Shapiro, W R.; Basler, G A.; and Posner, J B., "Human brain tumor transplantation into nude mice." (1979). Subject Strain Bibliography 1979. 2465 ...
Inoculation of mice from appropriate crosses with two strain A tumours and one dba (subline 2) tumour showed close linkage of such a gene with the locus for fused. With the A strain it was shown that the gene was identical with that for antigen II present in the erythrocytes. The gene is therefore labelled $H_{2}$. Of sixty-nine backcross mice tested, both serologically and by tumour inoculation, sixty-five gave concordant results, four discordant results. In general, it appears that serological tests are preferable to tumour inoculation in the identification of genotypes. On serological grounds it is suggested that the dba gene is an allele of the above and should be called $H_{2}{}^{d}$. It is possible that there is a long series of alleles at this locus. The indicated genotype of the strains used is as follows: $A,H_{2}H_{2}$; $dba,H_{2}{}^{d}H_{2}{}^{d}$; CBA, C57 and $P,h_{2}h_{2}$; $CA,Fu$ $h_{2}/fu$ $h_{2}$. Further tests may show differences in the $h_{2}$ allele in the last four ...
A test that detects changing levels of tumour fragments in the blood may be an easy, non-invasive and quick way to predict who will benefit from...
A new cancer therapy, called checkpoint blockade, has had some striking successes, but unfortunately it hasnt shown potential for treating the most lethal tumors. Now scientists are testing a way to spur checkpoint blockade into more potent action using nanoparticles.
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 enhanced IL-2 responsiveness, in the CD8+ T cells in the fragments and emerging from the ...
BioAssay record AID 710427 submitted by ChEMBL: Binding affinity to TLR2 in human SU.86.86 cells xenografted in Harlan athymic nude mouse tumor assessed as increase in fluorescence at 100 nmol/kg, iv measured up to 24 hrs.
Apffel, C A. and Peters, J H., "Successful heterotransplantation of l1210 mouse leukosis into un- treated adult hamsters. Abstr." (1968). Subject Strain Bibliography 1968. 45 ...
Many cancer cell types, as well as their metastases, express high levels of CD44. Whereas some tumors, such as gliomas, exclusively display CD44s, other neoplasms, including brain metastases, gastrointestinal cancer, pancreatic adenocarcinoma, bladder cancer, uterine cervical cancer, breast cancer and non-Hodgkins lymphomas, additionally and sometimes preferentially express CD44 variants. Hence, CD44, particularly its variants, may be used as diagnostic or prognostic markers of at least some human malignant diseases. Furthermore, it has been demonstrated in animal models that upon transfection with CD44s, or CD44v cDNA, nonmetastatic tumor cells acquire metastatic potential. In addition, injection of reagents interfering with CD44-ligand interaction (e.g. CD44s- or CD44v-specific mAb) inhibit local tumor growth and metastatic spread in murine species. In this context, CD44 may confer a growth advantage on some neoplastic cells, and consequently could be used as a target for cancer therapy. The ...
Maloney began by explaining that CAR-T cells produced from distinct T-cell subsets differ in potency. NSG mice bearing Raji tumors (0.5x10 6tumor cell inoculation; day 0) were treated with human CAR-T cells manufactured from distinct T-cell subsets (on day 7). CAR-T cells produced from CD8 +T CMcells were highly potent ( Sommermeyer et al.2015).. Engineering selected T-cell subsets could enhance potency and allow delivery of the same cell product in all patients, potentially providing more uniform data on dose response and toxicity.. Pre-clinical studies have established that a defined composition of CD8 +T CMderived and CD4 +derived CAR T-cells provides optimal potency.. ...
Our groups cover a broad spectrum of interdisciplinary expertise, from mathematical modeling, cell biology, biochemistry, structural, developmental and stem cell biology to immunology, experimental tumor models and clinical oncology.. We place special emphasis on the translation of scientific findings into the clinics for the development of novel therapies, including drugs, gene and cell therapy approaches, and collaborate closely with clinically oriented groups at the Charité - Universitätsmedizin Berlin.. ...
Murine leukemia L1210 has been treated with cyclophosphamide and 4 sublines have been developed from the tumor cells surviving drug therapy. Biologic studies have demonstrated a marked alteration of virulence compared to the parent tumor and striking cytogenetic modifications have been found to exist. Serial examinations over an interval of 22 weekly transplant generations have demonstrated a biologic and cytogenetic instability characterized by, generally, a tendency for return toward control values.. ...
Carcinoembryonic antigen (CEA) was purified from GW-39 human tumor xenografts in hamsters by immunoaffinity chromatography. Binding of the antigen to immobilized monoclonal antibody provided a high degree of purification of CEA in a single step. A recovery of 79% and a 750-fold purification were obtained. The purified CEA has a molecular size of 180 kilodaltons, an isoelectric point of 4.4, and a specific activity of 0.94. About 73% of the radiolabeled GW-39 CEA reacted with goat anti-CEA serum ...
nude mouse definition: a mouse with an inherited problem that prevents all of them from developing locks also stops them from immunologically rejecting personal cells and tissues; popular in preclinical…
The ability to generate a large number of tumor-reactive T lymphocytes is the most critical requirement for adoptive immunotherapy. Our laboratory has previously demonstrated that cells from tumor-draining lymph nodes (LNs) are an excellent source of tumor-reactive T lymphocytes. After activation with anti-CD3, these cells readily proliferate in low concentrations of interleukin 2 and acquire effector functions. The adoptive transfer of these cells is capable of mediating the regression of tumors established in the lung as well as in the brain. Here, we analyzed several adhesion molecules on the tumor-draining LN T cells and separated them based on l-selectin expression. The homing receptor l-selectin mediates adhesion to the luminal surface of specialized high endothelial venules, thus regulating lymphocyte recirculation through peripheral LNs. In response to progressive tumor growth, a small population of draining LN T cells down-regulated l-selectin and increased the expression of CD44 and ...
Summary Simian virus 40 (SV40)-transformed cells express the SV40-specific tumour transplantation antigen (TSTA) on the cell surface and the SV40-coded tumour antigen in their nuclei. TSTA is defined by SV40-specific transplantation immunity, whereas T-antigen (T-Ag) can be detected serologically by indirect immunofluorescence. Both antigens, however, are derived from the A gene of SV40. We therefore analysed SV40-transformed cells for the presence of serologically detectable T-Ag-related molecules. Such antigens could not be detected on the surface of living SV40-transformed cells in monolayers. However, after a short formaldehyde fixation it was possible to stain the cell surfaces of SV40-transformed cells with sera from rabbits immunized with purified SDS-denatured T-Ag, but not with sera from hamsters bearing SV40-induced tumours. T-Ag-related antigens could be detected with both types of antisera by applying a more sensitive 125I-protein A assay. The T-Ag specificity of the binding of hamster SV40
It is well understood by oncologists that tumor growth and metastasis depend on changes in the tumor microenvironment or stroma. Stromal changes have been the focus of numerous research publications and have led to insights in both tumor development and promising new avenues for treatment [1-7].. In order to study molecular changes in stroma from tissue samples, it is necessary to separate tumor tissue from stromal tissue. Without this separation we have sample heterogeneity, which is well known to severely limit the conclusions that can be made about the specificity of molecular changes and their biological causes [5, 7-11]. This separation can be difficult in contexts where tumors are small or not well differentiated. For example, in mouse tumor xenograft models, human cancer cells are grown in immune-suppressed mice [12-15]. These models are popular in oncologic research for studying mechanisms of tumor growth and metastasis, as well as drug response. In such studies, secondary tumors (at ...
Background: The reasons why the lungs are preferential metastatic targets for some human cancers are unknown.. Aims: To unravel the mechanism of tumor pneumotropism.. Methods: Several mouse and human tumor cell lines were genotyped for key oncogenes and tumor suppressors. Their potential for spontaneous lung metastasis was assessed by subcutaneous inoculation into receptive host mice. Mutant oncogenes were silenced via shRNA or introduced using relevant expression vectors. Chemokine signaling was studied using microarray, qPCR, ELISA and immunobloting and was abrogated using chemokine receptor-deficient mice.. Results: Spontaneous lung metastasis co-segregated with the presence of NRAS mutations detected in 3 of 11 cell lines studied. The expected frequency of NRAS mutations based on COSMIC (http://cancer.sanger.ac.uk/cosmic/) was tightly correlated (P=0.0000054, R2=0.652) with lung metastasis at necropsy in 3827 patients with various cancers (Disibio, G. et al. Arch Pathol Lab Med ...
A competent and expanding vascular supply is a necessary component of the progressive growth of solid tumors because cells in solid tumors, like normal tissue, must receive oxygen and other nutrients to survive and grow (17) . The connection between oxygen supply and tumor growth was first made in the 1950s by radiobiologists who were aware of oxygen as a radiosensitizer and the fact that hypoxic cells in tumors are resistant to radiation therapy (18) . Histological analyses of human and rodent tumors performed by Thomlinson and Gray (18) were the first studies to suggest that regions of viable cells exist close to tumor blood vessels and that these walls or cords of viable tumor cells correspond in thickness to the distance that oxygen can diffuse (1-2 mm3). The "tumor cord" model implied that hypoxic cells exist in a state of oxygen and nutrient starvation at the limits of the diffusion range of oxygen, and it was hypothesized that tumor cells could proliferate and grow only if they were close ...
Animal models for human tumor xenografts are used for the study of biology and treatment of human cancer. The aim of this study was to develop a model for long-term tumor observations with the...
Note: This cell line was derived from a 4th passage nude mouse xenograft of tumor fragments obtained from a patient prior to therapy. This cell line is a pseudodiploid human cell line an and has a high concentration of receptors for EGF. This cell line has lost both chromosomes 8 and 11 while SNU-C2A has lost only chromosome 11. Penicillin-streptomycin were added to culture media (final concentration, 100 U/mL ...
OUTLINE: Previously collected breast tumor fragments are implanted into the renal capsule site of SCID mouse hosts (mouse with severe combined immune deficiency) to establish metastatic spread patterns, and both histologic and molecular tumor characteristics.. Patients medical charts are reviewed to obtain relevant information, including general demographics, smoking and alcohol use, as well as outcome data such as survival and response to treatment. ...
OUTLINE: Previously collected breast tumor fragments are implanted into the renal capsule site of SCID mouse hosts (mouse with severe combined immune deficiency) to establish metastatic spread patterns, and both histologic and molecular tumor characteristics.. Patients medical charts are reviewed to obtain relevant information, including general demographics, smoking and alcohol use, as well as outcome data such as survival and response to treatment. ...
Fingerprint Dive into the research topics of Enhanced metastatic potential of tumor cells harvested from spontaneous metastases of heterogeneous murine tumors. Together they form a unique fingerprint. ...
Abstract. Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. While former studies have indicated that T-cell dependent processes mediate CR in hosts bearing immunogenic small tumors, the most universal manifestation of CR induced by immunogenic and non-immunogenic large tumors had been associated with an antitumor serum factor that remained an enigma for many years. In a recent paper, we identified that elusive factor(s) as an equi-molar mixture of meta-tyrosine and ortho-tyrosine, two isomers of tyrosine that are not present in normal proteins and that proved to be responsible for 90% and 10%, respectively, of the total serum anti-tumor activity. In this work, we have extended our previous findings demonstrating that a periodic intravenous administration of meta-tyrosine induced a dramatic reduction of lung and hepatic metastases generated in mice bearing two different metastatic murine tumors ...
Includes syngeneic models, human tumor xenograft models, orthotopic models, metastatic models, transgenic models, and gene knockout models Provides
Annibale Carracci Fine Art Open Edition Gicl e:A Male Nude Seated with His Back Turned Artist: Annibale Carracci Title: A Male Nude Seated with His Back Turned Size: 30 x 19.9 Edition: Open Edition Medium: Fine Art Giclee on Paper ...
TY - JOUR. T1 - Clodronate-Liposome Mediated Macrophage Depletion Abrogates Multiple Myeloma Tumor Establishment In Vivo. AU - Opperman, Khatora S.. AU - Vandyke, Kate. AU - Clark, Kimberley C.. AU - Coulter, Elizabeth A.. AU - Hewett, Duncan R.. AU - Mrozik, Krzysztof M.. AU - Schwarz, Nisha. AU - Evdokiou, Andreas. AU - Croucher, Peter I.. AU - Psaltis, Peter. AU - Noll, Jacqueline E.. AU - Zannettino, Andrew. PY - 2019/8/1. Y1 - 2019/8/1. N2 - Multiple myeloma is a fatal plasma cell malignancy that is reliant on the bone marrow microenvironment. The bone marrow is comprised of numerous cells of mesenchymal and hemopoietic origin. Of these, macrophages have been implicated to play a role in myeloma disease progression, angiogenesis, and drug resistance; however, the role of macrophages in myeloma disease establishment remains unknown. In this study, the antimyeloma efficacy of clodronate-liposome treatment, which globally and transiently depletes macrophages, was evaluated in the ...
Looking for online definition of Athymic nude mouse in the Medical Dictionary? Athymic nude mouse explanation free. What is Athymic nude mouse? Meaning of Athymic nude mouse medical term. What does Athymic nude mouse mean?
Purpose: The avascular cornea is predestined to study neovascular responses. First experiences with this model date back to 1972, when Gimbrone et al heterotopically implanted tumor fragments in rabbit corneal pockets. Different assays in rabbit, rat, and mouse corneas have since been published including placement of (anti-)angiogenic growth factor releasing pellets or proangiogenic corneal sutures. Using murine corneas is surgically more intricate but advantageous due to the well-defined genetic background and availability of genetically modified animals. In mice, so far tumor-associated angiogenesis has been studied by inserting pre-grown tumor fragments into corneal pockets. Here we describe an alternative approach, where a suspension of cultured tumor cells is directly injected into the corneal stroma.. Methods: One µl of B16F10 melanoma cells suspended in PBS (100.000 cells/µl) and pre-stained with FITC+ CellTracker Green was injected into the paracentral corneal stroma of C57Bl/6 mice ...
A two-stage modification of the leucocyte adherence inhibition (LAI) test is described, which quantitates cell-mediated immunity (CMI) in vitro with 0.5-ml samples of blood from mice exposed to methylcholanthrene-induced tumors. The total blood cells are washed and incubated for 30 min with tumor antigen, then centrifuged, and the supernatant assayed in the LAI test with normal peritoneal cells. The first stage of the reaction depends on the rapid formation of a soluble mediator which appears to be a lymphokine. By this method, the daily changes in specific CMI were followed in individual mice after syngeneic tumor transplantation ...
This is one of 14 colorectal carcinoma cell lines derived by J.G. Park and associates during the years 1982 through 1985. The line was obtained from a fourth passage nude mouse xenograft of tumor fragments obtained from a patient prior to therapy (see also ATCC CCL-250.1 which was derived from the third nude mouse passage).
In control arm, the tumor grew the fastest within the first couple weeks. As the tumor enlarged, we noticed a decline in growth rate of these tumors. In the control arm, the tumor growth rate was significantly higher in the first 15 days compared to the second 15 days. The tumor volume doubling time changed from 103 h in the first 15 days to 144 h in the second 15 days (P , 0.01). However, in the 2 mg T and 5 mg T arms, the opposite results were found. The data demonstrated that in 2 mg T and 5 mg T arms, the tumor growth rate was significantly lower in the first 15 days compared to the second 15 days, (184 h vs 133 h in 2 mg T arm, P , 0.05, 206 h vs 140 h in 5 mg T arm, P , 0.01). When comparing the growth rates of the control arm and the 2 mg T and 5 mg T arms in the first 15 days, the growth rates were much higher in the control arm (P , 0.01). However, in the second 15 days there was no significant difference in tumor growth rates in the control arm, 2 mg T arm, and 5 mg T arms (Fig. 4). ...
Tumors adapt to an unfavorable microenvironment by controlling the balance between cell proliferation and cell motility, but the regulators of this process are largely unknown. Here, we show that an alternatively spliced isoform of syntaphilin (SNPH), a cytoskeletal regulator of mitochondrial movements in neurons, is directed to mitochondria of tumor cells. Mitochondrial SNPH buffers oxidative stress and maintains complex II-dependent bioenergetics, sustaining local tumor growth while restricting mitochondrial redistribution to the cortical cytoskeleton and tumor cell motility. Conversely, introduction of stress stimuli to the microenvironment, including hypoxia, acutely lowered SNPH levels, resulting in bioenergetics defects and increased superoxide production. In turn, this suppressed tumor cell proliferation but increased tumor cell invasion via greater mitochondrial trafficking to the cortical cytoskeleton. Loss of SNPH or expression of an SNPH mutant lacking the mitochondrial localization ...
Adoptive cell transfer of tumor infiltrating lymphocytes has shown clinical efficacy in the treatment of melanoma and is now also being explored in other tumor types. Generation of sufficient numbers of effector T cells requires extensive ex vivo expansion, often at the cost of T cell differentiation and potency. For the past 20 years, IL-2 has been the key cytokine applied in the expansion of TIL for ACT. However, the use of IL-2 has also led to collateral expansion of regulatory T cells (Tregs) and progressive T cell differentiation, factors known to limit in vivo persistence and activity of transferred TIL. The use of alternative T cell growth factors is therefore warranted. Here, we have compared the effects of IL-2, -15 and −21 cytokines on the expansion and activation of TIL from single-cell suspensions of non-small cell lung cancer, ovarian cancer and melanoma. We applied the K562-based artificial APC (aAPC) platform for the direct and rapid expansion of tumor infiltrating lymphocytes isolated
Consistent with previous observations, c-Met Inhibitors staining exposed substantial regions of hemorrhagic necrosis devoid of CD31 staining along with viable tumor cells and CD31 blood vessels in the tumor rim. Interestingly, CD31 immunostained sections of orthotopic MCA tumors showed a really selective vascular response to DMXAA with intact vasculature noticeable in the neighboring muscle tissue.. Evaluation of R1 values of muscle tissue had been consistent with this observation and showed no statistically important big difference amongst handle and treatment method groups. Ultimately, we determined if the differential vascular response to DMXAA among ectopic and orthotopic MCA tumors correlated with intratumoral levels of TNF, a principal cytokine concerned in antivascular activity of DMXAA. Differences in intratumoral VEGF ranges have been also analyzed. As proven in Fig. 5A, untreated handle MCA tumors established at ectopic and orthotopic tissue sites showed very reduced amounts of TNF, ...
LY294002 price The sole reproducible distinction among wild variety and NG2 null specimens was the lowered num ber of lesions obvious at early time points in the absence of NG2, reinforcing the conclusions acquired from your total mount staining. Progression of transplanted mammary tumors Donor MMTV PyMT tumor fragments were transplanted into mammary extra fat pad web sites in 4 month old female wild sort and NG2 null mice that didnt carry the MMTV PyMT transgene. In wild style mice, 50% of transplantation web-sites had detectable tumors at 40 days post implantation. In NG2 null mice, the time for 50% incidence was extended to 80 days. Comparable outcomes had been obtained in a 2nd experiment using two month previous recipient females. These changes in tumor latency concerning wild kind and NG2 null mice therefore mimic the differences in latency seen with spontaneous mammary tumor advancement. Progression of mammary tumors from cell lines The Py230 and Py8119 cell lines were the two derived ...
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.. ...
www.MOLUNA.de Systems Biology of Tumor Dormancy [4197128] - This volume is based on the Workshop on Systems Biology of Tumor Dormancy meeting, held July 25th to July 28th, 2011. The first annual CCSB workshop brought together biologists, clinicians, mathematicians, and computer scientists to discuss various aspects of tumor dormancy and develop novel mathematical/computational models with the keynote speakers.
MSpace maintenance is scheduled to be performed between 9:00AM and 12:00PM CST on Thursday Jan 23, 2020. Access will be unavailable intermittently during that time. Please plan your submissions accordingly. Any in-progress submissions should be saved before the maintenance period.. ...
The majority of in vivo models of metastasis determine the effect of experimental conditions (usually via knock-out mice) by relying on the end point of secondary tumor formation at a distal site (14). However, the steps occurring between tumor cell injection and metastatic tumor formation are effectively shrouded in these models (15). Despite advances in imaging to monitor these processes, a crucial step of metastasis-the invasion and colonization of cancer cells upon extravasation-remains an elusive target. This study describes a three-dimensional culture system developed to model this phase in vitro and establishes the efficacy of this novel system by demonstrating that cells from disparate phases of melanoma invade the matrix in a manner proportional to their known metastatic capabilities. Specifically, the highly metastatic C8161.9 stayed true to its documented in vivo behavior (21), ferociously staking claim to much of the surrounding matrix (Fig. 1A-C). The sporadically metastatic M14 ...
Cancer is a class of diseases in which a group of cells displays uncontrolled growth and invasion that destroys adjacent tissues, and sometimes send metastasis to other locations in the body. When one is interested in cancer research, mice will be the preferred animal. Murine models of cancer include transplantable models, spontaneous and autochthonous models, human tumor xenografts, orthotopic models, models of metastasis and transgenic tumor models.
PDT in tumor-bearing mice. (a) 4T1 cells were injected subcutaneously in two separate locations on the back of BALB/c mice. After tumors were established (marke
A xenograft is cells or sections of tissue that are removed from one species and grafted onto another species. The main reason for...
TY - JOUR. T1 - Single-dose versus fractionated radioimmunotherapy of human colon carcinoma xenografts using 131I-labeled multivalent CC49 single-chain Fvs1. AU - Goel, A.. AU - Augustine, S.. AU - Baranowska-Kortylewicz, Janina. AU - Colcher, D.. AU - Booth, B. J M. AU - Pavlinkova, G.. AU - Tempero, M.. AU - Batra, Surinder Kumar. PY - 2001/2/12. Y1 - 2001/2/12. N2 - The prospects of radiolabeled antibodies in cancer detection and therapy remain promising. However, efforts to achieve cures, especially of solid tumors, with the systemic administration of radiolabeled monoclonal antibodies (MAbs) have met with limited success. Using genetic engineering techniques, MAbs have been tailored to improve the therapeutic index (tumor:normal tissue ratio) in clinical radioimmunotherapy. In the present study, we investigated the potential of tetravalent {[sc(Fv)2]2} and divalent [sc(FV)2] single chain Fvs of MAb CC49 for therapy in athymic mice bearing s.c. LS-174T human colon carcinoma xenografts. Mice ...
Studies investigating the oxygenation status and the development of hypoxia in microscopic tumors are sparse. The purpose of this study was to measure the extent of hypoxia in microscopic melanoma xenografts and to search for possible mechanisms leading to the development of hypoxia in these tumors. A-07, D-12, R-18, and U-25 human melanoma xenografts grown in dorsal window chambers or as flank tumors were used as preclinical tumor models. Morphologic and functional parameters of vascular networks were assessed with intravital microscopy, and the expression of angiogenesis-related genes was assessed with quantitative PCR. Microvessels, pericytes, and the extent of hypoxia were assessed by immunohistochemistry in microscopic tumors by using CD31, αSMA, and pimonidazole as markers, and the extent of radiobiological hypoxia was assessed in macroscopic flank tumors. Macroscopic R-18 and U-25 tumors showed extensive hypoxia, whereas macroscopic A-07 and D-12 tumors were less hypoxic. R-18 and U-25 tumors
Sixteen children underwent 18 operations for radical resection of chiasmatic-hypothalamic tumors. The clinical presentation correlated with age: infants under 1 year of age presented with macrocephaly, failure to thrive, and severe visual failure; children aged 1 to 5 years predominantly had precocious puberty with mild visual deficits; and older children (greater than 5 years old) had slowly progressive loss of vision. All three infants had biologically aggressive tumors in spite of low-grade histology, and died from progressive tumor growth. Eleven of the 13 children aged 1 year or over are alive and well, without clinical or radiographic evidence of disease progression, 4 months to 4 1/2 years following surgery. Six of these patients, with a follow-up period of 10 months to 4 1/2 years (mean 27 months), have had no adjuvant therapy following radical surgical resection. The authors conclude that: 1) radical surgical resection of chiasmatic-hypothalamic tumors can be performed with minimal ...
TY - JOUR. T1 - In Situ Selection of a Human Rhabdomyosarcoma Resistant to Vincristine with Altered β-Tubulins. AU - Houghton, Janet A.. AU - Houghton, Peter J. AU - Hazelton, Bonni J.. AU - Douglass, Edwin C.. PY - 1985/6/1. Y1 - 1985/6/1. N2 - In order to simulate more closely conditions in which resistance to vincristine (VCR) is selected in human solid tumors, a human rhabdomyosarcoma grown as a xenograft in immune-deprived mice has been selected for resistance in situ. Karyotype analysis showed the resistant line, HxRh18/VCR-3, to have a diploid modal number, with no apparent translocations, whereas the predominant population in the parental, sensitive HxRh18 xenograft demonstrated a modal number near-tetrapbid with many marker chromosomes. From the rapid rate at which resistance was selected and from karyotypic evidence, data strongly suggest that HxRh18/VCR-3 was a subpopulation within the parent tumor. When grown in the same host, HxRh18/VCR-3 tumors accumulated less drug, and the rate ...
In this report, we describe PD 0332991 as a potent and highly selective inhibitor of Cdk4 and Cdk6 and show that suppression of these enzymes in human tumor xenografts results in significant antitumor activity. Given that a major obstacle to establishing the usefulness of a Cdk4/6 inhibitor has been the difficulty in obtaining a molecule with complete specificity for these enzymes versus other Cdks and protein kinases, considerable effort was taken to establish the selectivity of this compound. PD 0332991 was tested against 39 individual serine, threonine, and tyrosine kinases, representing most of the primary protein kinase families (84). Other than Cdk4 and Cdk6, the compound had little or no activity against any of these enzymes. Based on the understood role of Cdk4/6 in cell cycle progression, a specific Cdk4/6 inhibitor is predicted to produce an exclusive G1 arrest. Consistent with this expectation, cells treated with concentrations of PD 0332991 as high as 200-fold above the IC50 for ...
Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular
Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular