor-infiltrating immune cells analyzed by immunohistochemistry are reported as alternative prognostic factors to supplement TNM staging in operable non-small cell lung cancer (NSCLC), but little is done by flow cytometry. Method: We established a protocol to analyze immune cells in tumor, distant lung (far from tumor) and peripheral blood mononuclear cells (PBMCs) by 8 color flow cytometry. 30 NSCLC patients with adenocarcinoma, squamous cell carcinoma and more uncommon histotypes were included and statistical analyses of cell subsets were performed. Results: We have identified the following tumor-infiltrating immune cells: CD45+ leukocytes, granulocytes, CD19+ B cells, CD4+ and CD8+ T cells with naïve/memory phenotype, CD56+CD16+ and CD56+CD16- NK ...
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D. Synonyms and Keywords: Malignant melanoma; Acral lentiginous melanoma; Lentiginous melanoma; Lentigo maligna melanoma; Nodular melanoma; Amelanotic melanoma; Familial melanoma; Non-pigmented melanoma; MM; Metastatic melanoma; Metastatic malignant melanoma; Cutaneous melanoma; Actinic melanosis; Solar melanoma; Melanose; Malignant nevus; Melanocyte malignancy; Melanotic cancer ...
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.Sabawoon Mirwais, M.B.B.S, M.D.[2] Synonyms and Keywords: Malignant melanoma; Acral lentiginous melanoma; Lentiginous melanoma; Lentigo maligna melanoma; Nodular melanoma; Amelanotic melanoma; Familial melanoma; Non-pigmented melanoma; MM; Metastatic melanoma; Metastatic malignant melanoma; Cutaneous melanoma; Actinic melanosis; Solar melanoma; Melanose; Malignant nevus; Melanocyte malignancy; Melanotic cancer ...
AbstractImmune cells contribute to determining the prognosis of gastric cancer. However, their exact role is less clear.We determined the prognostic significance of different immune cells in intratumoral tissue (T), stromal tissue (S), and adjacent normal tissue (N) of 166 gastric cancer cases and their interactions, including CD3+, CD4+, CD8+, CD57+, CD68+, CD66b+, and Foxp3+ cells, and established an effective prognostic nomogram based on the immune reactions.We found high densities of TCD3+, TCD4+, TCD8+, SCD3+, SCD4+, SCD57+, SCD66b+, and NFoxp3+ cells, as well as high TCD8+/SCD8+ ratio, TCD68+/SCD68+ ratio, TCD3+/TFoxp3+ ratio, TCD4+/TFoxp3+ ratio, TCD8+/TFoxp3+ ratio, SCD3+/SFoxp3+ ratio, and SCD4+/SCD8+ ratio were associated with better survival, whereas high densities of TCD66b+, TFoxp3+, SFoxp3+ and NCD66b+ cells as well as high ...
TY - JOUR. T1 - Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study. AU - Di Giacomo, A. M.. AU - Ascierto, P. A.. AU - Queirolo, P.. AU - Pilla, L.. AU - Ridolfi, R.. AU - Santinami, M.. AU - Testori, A.. AU - Simeone, E.. AU - Guidoboni, M.. AU - Maurichi, A.. AU - Orgiano, L.. AU - Spadola, G.. AU - Del Vecchio, M.. AU - Danielli, R.. AU - Calabrò, L.. AU - Annesi, D.. AU - Giannarelli, D.. AU - Maccalli, Cristina. AU - Fonsatti, E.. AU - Parmiani, G.. AU - Maio, Michele. PY - 2015/4/1. Y1 - 2015/4/1. N2 - Background: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. Patients and methods: This analysis captured the 3-year outcome ...
Previous reports showed that the Steroidal Glycoalkaloid Solamargine inhibited proliferation of non-melanoma skin cancer cells. However, Solamargine was not tested systematically on different types of melanoma cells and was not simultaneously tested on normal cells either. In this study we aimed to investigate the effect of Solamargine and the mechanism involved in inhibiting the growth of different types of melanoma cells. Solamargine effect was tested on normal cells and on another three melanoma cell lines. Vertical growth phase metastatic and primary melanoma cell lines WM239 and WM115, respectively and the radial growth phase benign melanoma cells WM35 were used. The half inhibitory concentration IC50 of Solamargine was determined using Alamarblue assay. The cellular and subcellular changes were ...
While breast cancer has not been considered a cancer amenable to immunotherapeutic approaches, recent studies have demonstrated evidence of significant immune cell infiltration via tumor-infiltrating lymphocytes in a subset of patient tumors. In this review we present the current evidence highlighting the clinical relevance and utility of tumor-infiltrating lymphocytes in breast cancer. Retrospective and prospective studies have shown that the presence of tumor-infiltrating lymphocytes is a prognostic marker for higher responses to neoadjuvant chemotherapy and better survival, particularly in triple negative and HER2-positive early breast cancer. Further work is required to determine the immune subsets important in this response and to discover ways of encouraging immune infiltrate in tumor-infiltrating lymphocytes-negative patients.
Clinical trial for Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 | Mucosal Melanoma | Acral Lentiginous Melanoma | Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 | Pathologic Stage IV Cutaneous Melanoma AJCC v8 | Pathologic Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIID Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIA Cutaneous Melanoma AJCC v8 | Clinical Stage IV Cutaneous Melanoma AJCC v8 | Clinical Stage III Cutaneous Melanoma AJCC v8 , Pembrolizumab in Treating Patients With Stage III-IV High-Risk Melanoma Before and After Surgery
Conditions: Clinical Stage 0 Cutaneous Melanoma AJCC v8; Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Colitis; Diarrhea; Malignant Genitourinary System Neoplasm; Pathologic Stage 0 Cutaneous Melanoma AJCC v8; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma ...
Pets get melanoma too! But unlike people, it is not usually a result of too many hours lying on the beach. Canine melanoma on the skin presents as a pigmented or non-pigmented skin mass most commonly on the face, trunk, feet or scrotum. Feline melanoma on the skin presents on the head or ears. Oral melanoma grows inside the mouth.. Up to half of skin melanomas and most oral melanomas are malignant. Diagnosis can often be made with a fine needle aspirate biopsy, but sometimes a surgical biopsy is required. Surgery is the first step for treatment of pet melanoma. Skin melanomas require removal with surrounding margins of healthy tissue. Oral melanomas also require excision with margins, and this often entails removal of a part of the jaw to ensure that adequate margins are removed. Malignant melanomas can spread, and the first sites of spread are the local lymph nodes and the lungs. The vet will probably stage the disease by checking local lymph nodes and taking chest X-rays prior to any major ...
Recent progress in the structural identification of human melanoma antigens recognized by autologous cytotoxic T cells has led to the recognition of a new melanocyte differentiation antigen, Melan-A(MART-1). To determine the properties of the Melan-A gene product, Melan-A recombinant protein was produced in Escherichia coli and used to generate mouse monoclonal antibodies (mAbs). Two prototype mAbs, A103 and A355, were selected for detailed study. Immunoblotting results with A103 showed a 20-22-kDa doublet In Melan-A mRNA positive melanoma cell lines and no reactivity with Melan-A mRNA-negative cell lines. A355, in addition to the 20-22-kDa doublet, recognized several other protein species in Melan-A mRNA-positive cell lines. Immunocytochemical assays on cultured melanoma cells showed specific and uniform cytoplasmic staining in Melan-A mRNA-positive cell lines. Immunohistochemical analysis of normal human tissues with both mAbs showed ...
Clinical trial for Stage III Cutaneous Melanoma AJCC v7 | Unresectable Cutaneous Melanoma | Mucosal Melanoma | Stage IV Cutaneous Melanoma AJCC v6 and v7 | Stage IIIA Cutaneous Melanoma AJCC v7 | Advanced Melanoma | Melanoma of Unknown Primary | Stage IIIB Cutaneous Melanoma AJCC v7 | Stage IIIC Cutaneous Melanoma AJCC v7 | Unresectable Melanoma | Refractory Melanoma , Testing Treatment With Ipilimumab and Nivolumab Compared to Treatment With Ipilimumab Alone in Advanced Melanoma
1059 Certain aggressive melanoma cell lines exhibit a dedifferentiated phenotype, expressing multiple molecular markers that are specific for various cell types including endothelial, neural, and even stem cells. These cells are able to participate in vasculogenic mimicry in vitro and respond to ischemic microenvironmental cues by participating in neovascularization in vivo. We examined the potential plasticity of human metastatic melanoma cells by exposing them to a developmental microenvironment in zebrafish embryos. The data reveal that the zebrafish embryos make a powerful model system in which to investigate tumor-microenvironment interactions and tumor cell plasticity. We show here that fluorescently labeled human metastatic melanoma cells transplanted into zebrafish embryos survive for up to two weeks, exhibit motility, seem to proliferate and most importantly, are no ...
Melanoma skin cancer (as opposed to non-melanoma skin cancer) is less common, but more serious than other types of skin cancer. Early detection is key to successfully treating melanoma skin cancers. Turley Hansen represents a number of 9/11 responders and survivors with melanoma skin cancer.. Melanoma cancer is sometimes called malignant melanoma and cutaneous melanoma. Most melanoma tumors are brown or black, but some melanomas can appear pink, tan, or even white. Melanomas can develop anywhere on the skin, but they are more likely to start on the chest and back in men and on the legs in women. The neck and face are other common sites. Melanoma cancer can also appear in the eye.. Based on the stage of the cancer, treatment options may include:. ...
TY - JOUR. T1 - Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ. T2 - A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. AU - on behalf of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. AU - Dieci, Maria Vittoria. AU - Radosevic-Robin, Nina. AU - Fineberg, Susan. AU - van den Eynden, Gert. AU - Ternes, Nils. AU - Penault-Llorca, Frederique. AU - Pruneri, Giancarlo. AU - DAlfonso, Timothy M.. AU - Demaria, Sandra. AU - Castaneda, Carlos. AU - Sanchez, Joselyn. AU - Badve, Sunil. AU - Michiels, Stefan. AU - Bossuyt, Veerle. AU - Rojo, Federico. AU - Singh, Baljit. AU - Nielsen, Torsten. AU - Viale, Giuseppe. AU - Kim, Seong Rim. AU - Hewitt, Stephen. AU - Wienert, Stephan. AU - Loibl, Sybille. AU - Rimm, David. AU - Symmans, Fraser. AU - Denkert, Carsten. AU - Adams, Sylvia. AU - Loi, Sherene. AU - ...
Characterization of tumour-infiltrating lymphocytes and apoptosis in colitis-associated neoplasia: comparison with sporadic colorectal cancer
Intratumoral tumor-infiltrating lymphocyte level and prominent peritumoral Crohns-like lymphoid reaction appear to be independent prognostic factors for survival in colorectal cancer, according to a study reported by Rozek et al in the Journal of the National Cancer Institute. The findings suggest that enhanced lymphocytic reaction may be associated with improved survival.. Study Details. The study involved assessment of 2,369 incident colorectal cancers from a population-based case-control study in northern Israel. Multivariate analysis for colorectal cancer-specific and overall survival included tumor-infiltrating lymphocyte level, Crohns-like lymphoid reaction, microsatellite instability, age, sex, ethnicity, grade, and stage. In grading Crohns-like lymphoid reaction, the advancing edge of the tumor was assessed for prominent inflammatory reaction, defined as a minimum of three lymphoid aggregates per section; if the advancing edge of the tumor was not present, the field was graded as ...
Previous studies identified a prominent role of S1PR1 in tumor progression linked to persistent STAT3 activation in tumor and myeloid cells (Lee et al., 2010; Deng et al., 2012; Degagné et al., 2014). We previously noticed STAT3 signaling downstream of S1PR1 in human macrophages, which contributed to establishing an anti-inflammatory phenotype (Weis et al., 2009). However, in the present study, S1PR1 signaling in CD11bhi CD206+ TAMs did not affect typical STAT3 target genes in macrophages. Rather, a so-far-unexplored S1PR1 signaling circuit in macrophages promoted lymphangiogenesis via NLRP3-dependent IL-1β secretion.. Our global mRNA expression data in TAMs failed to identify previously described macrophage-derived prolymphangiogenic factors such as VEGF-C or VEGF-D as targets of S1PR1 signaling (Kerjaschki, 2005). Rather, NLRP3 expression and the concomitant IL-1β release promoted lymphangiogenesis. Although an involvement of VEGFs in the prolymphangiogenic properties of ...
The tumor immune microenvironment (TIME) is the cellular environment in which tumors exist. This includes: surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules, immune checkpoint proteins and the extracellular matrix (ECM). The TIME plays a critical role in cancer progression and regulation. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells. The molecules and cells in the TIME influence disease outcome by altering the balance of suppressive versus cytotoxic responses in the vicinity of the tumor. Having a better understanding of the tumor immune microenvironment will pave ...
In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population ...
Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) achieved impressive clinical results with response rates of up to 50% in patients with metastatic melanoma.. Previous trials investigating TIL therapy for patients with renal cell carcinoma (RCC) have shown limited success, however none of these early trials used current TIL manufacturing methods and preparative chemotherapy regimens. RCC is an obvious candidate for implementation of TIL therapy because of its known immunogenicity. ...
TY - JOUR. T1 - Tumor immune microenvironment characteristics of papillary thyroid carcinoma are associated with histopathological aggressiveness and BRAF mutation status. AU - Means, Casey. AU - Clayburgh, Daniel. AU - Maloney, Lauren. AU - Sauer, David. AU - Taylor, Matthew H.. AU - Shindo, Maisie. AU - Coussens, Lisa. AU - Tsujikawa, Takahiro. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Background: Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30% of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. Methods: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAF V600E mutational status. ...
We have previously reported the TCR inhibitory molecule CD5 impairs reactivity of tumor-specific PBL-derived T-cell clones against the cognate target and controls their susceptibility to activation-induced cell death (AICD) triggered by tumor cells. In this report, we compared the antitumor T-cell response developed against the B16F10 melanoma engrafted in CD5-deficient and wild-type (wt) C57BL/6 mice. Our results indicate that CD5 knock out mice elicit a delayed tumor growth as compared to wt mice, which is associated with tumor infiltration by more activated tumor-reactive T lymphocytes. Our data also indicate that tumor suppression in CD5-deficient mice is transient and that tumor flare up correlates with increase in AICD of tumor-infiltrating CD8+ T cells. Our data suggest that tumor T lymphocyte infiltration occurs at early stages of cancer development and that tumor-mediated AICD is most likely involved in the induction of T-cell ...
Vol 1: Vascular normalization: a strategy to recondition the tumor immune microenvironment.. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Foy, J-P. ; Bertolus, C. ; Michallet, M-C. ; Deneuve, S. ; Incitti, R. ; et. al. The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade. In: Annals of Oncology, (2017 ...
T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor expressed by activated T cells, Tregs, and NK cells. Here, we determined that TIGIT is upregulated on tumor antigen-specific (TA-specific) CD8+ T cells and CD8+ tumor-infiltrating lymphocytes (TILs) from patients with melanoma, and these TIGIT-expressing CD8+ T cells often coexpress the inhibitory receptor PD-1. Moreover, CD8+ TILs from patients exhibited downregulation of the costimulatory molecule CD226, which competes with TIGIT for the same ligand, supporting a TIGIT/CD226 imbalance in metastatic melanoma. TIGIT marked early T cell activation and was further upregulated by T cells upon PD-1 blockade and in dysfunctional PD-1+TIM-3+ TA-specific CD8+ T cells. PD-1+TIGIT+, PD-1-TIGIT+, and PD-1+TIGIT- CD8+ TILs had ...
Notch intercellular communication instructs tissue-specific T-cell development and function. In this study, we explored the roles of dendritic cell (DC)-expressed Notch ligands in the regulation of T-cell effector function. We generated mice with CD11c lineage-specific deletion of Notch Delta-like ligand (Dll)1 and Jagged (Jag)2. Using these genetically-ablated mice and engineered pharmacological Notch ligand constructs, the roles of various Delta-like and Jagged ligands in the regulation of T-cell-mediated immunity were investigated. We assessed tumor growth, mouse survival, cytokine production, immunophenotyping of myeloid and lymphoid populations infiltrating the tumors, expression of checkpoint molecules and T-cell function in the experimental settings of murine lung and pancreatic tumors and cardiac allograft rejection. Correlative studies were also performed for the expression of NOTCH ligands, NOTCH receptors and PD-1 on various subsets of myeloid and lymphoid cells ...
Lion Biotechnologies, Inc. (Nasdaq: LBIO), a biotechnology company that is developing novel cancer immunotherapies based on tumor infiltrating lymphocytes (TIL), today announced that researchers from Moffitt Cancer Center reported positive results from a pilot trial of TIL and ipilimumab in patients with metastatic melanoma. The data from the trial, which Lion partially sponsored, were presented at the Society of Surgical Oncology 2015 meeting in Houston, TX on Friday, March 27, 2015.. "The Phase 1 trial was conducted at Moffitt Cancer Center in 12 patients with metastatic melanoma, with the objective of determining the safety and feasibility of combining TIL therapy with the CTLA-4 checkpoint inhibitor, ipilimumab. Patients were treated with ipilimumab one week prior to tumor harvest for TIL expansion, a second time while their TIL were being expanded, and two more times following TIL transfer.. "Of the 12 patients enrolled in the trial, 11 ...
Recently, we showed that high T-cell infiltration correlates with favorable clinical outcome in high-risk neuroblastoma patients (13). Herein, we demonstrate that TILs express PD-1 and LAG3, two negative regulators of T-cell function (33), and that neuroblastoma cells either express PD-L1 or HLA-I. According to the density of PD-L1+ and HLA-I+ tumor cells and regardless of infiltrating T-cell density, MYCN amplification status, INSS stage, and age at diagnosis, we could distinguish two PD-L1/HLA-I combinations: one associated with good prognosis (high HLA-I and low or no PD-L1) and the other associated with poor prognosis (low HLA-I and high or no PD-L1). Our findings provide a proof of principle that PD-L1 in combination with HLA-I expression may serve as a biomarker in neuroblastoma, although this has to be further confirmed by a prospective study with a larger number of samples.. Of note, a good PD-L1/HLA-I combination ...
There are many ways to fight cancer using the bodys own immune system. Some methods include the administration of vaccines while others involve stimulatory factors injected near tumors. One promising method is enlisting the help of T cells. To fight cancer effectively, T cells must be able to recognize cancerous antigens and the environment in which these T cells reside must be conducive to their function, survival, and proliferation. This paper discusses a method of providing such an environment called adoptive cell transfer, as well as the elements that effect this protocol and the ways in which the environment can be manipulated to increase the effectiveness of adoptive cell transfer. Many factors contribute to the observation that the effectiveness of adoptive cell transfer increases as immunodepletion increases, namely, the depletion of regulatory T cells. Additionally, ...
Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αβT cells. Although αβT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity ...
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed ...
Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3(+), CD4(+), and CD8(+) cytotoxic lymphocytes (CTLs) as well as CD56(+) NK cells and CD68(+) macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3(+) (FOXP3(+)) Tregs were found in intratumoural tissue. Additionally, regarding ICOS(+) FOXP3(+) Tregs, an increased prevalence in carcinoma was not only associated with the ...
Vasculogenic mimicry is associated with increased tumor-infiltrating neutrophil and poor outcome in esophageal squamous cell carcinoma Jingxin Zhang,1,* Guoxia Zhang,2,* Pingping Hu,3 Guodong Deng,4 Qiqi Liu,4 Lili Qiao,4 Hui Luo,1 Jiandong Zhang3 1Department of Oncology, Weifang Medical College, Weifang, 2Department of Pathology, 3Department of Radiation Oncology, Qianfoshan Hospital Affiliated to Shandong University, 4Department of Oncology, Shandong University School of Medicine, Jinan, China *These authors contributed equally to this work Purpose: Vasculogenic mimicry (VM) is known to be a mechanism to nourish the tumor, but little is known about its prognostic significance in esophageal squamous cell carcinoma (ESCC). We characterized the predictive relevance of VM expression and tumor-infiltrating neutrophil (TIN) density in patients with resectable ESCC.Methods: We retrospectively collected clinicopathologic characteristics of 117 esophageal cancer (EC) patients ...
Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Dele …
Definition of Counter-attacks in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is Counter-attacks? Meaning of Counter-attacks as a legal term. What does Counter-attacks mean in law?
Adoptive transfer of tumor-infiltrating lymphocytes (TIL) is in development for the treatment of metastatic melanoma. In phase II clinical trials, patients with metastatic melanoma that received TIL after preconditioning had a 50-70% clinical response rate. The current approach to generate TIL is to culture melanoma enzyme digests in the presence of IL-2 for a 10- to 20-day period followed by 2 weeks of rapid expansion (REP). Prior to administration, cell therapies are characterized and tested for purity. TIL are characterized by CD3 surface marker expression, and purity is assessed by the amount of tumor remaining in culture. Evaluating TIL purity has traditionally been done by immunohistochemistry, which is often considered semiquantitative. To generate a quantitative assay, we used multiparameter flow cytometry to evaluate the presence of viable tumor cells by staining TIL populations with a viability dye and an antibody cocktail that detects ...
Purpose: Cultured tumor fragments from melanoma metastases have been used as a source of tumor-infiltrating lymphocytes (TIL) for adoptive cell therapy. The expansion of tumor-reactive CD8+ T cells with IL-2 in these early cultures is critical in generating clinically active TIL infusion products, with a population of activated 4-1BB CD8+ T cells recently found to constitute the majority of tumor-specific T cells. Experimental Design:We used an agonistic anti-4-1BB antibody added during the initial tumor fragment cultures to provide in situ 4-1BB co-stimulation. Results: Addition of an agonistic anti-4-1BB antibody could activate 4-1BB signaling within early cultured tumor fragments and accelerated the rate of memory CD8+ TIL outgrowth that were highly enriched for melanoma antigen specificity. This was associated with NFkappaB activation and the induction of T-cell survival and memory genes, as well as ...
Repurposing existing drugs for cancer treatment is an effective strategy. An approved antipsychotic drug, trifluoperazine (TFP), has been reported to have potential anticancer effects against several cancer types. Here, we investigated the effect and molecular mechanism of TFP in colorectal cancer (CRC). In vitro studies showed that TFP induced G0/G1 cell cycle arrest to dramatically inhibit CRC cell proliferation through downregulating cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, and cyclin E and upregulating p27. TFP also induced apoptosis, decreased mitochondrial membrane potential, and increased reactive oxygen species levels in CRC cells, indicating that TFP induced mitochondria-mediated intrinsic apoptosis. Importantly, TFP significantly suppressed tumor growth in two CRC subcutaneous tumor models without side effects. Interestingly, TFP treatment increased the expression levels of programmed death-1 ligand 1 (PD-L1) in CRC cells ...
Tumor-infiltrating lymphocytes (TILs) are widely associated with positive outcomes, yet carry key indicators of a systemic failed immune response against unresolved cancer. Cancer immunotherapies can reverse their tolerance phenotypes while preserving tumor reactivity and neoantigen specificity shared with circulating immune cells. We performed comprehensive transcriptomic analyses to identify gene signatures common to circulating and TILs in the context of clear cell renal cell carcinoma. Modulated genes also associated with disease outcome were validated in other cancer types. Through comprehensive bioinformatics analyses, we identified practical diagnostic markers and actionable targets of the failed immune response. On circulating lymphocytes, 3 genes (LEF1, FASLG, and MMP9) could efficiently stratify patients from healthy control donors. From their associations with resistance to cancer immunotherapies and microbial infections, we uncovered not only ...
Cancer Immun 2009; 9: 3. 19. Uppaluri R, Dunn GP, Lewis JS Jr. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in head and neck cancers. Cancer Immun 2008; 8: 16. 20. Yamada N, Oizumi S, Kikuchi E, et al. CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection. Cancer Immunol Immunother 2010; 59: 1543-9. 21. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol 2004; 22: 329-60. 22. The second involves the activation of cytotoxic lymphocytes. Reversal of the Immunosuppressive Tumor Microenvironment Numerous monoclonal antibodies have been developed to target and activate myeloid antigenpresenting cells for use as cancer immunotherapeutics. These therapies have been generated with a rationale of altering the immunosuppressive environment as well as improving antigen presentation/activation of T cells. Examples of targets for ...
Regulatory T cells (Tregs) exert various suppressive mechanisms to dampen the host immune response which can help tumor cells to escape immune surveillance. However, the prognostic value of tumor-infiltrating Tregs (Ti-Tregs) is controversial based on the expression of FoxP3 marker in cancer patients. Here, we decipher the phenotype of Tregs infiltrating human lung cancer to determine their role in shaping the immune response against tumor cells. Our aim was to study the differentiation, activation, and immunosuppression status of Ti-Tregs in different areas of human lung tumors. Immunohistochemistry was performed on paraffin-embedded tissue sections for CD3 and FoxP3 stainings, and phenotypic analysis was carried out on fresh human lung cancer specimens (n=50) by flow cytometry. In lung cancer patients, Ti-Tregs localize in the different part of the tumor i.e. tumor nests, ...
Adoptive T cell therapy (ATT) can be highly effective in treating individuals with late stage cancer. Treating metastatic melanoma with in vitro expanded tumor-infiltrating lymphocytes achieved objective response rates (49-72%), depending on the preconditioning regimen (Rosenberg et al., 2011). This represents one of the most effective therapies of metastatic melanoma for patients amenable to ATT. Nevertheless, in 74/93 patients, tumors recurred within 3 yr after treatment (Rosenberg et al., 2011). Tumor recurrence can be attributed to the transferred T cells, the cancer, or the host. Metastatic melanoma trials suggested loss of the target antigen (Melan-A/Mart-1) as escape mechanism (Yee et al., 2002; Mackensen et al., 2006), likely because of the poor binding of Melan-A/Mart-1 epitope to MHC class I (MHC-I) restriction element (HLA-A*0201), a factor that predicts tumor escape (Engels et al., 2013). In other cases, loss of the ...
Molecular subtypes of breast cancer and presence of tumor-infiltrating immune cells have both been implicated as important predictive and prognostic factors for improved risk stratification and treatment individualization of breast cancer patients. Their association, however, has not been studied in detail. The aim of this study was to evaluate the expression of the T cell markers CD8, FoxP3, CD3 and ζ-chain in molecular subtypes of the invasive margin and tumor center of breast cancer and corresponding sentinel nodes and to deduct prognostic information from these findings. Tumor and sentinel node sections from 177 patients with primary, invasive, unilateral early-stage breast cancer were stained by immunohistochemistry and T-cell phenotypes quantified manually. Clinical data were collected from medical records. The degree of T-cell infiltration and expression of all markers differed significantly among the molecular subtypes, being highest ...
Background: The anti-programmed cell death 1 (PD-1) antibody pembrolizumab is clinically active against non-small cell lung cancer (NSCLC). In addition to T-cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of advanced NSCLC patients, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC. Methods: In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1% were randomly allocated to group A (55 patients, pembrolizumab plus NK cells) and group B (54 patients, pembrolizumab alone). The patients received intravenous pembrolizumab (10 mg/kg) once every 3 weeks and continued ...
Scientifica is a peer-reviewed, Open Access journal that publishes research articles, review articles, and clinical studies covering a wide range of subjects in the life sciences, environmental sciences, health sciences, and medicine. The journals Editorial Board is divided into the 65 subject areas included within the journals scope.
Tumor-infiltrating neutrophil (TIN) has been reported to be an independent predictor in multiple tumors, but its role in the development of adenocarcinoma of the esophagogastric junction (AEG)...
OUTLINE: This is a pilot study. Patients are stratified according to treatment (intravenous [IV] tumor-infiltrating lymphocytes [TIL] after a nonmyeloablative preparative regimen vs intra-arterial [IA] TIL after a nonmyeloablative preparative regimen vs IV TIL after a myeloablative preparative regimen with chemotherapy and total-body irradiation).. Patients undergo positron emission tomography with fludeoxyglucose F 18 (FDG-PET)/CT fusion imaging at baseline (before starting TIL infusion), once between days 1-4 after TIL infusion, and once between days 5-8 after TIL infusion.. PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study. ...
Merkel cell carcinoma (MCC) is a lethal, virus-associated cancer that lacks effective therapies for advanced disease. Agents blocking the PD-1/PD-L1 pathway have shown objective, durable tumor regressions in patients with advanced solid malignancies and efficacy has been linked to PD-L1 expression in the tumor microenvironment. To investigate whether MCC might be a target for PD-1/PD-L1 blockade, we examined MCC PD-L1 expression, its association with tumor-infiltrating lymphocytes (TIL), Merkel cell polyomavirus (MCPyV), and overall survival. Sixty-seven MCC specimens from 49 patients were assessed with immunohistochemistry for PD-L1 expression by tumor cells and TILs, and immune infiltrates were characterized phenotypically. Tumor cell and TIL PD-L1 expression were observed in 49% and 55% of patients, respectively. In specimens with PD-L1(+) tumor cells, 97% (28/29) showed a geographic ...
Lymphocytes were isolated from 43 surgical samples of breast cancer after tumor enzyme digestion and Ficoll/Verographine procedure. In all, 23 specimens from lymphocytic-tissue infiltrates were analyzed (in some cases, material from 2 or 3 patients was combined). The ability of tumor-infiltrating lymphocytes (TIL) to convert androstenedione was demonstrated, as evaluated by hard-water release from the androgenic precursor 3H-1beta-androstenedione. In material obtained from menopausal women this ability was higher than in the women of reproductive age. A positive correlation was revealed between the level of androstenedione conversion in TIL and aromatase activity in tumor tissue, while no correlation was shown between androstenedione conversion in TIL and percentage of tumor cells in lymphocytic suspension. The data obtained suggest that factors secreted by a neoplasm are able to induce aromatase gene expression in TIL ...
TIL from metastatic melanoma proliferated by greater than 1,000-fold (840-3,675, mean 1,543) after 6 wk in culture of mixtures of TIL and tumor cells with rIL-2 alone. Cytolysis was restricted to autologous tumor cells. CD8+ T cells were the predominant population of TIL before and after expansion, and were primarily responsible for autologous tumor-specific CTL activity. No other rIL-2-activated lymphocytes from peripheral blood, lymph nodes with melanoma metastasis, or TIL from sarcoma or renal cell carcinoma had autologous tumor-specific CTL activity. There were few or no CD16+ NK cells in TIL from metastatic melanoma before or after incubation with rIL-2, respectively. However, TIL from sarcoma or renal cell carcinoma contained a substantial proportion of CD3-CD16+ NK cells, which increased in number in culture with rIL-2. Purified CD16+ ...
Keywords: DNA destabilizers, chemotherapy, light, histone deacetylase inhibitor, PD-L1, CTLA-4 1. Launch Principal and repeated solid malignancies are characterized by the intratumoral existence of several resistant cells frequently, t lymphocytes particularly, C cells, NK SR141716 cells, macrophages and various other antigen promoting cells. Deposition of Compact disc3+ Tumor-Infiltrating Lymphocytes (TILs) is normally a advantageous prognostic signal in most solid malignancies. Particularly, the existence of cytotoxic Compact disc8+ TILs is normally prognostic for success extremely, suggesting a useful function for these cells in the control of cancers development. This also suggests that healing realtors that concomitantly wipe out cancer tumor cells and induce or beef up web host anti-tumor defenses will ...
TY - JOUR. T1 - Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma. T2 - Implications for PD-1 pathway blockade. AU - Taube, Janis M. AU - Young, Geoffrey D.. AU - McMiller, Tracee L.. AU - Chen, Shuming. AU - Salas, January T.. AU - Pritchard, Theresa S.. AU - Xu, Haiying. AU - Meeker, Alan Keith. AU - Fan, Jinshui. AU - Cheadle, Chris. AU - Berger, Alan E.. AU - Pardoll, Andrew Mark. AU - Topalian, Suzanne. PY - 2015/9/1. Y1 - 2015/9/1. N2 - Purpose: Blocking the immunosuppressive PD-1/PD-L1 pathway has antitumor activity in multiple cancer types, and PD-L1 expression on tumor cells and infiltrating myeloid cells correlates with the likelihood of response. We previously found that IFNG (interferon-gamma) was overexpressed by tumor-infiltrating lymphocytes in PD-L1+ versus PD-L1(-) melanomas, creating adaptive immune resistance by promoting PD-L1 display. This study was undertaken to identify ...
Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passaging of Kras-mutated, p53-deficient murine lung cancer cells (p53R172HΔg/+K-rasLA1/+) in a syngeneic host exposed to repetitive dosing with anti-mouse PD-1 antibodies. PD-L1 (CD274) expression did not differ between the resistant and parental tumor cells. However, the expression of important molecules in the antigen presentation pathway, including MHC class I and II, as well as β2-microglobulin, were significantly downregulated in the anti-PD-1-resistant tumors compared with parental tumors. Resistant tumors also contained fewer CD8+ (CD8α) and CD4+ tumor-infiltrating lymphocytes and reduced production of IFNγ. ...
View more ,Triple-negative breast cancers (TNBCs) constitute a heterogeneous subtype of breast cancers that have a poor clinical outcome. Although no approved targeted therapy is available for TNBCs, molecular-profiling efforts have revealed promising molecular targets, with several candidate compounds having now entered clinical trials for TNBC patients. However, initial results remain modest, thereby highlighting challenges potentially involving intra- and intertumoral heterogeneity and acquisition of therapy resistance. We present a comprehensive review on emerging targeted therapies for treating TNBCs, including the promising approach of immunotherapy and the prognostic value of tumor-infiltrating lymphocytes. We discuss the impact of pathway rewiring in the acquisition of drug resistance, and the prospect of employing combination therapy strategies to overcome challenges towards identifying clinically-viable targeted treatment options for TNBC ...
Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells. In the 1960s, lymphocytes were discovered to be the mediators of allograft rejection in animals. Attempts to use T cells to treat transplanted murine tumors required cultivating and manipulating T ...
The primary endpoints of this pilot trial will be the safety and feasibility of administering ipilimumab with Adoptive Cell Therapy (ACT) using TIL. The data analysis will mainly be descriptive. All study results will be preliminary and of exploratory in nature due to the pilot status and small sample size of the trial. Feasibility is defined as the ability to deliver at least 50% (i.e., two out of four) of the planned doses of ipilimumab and successfully treat at least 60% (i.e., ≥ 6/10) of the patients with TIL. All participants will be evaluable for toxicity from the time of their first protocol treatment. Toxicity will be reported by type and severity according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4 ...
T cells in tumors-the so-called tumor infiltrating lymphocytes (TIL) have been studied intensively over the past years. Compelling evidence point to a clinical relevance for high numbers of T cells at the tumor site with CD8 memory T cells as a key denominator for overall survival (OS) in patients with colo-rectal cancer (CRC), and also for others solid cancers. These data goes hand in hand with studies of clonality of TIL showing the T cells among TIL are expanded clonally, and also that tumor specific T cells of CD4 as well as CD8 type are enriched at the tumor site. The tumor microenvironment is hostile to T cell function e.g., due to expression of enzymes that depletes the amino acids tryptophan and arginine, high concentration of tumor secreted lactate, and presence innate cells or ...
Intellicyt Corporation®, Part of the Sartorius Group. 5700 Pasadena Ave. NE, Albuquerque, NM 87113. A critical process in bio-manufacturing of adoptive cell therapies such chimeric antigen receptor (CAR) T and tumor infiltrating lymphocyte (TIL) therapies is the ex vivo expansion of T cells. Recent clinical studies show a correlation between in vivo expansion and persistence of infused T cells and patient outcomes. Additional studies show that a subset of functional memory T cells including T memory stem cells (Tscm), central memory T cells (Tcm) and other less differentiated T cell subsets are responsible for the majority of in vivo expansion and persistence leading to increased anti-tumor responses. This suggests that ex vivo protocols generating higher percentages of Tscm and Tcm in the total cell product will lead to significant clinical ...
TY - JOUR. T1 - Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms. T2 - An open-label study. AU - Kang, Dae Wook. AU - Adams, James. AU - Gregory, Ann C.. AU - Borody, Thomas. AU - Chittick, Lauren. AU - Fasano, Alessio. AU - Khoruts, Alexander. AU - Geis, Elizabeth. AU - Maldonado, Juan. AU - McDonough-Means, Sharon. AU - Pollard, Elena L.. AU - Roux, Simon. AU - Sadowsky, Michael J.. AU - Lipson, Karen Schwarzberg. AU - Sullivan, Matthew B.. AU - Caporaso, J. Gregory. AU - Krajmalnik-Brown, Rosa. PY - 2017. Y1 - 2017. N2 - Background: Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal ...
Time: 12:30-1:30 p.m.. Abstract: Through flow cytometry analysis, cell sorting and in vitro techniques, AgonOx has developed a workflow for detecting, isolating and expanding endogenous tumor antigen-specific CD8 T cells from individuals own tumor tissue (Duhen, et al, Nature Communications, volume 9, Article number: 2724 (2018)). The highly enriched tumor-reactive T cells are grown in vitro with a method optimized to achieve large cellular expansion and to maintain a broad repertoire of tumor-reactive T cell clones. The expanded T cell product typically retains much of its original T cell clonal diversity and preserves or reinvigorates its tumor-lytic potential. This platform yields a uniquely personalized subject-derived product for individuals from a wide variety of tumor types. This tumor-specific T cell product is specific/personalized for each subject and has clinical research applications in the immune oncology field. ...
Increased levels of myeloid cells, especially myeloid-derived suppressor cells (MDSCs), have been reported to correlate with bad prognosis and reduced survival in cancer patients. However, limited data are available on their conclusive phenotypes and their correlation with clinical settings. The aim of this study was to investigate levels and phenotype of myeloid cells in peripheral blood and tumor microenvironment of colorectal cancer (CRC) patients, compared to blood from healthy donors (HDs) and paired, adjacent non-tumor colon tissue. Flow cytometric analysis was performed to examine the expression of different myeloid markers in fresh peripheral blood samples from CRC patients and HDs, and tissue-infiltrating immune cells from CRC patients. We found significantly higher levels of ...
Immune regulation is crucial for the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL). It has been reported that Th17 cells as a newly identified subset of CD4+ T cells are involved in the pathogenesis of several hematological disorders. However, the role of Th17 cells in the pathophysiology of B-ALL is still unclear. The frequencies of T cells were determined by flow cytometry in the peripheral blood and bone marrow of 44 newly diagnosed B-ALL patients and 25 age-matched healthy donors. The cell viability and apoptosis were determined by CCK-8 assay and Annexin V staining, respectively. Western blot was applied to identify the level of Akt and Stat3 phosphorylation. We assessed and observed a significantly increased frequency of Th17 cells and a drastically decreased frequency of Th1 ...
The drug capecitabine (CAP) is a thymidine Pi-deoxyribosyltransferase (TP) activated oral fluorpyrimidine that generates 5-fluorouracil (5-FU), prefentially, within tumors. Here, in 38 patients with pancreatic cancer we analyzed immunohistochemical TP expression in pancreatic cancer tissue (PCT) and adjacent nonmalignant pancreatic tissue (ANMPT). In addition, a correlation with the main clinical pathological features was made. Furthermore, TP-positive macrophages (MO) isolated from neoplastic tissue were determined. The mean of TP-positive epithelial cells and endothelial cells in terms of microvessel density was significantly higher in PCT than in ANMPT. Because pancreatic cancer is sensitive to 5-FU, TP-activated oral CAP in tumoral and endothelial cells and tumor infiltrating MO could increase the concentration of 5-FU at tumor site, thus resulting in an enhanced antitumor activity.. ...
The possibility of tumors with a precision controlled dose of heat can be used destroy tumors destroy tumors at higher temperatures, in order to treat tumors in combination with chemotherapy and / or radiation at moderate temperatures for increased efficacy and reduced toxicity and the controlled release of therapeutic elicit drugs and genes at tumor sites at lower temperatures. Forward looking statementsechnology has from the Massachusetts Institute of Technology, Medifocus has further precision of the microwave focusing and control ability of refined and developed a commercial system exclusively devoted to the treatment of breast cancer... At the University of Oklahoma Health Sciences Center, was the Principal Investigator of the multi-institutional study, which was conducted on 10 breast centers in the United States and the United Kingdom.. This study was. Reports Improved Clinical Efficacy in Phase II, randomized clinical trial for the treatment of early breast cancer cancer - Medifocus Inc. ...
Targeting the dynamic tumor immune microenvironment (TIME) can provide effective therapeutic strategies for cancer. Neutrophils are the predominant leukocyte population in mice and humans, and mounting evidence implicates these cells during tumor growth and metastasis. Neutrophil extracellular traps (NETs) are networks of extracellular neutrophil DNA fibers that are capable of binding tumor cells to support metastatic progression. Here, we demonstrate that circulating NET levels are elevated in advanced esophageal, gastric, and lung cancer patients compared with local cancers and healthy controls. Using preclinical murine models of lung and colon cancer, in combination with intravital video microscopy, we show that NETs functionally regulate disease progression and that blocking NETosis through multiple strategies significantly inhibits spontaneous metastasis to the lung and liver. Furthermore, we show how inhibiting ...
While chemotherapy is one of the most used treatments in oncology, the systemic administration of chemotherapeutics generally results in undesired damages to healthy tissues and cells, side effects such as severe nausea and leukopenia, and reduced efficacy due to multidrug resistance and poor target accessibility. The limitations of conventional chemotherapy formulation has prompted the development of alternative nanomaterials-based strategies to achieve targeted and stimuli sensitive payload delivery to reach optimal local drug concentration at tumor sites. In this study, the anticancer drug chlorambucil (Clb) was conjugated to the surface of silica coated lithium niobate (LNO) harmonic nanoparticles (HNPs) using a photocaging tether based on coumarin-4-yl methyl derivative. Upon laser pulsed femtosecond irradiation at 790 nm, the second harmonic emission from the metal oxide core induced the efficient release of Clb, with concomitant contribution from the nonlinear ...
Adoptive T-cell therapies for hard-to-treat blood disorders and cancers have been all the rage since 2015. Even so, these potentially game-changing treatments have run into a host of safety problems and have even led to the death of a handful of patients, especially when companies have combined these experimental cell therapies with highly toxic chemotherapies in order to juice their efficacy.. Houston-based Bellicum Pharmaceuticals (NASDAQ:BLCM) is working to change this outlook by incorporating powerful molecular switches into its cell therapies. These switches are "designed to eliminate, reduce or activate therapeutic cells," thereby enhancing their safety and efficacy. To date, the company has reported extremely encouraging results for its lead product candidate, BPX-501, in the haploidentical transplant setting in children with a range of deadly blood disorders.. Going forward, Bellicum is close to initiating clinical trials for its other adoptive cell ...
Buy the best and highest quality mobile suit gundam chars counterattack products at the cheapest price only from animeprintz.com. Fast home delivery.
Feucht, Judith; Opherk, Kathrin; Lang, Peter; Kayser, Simone; Hartl, Lena; Bethge, Wolfgang; Matthes-Martin, Susanne; Bader, Peter; Albert, Michael H.; Maecker-Kolhoff, Britta; Greil, Johann; Einsele, Hermann; Schlegel, Paul-Gerhardt; Schuster, Friedhelm R.; Kremens, Bernhard; Rossig, Claudia; Gruhn, Bernd; Handgretinger, Rupert; Feuchtinger, Tobias ...
We have demonstrated that transgenic expression of proexendin-4 is associated with the development of lymphocytic infiltration and immune system activation in MT-Exendin transgenic mice. Moreover, the immune response in MT-Exendin mice appears to be T-cell mediated, as lymphocytic infiltrates were found in multiple tissues. However, despite the occurrence of lymphocytic infiltrates, MT-Exendin mice do not appear to have a general breakdown in tolerance as evidenced by a lack of anti-ssDNA or anti-dsDNA antibody production. Furthermore, the development of lymphocytic infiltrates was sporadic and varied considerably in mice of different ages.. MT-Exendin transgenic mice develop antibodies to Ex-4; however, whether or not these antibodies are neutralizing was not determined. We also found that antibody production against proexendin-4-derived peptides can be triggered in wild-type mice upon repeated immunization with Ex-4 or ENTP in the presence, but not in the absence, of Freunds adjuvant. Ex-4 ...
The goal of cancer immunotherapy is to activate pathways to lyse tumour cells. Monoclonal antibodies, tumour peptide vaccines, adoptive cell therapy and use of
Peripheral blood lymphocytes derived from patients with renal cell carcinoma were stimulated with interleukin 2 and tested in a 4-hour 51chromium-release cytotoxicity assay against autologous cultured tumor and myeloid K562 cells. Of 23 patients auto
CD8+ cytotoxic T lymphocytes (CTLs) have potent antitumor activity and therefore are leading candidates for use in tumor immunotherapy. The application of CTLs for clinical use has been limited by the susceptibility of ex vivo-expanded CTLs to become dysfunctional in response to immunosuppressive microenvironments. Here, we developed a microRNA-targeting (miRNA-targeting) approach that augments CTL cytotoxicity and preserves immunocompetence. Specifically, we screened for miRNAs that modulate cytotoxicity and identified miR-23a as a strong functional repressor of the transcription factor BLIMP-1, which promotes CTL cytotoxicity and effector cell differentiation. In a cohort of advanced lung cancer patients, miR-23a was upregulated in tumor-infiltrating CTLs, and expression correlated with impaired antitumor potential of patient CTLs. We determined that tumor-derived TGF-β directly suppresses CTL immune function by elevating miR-23a and downregulating BLIMP-1. Functional blocking of miR-23a ...
Vol 17: Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer.. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Control of gene expression is a key issue for adoptive immunotherapy because current technologies do not allow titration of the timing or levels of therapeutic activity. This has made many potential applications difficult or impossible to deploy safely and effectively. The lack of tunability also makes it difficult to safely express potent proteins with narrow therapeutic windows or transient expression.. Obsidians current focus is Adoptive Cell Therapy (ACT) for cancer, where tremendous progress has been made in recent years but where todays therapies remain difficult to titrate, control, or modulate. Among the challenges with current approaches are:. ...
Despite the numerous constraints on p53 function in RCC [24-27], sunitinib treatment does induce the expression of several p53-dependent genes (e.g. NOXA, HDM2, p21waf) in RCC xenografts. The induction of these genes is, however, limited to the interval during which tumor growth is suppressed and is attenuated once resistance develops. Although several factors have been shown to block p53 transcriptional activity in RCC, these are for the most part stable genetic alterations (e.g. KR-POK expression) that are not known to be subject to regulation by hypoxia or other metabolic changes that occur during treatment with angiogenesis inhibitors.. The factor(s) responsible for the transient activation and subsequent inactivation of p53 transcriptional activity during the course of treatment with sunitinib are unknown but at least one well-characterized p53 transcriptional suppressant (i.e. HDMX) appears to be temporally linked to p53 function in our xenograft models and may therefore be a candidate. ...
However, clinical research is still at an early stage and only few evidences of efficacy of adoptive immunotherapy in EOC have been reported, in particular regarding the addition of a maintenance therapy with CIK or TIL to front line standard treatments. This additional therapy seems to be able to improve clinical outcome prolonging PFS and OS in patients with a newly diagnosed EOC [42, 55]. On the contrary, the few published clinical trials with NK in other clinical settings such as multi-resistant EOC, were not able to demonstrate any activity of adoptive immunotherapy ...
A higher number of mutations in melanoma cells, coupled with increased T-cell activation, increases survival of patients receiving adoptive T-cell therapy
14 February 2013. Accra, Feb. 12, Ghana News Agency - Tablet India Limited (TIL), a leading pharmaceutical manufacturer and marketer of high quality products globally, has unveiled Miss Nadia Buari, as its brand ambassador in Accra. This collaboration is aimed to raise more awareness about the products of TIL and help popularize TIL products across the West African region. Some products of TIL whic.... Read More ...
Lets see what we can do here:. 1. The "psychic eyeroll" is purely for dramatic effect, since it looks kinda boring just having a mentally-powerful person just sitting there or checking Facebook on their phone for the umpteenth time.. 2. Its never stated that the Dio Sukuri copies can merge, although that would explain why the excess ones just kinda disappear. Chalk that up to lousy writing!. 3. Scapula is somehow less vile than Ren and even less vile and douchey than John Kricfalusi.. Hope that helps!. ...
low lymphocytes - MedHelps low lymphocytes Center for Information, Symptoms, Resources, Treatments and Tools for low lymphocytes. Find low lymphocytes information, treatments for low lymphocytes and low lymphocytes symptoms.
Apple Watch Series 2 Nike+, 42mm, sølvfarve og med Nike rem. Normalpris med 42mm urkasse kr. 3.499,- spar kr. 500,- Rem med urkasse på 42mm passer til håndled på 140-210 mm. Uret er uafhængig af Iphone, og du kan frit bruge den indbyggede GPS til at mål
Køb CIALIS til EKSTRA LAVE PRISER. Mange forskellige generiske og mærkevare pakker. Generisk CIALIS af BEDSTE kvalitet med 100% garanteret tilfredshed! Krop Vænne Sig Til Cialis

New YorkNew York

... and explore the secret of a healthy cell from cell death to phagocytosis. Such genes coding cell death may result in severe ... 80 years till now, the diabetic patients can’t eradicate the disease for life or have other fundmental treatment drugs aside ... ※ Winners of Nobel Prize in Physiology & Medicine of 1923 disclosed the mysterious path connection between insulin and ... and illustrated that tumor virus can enter normal cells through the same path and the cells can be transformed to tumor cells. ...
more infohttp://www.medical-supply-company.org/medicalsupply/new-york

Stem cells from diabetic patients coaxed to become insulin-secreting cells | Veterinary Sciences TomorrowStem cells from diabetic patients coaxed to become insulin-secreting cells | Veterinary Sciences Tomorrow

Stem cells from diabetic patients coaxed to become insulin-secreting cells. Posted on June 1, 2016. by Vetscite ... Louis and Harvard University have produced insulin-secreting cells from stem cells derived from patients with type 1 diabetes. ... "The cells weve manufactured sense the presence of glucose and secrete insulin in response. And beta cells do a much better job ... own stem cells to manufacture new cells that make insulin.. The researchers showed that the new cells could produce insulin ...
more infohttp://vetscite.org/2016/06/stem-cells-from-diabetic-patients-coaxed-to-become-insulin-secreting-cells/

Human | Veterinary Sciences Tomorrow | Page 2Human | Veterinary Sciences Tomorrow | Page 2

Stem cells from diabetic patients coaxed to become insulin-secreting cells. Posted on June 1, 2016. by Vetscite ... Louis and Harvard University have produced insulin-secreting cells from stem cells derived from patients with type 1 diabetes. ... If damaged cells are replaceable, type 1 diabetics wouldnt need insulin shots. Signaling a potential new approach to treating ... In Cell Stem Cell on June 30, bioethicist Leigh Turner (@LeighGTurner) and stem cell […] ...
more infohttp://vetscite.org/tag/human/page/2/

New battery could steer China into lead in electric-car marketNew battery could steer China into lead in electric-car market

Stem cells from diabetic patients coaxed to become insulin-secreting cells. *. Invention turns energy in the air into ...
more infohttp://www.innovationtoronto.com/2010/11/new-battery-could-steer-china/

ASAIO JournalASAIO Journal

Insulin-Secreting Cells from PDX1-Overexpressing Human-Induced Pluripotent Stem Cell Derived from Diabetic Patient. Rajaei, ... In Vitro Generation of Glucose-Responsive Insulin-Secreting Cells from PDX1-Overexpressing Human-Induced Pluripotent Stem Cell ... Repeated Ramp Tests on Stable LVAD Patients Reveal Patient-Specific Hemodynamic Fingerprint. Imamura, Teruhiko; Burkhoff, ... Impact of Patient Distance From Ventricular Assist Device-Implanting Center on Short- and Long-Term Outcomes. ...
more infohttps://journals.lww.com/asaiojournal/pages/default.aspx

124(5)124(5)

Diabetic patients exhibit a reduction in β cells, which secrete insulin to help regulate glucose homeostasis; however, little ... EndoC-βH1 cells display many functional properties of adult β cells, including expression of β cell markers and insulin ... expression, leading to an arrest of cell proliferation and pronounced enhancement of β cell-specific features such as insulin ... H3K9me2 was found at high levels in naive Th cells and was lost following Th cell activation. Loss of G9A in naive T cells was ...
more infohttps://www.jci.org/124/5

JoVE | Peer Reviewed Scientific Video Journal - Methods and ProtocolsJoVE | Peer Reviewed Scientific Video Journal - Methods and Protocols

cell replacement may efficiently cure type 1 diabetic (T1D) patients whose insulin-secreting ?-cells have been selectively ... To generate insulin-secreting cells we used two cell sources: rat multipotent adult progenitor cells (rMAPC) and the highly ... Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells. ... in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and ...
more infohttps://www.jove.com/visualize?author=Felipe%20Pr%C3%B3sper%20

Research on stem cells wins first prize for Hebrew University ... (	 Jerusalem June 20 2010 -- World-reco...)Research on stem cells wins first prize for Hebrew University ... ( Jerusalem June 20 2010 -- World-reco...)

... cell that may differentiate ...,Research,on,stem,cells,wins,first,prize,for,Hebrew,University,researcher,biological,biology ... direct human ES cells to differentiate into insulin-secreting pancreatic beta cells for transplantation into diabetic patients ... Although the exogenous insulin therapy has dramatically reduced mortality from diabetes, patients often succumb to the long- ... Human ES cells may offer an unlimited source of beta cells for transplantation, once an effective differentiation protocol is ...
more infohttp://www.bio-medicine.org/biology-news-1/Research-on-stem-cells-wins-first-prize-for-Hebrew-University-researcher-14022-1/

Top 15 Benefits of Indian Gooseberry or Amla | Organic FactsTop 15 Benefits of Indian Gooseberry or Amla | Organic Facts

It stimulates the isolated group of cells that secrete insulin, thus reducing blood sugar in diabetic patients. When blood ... A 2011 research study on the effect of the amla fruit on blood glucose and lipid profile of type 2 diabetics stated that it has ... Amla juice, in Ayurveda, is often used to increase the white blood cells in the body, which are the main line of defense for ... White blood cells attack and eliminate foreign toxins and substances into the bloodstream throughout the body. ...
more infohttps://www.organicfacts.net/health-benefits/fruit/indian-gooseberry-amla.html?utm_source=internal&utm_medium=link&utm_campaign=also-see

Endoplasmic reticulum stress in beta cells: latent mechanism of secondary sulfonylurea failure in type 2 diabetes?Endoplasmic reticulum stress in beta cells: latent mechanism of secondary sulfonylurea failure in type 2 diabetes?

... are still largely used for treatment of type 2 diabetic patients. More recently concern has been raised with respect to ... Sulfonylureas, by stimulating beta cell to secrete insulin, are still largely used for treatment of type 2 diabetic patients. ... Insulin-Secreting Cells / drug effects, physiology*. Models, Biological. Sulfonylurea Compounds / therapeutic use*. Treatment ... like favoring beta cell apoptosis and beta cell exhaustion, which is believed as the reason for high rate secondary ...
more infohttp://www.biomedsearch.com/nih/Endoplasmic-reticulum-stress-in-beta/18786775.html

Defymed to Develop an Implantable Device for Insulin Delivery and Improved Diabetes ManagementDefymed to Develop an Implantable Device for Insulin Delivery and Improved Diabetes Management

Read about how French medical device manufacturer Defymed is developing an insulin delivery device designed to be implanted ... into the abdomen of patients with type 1 diabetes ... insulin-secreting cells into a diabetic patient without the ... "With ExOlin, Defymed shall offer diabetic patients a more physiological approach for delivering insulin," said Dr. Séverine ... Patients with type 1 diabetes - and some with type 2 - control their blood sugar using a variety of subcutaneous insulin ...
more infohttps://xtalks.com/implantable-device-insulin-delivery-diabetes-848/

Term Paper: In Vitro Fertilization … | 8 PagesTerm Paper: In Vitro Fertilization … | 8 Pages

... stem cells have the ability to create insulin-secreting cells that have potential for normalizing blood glucose in diabetics. ... Therapies derived from the patients own stem cells have little probability of rejection. It has been found that only adult ... They are allowed to develop from a few cells to about a 100 cells for about 12 days and then the human embryonic stem cells ... Pluripotent stem cells can however be extracted from the placentas left over from healthy live births, cord blood, adult bone ...
more infohttps://www.essaytown.com/subjects/paper/vitro-fertilization/5695552

Cytoadherence of Lymphocytes From Type I Diabetic Subjects to Insulin-Secreting Cells: Marker of Anti-β-Cell Cellular Immunity ...Cytoadherence of Lymphocytes From Type I Diabetic Subjects to Insulin-Secreting Cells: Marker of Anti-β-Cell Cellular Immunity ...

We studied the ability of lymphocytes from type I (insulin-dependent) diabetic patients to adhere to murine β-cells. ... Cytoadherence of Lymphocytes From Type I Diabetic Subjects to Insulin-Secreting Cells: Marker of Anti-β-Cell Cellular Immunity ... Cytoadherence of Lymphocytes From Type I Diabetic Subjects to Insulin-Secreting Cells: Marker of Anti-β-Cell Cellular Immunity ... Cytoadherence of Lymphocytes From Type I Diabetic Subjects to Insulin-Secreting Cells: Marker of Anti-β-Cell Cellular Immunity ...
more infohttp://diabetes.diabetesjournals.org/content/36/12/1356

Therapeutic Cloning, and Stem Cell Research | Science Features | Naked ScientistsTherapeutic Cloning, and Stem Cell Research | Science Features | Naked Scientists

Most clones are created through a process called somatic cell nuclear transfer. Essentially, a scientist uses a tiny needle ... to pull DNA material from the nucleus of a donor cell and transfer it into a hollow egg. The egg has had its own nucleus and ... Therapeutic cloning involves the replication of human embryos to harvest stem cells for medical uses. ... paralysis or Parkinsons patients; or new insulin-secreting pancreas cells for diabetics. Down the road, scientists believe it ...
more infohttps://www.thenakedscientists.com/articles/science-features/therapeutic-cloning-and-stem-cell-research

Profile: Nan Gao | Rutgers-Newark Colleges of Arts & SciencesProfile: Nan Gao | Rutgers-Newark Colleges of Arts & Sciences

The pancreatic beta-cells of diabetic patients are incompetent to secrete insulin in response to glucose stimulations. Although ... Foxa2 controls vesicle docking and insulin secretion in mature beta cells. Cell Metabolism (2007); 6(4):267-79. ... the glucose-directed insulin granule vesicular exocytosis in healthy and diabetic beta-cells. We derive and characterize ... One of the cell biology enigmas is how cells achieve asymmetry to facilitate their directional migration, secretion, asymmetric ...
more infohttps://www.ncas.rutgers.edu/nan-gao

In Vitro Proliferation of Porcine Pancreatic Islet Cells for β-Cell Therapy ApplicationsIn Vitro Proliferation of Porcine Pancreatic Islet Cells for β-Cell Therapy Applications

... attempts are being made to develop alternative sources of insulin-secreting cells. Stem cells differentiation and reprograming ... through transplantation is the only curative treatment to establish a long-term stable euglycemia in diabetic patients. Owing ... thus suggesting that the cells may be redifferentiated into insulin-secreting β-like cells. ... β-cells phenotype. In this study, we cultured islet-derived cells in vitro and examined the expression of β-cell genes during ...
more infohttps://www.hindawi.com/journals/jdr/2016/5807876/abs/

Secret Sauce for Personalized, Functional Insulin-Producing..."Secret Sauce" for Personalized, Functional Insulin-Producing...

Salk scientists have solved a longstanding problem in the effort to create replacement cells for diabetic patients. The team ... "Secret Sauce" for Personalized, Functional Insulin-Producing Cells News Apr 14, 2016 ... "When we added ERR-gamma to pre-diabetic beta cells in a dish, we successfully created a glucose-responsive, beta-like cell," ... The Salk technology begins with induced pluripotent cells (iPSC), a stem cell technique where tissue from a patient-such as ...
more infohttps://www.technologynetworks.com/cell-science/news/secret-sauce-for-personalized-functional-insulinproducing-cells-209002

Nutritional and Botanical Agents: Management Type 2 Diabetes Mellitus (April 2014) Townsend Letter for Doctors & PatientsNutritional and Botanical Agents: Management Type 2 Diabetes Mellitus (April 2014) Townsend Letter for Doctors & Patients

... secrete and activate insulin receptors on the cell. Studies have shown that adding zinc to diabetic patients can be helpful. ... Zinc also has an antioxidant effect on cells in diabetic patients. *Chromium polynicotinate: Chromium has a vital role in ... Insulin resistance is the key metabolic abnormality in type 2 diabetic patients, resulting in increased appetite, elevated ... One study showed that giving taurine to diabetic patients for a month required a reduction in their insulin dosing, to avoid ...
more infohttp://www.townsendletter.com/April2014/rolenut0414.html

The pancreas in idiopathic Addisons disease--a search for a prediabetic pancreas.  - PubMed - NCBIThe pancreas in idiopathic Addison's disease--a search for a prediabetic pancreas. - PubMed - NCBI

While there was no evidence of diabetes or destruction of insulin-secreting beta cells in the remaining 10 patients, islets in ... One patient had been diabetic for 12 years and three patients were found to be diabetic during their terminal admission. ... These included the presence of alpha-interferon in endocrine cells, hyper-expression of class I major histocompatibility ... Autopsy pancreases were studied from 14 patients who had idiopathic Addisons disease. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/3397044?dopt=Abstract

Stem cells: Therapy, controversy, and researchStem cells: Therapy, controversy, and research

They are nonspecific cells that could develop into any kind of cell in the body. Scientists hope to use them one day in ... However, there is controversy about some uses of stem cells. Find out more. ... Stem cells from diabetic patients coaxed to become insulin-secreting cells. https://medicine.wustl.edu/news/stem-cells-diabetic ... the new cells may either become another stem cell or a specific cell, such as a blood cell, a brain cell, or a muscle cell. ...
more infohttps://www.medicalnewstoday.com/articles/200904.php?sr

Stem cells: Therapy, controversy, and researchStem cells: Therapy, controversy, and research

They are nonspecific cells that could become any kind of cell in the body. There is hope that they may be used in regenerative ... However, there is controversy about some uses of stem cells. Find out more. ... Stem cells are a type of cell that we all produce. ... cells-diabetic-patients-coaxed-develop-insulin-secreting-cells/ ... When a stem cell divides, the new cells may either become a stem cell or a specific cell, such as a blood cell, a brain cell, ...
more infohttps://www.medicalnewstoday.com/articles/200904.php

Diabetes type 1 caused by diet, how to relieve muscle pain in chest, natural remedies diabetes mellitus quizlet, insulin...Diabetes type 1 caused by diet, how to relieve muscle pain in chest, natural remedies diabetes mellitus quizlet, insulin...

minor wound care diabetic patients, type 2 diabetes and multidrug-resistant tuberculosis, type 1 diabetes diet example, herbal ... patients need a daily dosage of this vitamin E as it helps to prevent cell damage which is essential for a diabetic patient. ... The beta cells in the islets of Langerhans in the human pancreas secrete a hormone known as the insulin.. In this type of ... Pancreatic cells are stimulated to secrete required amount of insulin so that it may help in oxidation of sugar or glucose ...
more infohttp://s3.amazonaws.com/brat4drdiabete/natural-remedies-diabetes-mellitus-quizlet.html

Pw xtreme top 100 dj, diabetes low blood sugar death font, insulin secretion in type 2 diabetes mellitus gevolgen, sindrome...Pw xtreme top 100 dj, diabetes low blood sugar death font, insulin secretion in type 2 diabetes mellitus gevolgen, sindrome...

... insulin secretion in type 2 diabetes mellitus gevolgen, jan kriekels innovate or die, type 2 diabetes causes risk factors, type ... 2 hypersensitivity treatment guidelines, type 2 diabetes insulin weight gain xanax ... cell and insulin inadequacy (3;4). Most remarkably, many obese diabetic patients who undergo RYGB are relieved of their anti- ... which consist of several cell types secreting different hormones: -cells (insulin), -cells (glucagon), -cells (somatostatin), ...
more infohttp://s3.amazonaws.com/brat4drdiabete/insulin-secretion-in-type-2-diabetes-mellitus-gevolgen.html

Semma Therapeutics Announces $44 Million in Funding Led by MPM Capital to Develop Cell Therapy for Treating Type 1 Diabetes;...Semma Therapeutics Announces $44 Million in Funding Led by MPM Capital to Develop Cell Therapy for Treating Type 1 Diabetes;...

44M in Funding Led by MPM Capital to Develop Cell Therapy for Treating Type 1 Diabetes; Signs Agreement with Global Phar ... These cells are responsible for keeping blood sugar levels in balance and are destroyed in Type 1 diabetic patients. The ... to generate a nearly unlimited supply of pancreatic beta cells that secrete the hormone insulin in a regulated manner. ... replacement for the missing beta cells in a diabetic patient without immunosuppression. Semma Therapeutics is working to bring ...
more infohttps://www.businesswire.com/news/home/20150324005109/en/Semma-Therapeutics-Announces-44-Million-Funding-Led

Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on...Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on...

Insulin-Secreting Cells/physiology*. *Lymphocyte Subsets/immunology. *Male. *Placebos. *Registries. *Time Factors ... A 6 day ChAglyCD3 treatment can suppress the rise in insulin requirements of recent-onset type 1 diabetic patients over 48 ... The aim of the study was to examine the 48 month outcome of treating recent-onset type 1 diabetic patients for 6 days with ... controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed?cmd=Retrieve&dopt=Abstract&list_uids=20225393
  • Results showed that cell adhesion and growth of mesenchymal stem cells, cardiomyocytes, and cardiac fibroblasts in vitro was dependent on the polymer substrate, with PHB and PCL polymers permitting the greatest adhesion/growth of cells. (jove.com)
  • The review's authors, Dr Jessica Quimby, of the Department of Veterinary Clinical Sciences at Ohio State University, and Dr Dori Borjesson, of the Veterinary Institute for Regenerative Cures at the University of California-Davis, consider the emergence of this new therapeutic strategy and the current understanding of the biology and immunology of mesenchymal stem cells. (brightsurf.com)
  • They also summarise the outcome of clinical trials that have investigated the use of mesenchymal stem cells in the treatment of a number of inflammatory, degenerative and immune-mediated diseases of cats. (brightsurf.com)
  • Therefore, the purpose of this study was to examine whether Neuregulin-1b (NRG-1b) treatment could enhance in vitro generation of mature "working-type" CMs from induced pluripotent stem cells (iPS) and assessed the regenerative effects of these CMs on cardiac tissue following acute myocardial infarction (AMI). (jove.com)
  • In conclusion, we have demonstrated that combined treatment with NRG-1b and DMSO leads to efficient differentiation of iPS into mature ventricular-like cardiac cells, which are capable of preserving cardiac function and tissue viability when transplanted into a mouse model of AMI. (jove.com)
  • They also have been able to induce differentiation of the ES cells by placing them next to a developing tissue in a chick. (bio-medicine.org)
  • They are allowed to develop from a few cells to about a 100 cells for about 12 days and then the human embryonic stem cells that will form the various types of tissue, are harvested to be grown into specific types. (essaytown.com)
  • they have the potential to form any cell or tissue in the human body. (thenakedscientists.com)
  • Think of an embryonic stem cell as a kind of master cell, an early-stage cell that retains the ability to form almost any kind of cell or tissue type in the human body. (thenakedscientists.com)
  • Owing to the shortage of donor tissue, attempts are being made to develop alternative sources of insulin-secreting cells. (hindawi.com)
  • The cells proliferated well in tissue culture plates and were subcultured for no more than 5 passages. (hindawi.com)
  • For instance, if someone's heart contains damaged tissue, doctors might be able to stimulate healthy tissue to grow by transplanting laboratory-grown stem cells into the person's heart. (medicalnewstoday.com)
  • The results showed a 40 percent reduction of the size of scarred heart tissue caused by heart attacks when doctors transplanted stem cells to the damaged area. (medicalnewstoday.com)
  • For instance, if someone has damaged tissue in their heart, it might be possible to stimulate the growth of healthy tissue by transplanting laboratory-grown stem cells into the patient's heart. (medicalnewstoday.com)
  • The alternative is to use embryonic stem cells or induced pluripotent stem (iPS) cells--which have the ability to transform into many types of cell to create what is called an organoid--a simplified three-dimensional tissue that resembles the structure of a real organ. (brightsurf.com)
  • Adding the two chemicals to the mix induced the cells to form tissue that genetic analysis revealed was very similar to actual developing salivary glands in the embryo. (brightsurf.com)
  • When the organoids were transplanted along with mesenchymal tissue--another embryonic tissue that is important as it forms the connecting tissue that allows the glands to attach to other tissues--the implanted tissues were found to be properly connected to the nerve tissue, and in response to the stimulation secreted a substance that was remarkably similar to real saliva. (brightsurf.com)
  • And what impact does tissue donor status have on stem cell function? (brightsurf.com)
  • Advances in stem cell research offer hope for treatments that could help patients regrow heart muscle tissue after heart attacks, a key to achieving more complete recovery. (brightsurf.com)
  • The scientists set out to show that by growing stem cell-derived heart tissue in a petri dish, with attention to blood vessels' construction, they could improve the tissue's incorporation with existing heart vessels. (brightsurf.com)
  • Heart muscle grown from stem cells must not only survive and integrate with the host tissue, but it must also restore adequate blood flow, explained Murry. (brightsurf.com)
  • When we implanted the patch, we saw that the stem cell-derived tissue integrated effectively with the host's coronary circulation. (brightsurf.com)
  • This suggested that nurturing the tissue in the lab had a meaningful benefit for the heart cells before they were implanted into the rats' hearts, the researchers said. (brightsurf.com)
  • Together, these results demonstrate the ability to culture and manipulate a rare population of human tissue-specific stem cells and suggest that these PAX7 + satellite cells have potential to restore gene function in muscular dystrophies. (jci.org)
  • In the process of tissue reconstruction, cells are extracted from a patient's biopsy and the stroma and the epithelium are enzymatically separated using thermolysin. (hindawi.com)
  • The ability to generate glucose-responsive, human beta cells through controlled differentiation of stem cells will accelerate the development of new therapeutics and I am thrilled and honored to be part of it," said Robert Millman, co-founder of Semma and MPM Capital Managing Director who is joining Semma as Chief Executive Officer. (businesswire.com)
  • After the device is implanted into a patient's abdomen, they can self-administer insulin directly into the intraperitoneal space, which is a more physiologically appropriate location compared to subcutaneous injection. (xtalks.com)
  • Therapies derived from the patient's own stem cells have little probability of rejection. (essaytown.com)
  • Kadimastem's astrocytes will be transplanted into a patient's spinal cord fluid to compensate for malfunctioning ones in ALS patients, she adds. (biotuesdays.com)
  • Millman, whose laboratory is in the Division of Endocrinology, Metabolism and Lipid Research, began his research while working in the laboratory of Douglas A. Melton, PhD, Howard Hughes Medical Institute investigator and a co-director of Harvard's Stem Cell Institute. (vetscite.org)
  • Diabetic damage occurs because of increased reactive oxygen species, such as superoxide anion radicals, hydroxyl radicals, peroxynitrite radicals, and lipid peroxidation. (townsendletter.com)
  • The self-assembly technique is a method used to reconstruct tissues free of exogenous materials using only patients' cells (Figure 1 ). (hindawi.com)
  • Multiple mechanisms exist that avoid damaging T cell responses to the fetus, whereas activation of uNK cells is probably physiological. (jci.org)
  • With ExOlin, Defymed shall offer diabetic patients a more physiological approach for delivering insulin," said Dr. Séverine Sigrist, CEO and founder of Defymed. (xtalks.com)
  • The control of ALOX12 activity appears to rest principally on the availability of its polyunsaturated fatty acid (PUFA) substrates which are released from storage in membrane phospholipids by cell stimulation. (wikipedia.org)
  • Using genetic lineage tracing, we are now able to mark these stem cells and track their descendents, and investigate the developmental consequences of mutant stem cells harboring targeted mutations in key polarity genes. (rutgers.edu)
  • DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells. (brightsurf.com)
  • Allorecognition of fetal placental cells by uNK cells is emerging as the key maternal-fetal immune mechanism that regulates placentation. (jci.org)
  • Poly(3-hydroxybutyrate) (PHB), poly(e-caprolactone) (PCL), silk, poly-lactic acid (PLA), and polyamide (PA) scaffolds were generated by electrospinning, and cell compatibility in vitro, and immune response and cardiac function in vitro and in vivo were compared with a noncrosslinked collagen membrane (Col) control material. (jove.com)
  • Amla juice, in Ayurveda, is often used to increase the white blood cells in the body , which are the main line of defense for the immune system. (organicfacts.net)
  • The ExOlin medical device is composed of a biocompatible membrane that is permeable to insulin. (xtalks.com)
  • Sulfatide is primarily found on the extracellular leaflet of the myelin plasma membrane produced by the oligodendrocytes in the central nervous system and in the Schwann cells in the peripheral nervous system. (wikipedia.org)
  • However, sulfatide is also present on the extracellular leaflet of the plasma membrane of many cells in eukaryotic organisms. (wikipedia.org)
  • Aside from being a membrane component, sulfatide functions in protein trafficking, cell aggregation and adhesion, neural plasticity, memory, and glial-axon interactions. (wikipedia.org)
  • The basolateral domain faces neighboring epithelial cells and the extracellular matrix, and contains extracellular matrix receptors, ion channels and solute transporters that facilitate the transduction of nutrients into the blood vessels. (rutgers.edu)
  • Human embryonic stem (ES) cells may give rise to many cell types of the body, such as nerve, muscle, liver, heart and blood, and thus they hold the promise to change the face of transplantation medicine. (bio-medicine.org)
  • Benvenisty cautions that the issue of transplantation of human ES cells also brings up the challenge of their possible rejection. (bio-medicine.org)
  • β -Cell replacement through transplantation is the only curative treatment to establish a long-term stable euglycemia in diabetic patients. (hindawi.com)
  • This makes it difficult to tell whether the improvement in heart function resulted from the transplantation of stem cells or whether it was due to something else. (medicalnewstoday.com)
  • Transplantation of human muscle fiber fragments into irradiated muscle of immunodeficient mice resulted in robust engraftment, muscle regeneration, and proper homing of human PAX7 + satellite cells to the stem cell niche. (jci.org)
  • Further, we determined that subjecting the human muscle fiber fragments to hypothermic treatment successfully enriches the cultures for PAX7 + cells and improves the efficacy of the transplantation and muscle regeneration. (jci.org)
  • Adam Nash was born after genetically screening 10 embryos so that he could help donate stem cells to replace his sister Molly's bone marrow. (essaytown.com)
  • We derive and characterize genetically engineered mouse models, apply classic biochemistry and modern cell biology tools to explore the molecular mechanisms underlying the interfaces of cell polarity, development, stem cell and cancer. (rutgers.edu)
  • Renowned stem cell expert, Swedish researcher Olle Lindvall, in an article at NewScientist.com (November 7, 2003), says he expects to be able to transform stem cells into the dopamine-producing neurons Parkinson's patients so badly need. (thenakedscientists.com)
  • Stem cells could potentially be used for the treatment of Parkinson's disease -- but it's a very difficult problem to generate large numbers of dopamine-producing neurons, which are the cells we need," Lindvall says. (thenakedscientists.com)
  • Research has shown that astrocytes malfunction in ALS patients and even attack neurons. (biotuesdays.com)
  • We evaluated the feasibility, safety, and efficacy of the administration of 4 sequential doses (intravenously administered on days 1, 4, 11, and 18) of cryopreserved bone marrow-derived mesenchymal stromal cells (MSC) expanded with platelet lysate and obtained from third-party donors as a second-line treatment for steroid-refractory acute graft-versus-host (aGVHD) disease in a series of 25 patients. (jove.com)
  • The use of bone marrow-derived stem cells is well established in the treatment of human cancer patients, and veterinary applications for bone marrow- and adipose-derived stem cells are being evaluated. (brightsurf.com)
  • During the past ten years, the research coming out of this laboratory has been published in over 50 papers, with many of the articles on human ES cells appearing as a cover story in the various journals in which they were published. (bio-medicine.org)
  • In younger patients this effect is associated with reduced deterioration of metabolic variables. (nih.gov)
  • however, exactly how uNK cells function in normal and pathological pregnancy is still unclear, and any therapies aimed at suppressing NK cells must be viewed with caution. (jci.org)
  • Stem cells could have vast potential in developing new therapies. (medicalnewstoday.com)
  • On top of that, the CDC shows that 68% of Americans are either overweight or obese, and visceral weight is a key factor in insulin resistance. (townsendletter.com)
  • Exercise - including aerobic, resistance, and high-intensity interval training - needs to be offered in ways that motivate patients to perform it regularly. (townsendletter.com)
  • Endoplasmic reticulum (ER) stress often occurred when load of client protein exceed the folding capacity in secretory cell. (biomedsearch.com)
  • Young women who received the human papillomavirus (HPV) vaccine through a school-based program had fewer cervical cell anomalies when screened for cervical cancer, found a new study in CMAJ (Canadian Medical Association Journal). (vetscite.org)
  • As demonstrated by indirect immunofluorescence studies, these diabetic rosettes contained 54% of T-lymphocytes (OKT3 + , OKT4 + , or OKT8 + ), whereas only 20% of T-lymphocytes were found in background rosettes. (diabetesjournals.org)
  • The 'secret sauce,' the Salk team found, was one particular switch the Evans lab had studied for years for its role in cell signaling. (technologynetworks.com)
  • One patient had been diabetic for 12 years and three patients were found to be diabetic during their terminal admission. (nih.gov)
  • Linvall's research has shown that the brain of a rat, after a stroke, actually produces new brain cells that travel to the damaged area. (thenakedscientists.com)
  • Pretreatment of cells with the stable peptide effectively blocked virus entry. (jci.org)
  • In the ChAglyCD3 subgroup with higher initial beta cell function, 0/11 patients became C-peptide-negative over 48 months vs 4/9 in the corresponding placebo subgroup. (nih.gov)
  • Perhaps that process -- plus some encouragement from drugs and combined with stem cells treatments - may be the eventual treatment for Parkinson's. (thenakedscientists.com)
  • This advance will result in a better controlled insulin response than currently available treatments," says Michael Downes, co-senior author and a Salk senior staff scientist. (technologynetworks.com)
  • Pluripotent stem cells can however be extracted from the placentas left over from healthy live births, cord blood, adult bone marrow, and even fat thus human embryos need not be an exclusively pursued avenue of medical discovery . (essaytown.com)
  • There is some evidence that stem cells derived from adults may in fact be a better source than live human embryos. (essaytown.com)
  • In 2001, Great Britain became the first country in the world to legalize the creation of human embryos -- not to create living human clones, but to create embryos whose stem cells can be taken for experimental use. (thenakedscientists.com)
  • What we're envisioning is an outpatient procedure in which some sort of device filled with the cells would be placed just beneath the skin," he said. (vetscite.org)
  • In summary, we can conclude that sequential cryopreserved third-party MSC therapy administered on days 1, 4, 11, and 18 is a safe procedure for patients with steroid-refractory aGVHD. (jove.com)
  • ACT is one of the very few private companies in the United States that kept working on stem cell research after the U.S. government dried up federal funds for the procedure. (thenakedscientists.com)
  • I am convinced that stem cell technology can become in the future a cure for conditions leading to brain injury -- but I think we have a long way to go. (thenakedscientists.com)
  • Essentially, a scientist uses a tiny needle to pull DNA material from the nucleus of a donor cell and transfer it into a hollow egg. (thenakedscientists.com)
  • Independent of donor age, as few as 2 to 4 PAX7 + satellite cells gave rise to several thousand myoblasts. (jci.org)
  • Kadimastem (TASE:KDST) hopes its pre-IND meeting with the FDA in November will outline a protocol for a Phase 1/2a clinical trial of its stem cell therapy for the treatment for Amyotrophic Lateral Sclerosis (ALS) to begin at the end of 2016. (biotuesdays.com)
  • However, with the exception of some organs such as hair follicles, those precursor cells are only present during early development. (brightsurf.com)
  • Stem cell-derived cardiomyocytes (CMs) are often electrophysiologically immature and heterogeneous, which represents a major barrier to their in vitro and in vivo application. (jove.com)
  • Still today, patients in several clinical trials have been given beta cell transplants with some success. (vetscite.org)
  • Defymed plans to launch a small clinical trial testing ExOlin in eight European patients, with the option to recruit more patients if initial study results are promising. (xtalks.com)
  • The present and potential clinical applications of mesenchymal stem cell therapy in cats are explored in a state-of-the-art review article published this month in the Journal of Feline Medicine and Surgery . (brightsurf.com)