tbuckley/cabot-search huggingface dataset:
Is ERCC1 a reliable prognostic protein biomarker in non-small-cell lung cancer?
Authors: Hannah J Durrington
Journal: Thorax (2013)

Is ERCC1 a reliable prognostic protein biomarker in non-small-cell lung cancer?After resection for non-small-cell lung cancer (NSCLC) cisplatin-based postoperative chemotherapy may be administered.How do we predict which patients will benefit from cisplatin chemotherapy?This group previously published that the excision repair cross-complementation group 1 (ERCC1) protein acts as a prognostic biomarker, predicting the benefit of cisplatin-based chemotherapy after NSCLC resection.ERCC1 plays a crucial role in repairing DNA structures, damaged by cisplatin-based chemotherapy.Using immunohistochemical analysis, patients with NSCLC and no detectable ERCC1 had longer disease-free survival after cisplatin-based chemotherapy than those positive for ERCC1.Debate over the specificity of the antibody 8F1, used to stain for ERCC1, led this group to evaluate its use.They showed that 8F1 had lost its predictive value in determining the response of NSCLC to cisplatin-based chemotherapy.When 8F1 was used to re-stain tissue sections in which it had previously had a predictive value, its ability was lost.The authors' postulate, that this loss of predictive value could be due to a new batch of 8F1 antibody.Sixteen antibodies for ERCC1 were assayed by immunoblot to determine their ability to detect specific isoforms of ERCC1.None of these antibodies could determine just one isoform of ERCC1.The expression of non-functional ERCC1 isoforms may lead to discrepant results.The authors show that of the four isoforms of ERCC1, only ERCC1-202 was active.Strong homology between the four isoforms means developing a ERCC1-202-specific antibody would be difficult.This paper highlights the technical issues that may interfere when using an immunohistochemical signal as a predictive biomarker.The need to assess multiple isoforms is paramount, before a biomarker is used to determine clinical practice.Questions ▸ Do any other commercially available antibodies stain for ERCC1 in immunohistochemistry analysis?▸ Have you checked the validity of the antibody 8F1 in other tumours such as cholangiocarcinoma, gastric cancer etc? ▸ What is your next step-it seems that producing an isoform-specific ERCC1-202 antibody is impossible?Can we rely on mRNA detection?What 'functional' analysis of ERCC1 could you do in tissue samples?
Bundling Payments for Episodes of Surgical Care
Authors: Thomas C. Tsai, David C. Miller
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
Ciprofloxacin plus Piperacillin Compared with Tobramycin plus Piperacillin as Empirical Therapy in Febrile Neutropenic Patients
Authors: James E. Peacock, Deirdre A. Herrington, James C. Wade, Hillard M. Lazarus, Michael D. Reed, Jane W. Sinclair, Daniel C. Haverstock, Steven F. Kowalsky, David D. Hurd, Deborah A. Cushing, Colleen P. Harman, Gerald R. Donowitz
Journal: Annals of Internal Medicine (2002)

Background: Therapy with an aminoglycoside and a β-lactam remains common empirical therapy for febrile neutropenic patients. Concerns of aminoglycoside-induced ototoxicity and nephrotoxicity have led to studies of alternate regimens. Objective: To determine whether ciprofloxacin–piperacillin is equivalent to tobramycin–piperacillin as empirical therapy for neutropenic fever. Design: Randomized, double-blind multicenter trial. Setting: Seven U.S. university-affiliated hospitals and one private research center. Patients: Febrile (temperature ≥ 38 °C), neutropenic (neutrophil level < 1 × 109 cells/L) hospitalized patients who had leukemia, lymphoma, or solid tumors, or were undergoing bone marrow transplantation. Interventions: Patients received piperacillin, 50 mg/kg of body weight intravenously every 4 hours, and ciprofloxacin, 400 mg intravenously every 8 hours, or tobramycin, 2 mg/kg intravenously every 8 hours. Measurements: Success was defined as resolution of infection and previously positive cultures without the need to give additional antimicrobial agents. Results: 543 febrile episodes were evaluated, of which 471 were clinically evaluable (234 in the ciprofloxacin–piperacillin group and 237 in the tobramycin–piperacillin group). Success rates in the ciprofloxacin–piperacillin group (63 of 234 febrile episodes) and tobramycin–piperacillin group (52 of 237 episodes) were similar (27% vs. 22%, respectively; difference, 5.0 percentage points [95% CI, −2.3 to 12.8 percentage points]), as was survival (96.2% of patients receiving ciprofloxacin–piperacillin versus 94.1% of patients receiving tobramycin–piperacillin; difference, 2.1 percentage points [CI, −2.2 to 6.4 percentage points]). Additions to the initial antimicrobial regimen were the most common reason for treatment failure in both groups (accounting for 67% of failures in the ciprofloxacin–piperacillin group and 72% in the tobramycin–piperacillin group; difference, 5.0 percentage points [CI, −13.8 to 3.7 percentage points]). Fevers resolved faster in patients receiving ciprofloxacin–piperacillin than in patients receiving tobramycin–piperacillin (mean, 5 vs. 6 days) (P = 0.005). No significant differences in adverse events or toxicity were noted (P = 0.083). Conclusion: Ciprofloxacin–piperacillin is as safe and effective as tobramycin–piperacillin for empirical therapy of neutropenic fever.
Spontaneous Vitiligo in an Animal Model for Human Melanoma
Authors: Renée Lengagne, Frédérique-Anne Le Gal, Marylène Garcette, Laurence Fiette, Patrick Ave, Masashi Kato, Jean-Paul Briand, Christian Massot, Izumi Nakashima, Laurent Rénia, Jean-Gérard Guillet, Armelle Prévost-Blondel
Journal: Cancer Research (2004)

Abstract Tumor antigen-reactive T cells can be detected in a large proportion of melanoma patients, but their efficacy on tumor control in vivo remains unclear. On the other hand, vitiligo, a skin disorder characterized by patchy depigmented macules, may occur spontaneously or after antitumor therapies. Moreover, vitiligo is significantly associated with positive clinical response, but the mechanism is not understood. Therefore, the establishment of a relevant animal model in which melanoma and vitiligo spontaneously develop stepwise may be useful for better understanding of the parameters involved in the destruction of both benign and malignant melanocytes. In a previous work, we established a mouse model for melanoma in which MT/ret transgenic mice express the ret oncogene fused to the metallothionein promoter. Here we report that melanoma leads to spontaneous vitiligo. We further investigate, for the first time in this model, the natural antitumor T-cell response and evaluate the role of cellular immunity in the development of the disease. Interestingly, the occurrence of spontaneous tumor nodules in MT/ret mice with melanoma-associated vitiligo is significantly delayed when compared in melanoma mice without vitiligo. Moreover, a significant proportion of mice with melanoma-associated vitiligo resisted a challenge with syngeneic melanoma cells in contrast to animals without vitiligo. Our results confirm that vitiligo is associated with clinical benefit and further demonstrate the crucial role of CD8+ T cells for tumor control in melanoma-associated vitiligo.
Clinical Characteristics and 30-Day Outcomes for Influenza A 2009 (H1N1), 2008-2009 (H1N1), and 2007-2008 (H3N2) Infections
Authors: Edward A. Belongia, Stephanie A. Irving, Stephen C. Waring, Laura A. Coleman, Jennifer K. Meece, Mary Vandermause, Stephen Lindstrom, Debra Kempf, David K. Shay
Journal: JAMA (2010)

The clinical characteristics of pandemic 2009 influenza A(H1N1) infections have not been compared directly with illnesses caused by other influenza A strains.To compare clinical features and outcomes for 2009 H1N1, seasonal H1N1, and H3N2 influenza in a population-based cohort.Active surveillance with 30-day follow-up for influenza cases among children and adults living in a 14-zip code area in Wisconsin. Patients with subjective fever, chills, or cough of fewer than 8 days' duration were screened for eligibility during an outpatient or inpatient encounter. Consenting patients were interviewed and tested for influenza A during the 2007-2008 and 2008-2009 influenza seasons and from May to November 2009; 6874 patients (70%-86% of eligible patients) agreed to participate. Medical records were reviewed to assess outcomes.Hospital admission, radiographically confirmed pneumonia, and clinical characteristics of influenza A by strain.We identified 545 2009 H1N1, 221 seasonal H1N1, and 632 H3N2 infections. The median ages of infected participants were 10, 11, and 25 years, respectively (P < .001). Hospital admission occurred within 30 days for 6 of 395 children with 2009 H1N1 (1.5%; 95% confidence interval [CI], 0.6%-3.1%), 5 of 135 with seasonal H1N1 (3.7%; 95% CI, 1.4%-8.0%), and 8 of 255 with H3N2 (3.1%; 95% CI, 1.5%-5.9%). Among adults, hospital admission occurred in 6 of 150 with 2009 H1N1 (4.0%; 95% CI, 1.6%-8.1%), 2 of 86 with seasonal H1N1 (2.3%; 95% CI, 0.3%-8.1%), and 17 of 377 with H3N2 (4.5%; 95% CI, 2.7%-7.0%). Pneumonia occurred in 10 children with 2009 H1N1 (2.5%; 95% CI, 1.3%-4.5%), 2 with seasonal H1N1 (1.5%; 95% CI, 0.2%-5.2%), and 5 with H3N2 (2.0%; 95% CI, 0.7%-4.3%). Among adults, pneumonia occurred in 6 with 2009 H1N1 (4.0%; 95% CI, 1.6%-8.1%), 2 with seasonal H1N1 (2.3%; 95% CI, 0.3%-8.1%), and 4 with H3N2 (1.1%; 95% CI, 0.3%-2.7%).In this population, individuals with 2009 H1N1 infection were younger than those with H3N2. The risk of most serious complications was not elevated in adults or children with 2009 H1N1 compared with recent seasonal strains.
Expression profiles of regulatory and helper <scp>T</scp>‐cell‐associated genes in nasal polyposis
Authors: C. W. Li, K. K. Zhang, T. Y. Li, Z. B. Lin, Y. Y. Li, M. A. Curotto de Lafaille, L. Shi, D. Y. Wang
Journal: Allergy (2012)

Abstract Background Nasal polyposis ( NP ) is a Th2‐skewed inflammatory disorder, but it is unclear what role regulatory T cells ( T ‐reg) play in disease pathology. We investigated the expression profiles of T ‐reg and T ‐helper‐cell‐associated genes and their response to glucocorticosteroid ( GC ) treatment in C hinese patients with NP . Methods Biopsies were obtained from 29 non‐treated NP patients for comparison with inferior turbinates collected from healthy controls. In 13 patients, NP samples were collected both before and after short‐term oral GC treatment. Levels of mRNA for T ‐cell markers were determined by microarray and quantitative PCR . Cellular infiltrates were assessed by histo‐ and immunohistochemistry. Results FOXP 3 + T ‐reg were increased in GC ‐naïve NP , and numbers were negatively correlated with eosinophil infiltration. Helios staining was not detected, suggesting that FOXP 3 + cells in NP are not thymus‐derived T ‐reg. Compared with controls, mRNA levels corresponding to T ‐reg genes were significantly increased in NP ( FOXP 3, TGFB 1, IL 10, SMAD 3, IL 2 RA , and JAK 3), but transcription factors associated with Th2 ( GATA 3) or Th17 responses ( ROR c) were significantly reduced. FOXP 3 mRNA levels positively correlated with other T ‐reg cell markers. Microarray analysis showed that most Th2‐related markers (e.g., Eotaxin‐1, CCL 13, and CCL 18) were upregulated in GC ‐naïve NP vs controls. GC therapy significantly suppressed eosinophilic inflammation in NP , but did not significantly alter the expression levels of T‐reg/Th2‐associated genes. Conclusions Upregulation of FOXP 3 + ‐inducible T ‐reg cells and downregulation of Th2 and Th17 markers in NP indicate a regulatory response occurring at a site of persistent mucosal inflammation. However, immune regulation fails to control the underlying tissue pathology. Expression of T‐reg/Th2 markers after GC treatment was unaltered, suggesting that T ‐cell‐driving NP inflammatory mediators are GC resistant.
Infectious diseases expert convicted over missing plague bacteria
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

A jury in the US state of Texas convicted plague expert Dr Thomas Campbell Butler, professor of medicine and head of the infectious diseases division at Texas Tech University Health Sciences Center in Lubbock, Texas, on 47 of 69 charges this week, including theft, fraud, embezzlement, and unauthorised export of plague bacteria.

He was cleared of the most serious charge, however, that he lied to FBI agents when he said that 30 phials of …
Selection by two powerful antigens may account for the presence of the major population of human peripheral gamma/delta T cells.
Authors: G De Libero, G Casorati, C Giachino, C Carbonara, N Migone, P Matzinger, A Lanzavecchia
Journal: The Journal of Experimental Medicine (1991)

V gamma 9/V delta 2 cells represent a fraction of human gamma/delta cells that is expanded after birth in the periphery, carries markers of activated cells, and becomes a major population in peripheral blood. We found that these cells do not comprise a single population but actually represent two nested sets, the smaller of which, specific for Mycobacterium tuberculosis-pulsed antigen-presenting cells (APC), is contained in a larger set specific for an antigen found on the Molt-4 lymphoma. The larger set, representing 40-80% of all blood gamma/delta cells, is comprised of cells bearing the V gamma 9/C gamma 1 chain. Cells in the smaller, included set have an additional requirement for V delta 2 (and probably for certain permissive junctional regions, since a very small percentage of V gamma 9/V delta 2 cells do not react against mycobacteria-pulsed APC). Optimal stimulation by mycobacteria is dependent on the presence of APC, and is not restricted by classical major histocompatibility complex molecules. Some of the V gamma 9/V delta 2 mycobacteria-specific clones are also stimulated by APC pulsed with different bacteria, such as Listeria monocytogenes and Escherichia coli, indicating that the population includes several different patterns of reactivity. These data establish a relationship in humans between specificity and V gamma/V delta gene usage, and offer an explanation for the peripheral expansion of these gamma/delta cells.
GLI1 Modulates EMT in Pancreatic Cancer—Letter
Authors: Shingo Inaguma, Kenji Kasai, Mitsuyoshi Hashimoto, Hiroshi Ikeda
Journal: Cancer Research (2012)

Joost and colleagues reported that GLI1 directly transactivates E-cadherin expression and modulates the TGFβ-induced epithelial–mesenchymal transition in pancreatic cancer cells ([1][1]). This conclusion was mainly drawn from the observation that siRNA-mediated knockdown of GLI1 and GLI2
Parallel expression of macrophage metalloelastase (MMP-12) in duodenal and skin lesions of patients with dermatitis herpetiformis
Authors: M T Salmela
Journal: Gut (2001)

<h3>BACKGROUND</h3> Dermatitis herpetiformis (DH) is a specific dermatological manifestation of coeliac disease and 80% of DH patients have gluten sensitive enteropathy manifested by crypt hyperplasia and villous atrophy. Matrix degradation mediated by collagenase 1 (MMP-1) and stromelysin 1 (MMP-3) has previously been implicated in the pathobiology of coeliac intestine and cutaneous DH blisters. <h3>AIMS</h3> To study expression of stromelysin 2, metalloelastase, collagenase 3, and matrilysin in the intestine and skin of DH patients. <h3>METHODS</h3> In situ hybridisation using <sup>35</sup>S labelled cRNA probes was performed on duodenal biopsies of 15 DH patients, three samples each of control duodenal or jejunal mucosa, fetal ileal explants, lesional DH skin, and 19 serial biopsies of experimental DH blisters. Immunostaining was used to examine type IV collagen, macrophages (CD68), and 92 kDa gelatinase (MMP-9) in the specimens. <h3>RESULTS</h3> Metalloelastase (MMP-12) was abundantly expressed by subepithelial macrophages in both coeliac intestine and spontaneous and induced DH rash. It was also upregulated in the experimental model of coeliac disease (staphylococcal endotoxin B stimulated fetal explants). The only other MMP detected was MMP-9 which did not colocalise with MMP-12. <h3>CONCLUSIONS</h3> Upregulation of metalloelastase is associated with T cell mediated immune responses both in the intestine and skin. In addition to modulating macrophage migration, it may contribute to degradation of proteoglycans or basement membrane components in the subepithelial mucosa.
Mutations in anionic trypsinogen gene are not associated with tropical calcific pancreatitis
Authors: M M Idris
Journal: Gut (2005)

Pancreatitis is considered to be an autodigestive disease due to premature activation of trypsinogen inside the pancreas. Its genetic basis has recently been established with the identification of causal mutations in cationic trypsinogen gene ( PRSS1 ) in patients with hereditary1 and non-hereditary pancreatitis.2 Mutations in other genes such as SPINK1 (encoding pancreatic secretory trypsin inhibitor)3 and cystic fibrosis transmembrane conductance regulator ( CFTR )4,5 genes have also been associated with the disease. Tropical calcific pancreatitis is a type of idiopathic pancreatitis, reported particularly in the tropics. Recently, we and others demonstrated absence of PRSS1 mutations but significant prevalence of the N34S mutation …
Inhibitory Effect of Actinomycin D on the Induction of Rat Mammary Tumors by in Vitro Exposure to 7,12-Dimethylbenz(a)anthracene
Authors: Takeshi Tominaga, Noriyuki Tei, Tetsuo Taguchi, Yoshifumi Takeda
Journal: Cancer Research (1975)

The inhibitory effect of actinomycin D on the induction of tumors by in vitro exposure of mammary glands to 7,12-dimethylbenz(a)anthracene was studied. When actinomycin D was given i.p. 24 hr before excision of the mammary glands, the induction of tumors by in vitro exposure of the glands to 7,12-dimethylbenz(a)anthracene was significantly decreased. On the other hand, when actinomycin D was administered 24 hr after excision, it had no effect on the induction of tumors.

In vitro exposure of excised glands to 7,12-dimethylbenz-(a)anthracene and actinomycin D significantly decreased tumor induction. However, the order of exposure to 7,12-dimethylbenz(a)anthracene and actinomycin D influenced the inhibitory effect of actinomycin D on tumor induction. Results indicated that this might be due to a difference in the amounts of 7,12-dimethylbenz(a)anthracene and actinomycin D bound to the mammary glands.
Enhancement of the Antibody-Dependent Cellular Cytotoxicity of Low-Fucose IgG1 Is Independent of FcγRIIIa Functional Polymorphism
Authors: Rinpei Niwa, Shigeki Hatanaka, Emi Shoji-Hosaka, Mikiko Sakurada, Yukari Kobayashi, Aya Uehara, Haruhiko Yokoi, Kazuyasu Nakamura, Kenya Shitara
Journal: Clinical Cancer Research (2004)

The most common polymorphic variant of Fcgamma receptor type IIIa (FcgammaRIIIa), FcgammaRIIIa-158F, has been associated with inferior clinical responses to anti-CD20 chimeric IgG1 rituximab compared with FcgammaRIIIa-158V. As we previously found that removal of fucose residues from the oligosaccharides of human IgG1 results in enhanced antibody-dependent cellular cytotoxicity, we compared the effects of the FcgammaRIIIa gene (FCGR3A) polymorphism on normal and low-fucose versions of rituximab on antibody-dependent cellular cytotoxicity.The polymorphism at position 158 of FcgammaRIIIa was determined for the peripheral blood mononuclear cells (PBMCs) of 20 healthy donors. The PBMCs were then used as effector cells to compare the antibody-dependent cellular cytotoxicity of rituximab and a low-fucose version, KM3065. The contributions of the different cell types within the PBMC to antibody-dependent cellular cytotoxicity were examined.We found KM3065-mediated antibody-dependent cellular cytotoxicity was increased 10 to 100-fold compared with rituximab for each of the 20 donors. In contrast to rituximab, KM3065 antibody-dependent cellular cytotoxicity enhancement was similar for both FCGR3A alleles and thus independent of genotype. In addition, antibody-dependent cellular cytotoxicity of both KM3065 and rituximab requires natural killer cells but not monocytes nor polymorphonuclear cells. The antibody-dependent cellular cytotoxicity (ADCC) of each of the 20 donors correlated with the natural killer cell numbers present in the PBMCs. Importantly, using KM3065, the ADCC mediated by effector cells bearing the lower affinity variant FcgammaRIIIa-158F was significantly increased compared with rituximab-mediated ADCC using effector cells bearing the higher affinity FcgammaRIIIa-158V receptors.The use of low-fucose antibodies might improve the therapeutic effects of anti-CD20 therapy for all patients independent of FcgammaRIIIa phenotype beyond that currently seen with even the most responsive patients.
Lung Cancer Staging Techniques and Induction Therapy: Maybe Timing Is Everything
Authors: Harvey I. Pass
Journal: Journal of Clinical Oncology (2008)

Surgeons would argue that this is exactly the group for which the greatest benefit will be seen by using surgery as a local modality, whereas medical oncologists will extol the benefits of chemotherapy and argue that maybe this subgroup of patients with such a fabulous response don’t need surgery at all. The bottom line is, How do we convince ourselves that we can query the mediastinum with the greatest fidelity at some reasonable time point after treating the patient, with the least cost to our patients and to us? What we, as clinicians, do with this mediastinal information (which, up to this point, has been difficult to procure without a surgeon invading some cavity) is the subject of other editorials. When all else fails, it is time to invoke new technology. Specifically for this question of mediastinal response, the first new technology invoked was positron emission tomography (PET)-computed tomography (CT). In a frenzy of articles, culminating in De Leyn’s 4 comparison of repeat mediastinoscopy to PET-CT study, it was determined that the sensitivity, specificity, and accuracy of PET-CT were 77%, 92%, and 83%, respectively, whereas those for repeat mediastinoscopy were 29%, 100%, and 60%, respectively. Moreover, sensitivity (P .0001) and accuracy (P .012) were significantly better for PET-CT compared with repeat mediastinoscopy. No matter which is better, it is apparent that PET-CT and histologic confirmation are, for the time being, immutably linked at the hip to classify these patients because the vagaries of PET-CT including the timing of when to do it, the influence of background inflammatory reaction, and the added influence of radiotherapy in combined modality inductions keeping it from achieving 100% accuracy. Proponents of repeat mediastinoscopy rightfully argue that the sensitivity in the De Leyn study was unusually low, and that present sensitivity, specificity, and accuracy for repeat mediastinoscopy are 70%, 100%, and 80% in the hands of the few surgeons who routinely perform mediastinoscopy. 5 Repeat