Title:Conventional Chemotherapy and Emerging Targeted Therapy for Advanced Adrenocortical Carcinoma. VOLUME: 13 ISSUE: 2. Author(s):Yun-Ze Xu and Yu Zhu. Affiliation:Department of Urology, Shanghai Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, No.197, Ruijin Er Road, Shanghai, 200025, China.. Keywords:Advanced adrenocortical carcinoma, Chemotherapy, Mitotane, Molecular target, Target therapy Abstract:Adrenocortical carcinoma (ACC) is a rare but typically aggressive malignancy. Radical surgery remains the potentially curative option. However, about one third of patients initially present with distant metastases. Regarding to chemotherapy, mitotane alone or in combination with cytotoxic drugs should be the first selection. Meanwhile, a phase lll clinical trial of etoposide, doxorubicin, cisplatin plus mitotane or streptozotocin plus mitotane is currently undergoing worldwide. The study on molecular pathogenesis of ACC is progressing. A lot of targeted therapies are also ...
TY - JOUR. T1 - Surgical Resection of Synchronously Metastatic Adrenocortical Cancer. AU - Dy, Benzon M.. AU - Strajina, Veljko. AU - Cayo, Ashley K.. AU - Richards, Melanie L.. AU - Farley, David R.. AU - Grant, Clive S.. AU - Harmsen, William S.. AU - Evans, Doug B.. AU - Grubbs, Elizabeth G.. AU - Bible, Keith C.. AU - Young, William F.. AU - Perrier, Nancy D.. AU - Que, Florencia G.. AU - Nagorney, David M.. AU - Lee, Jeffrey E.. AU - Thompson, Geoffrey B.. N1 - Publisher Copyright: © 2014, Society of Surgical Oncology.. PY - 2015. Y1 - 2015. N2 - Introduction: Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown.Methods: A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral ...
Adrenocortical Carcinoma (Adrenal Cortex Cancer)-Pipeline Review, H1 2015. Summary. Global Markets Directs, Adrenocortical Carcinoma (Adrenal Cortex Cancer)-Pipeline Review, H1 2015, provides an overview of the Adrenocortical Carcinoma (Adrenal Cortex Cancer)s therapeutic pipeline.. This report provides comprehensive information on the therapeutic development for Adrenocortical Carcinoma (Adrenal Cortex Cancer), complete with comparative analysis at various stages, therapeutics assessment by drug target, mechanism of action (MoA), route of administration (RoA) and molecule type, along with latest updates, and featured news and press releases. It also reviews key players involved in the therapeutic development for Adrenocortical Carcinoma (Adrenal Cortex Cancer) and special features on late-stage and discontinued projects.. Global Markets Directs report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data ...
Adrenocortical carcinoma is a rare malignancy with a poor prognosis and presents with mass effects and less often with signs of hormone excess (approximately 60% of all adrenocortical carcinomas). Hormonally active adrenocortical carcinomas most commonly secrete cortisol while the co-secretion of multiple steroid hormones is rare. We report the case of a 59 year-old woman with a medical history of hyperaldosteronism due to a right adrenal adenoma. During follow up, she showed symptoms of hypercortisolism and hyperandrogenemia and a rapid growth of the adrenal mass. She underwent right adrenalectomy and the histology revealed the presence of an adrenocortical carcinoma. Six months post-operatively being on treatment with mitotane, she was diagnosed of metastatic disease to the liver. She underwent right hepatectomy and was started on systemic chemotherapy, with no signs of tumour recurrence during the following six months. The hormonal status should be carefully investigated in all cases of suspected
The Firm-ACT trial is the first ever conducted randomized controlled phase III trial in adrenocortical carcinoma (ACC), a rare malignancy with poor prognosis. It will provide results leading to the establishment of an urgently needed gold standard chemotherapy regimen for patients with locally advanced or metastatic ACC. To this end the trial compares the two most promising drug combinations investigated in phase II trials, considered by the International Consensus Conference on Adrenal Cancer (Ann Arbor/USA, 2003) as valuable first line treatments for advanced ACC. The first regimen consists of etoposide, doxorubicin, cisplatin plus mitotane (EDP-M), the second regiment employs streptozotocin plus mitotane (Sz-M). Over a period of five years this international trial will include 300 patients with advanced ACC from different European countries. Blood mitotane concentrations will be monitored, aiming at drug levels between 14 - 20 mg/L. Patients not responding to the first line treatment will ...
Rare Cancer News & Clinical Trials » Trial - Adrenocortical Carcinoma » Cabozantinib in Unresectable/Metastatic Adrenocortical ...
Adrenocortical carcinoma is a rare entity. However, it is the most common type of cancerous adrenal gland tumor with poor prognosis. Approximately 4 to 12 per 1 million people develop this type of tumor, which begins in the adrenal cortex. Adrenocortical carcinoma can occur at any age. Women tend to be diagnosed slightly more often than men. In most cases, the cause of cancerous adrenal gland tumor remains unknown. However, people with certain hereditary conditions have a higher risk. Adrenocortical carcinoma can be a functional or nonfunctional tumor. If the tumor is functional, it may produce hormones causing symptoms such as high blood pressure, low potassium level, heart palpitations, nervousness, feelings of anxiety or panic attacks, excessive perspiration, diabetes, Cushing syndrome, unexplained weight gain or weight loss, weakness, abdominal stretch marks, excessive hair growth, changes in genitalia, change in libido, etc. If the tumor is nonfunctional, symptoms occur because the tumor ...
There are different types of treatment for patients with adrenocortical carcinoma.. Different types of treatments are available for patients with adrenocortical carcinoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.. Three types of standard treatment are used:. Surgery. Surgery to remove the adrenal gland (adrenalectomy) is often used to treat adrenocortical carcinoma. Sometimes surgery is done to remove the nearby lymph nodes and other tissue where the cancer has spread.. Radiation therapy. Radiation ...
Adrenocortical Carcinoma - Pipeline Review, H1 2017 Adrenocortical Carcinoma - Pipeline Review, H1 2017 Summary Global Markets Directs latest Pharmaceutical and Healthcare disease pipeline guide Adrenocortical Carcinoma - Market research report and industry analysis - 10909461
Patients will be randomized 2:1 to receive either single agent OSI-906 (Arm A) or placebo (Arm B) and will be stratified according to prior systemic cytotoxic chemotherapy for ACC, and Eastern Cooperative Oncology Group (ECOG) performance status, and use of ,= 1 oral antihyperglycemic therapy at ...
Adrenocortical cancer (ACC) is a rare disease that is often difficult to diagnose, and therefore often presents at an advanced stage. Various cytotoxic treatments have been tried with little success. Evaluation of new diagnostic methods and improvement of medical therapies are therefore crucial.. The diagnostic potential of 11C-metomidate positron emission tomography (PET) was evaluated in eleven ACC patients. PET visualized all viable tumors with high tracer uptake, including two lesions that CT failed to detect. Necrotic or fibrotic tumors were PET negative. Medication with adrenal steroid inhibitors and chemotherapy may decrease the tracer uptake.. We performed a phase-II study with streptozocin and o,p-DDD (SO) combination therapy in 40 ACC patients. The SO therapy was found to have impact on the disease-free interval (P = 0.02) as well as on survival (P = 0.01) in patients who received adjuvant therapy after curative resection. Complete or partial response was obtained in 36.4% of patients ...
Adrenocortical Carcinoma, also called adrenal cortical carcinoma, is the formation of cancer in the outer layer (cortex) of an adrenal gland. This is the forum for discussing anything related to this health condition
TY - JOUR. T1 - Laparoscopic Versus Open Adrenalectomy for Adrenocortical Carcinoma. T2 - Surgical and Oncologic Outcome in 152 Patients: Editorial Comment. AU - Cadeddu, Jeffrey A. PY - 2011. Y1 - 2011. UR - http://www.scopus.com/inward/record.url?scp=84937218160&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84937218160&partnerID=8YFLogxK. U2 - 10.1016/j.juro.2010.12.025. DO - 10.1016/j.juro.2010.12.025. M3 - Article. AN - SCOPUS:84937218160. VL - 185. SP - 1222. JO - Journal of Urology. JF - Journal of Urology. SN - 0022-5347. IS - 4. ER - ...
Aims: Structured multicentre efforts are needed if the prognosis of adrenocortical carcinoma (ACC) is to be improved. Data collection may be enhanced through standardised histopathological reporting using criteria such as the recently published Royal College of Pathologists (UK) minimum dataset (MDS). This study aimed to perform a clinicopathological review of the adult patients treated at the Royal Victoria Infirmary, Newcastle upon Tyne, in the 10 years preceding the MDS.. Methods: Case records were examined for all patients diagnosed with ACC between 1996 and 2006. Pathology was reviewed and compared with the Royal College of Pathologists MDS along with the original reports. A systematic evaluation of Ki-67 immunolabelling was also performed.. Results: Eleven patients with ACC were diagnosed and treated. Histopathological reporting according to the MDS identified more features of malignancy than in the original reports (8.5±1.2 versus 5.1±0.8, p,0.02). The median number of microscopic ...
Infinity also announced today that it is adding two additional cohorts to the combination expansion component of the study, one in mesothelioma and one in adrenocortical carcinoma (cancer of the adrenal gland). These two new cohorts are based in part ... ...
Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany. Available online 3 June 2009. Adrenocortical carcinoma (ACC) is a rare and ...
Find research articles on adrenocortical carcinoma, which may include news stories, clinical trials, blog posts, and descriptions of active studies.
Learn more about Adrenocortical Carcinoma at TriStar Southern Hills DefinitionCausesRisk FactorsSymptomsDiagnosisTreatmentPreventionrevision ...
Learn more about Adrenocortical Carcinoma at Portsmouth Regional Hospital DefinitionCausesRisk FactorsSymptomsDiagnosisTreatmentPreventionrevision ...
Adrenocortical carcinoma is an unusual tumor that tends to be larger than 100 g at diagnosis. Malignant adrenocortical tumors of less than 50 g have been reported rarely. We studied a small adrenocortical carcinoma that weighed 40 g and metastasized 3 1/2 years following bilateral adrenalectomy. The malignancy of adrenocortical tumors is frequently difficult to determine. Two recent studies have proposed histologic criteria for determining the malignancy of adrenal cortical tumors. Since the tumor we studied was initially judged to be benign, we sought to determine whether an extensive evaluation of this tumor using these recent criteria could have identified the tumors potential for metastasizing ...
Adrenocortical cancer is an extremely rare tumor presenting with extensive locoregional spread at the time of diagnosis. Due to the diagnostic difficulties
Dr. Park conferred with experts in pathology. She communicated with oncologists at St. Judes Childrens Hospital in Tennessee, where the leading research on adrenocortical carcinoma is being performed by Dr. Rodriguez-Galindo and Dr. Rubiero. They shared their protocol for treating this rare disease with Dr. Park, and she changed Katies chemo regimen to follow the St. Judes teams protocol. Although the most current treatment was given, and the primary tumor was removed after 5 rounds of chemotherapy, the cancer recurred within a few months (in spite of follow-on drug therapy, as well). The thinking about adrenocortical carcinoma is that it is a slow-growing cancer; this was clearly not the case for Katie! Obviously, more needs to be known about pediatric cancer, which is the main reason why Katie wanted her Endowment to fund solid tumor research. Katies preference was that it fund adrenocortical carcinoma research, but since that is such a rare disease, her Endowment funds solid tumor ...
At the time of disease discovery there may be no symptoms (the tumor may be found incidentally on imaging). In other patients there may be symptoms of hormone excess or complaints referable to an abdominal mass. Hormone excess presents clinically as Cushings syndrome, virilization, feminization, or, less frequently, hypertension with hypokalemia. Hormone hypersecretion can be found in as many as 73%-79% of ACC patients, although not all patients have symptoms (2). In one study, amongst 45 ACC patients, routine biochemistry documented hormone excess in 33 (73%) with excess glucocorticoid and adrenal androgen in 12, isolated glucocorticoid in 11, isolated adrenal androgen in 7, and 17β-estradiol excess in combination with glucocorticoid and adrenal androgen excess in two and one, respectively. Steroid profiling revealed predominantly immature, early-stage steroid precursors, and their production most likely a consequence of altered expression of steroidogenic enzymes in variably undifferentiated ...
The patient was treated with adjuvant mitotane therapy for a high grade stage III ACC. He developed a large recurrence (35 cm) that was treated with surgery. He subsequently received four cycles of etoposide, doxorubicin, and cisplatin (EDP), stretozotocin, and phase I trials for progressive metastatic disease. He died three years following his initial diagnosis. Both his daughter and father are being monitored using a whole-body imaging surveillance program and have not been found to have any new tumors.. Case 2: A 35 year old man presented with hypertension, hypokalemia, and overt signs of the Cushing syndrome. Imaging revealed a large right adrenal tumor with metastases to the liver and lungs. Biopsy of the mass confirmed a low-grade ACC with loco-regional invasion. Genetic tumor testing revealed the c.43C , T, p.R15X mutation in SDHC in the tumor. There was evidence suggestive of likely loss of heterozygosity of the entire chromosome 1 (as well as other chromosomes), including the SDHC locus ...
A 16-year-old girl with a masculinizing adrenal carcinoma treated surgically is presented. Following surgery a full clinical and steroid remission has been achieved, without any adjuvant chemotherapy. In the 7th year after the surgical treatment the patient became pregnant. Pregnancy and labour were uncomplicated. The patient continues in complete remission, and her son has been noted to have normal development at 21 mth of age.
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The main limitation of studying this cancer type is the limited access to human samples, together with the lack of representative cell lines, and the absence of a reliable small animal model of disease. This has significantly challenged the study of this neoplasm for a long time. Additionally, it is difficult to successfully culture the ACC primary tumour cells for periods enough to carry out truly mechanistic studies in the lab. However, with new advances in tissue engineering techniques and biomaterials, we intend to reproduce an ACC tumour by culturing in 3D using collagen-I biomaterial and co-culturing with macrophages. Also, previous research within this field has informed us of several mutated genes such as Steroidogenic factor 1 or SF1. SF-1 is a nuclear receptor that belongs to the NR5A of orphan receptors which binds nuclear DNA. It is involved in adrenal and gonadal development, sexual determination, reproduction, and steroidogenesis. However, several other genes are mutated, and more ...
A new study showed staging system that incorporates the patients age better and predicts 5-year survival among patients with stages I/II ACC. Consideration should be given to include age in staging for ACC, because it may better inform providers about treatment and prognosis.[2] ...
Katies Comforters Guild is listed as one of the guilds that supports cancer research. The guilds connection to cancer research is 1) because Katie died of cancer, 2) our family and friends created the Katie Gerstenberger Endowment for Cancer Research in 2007 and 3) we began our work by sewing quilts for children in the cancer ward at Seattle Childrens Hospital - and weve now expanded to blanket the entire hospital. As you know, Katies endowment is for solid tumor research, to help find a cure for the kind of tumor she had (adrenocortical carcinoma). Since adrenocortical carcinoma is very rare, Katies endowment supports ALL solid tumor research with the income that is generated by the principal in the endowment. At last count, the principal was just over $100,000. ...
This page was last edited 16:23, 25 September 2017 by Mohammed Medhat. Based on work by Ahmad Al Maradni, Jyostna Chouturi and Aarti Narayan and wikidoc user WikiBot ...
This is an open-label Phase 1/2 study to assess the maximum tolerated dose of cintredekin besudotox (IL-13PE, hlLl3-PE38QQR) and the therapeutic respons
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Abnormal expression of membrane receptors has been previously described in benign adrenocortical neoplasms causing Cushings syndrome. In particular, we have observed that, in some adreno corticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia tissues, cortisol secretion is controlled by ectopic serotonin7 (5-HT7) receptors. The objective of the present study was to investigate in vitro the effect of serotonin (5-hydroxy tryptamine; 5-HT) on cortisol and renin production by a left adrenocortical carcinoma removed from a 48-year-old female patient with severe Cushings syndrome and elevated plasma renin levels. Tumor explants were obtained at surgery and processed for immunohistochemistry, in situ hybridization and cell culture studies. 5-HT-like immunoreactivity was observed in mast cells and steroidogenic cells disseminated in the tissue. 5-HT stimulated cortisol release by cultured cells. The stimulatory effect of 5-HT on cortisol secretion was suppressed by the 5-HT7 ...
With recent progress in understanding the pathogenesis of adrenocortical tumors (ACTs), identification of molecular markers to predict their prognosis has become possible. Transcription factor 21 (TCF21)/podocyte-expressed 1 (POD1) is a transcriptional regulatory protein expressed in mesenchymal cells at sites of epithelial-mesenchymal transition during the development of different systems. Adult carcinomas express less TCF21 than adenomas, in addition, the KEGG pathway analysis has shown that BUB1B, among others genes, is negatively correlated with TCF21 expression. The difference between BUB1B and PTEN-induced putative kinase 1 (PINK1) expression has been described previously to be associated with survival in adult but not in pediatric carcinomas. Here, we analyzed the gene expression of TCF21, BUB1B, PINK1, and NR5A1 in adult and pediatric ACTs. We found a negative correlation between the relative expression levels of TCF21 and BUB1B in adult ACTs, but the relative expression levels of TCF21, ...
Adrenocortical carcinoma (ACC) is an aggressive tumor showing frequent metastatic spread and poor survival. Although recent genome-wide studies of ACC have contributed to our understanding of the disease, major challenges remain for both diagnostic and prognostic assessments. The aim of this study was to identify specific microRNAs (miRNAs) associated with malignancy and survival of ACC patients. miRNA expression profiles were determined in a series of ACC, adenoma, and normal cortices using microarray. A subset of miRNAs showed distinct expression patterns in the ACC compared with adrenal cortices and adenomas. Among others, miR-483-3p, miR-483-5p, miR-210, and miR-21 were found overexpressed, while miR-195, miR-497, and miR-1974 were underexpressed in ACC. Inhibition of miR-483-3p or miR-483-5p and overexpression of miR-195 or miR-497 reduced cell proliferation in human NCI-H295R ACC cells. In addition, downregulation of miR-483-3p, but not miR-483-5p, and increased expression of miR-195 or ...
Diagnostic and prognostic value of nucleolar proteins in the regulation of tumor cells proliferation in patients with lung carcinoma and adrenocortical cancer
A rare disease in which cancer cells are found in the adrenal cortex. Cancer of the adrenal cortex is also called adrenocortical carcinoma. The inside layer of the adrenal gland is called the adrenal medulla. Cancer that starts in the adrenal medulla is called pheochromocytoma.
Health, ... Sol H. Weiss shareholder at law firm Anapol Schwartz Weiss Coha...Philadelphia (PRWEB) August 20 2008 -- a href http://www.anapolschw...Weiss is currently co-plaintiffs liaison counsel for more than 800 v...Active in the legal community Weiss is a member of the American Pen...,Anapol,,Schwartz,Attorney,Named,to,Executive,Committee,of,American,Association,for,Justice,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
The semi-automated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) by viable cells, was employed for cytotoxic drug sensitivity testing of tumor cells from patients with hematological or solid tumors. In total, 390 samples from 20 diagnoses were tested with up to 12 standard cytotoxic drugs. The technical success rate for different tumor types ranged from 67 to 95%. Fluorescence was linearly related to cell number but variably steep depending on tumor type. Samples from most solid tumors thus showed higher signal-to-noise ratios than hematological samples. A wide spectrum of in vitro drug activity was obtained, with acute leukemias and non-Hodgkins lymphomas being sensitive to almost all tested drugs, whereas renal and adrenocortical carcinomas were essentially totally resistant. Between these extremes were samples of breast and ovarian carcinomas and sarcomas. When in vitro response was
Background:. MicroRNA (miRNA)-503 is known to be down-regulated in several types of cancer, including oral, hepatocellular, gastric, and endometrial, suggesting that it plays a tumor-suppressor role in carcinogenesis. In contrast, other recent reports have demonstrated up-regulation of miR-503 in adrenocortical carcinoma, parathyroid carcinoma, and retinoblastoma, compared with adjacent normal tissues. Collectively, miR-503 shows tissue- or disease-specific expression patterns. However, to the best of our knowledge, miR-503 expression pattern, its clinical significance and molecular mechanism in colorectal cancer (CRC) have not been investigated.. Materials and Methods:. We analyzed miR-503 expression in a subset of 69 tissue samples from normal colonic mucosa (n = 20), adenoma (n = 29) and CRC (n = 20). Next, we further quantified miR-503 expression in a larger, independent cohort, which included CRC tissues from 181 patients, and investigated the clinical significance of miR-503 in CRC. In ...
Background:. MicroRNAs (miRNAs) are a class of small non-coding RNAs that inhibit gene expression by binding to 3` untranslated regions of mRNAs and inhibiting their translation. MiRNAs crucially affect cellular processes such as development, proliferation, differentiation and apoptosis, which are deregulated in cancer. MiR-503 is located at Xq26.3 and belongs to an extended miR-16 family of miRNAs. MiR-503 is down-regulated in several types of cancer, including oral, hepatocellular, gastric, and endometrial cancer, suggesting that it plays a tumour-suppressor role in carcinogenesis. In contrast, other recent reports have demonstrated up-regulation of miR-503 in adrenocortical carcinoma, parathyroid and retinoblastoma, compared with adjacent normal tissue. These results suggest that miR-503 shows tissue- or disease-specific expression patterns. However, miR-503 expression patterns in esophageal cancer (EC) and normal esophageal tissue have not been compared and the correlation of miR-503 ...
Clinical trial for Adrenocortical carcinoma , Cabazitaxel Activity in Patients With Advanced AdrenoCortical-Carcinoma Progressing After Previous Chemotherapy Lines
A Weiss unit is based on the T4 DNA ligase catalyzed ATP-PPi exchange reaction as described by Bernard Weiss, Charles Richardson and colleagues (Weiss, B., et. al., (1968) |em|J. Biol. Chem.|/em|, 243, 4556).
U.S. 1930 Census, Madison, Dane County, Wisconsin, population schedule, ED 13-31, sheets 10B-11A, house 181, family 274, family of J F Weiss [Joseph Weiss]; digital image, Ancestry.com (http://www.ancestry.com/search/db.aspx?dbid=6224&enc=1 : accessed 8 Aug 2012); citing NARA microfilm T626, roll 2566.. ...
The basic regularities in the time course of adrenocortical lipids in acute cardiovascular stress and in injuries of different duration are shown. The author hypothesizes that the reticular zone of the cortical substance of the gland is not a zone of cell aging and death but, quite the contrary, a f...
Eric L. Weiss, MD is on CAP Network. CAP Network is a virtual workspace, to support collaboration among faculty, graduate students, postdocs and staff.
I believe that the deepest level of healing has nothing to do with changing ourselves. Rather, it is the lifelong process of fully embracing who we are, opening our hearts to ourselves and others in compassion, and taking our rightful place in the world. It is about living life in each moment with authenticity, integrity, and compassion. -Joanne G. Weiss. ...
Looking for online definition of adrenocortical carcinoma in the Medical Dictionary? adrenocortical carcinoma explanation free. What is adrenocortical carcinoma? Meaning of adrenocortical carcinoma medical term. What does adrenocortical carcinoma mean?
CONTEXT: Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane] is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumor. Mitotane is considered an adrenolytic
Mitotane (o,p′-DDD) is the standard treatment for advanced adrenocortical carcinoma (ACC). Monitoring of plasma mitotane levels is recommended to look for a therapeutic window between 14 and 20mg/L, but its positive predictive value requires optimization. We report the case of an ACC patient with a history of dyslipidemia treated with mitotane in whom several plasma mitotane levels ,30mg/L were found together with an excellent neurological tolerance. This observation led us to compare theoretical or measured o,p′-DDD and o,p′-DDE levels in a series of normolipidemic and dyslipidemic plasma samples to explore potential analytical issues responsible for an overestimation of plasma mitotane levels. We demonstrate an overestimation of mitotane measurements in dyslipidemic patients. Mitotane and o,p′-DDE measurements showed a mean 20% overestimation in hypercholesterolemic and hypertriglyceridemic plasma, compared with normolipidemic plasma. The internal standard p,p′-DDE measurements ...
TY - JOUR. T1 - Laparoscopic resection of adrenal cortical carcinoma. T2 - A cautionary note. AU - Gonzalez, Ricardo J.. AU - Shapiro, Suzanne. AU - Sarlis, Nicholas. AU - Vassilopoulou-Sellin, Rena. AU - Perrier, Nancy D.. AU - Evans, Douglas B.. AU - Lee, Jeffrey E.. AU - Inabnet, William B.. AU - Libutti, Steven K.. AU - Chen, Herbert. AU - Duh, Quan Yang. AU - Wilhelm, Scott. PY - 2005/12/1. Y1 - 2005/12/1. N2 - Background. While laparoscopic removal of small, benign, functioning adrenal tumors is accepted, laparoscopic resection of adrenal tumors that may be adrenal cortical carcinoma (ACC) remains controversial. Methods. The records of all patients with ACC evaluated at a single institution from 1991 through 2004 were reviewed retrospectively. Results. Among 170 patients with ACC, 153 patients underwent open anterior adrenalectomy, 6 underwent laparoscopic adrenalectomy, 1 was treated via an open flank approach, and 10 had no operation. At a median follow-up of 28 months, 115 (86%) of 133 ...
TY - JOUR. T1 - P-glycoprotein expression and multidrug resistance in adrenocortical carcinoma. AU - Flynn, Stuart D. AU - Murren, J. R.. AU - Kirby, W. M.. AU - Honig, J.. AU - Kan, L.. AU - Kinder, B. K.. PY - 1992. Y1 - 1992. N2 - Background. The response of adrenocortieal carcinoma (ACC) to adjuvant chemotherapy has been disappointing with no significant impact on survival. The normal adrenal cortex has very high levels of P-glycoprotein, an energy-dependent efflux pump of a variety of structurally unrelated chemotherapeutic agents. P-glycoprotein has been implicated as a cause of multidrug resistance in a variety of neoplasms. The purpose of this study was to evaluate P-glycoprotein expression in ACC. Methods. Eleven patients with ACC had paraffin-em bedded tumor evaluated for P-glycoprotein expression. These were analyzed by immunohistochemistry assay with a battery of four anti-P-glycoprotein antibodies (MRK-16, JSB-1, UIC-2, MDR). Results. All eleven cases showed intense, predominantly ...
Context: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. Objective: The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort. Design: Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Setting: MS-MLPA was performed in a training cohort of 50 patients with ACC to identify the best set of probes correlating with disease-free survival (DFS) and overall survival (OS). These outcomes were validated in an independent cohort from 21 ENSAT centers. Patients: The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors). Main Outcome Measures: DFS and OS. Results: In the training cohort, mean methylation of 4
The focus on the refinement, reduction and replacement of animal use in toxicity testing requires the development of cell-based systems that mimic the effects of xenobiotics in human tissues. The human adrenocortical carcinoma cell line, H295R, has been
The Official Patients Sourcebook on Adrenocortical Carcinoma: A Revised and Updated Directory for the Internet Age von Icon Health Publications und Buchbewertungen gibt es auf ReadRate.com. Bücher können hier direkt online erworben werden.
TY - JOUR. T1 - Mitotane enhances cytotoxicity of chemotherapy in cell lines expressing a multidrug resistance gene (mdr-1/P-glycoprotein) which is also expressed by adrenocortical carcinomas. AU - Bates, Susan E.. AU - Shieh, Ching Yi. AU - Mickley, Lyn A.. AU - Dichek, Helén L.. AU - Gazdar, Adi. AU - Loriaux, Donald (Lynn). AU - Fojo, Antonio Tito. PY - 1991/7. Y1 - 1991/7. N2 - P-Glycoprotein (Pgp), product of the mdr-1 gene, is a 130- to 180-kDa plasma membrane phosphoglycoprotein which mediates multidrug resistance in cell culture by increasing efflux of the natural product chemotherapeutic agents. High levels of expression of mdr-1/Pgp are found in both the normal adrenal and adrenocortical cancers. By RNA in situ hybridization the expression in adrenocortical cancer is shown to be widely distributed. The present study demonstrates that decreased drug accumulation mediated by mdr-1/Pgp can be overcome by clinically achieveable concentrations of mitotane (o,p′-DDD). The increase in drug ...
Abstract: Adrenocortical cancer (ACC) is a rare and aggressive endocrine tumor. The patient presented with a large retroperitoneum tumor and lung metastases. Removal of the adrenocortical tumor with part of the transverse colon and tail of the pancreas, spleen and kidney was successfully performed following chemotherapy. Levels of serum neuron-specific enolase (NSE) were found to be markedly high before surgery and may be clinically useful markers for monitoring tumor status during management. Immunohistochemical studies showed that the cancer cells were positive for NSE and overexpression of p53. We identified a novel germ line variant of the 177 mutant (Pro to Arg; P177R) of p53 by genomic sequencing. The genetic and biochemical data presented in this case confirm the importance of screening for p53 status in ACC with inherited cancer syndrome.. ...
Splenic arteriogastric fistula is a rare cause of upper gastrointestinal (GI) hemorrhage, only reported a handful of times in the literature. Herein, we present a case of a 49-year-old woman with metastatic adrenocortical carcincoma who developed a fistula between the splenic artery and gastric lumen as a result of local invasion of her primary tumor. This fistula led to several episodes of massive upper GI bleeding. Selective splenic artery embolization was successful in ceasing the GI bleed; however, the intervention was not timely enough for the patient to survive the hemorrhage. We outline several clinical and imaging findings to assist physicians with earlier detection of splenic arteriogastric fistulas, and advocate prophylactic selective splenic artery embolization when this rare but highly fatal entity is discovered.
TY - JOUR. T1 - Serum and growth factor requirements for proliferation of human adrenocortical cells in culture. T2 - Comparison with bovine adrenocortical cells. AU - Hornsby, Peter J.. AU - Sturek, Michael. AU - Harris, Sandra E.. AU - Simonian, Michael H.. PY - 1983/11. Y1 - 1983/11. N2 - Although bovine adrenocortical cells proliferate readily in cell culture, proliferation of fetal or adult human adrenocortical cells has been observed to be limited and preparation of pure proliferating cultures of human adrenocortical cells has not been reported. The growth requirements of fetal human definitive zone adrenocortical cells in culture were compared to the established requirements of bovine adrenocortical cells. The medium used was 1:1 Hams F12 and Dulbeccos modified Eagles medium supplemented with transferrin and insulin. Earlier experiments showed that human cells had a greater proliferative response to horse serum than to fetal bovine serum, whereas the opposite was true for bovine cells. ...
Mitotane (o,p′-DDD) is the standard treatment for advanced adrenocortical carcinoma (ACC). Monitoring of plasma mitotane levels is recommended to look for a therapeutic window between 14 and 20mg/L, but its positive predictive value requires optimization. We report the case of an ACC patient with a history of dyslipidemia treated with mitotane in whom several plasma mitotane levels ,30mg/L were found together with an excellent neurological tolerance. This observation led us to compare theoretical or measured o,p′-DDD and o,p′-DDE levels in a series of normolipidemic and dyslipidemic plasma samples to explore potential analytical issues responsible for an overestimation of plasma mitotane levels. We demonstrate an overestimation of mitotane measurements in dyslipidemic patients. Mitotane and o,p′-DDE measurements showed a mean 20% overestimation in hypercholesterolemic and hypertriglyceridemic plasma, compared with normolipidemic plasma. The internal standard p,p′-DDE measurements ...
To date, renin-producing tumors are very rare, and most of them are of renal origin. Of these, the juxtaglomerular cell tumor was the most frequent. An extrarenal renin-producing tumor is extremely rare.6 Non-renal renin-producing tumors include carcinoma of the lung, pancreas, urinary bladder and ovary.7 To the best of our knowledge, there have been only two cases of renin-producing adrenal tumor reported before. Our case is the third such case reported but it is different to the case reported by Iimura et al. in the steroid synthetic pattern (tumor produced corticosteroids and sex steroids) and to the case of K. Yamanaka et al. in the characteristics of Cushings syndrome. Our case only exhibited hyperreninism, hyperaldosteronism and hypertension, but Cushings syndrome or steroid overproduction were not observed. Maybe the huge adrenal tumor could compress the renal artery, which might elevate the PRA. After immunohistochemical staining, the diagnosis of renin-producing adrenocortical ...
Purpose: To define a mitotane dose for pediatric patients with adrenocortical cancer (ACC) that maintains therapeutic plasma levels (TL) between 14 and 20 mu g/mL and to verify its antitumor efficacy in association with 8 cycles of cisplatin, etoposide, and doxorubicin (CED). Methods: Powdered mitotane was dissolved in a medium chain triglyceride oil and administered to 11 children with ACC (2.4 to 15.4 y of age); an initial low dose was increased to 4 g/m(2)/d. Ten of the 11 children had a germline TP53 R337H mutation. Mitotane plasma levels were determined using high-performance liquid chromatography. Results: The mitotane dose to maintain TL in 7 patients ranged from 1.0 to 5.3 g/m(2)/d. Six children reached mitotane levels of 10 mu g/mL in 3.6 months (1.5 to 5.0mo), whereas 5 children took 8 months (6.5 to 12.5 mo). Minor to partial tumor remission was found in 5 patients (, 1 y) and complete remission was found in 2 patients. Of the 3 patients who are alive at the time of report, 1 patient ...
This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canadas national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc. ...
Purpose: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer, and no current effective therapy is available for locally advanced and metastatic ACC. Drug repurposing is an emerging approach for identifying new indications for existing drugs, especially for rare cancers such as ACC. The objective of this study was to use quantitative high-throughput screening to identify agents with antineoplastic activity against ACC. Experimental Design: A screening of 4,292 compounds was performed on three ACC cell lines: BD140A, SW-13, and NCI-H295R. Results: Twenty-one active compounds were identified, with an efficacy of ,80% in all three cell lines. Of these, niclosamide showed higher efficacy and lower IC50 than established anti-ACC drugs. We then validated niclosamide-inhibited cellular proliferation in all three ACC cell lines. Next, we investigated the mechanism by which niclosamide inhibited ACC cell proliferation, and found that it induced caspase-dependent apoptosis and G1 cell cycle ...
Gossypol and its derivatives are active against the HIV virus 15 and the herpes simplex virus type 2. [35] [Lin TS, Schinazi. Selective inhibition of human immunodeficiency virus type 1replication by the (-) but not the (+) enantiomer of gossypol. Antimicrob Agents Chemother. 1989 Dec;33(12):2149-51]. A trial evaluated the therapeutic efficacy of gossypol for the treatment of metastatic carcinoma of the endometrium or ovary, and as an antiviral and interferon inducer in patients with AIDS [36] [Wu D. An overview of the clinical pharmacology and therapeutic potential of gossypol as a male contraceptive agent and in gynaecological disease. Drugs . 1989;38:333-341]. At low doses (30 mg/kg), the drug reduces 65% the tumor size and induces tumor mortality (8%) in nude-mice SW-13 adrenocortical carcinoma [24] [Wu, Y.W., Chik, C. L., Knazek, R. A., An in vitro and in vivo study of antitumor effects of gossypol on human SW-13 adrenocortical carcinoma, Cancer Res. 1989, 49, 3754 -3758.] . Furthermore, in ...
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Treatment:. The main method of adrenal tumor treatment is surgery.. At the first stage of tumor development, when the formation does not exceed 5 cm and there is no metastasis, laparoscopic removal is performed.. If the tumor has reached the second stage of development and has grown more than 5 cm, then the method of removal is determined by doctors based on MRI or CT.. At stage 3 of adrenal cancer, when the tumor affects the lymph nodes, a cavitary surgery is indicated. During removal, the surgeon examines nearby organs and tissues for the presence of metastases.. Adrenal cancer of the 4th stage is usually accompanied by metastatic sprouting in the tissue of the kidneys, liver, etc. Such tumors are not always operable. The possibility of prompt removal is determined by the doctor individually.. As additional treatment, other methods are used. Radiotherapy is actively used in pheochromocytomas.. A patient can get a radioactive isotope injection, which kills cancer cells, reducing the size of the ...
Note 2: Except for histologies that have strictly histology-based CS schemas (for example lymphoma), all cases with primary site adrenal gland (C74._) are coded with this schema. However, only adrenal cortical carcinomas will have AJCC stage derived (7th Edition only). Adrenal cortical carcinoma is identified as C74.0 (adrenal cortex) with histology 8010, 8140, or 8370 OR C74.9 (adrenal gland, NOS) with histology 8370 ...
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An interesting phenomenon consists of adrenal collision tumors. Thus a contiguous adrenal adenoma and metastasis results in the adenoma component displaying a signal loss on opposed-phase MR images and the metastatic component increasing in signal intensity. At times neither a biopsy nor a resected specimen allows adequate evaluation of an adrenocortical tumor if only histologic criteria are employed; immunohistologic staining is often helpful. Nevertheless, even then the true nature of a tumor may not be apparent. For example, CT and US discovered an incidental homogeneous adrenal tumor in a 43-year-old woman; endocrine tests revealed preclinical Cushings syndrome. An adrenalectomy was performed, and histology revealed an adrenocorticaltumor of undetermined nature, 4 months later the patient presented with a metastatic cortisol and androgen-producing adrenocortical carcinoma ...
Purpose: ,p,Adrenal incidentalomas must be differentiated from adrenocortical cancer (ACC). Currently, size, growth, and imaging characteristics determine the potential for malignancy but are imperfect. The aim was to evaluate whether urinary small molecules (,800 Da) are associated with ACC.,/p, ,p,Experimental Design:,/p, ,p,Preoperative fasting urine specimens from patients with ACC (n=19) and benign adrenal tumors (n=46) were analyzed by unbiased ultra performance liquid chromatography/mass spectrometry. Creatinine-normalized features were analyzed by Progenesis, SIMCA, and unpaired t-test adjusted by false discovery rate. Features with an AUC ,0.8 were identified through fragmentation patterns and database searches. All lead features were assessed in an independent set from patients with ACC (n=11) and benign adrenal tumors (n=46) and in a subset of tissue samples from patients with ACC (n=15) and benign adrenal tumors (n=15) in the training set.,/p, ,p,Results:,/p, ,p,Sixty-nine features ...
Yahashiri, A., Jorgenson, M. A. & Weiss, D. S. (2017). The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division. J Bacteriol, 199(14), e00118-17. PMID: 28396350.. Ransom, E. M., Weiss, D. S. & Ellermeier, C. D. (2016). Use of mCherryOpt Fluorescent Protein in Clostridium difficile. Methods Mol Biol, 1476, 53-67. PMID: 27507333.. Yahashiri, A., Jorgenson, M. A. & Weiss, D. S. (2015). Bacterial SPOR domains are recruited to septal peptidoglycan by binding to glycan strands that lack stem peptides. Proc Natl Acad Sci U S A, 112(36), 11347-52. PMID: 26305949.. Weiss, D. S. (2015). Last but not least: new insights into how FtsN triggers constriction during Escherichia coli cell division. (Vols. 95). (6), pp. 903-9. Mol Microbiol. PMID: 25571948.. Ransom, E. M., Ellermeier, C. D. & Weiss, D. S. (2015). Use of mCherry Red fluorescent protein for studies of protein localization and gene expression in Clostridium difficile. Appl Environ ...
Samuel Weiss is a neurobiologist. Weiss was an undergraduate at McGill University, where he received a B.Sc. in Biochemistry. He then went on to take his Ph.D. in Neurobiology at the University of Calgary. From 1983 to 1988 he held two postdoctoral fellowships funded by the AHFMR and the Medical Research Council of Canada (now the Canadian Institutes of Health Research), the first at the Centre de Pharmacologie-Endocologie, Montpellier, France, and the second at the University of Vermont College of Medicine. In 1985 Dr. Weiss and Fritz Sladeczek discovered the metabotropic glutamate receptor, currently an extremely important area of research for neurological disorders. Dr. Weiss was appointed Assistant Professor and MRC Scholar at The University of Calgary in 1988. In 1992, while working at the University of Calgary, Dr. Weiss and graduate student Brent Reynolds found cells in the brains of fetal and adult mice that divided to produce new cells. They claimed that they successfully isolated stem ...
Adrenal cortical carcinoma (ACC) is a rare cancer, with an annual incidence of about 1-2 per million [1]. ACC has a poor prognosis, with a 5-year overall survival rate of less than 40% for all cancers and 10% for metastatic cancers [2]. However, even in metastatic ACC, the prognosis is quite variable, with reported survival ranging from a few months to more than 10 years, suggesting the heterogeneity of these tumors [3]. Tumor, node, metastasis (TNM) staging has been used as a predictor of survival and has been modified to improve its prognostic power; currently, the eighth edition of TNM staging and European Network for the Study of Adrenal Tumors (ENSAT) staging systems are used [4,5,6]. Nevertheless, a significant proportion of patients with localized disease according to TNM staging experience recurrence after surgery (up to 70% within 3 years), which is the only curative treatment to date [2]. Tumor grade, as assessed by mitotic count and proliferation indices such as the Ki-67 index, has ...
Yin, A., Ettaieb, M. H. T., Swen, J. J., van Deun, L., Kerkhofs, T. M. A., van der Straaten, R. J. H. M., ... Moes, D. J. A. R. (2020). Population Pharmacokinetic and Pharmacogenetic Analysis of Mitotane in Patients with Adrenocortical Carcinoma: Towards Individualized Dosing. Clinical Pharmacokinetics. https://doi.org/10.1007/s40262-020-00913-y ...
Background: Adrenocortical carcinomas (ACCs) are among the most common childhood cancers occurring in infants affected with the Li-Fraumeni and Li- Fraumeni-like (LFS/LFL) syndromes, which are caused by dominant germline mutations in the TP53 gene. In Brazil, a particular mutation, occurring in the tetramerisation domain of the gene, p.R337H, is exceedingly common due to a founder effect and is strongly associated with ACC. In this report, we describe the phenotype and long-term clinical follow-up of a female child diagnosed with ACC and homozygous for the TP53 p.R337H founder mutation. Case presentation: At age 11 months, the patient was diagnosed with a virilising anaplastic adrenal cortical tumour, which was completely excised without disturbing the adrenal capsule. Family history was consistent with an LFL tumour pattern, and genotyping identified the TP53 p.R337H mutation in both alleles in genomic DNA from lymphocytes and fibroblasts. Haplotype analysis confirmed the occurrence of the ...
Fine-needle aspiration biopsy of the adrenal mass in patient with noncontrast CT attenuation coefficient value of , 10 HU. It cannot, however, always differentiate an adrenaocortical carcinoma from an adrenal adenoma. To avoid causing a possible hypertensive crisis, pheochromoctoma should always be excluded before this test. A mass that displays slow washout can be assumed to be a metastasis. If the patient has a known malignancy, the adrenal mass can be treated as part of the primary process. If there is no known primary malignancy, the mass could be the first manifestation of metastasis or a rare nascent adrenocortical carcinoma. Percutaneous needle biopsy can readily differentiate between these two possibilities, but it does involve risks, such as pneumothorax and tumor seeding. Alternatively, the mass can be removed laparoscopically and a pathologic analysis done. ...
Prostaglandins can be synthesized in an adrenocortical carcinoma, and they can work in an autocrine or paracrine fashion. In rabbit chondrocyte and human squamous carcinoma cell lines, EGF induced the secretion of PGE2 via up-regulation of the activities of phospholipase A2 (PLA2) and COX-2 (Sato et al. 1997, Huh et al. 2003). This may suggest that PGE2 acts as a secondary factor to EGF in the up-regulation of aromatase expression. Therefore, we checked whether PGE2 was secreted from NCI-H295R cells in response to EGF. In this study, NCI-H295R cells secreted PGE2 in response to EGF (Fig. 13), and PGE2 increased aromatase activity to a greater extent than other prostaglandins (Fig. 6). The inhibition of EGF-induced aromatase expression with PGE2 receptor antagonists confirmed that PGE2 is the secondary factor of aromatase expression with EGF (Fig. 14). PGE1 also increased aromatase activity to a degree similar to that of PGE2, but EGF could not stimu- late NCI-H295R cells to secrete a sufficient ...
Adrenocortical carcinomas (ACC) are aggressive cancers originating in the cortex of the adrenal glands. Despite the overall poor prognosis, ACC outcome is heterogeneous. CTNNB1 and TP53 mutations are frequent in these tumors, but the complete spectrum of genetic changes remains undefined. Exome sequencing and SNP array analysis of 45 ACC revealed recurrent alterations in known drivers (CTNNB1, TP53, CDKN2A, RB1, MEN1) and genes not previously reported to be altered in ACC (ZNRF3, DAXX, TERT and MED12), which were validated in an independent cohort of 77 ACC. The cell-surface transmembrane E3 ubiquitin ligase ZNRF36 was the gene the most frequently altered (21%), and appears as a potential novel tumor suppressor gene related to the ß-catenin pathway.Our integrated genomic analyses led to the identification of two distinct molecular subgroups with opposite outcome. The C1A group of poor outcome ACC was characterized by numerous mutations and DNA methylation alterations, whereas the C1B group with ...
Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-resolution single nucleotide polymorphism arrays (Affymetrix) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH). Genomic clustering showed good separation between adenomas and carcinomas, with best partition including only chromosome 5, which was highly amplified in 17/22 malignant tumors. The malignant tumors had more relevant genomic aberrations than benign tumors, such as a higher median number of recurrent CNA (2631 vs 94), CNAs ,100 Kb (62.5 vs 7) and CN losses (72.5 vs 5.5), and a higher percentage of samples with cnLOH (91% vs 29%). Within the carcinoma cohort, a precise genetic pattern (i.e. large gains at chr 5, 7, 12, and 19, and losses at chr ...
Li-Fraumeni syndrome is an autosomal-dominant familial cancer syndrome that results in an increased lifelong risk of what are considered Li-Fraumeni syndrome spectrum tumors (e.g., soft tissue sarcoma, osteosarcoma, brain tumor, premenopausal breast cancer, adrenocortical carcinoma, leukemia, lung bronchoalveolar cancer), among others. About 3/4 of patients have a mutation in the gene encoding the p53 tumor suppressor protein (TP53). The cancers arent limited to those listed above, however, and patients can have a wide range of malignancies, including melanoma, germ-cell tumors, gastric carcinoma, Wilms tumor, lymphoma, and lung, laryngeal, prostate, and pancreatic cancers ...
The majority of LFS (about 70 percent) is caused by mutations in a gene on chromosome 17 known as p53. Mutations in p53 confer an increased risk for early onset breast cancer, childhood sarcoma, osteosarcoma, brain tumors, leukemia, and adrenocortical carcinoma.. People with a p53 mutation have a 50 percent chance of developing one of the associated cancers by age 40 and a 90 percent chance of developing cancer by age 60. Breast cancer appears to be the greatest risk for women, but less than 1 percent of all breast cancer is thought to be related to LFS. For those affected by LFS, breast cancers generally occur in premenopausal women.. The p53 gene is a tumor suppressor gene, which usually controls cell growth and cell death. Both copies of a tumor suppressor gene must be altered, or mutated, before a person will develop cancer. With LFS, the first mutation is inherited from either the mother or the father and is therefore present in all cells of the body. This is called a germline mutation. ...
The majority of LFS (about 70 percent) is caused by mutations in a gene on chromosome 17 known as p53. Mutations in p53 confer an increased risk for early onset breast cancer, childhood sarcoma, osteosarcoma, brain tumors, leukemia, and adrenocortical carcinoma.. People with a p53 mutation have a 50 percent chance of developing one of the associated cancers by age 40 and a 90 percent chance of developing cancer by age 60. Breast cancer appears to be the greatest risk for women, but less than 1 percent of all breast cancer is thought to be related to LFS. For those affected by LFS, breast cancers generally occur in premenopausal women.. The p53 gene is a tumor suppressor gene, which usually controls cell growth and cell death. Both copies of a tumor suppressor gene must be altered, or mutated, before a person will develop cancer. With LFS, the first mutation is inherited from either the mother or the father and is therefore present in all cells of the body. This is called a germline mutation. ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015 ...
Another area of interest is the role of GATA factors in the regulation of steroidogenic cell differentiation. Our experimental system takes advantage of the observation that GATA-4 normally is expressed in gonadal but not adrenocortical steroidogenic cells of the adult mouse. Interestingly, certain inbred strains of mice develop sex steroid-producing adrenocortical neoplasms in response to prepubertal gonadectomy. This phenomenon is thought to reflect metaplasia of competent cells in the adrenal gland, which transform into gonadal-like stroma in response to changes in the hormonal milieu, and increased expression of GATA4 is a hallmark of this transformation. To examine the signaling pathways involved in this form of tissue-type switching, we have created new inbred and transgenic models of adrenocortical neoplasia .. ...
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Small, M; Lasser, weiss M.; and Daniel, V, Release of immature cells from the thymus during solid tumor growth: identification by assay of tdt activity. (1979). Subject Strain Bibliography 1979. 4628 ...
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Jodi Weiss 19 and Assistant Professor of Biology Natalie Nannas attended the 60th Annual Maize Genetics Conference. The international meeting took place i
Marvin Weiss is retired as a tenured professor of the Accounting and Business School at the New York Institute of Technology. He has been a visiting faculty member at Fordham, NYU and Columbia University. He holds a PhD in Business from NYU-GBA.