tbuckley/cabot-search huggingface dataset:
Hematopoietic progenitor cell line 32D cl 3 and squamous cancer cell line SCC-VII are sensitized to ionizing irradiation by thalidomide
Authors: Emily E. Greenberger, Michael W. Epperly, Darcy Franicola, Xichen Zhang, Samuel Jacobs, Joel S. Greenberger
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4395 

Thalidomide (TL) has been used in the treatment of multiple myeloma and due to its anti-angiogenic effects has been postulated to be a potential radiosensitizer for squamous cancers in vivo. We first investigated the effect of TL on growth of IL-3 dependent murine hematopoietic 32D cl 3 cells in semisolid methylcellulose containing medium also supplemented with TL ranging from 0 to 200 μM. The cells were incubated at 37°C for 7 days at which time colonies of greater than 50 cells were counted. TL increased cell colony formation 2-fold over the dose range of 10 to 100 μM. In serially decreasing concentrations of IL-3, TL (50 μM) was growth stimulatory of 32D cl 3 colony formation in 15% IL-3 and 10% IL-3 conditioned medium (146.2 ± 7.2 and 89.3 ± 2.4 colonies/500 cells plated in TL vs. 110.8 ± 11.4 and 58.0 ± 2.1 without TL, p = 0.0304 or 0.0006). To determine whether TL was a radiosensitizer, cells were placed in: 0, 50, or 150 μM TL in three protocols: 1) 1 hour before irradiation; 2) 1 hour before irradiation plus also in methylcellulose following irradiation; or 3) were placed in TL containing methylcellulose only following irradiation. Cells were irradiated to doses ranging from 0 to 800 cGy and plated in methylcellulose containing medium. Seven days later, colonies of greater than 50 cells were counted and analyzed by single hit, multi-target or linear quadratic models. Cells grown in 50 μM TL which stimulated cell growth resulted in an increased radiation resistance compared to control irradiated cells (D = 1.87 ± 0.02 vs. 1.30 ± 0.09 Gy, respectively, p = 0.0366). However, 150 μM TL (which did not stimulate cell growth) increased radiation sensitivity compared to control irradiated cells (D = 1.22 ± 0.5 vs. 1.64 ± 0.11 Gy, respectively, p = 0.0245). To determine whether TL radiosensitized tumor cells in the therapeutic 150 μM range, SSC-VII murine squamous cell carcinoma cells were grown in TL at concentrations ranging from 0 to 200 μM and were assayed for colony formation. In contrast, SSC-VII cells showed no detectable stimulation or inhibition of cell growth for unirradiated cells in any concentration of TL. However, at 150 μM TL, SSC-VII cells were radiosensitive when incubated in TL before irradiation compared to control irradiated cells (D = 2.02 vs. 2.55 Gy, respectively). Thus, thalidomide may be a clinically valuable radiosensitizer.
Press: Selling drugs---with a little help from a journalist
Authors: B. Burton
Journal: BMJ (2001)

How exactly are journalists recruited to work on behalf of corporate clients? An advertisement placed earlier this year by public relations firm Chandler Chicco Agency offers an insight.

In August, CCA was seeking to hire a freelance journalist to attend a diabetes conference. Brynn Thomas from the New York office of CCA, a specialist in public relations for the pharmaceutical and biotech industries, arranged for a small ad to be distributed to a jobs email list of US science writers. “Healthcare public relations agency is seeking a freelance journalist to attend the EASD (European Association for the Study of Diabetes) meeting in Glasgow, September 9-13, 2001,” the ad read. …
Selective vs Nonselective Nonsteroidal Anti-inflammatory Drugs and Anastomotic Leakage After Colorectal Surgery
Authors: Kevin Doody, Margaret Coleman
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Use of Placebo in Heart Failure Research
Authors: Laszlo Littmann, Lance K. Stell
Journal: Circulation (2000)

The recently published Symptom, Tolerability, Response to Exercise Trial of Candesartan Cilexetil in Heart Failure (STRETCH), a multinational study of 844 patients with class II to III systolic congestive heart failure (CHF), investigated the effects of the angiotensin II receptor blocker candesartan cilexetil on exercise time and the signs and symptoms of CHF. 1 In the 59% of patients who were receiving prior therapy with angiotensin-converting enzyme (ACE) inhibitors, the ACE inhibitors were withdrawn.A 2-week washout period was followed by a 4-week placebo run-in.At that point, patients were randomized to receive placebo or 4, 8, or 16 mg of candesartan cilexetil daily for an additional 12 weeks.No patient received an ACE inhibitor for a minimum of 16 to 18 weeks.In addition, none of the patients were treated with either an ACE inhibitor or an angiotensin II receptor blocker for 4 to 6 weeks and, in the placebo arm, 25% of all patients (nϭ211) did not receive an ACE inhibitor or an angiotensin II receptor blocker for the duration of the entire study (ie, for 16 to 18 weeks).Concomitant therapy with cardiac glycosides, long-acting nitrates, or diuretics was kept constant, and the use of other cardioactive agents was not permitted. 1he authors state that "the study was conducted according to the Declaration of Helsinki, the European Guidelines on Good Clinical Practice, and relevant national and regional authority requirements and ethics committees." 1 It was not specifically disclosed whether informed consent was obtained or how the placebo arm was explained to subjects.We are concerned about the apparent discrepancy between the authors' assurance of compliance and the explicit statements regarding the use of placebo contained in the Declaration of Helsinki.In patients with symptomatic CHF, treatment with ACE inhibitors has proven efficacy in both symptom reduction and prolonged survival. 2The greatest effect of ACE inhibitors on survival is seen in the first 3 months of therapy. 2 Evidence of their efficacy in providing symptom relief and in improving survival is so strong that the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines supports the use of ACE inhibitors "in all patients with symptomatic heart failure, unless the inhibitors are contraindicated or not tolerated." 3It follows that in patients with symptomatic CHF, the use of placebo seems to violate the Declaration of Helsinki, which states that "The potential benefits, hazard, and discomfort of a new method should be weighed against the advantages of the best current diagnostic and therapeutic methods," and that "In any medical study, every patient-including those of a control group, if any-should be assured of the best proven diagnostic and therapeutic method.This does not exclude the use of inert placebo in studies where no proven diagnostic or therapeutic method exists.
PEST‐domain‐enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice
Authors: D. D. Obiri, N. Flink, J. V. Maier, A. Neeb, D. Maddalo, W. Thiele, A. Menon, M. Stassen, R. A. Kulkarni, M. J. Garabedian, A. M. Barrios, A. C. B. Cato
Journal: Allergy (2011)

To cite this article: Obiri DD, Flink N, Maier JV, Neeb A, Maddalo D, Thiele W, Menon A, Stassen M, Kulkarni RA, Garabedian MJ, Barrios AM, Cato ACB. PEST‐domain‐enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice. Allergy 2012; 67 : 175–182. Abstract Background: PEST‐domain‐enriched tyrosine phosphatase (PEP) is a protein tyrosine phosphatase exclusively expressed in hematopoietic cells. It is a potent negative regulator of T‐cell receptor signalling that acts on receptor‐coupled protein tyrosine kinases. PEST‐domain‐enriched tyrosine phosphatase is also expressed in mast cell and is positively regulated by glucocorticoids, but its function is unknown. In this communication, the function of PEP is analysed in mast cells. Methods: Signal transduction cascades following IgE receptor cross‐linking were compared in bone marrow‐derived mast cells (BMMC) from PEP −/− and PEP +/+ mice. Furthermore, antigen‐induced passive systemic anaphylaxis (PSA) was analysed in PEP +/+ and PEP −/− mice. Results: Bone marrow‐derived mast cells from PEP −/− mice showed impaired PLCγ1 phosphorylation and Ca 2+ mobilization. Additionally, mice deficient in PEP showed impaired mast cell degranulation and were less susceptible to PSA. Treatment of wild‐type BMMC or mice with an Au(I)–phosphine complex that selectively inhibits PEP activity produced defects in Ca 2+ signalling pathway and reduced anaphylaxis similar to that caused by the deletion of the PEP gene. Glucocorticoid that negatively regulates a wide range of mast cell action increased PEP expression and only partially inhibited anaphylaxis. However, glucocorticoid potently inhibited anaphylaxis when combined with the PEP inhibitor. Conclusions: PEST‐domain‐enriched tyrosine phosphatase is an important positive regulator of anaphylaxis. Pharmacological inhibition of its activity together with glucocorticoid administration provide an effective rescue for PSA in mice.
Biomarkers of metastatic tumor microenvironment induced drug resistance
Authors: Sumanta Goswami
Journal: Clinical Cancer Research (2007)

B59   Metastasis and drug resistance are major hurdles in curative cancer treatment. More attention is needed in decoding these aspects of cancer in order to develop more effective therapies. Recently we have discovered that the invasive mammary cancer cells in rodent models are resistant to chemotherapeutic drugs. Identification of molecular markers for both invasive and drug resistant cells from within the primary tumor would open a new vista in cancer molecular diagnosis. These would also potentially identify new pathways for therapeutic intervention which will be a useful adjunct to conventional therapies, interfering with tumor progression at several pivotal points.  We have developed an in vivo invasion assay, which provides an opportunity to collect primary tumor cells that are actively in the process of invasion. The in vivo invasion assay has been combined with array-based gene expression analyses to investigate the gene expression patterns of carcinoma cells in primary mammary tumors during invasion. The expression of genes involved in cell division and survival, and cell motility were most dramatically changed in invasive cells indicating a population that is neither dividing nor apoptotic but intensely motile. We have performed biological assays to show in two different rodent models that the invasive carcinoma cells are hypoproliferative and drug resistant even before any therapeutic intervention is done on them. This invasion signature provides a general resource of possible targets for future anti-invasion and drug resistance therapy. Currently we are identifying biomarkers that can predict the potentially invasive and drug resistant cells in the primary tumor. We are utilizing unique RNA amplification methods along with  in situ  amplification and detection methods to detect the biomarker RNA either from or in the tissue.  We have also performed florescence microscopy on the invasive mammary cancer cells to determine their cell surface marker expression. Work is in progress to perform fluorescence microscopy and flowcytometry on the invasive cells to identify selective expression and stability of expression of different protein biomarkers belonging to the invasion signature as well as the drug resistance pathways. We have also been successful in isolating the cancer cells at different steps of the metastatic process and studied their gene expression pattern and have identified a set of genes whose expression is altered transiently due to the tumor microenvironment.
Long-Lived Plasma Cells Are Contained within the CD19−CD38hiCD138+ Subset in Human Bone Marrow
Authors: Jessica L. Halliley, Christopher M. Tipton, Jane Liesveld, Alexander F. Rosenberg, Jaime Darce, Ivan V. Gregoretti, Lana Popova, Denise Kaminiski, Christopher F. Fucile, Igor Albizua, Shuya Kyu, Kuang-Yueh Chiang, Kyle T. Bradley, Richard Burack, Mark Slifka, Erika Hammarlund, Hao Wu, Liping Zhao, Edward E. Walsh, Ann R. Falsey, Troy D. Randall, Wan Cheung Cheung, Iñaki Sanz, F. Eun-Hyung Lee
Journal: Immunity (2015)
Portrait of Nathalija Gontcharova and Mihajl Larionov
Authors: M. Therese Southgate
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Epstein-Barr virus involvement in the pathogenesis of hydroa vacciniforme: an assessment of seven adult patients with long-term follow-up
Authors: L. Verneuil, S. Gouarin, F. Comoz, F. Agbalika, C. Creveuil, M. Varna, A. Vabret, A. Janin, D. Leroy
Journal: British Journal of Dermatology (2010)

Background Hydroa vacciniforme (HV) is a chronic papulovesicular photodermatosis of childhood, with some cases persisting through adulthood. In children, the Epstein–Barr virus (EBV) has been detected in typical HV and in HV evolving into natural killer/T‐cell lymphoma. No exploration of EBV infection has been performed in adult patients with HV with long‐term follow‐up.
Identification of mutations in the α3(IV) and α4(IV) collagen genes in autosomal recessive Alport syndrome
Authors: Toshio Mochizuki, Henny H. Lemmink, Mariko Mariyama, Corinne Antignac, Marie-Claire Gubler, Yves Pirson, Christine Verellen-Dumoulin, Belinda Chan, Cornelis H. Schröder, Hubert J. Smeets, Stephen T. Reeders
Journal: Nature Genetics (1994)
Recombinant, ETA′-based CD64 immunotoxins: improved efficacy by increased valency, both <i>in vitro</i> and <i>in vivo</i> in a chronic cutaneous inflammation model in human CD64 transgenic mice
Authors: T. Ribbert, T. Thepen, M.K. Tur, R. Fischer, M. Huhn, S. Barth
Journal: British Journal of Dermatology (2010)

Dysregulated, activated macrophages play a pivotal role in chronic inflammatory diseases such as arthritis and atopic dermatitis. These cells display increased expression of the high-affinity Fcgamma receptor (CD64), making them ideal targets for CD64-specific immunotoxins. We previously showed that a chemically linked immunotoxin, the monoclonal H22-RicinA, specifically eliminated infiltrating activated macrophages and resolved chronic cutaneous inflammation. However, several disadvantages are associated with classic immunotoxins, and we therefore followed a fusion protein strategy to express the antigen-binding site alone (scFv H22) fused to a derivative of Pseudomonas exotoxin A (ETA').To assess the potential effect of increased valency on efficacy, we produced monovalent [H22(scFv)-ETA'] and bivalent [H22(scFv)(2)-ETA'] versions and evaluated their potential for eliminating activated macrophages both in vitro and in vivo.Both immunotoxins were produced by bacterial fermentation. Binding was assessed by flow cytometry on the monocytic CD64+ cell line U937. Toxicity was analysed by XTT and apoptosis induction by annexin V bioassay. The in vivo effect was tested in a human CD64 transgenic mouse model for cutaneous inflammation.The cytotoxic effects of both immunotoxins were clearly due to apoptosis with an IC(50) of 140 pmol L(-1) for monovalent and only 14 pmol L(-1) for the divalent version. In vivo treatment with H22(scFv)-ETA' reduced CD64+ activated macrophages to 21% of their initial numbers whereas H22(scFv)(2)-ETA' treatment reduced these cells to 4.8% (P < 0.001).These data clearly show increased efficacy due to increased valency of the anti-CD64 immunotoxin. Both recombinant immunotoxins have a low IC(50), making them suitable for the treatment of diseases involving dysregulated, activated macrophages.
Abstract 3622: Total loss of HLA class I expression by two sarcomatoid hepatocellular carcinoma cell lines sHCC29 and sHCC63 was caused by a ∼49-kbp deletion at chromosome 15q15 across the β2m gene locus
Authors: Wei-Yi Lei, Chin-Hsuan Hsieh, Chien-Chung Chang, Shao-Hsuan Wen, Chi-Tan Hu, Shuen-Kuei Liao
Journal: Cancer Research (2014)

Abstract Scanty information is available concerning the abnormalities in HLA class I antigen presentation in sarcomatoid hepatocellular carcinoma (sHCC), although this information can improve our understanding of sHCC-host interactions and assist in a rational design of T cell immunotherapy. In this study, we have established three sarcomatoid HCC cell lines, namely sHCC29, sHCC63, and sHCC74, from the tumor lesions in three patients; two of them were HBV carriers from which sHCC29 and sHCC63 were derived, while the other was a HCV carrier from which sHCC74 was generated. No viral DNA was detected in the culture supernatants or cell extracts from any of the three HCC cell lines by COBAS AmpliPre/TaqMan qPCR. In monolayer cell culture, both sHCC29 and sHCC74 showed similar elongated fibroblastic morphology, while sHCC63 exhibited a short-spindle shape and expanded in a density-sensitive manner. HLA class I molecules were abundantly expressed on sHCC74, but were not detected on sHCC29 and sHCC63 by cytofluorometric analysis. Cytoplasmic β2-microglobulin (β2m) was also undetected in the latter two cell lines, in spite of their baseline level of low-moderate cytoplasmic HLA class I heavy chain expression, which was 33-50% of that expressed by sHCC74 in terms of % positive cells. The observed HLA class I-loss phenotype was IFN-γ (300 μg/ml, 48 h)-uncorrectable. Inactivation of the β2m genes in both sHCC29 and sHCC63 was supported by the failure to detect their β2m mRNA transcripts and by the identification of a large (∼49,187 bp) deletion across the β2m gene locus at chromosome 15q15. This deletion, the largest reported to date, explains the loss of β2m protein and lack of assembly of HLA class I molecules in the sHCC29 and sHCC63 cell lines. Mapping of the deletion breaking point and validation by immunohistochemistry of β2m loss in the corresponding tumor lesions from which sHCC29 and sHCC63 were derived are currently underway. Citation Format: Wei-Yi Lei, Chin-Hsuan Hsieh, Chien-Chung Chang, Shao-Hsuan Wen, Chi-Tan Hu, Shuen-Kuei Liao. Total loss of HLA class I expression by two sarcomatoid hepatocellular carcinoma cell lines sHCC29 and sHCC63 was caused by a ∼49-kbp deletion at chromosome 15q15 across the β2m gene locus. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3622. doi:10.1158/1538-7445.AM2014-3622
Abstract 2867: EGFR expression in T1/T2 oral tongue and floor of the mouth carcinoma
Authors: Natalie Kelner, Clovis Antonio Lopes Pinto, Luiz Paulo Kowalski, Claudia Malheiros Coutinho-Camillo
Journal: Cancer Research (2014)

Abstract Epidermal growth factor receptor (EGFR) is a molecular maker that regulates the cell growth and plays an important role in tumor proliferation, invasion and metastasis formation. Objective: In this study we examined the association of immunohistochemical expression of EGFR with clinicopathological parameters, lymph node metastasis, regional recurrence and survival in selected cases of early squamous cell carcinoma (SCC) of the oral tongue and floor of the mouth. Methods: Patients with early stage SCC of oral tongue and floor of the mouth were treated surgically at a single institution from 1980 to 2010. Specimens from 139 patients were analyzed for EGFR expression using monoclonal antibody. Results: This study included 139 patients, 96 men (69%), with ages ranging from 21 to 85 years old (mean, 58 years). The tumor site was the tongue in 105 cases (75.5%) and the floor of the mouth in 34 (24.5%). With regard to pathological T-stage, 69 cases were pT1 (52.7%) and 62 were pT2 (47.3%). EGFR was overexpressed in 18 cases (13%) and was significantly associated with pT (p=0.017), thickness greater than 4mm (p=0.017), muscular invasion (p=0.014), desmoplastic reaction (p=0.021), inflammatory infiltrate (p=0.029), lymphatic embolization (p=0.016), mode of invasion (p=0.027) and perineural invasion (p=0.007). The overexpression of EGFR was also associated with lymph node metastasis (p=0.038) and regional recurrence (p=0.014). The cancer-specific survival in 5 years decreased from 90% in the group without EGFR expression to 75.3% in the EGFR overexpression group (p=0.019). Conclusion: The EGFR overexpression was associated with more aggressive pathological features, lymph node metastasis and regional recurrence in patients with early oral tongue and floor of the mouth squamous cell carcinoma. Citation Format: Natalie Kelner, Clovis Antonio Lopes Pinto, Luiz Paulo Kowalski, Claudia Malheiros Coutinho-Camillo. EGFR expression in T1/T2 oral tongue and floor of the mouth carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2867. doi:10.1158/1538-7445.AM2014-2867