tbuckley/cabot-search huggingface dataset:
Abstract 1773: The tyrosine phosphatase, SHP-2, is involved in regulating PD-L1 expression in non-small cell lung cancer
Authors: Keller Toral
Journal: Cancer Research (2019)

Abstract Immune checkpoint inhibitors (ICIs), specifically those which target the T-cell surface receptor Programmed Cell Death-1 (PD-1) and its ligand, Programmed cell death ligand-1 (PD-L1), have demonstrated substantial clinical benefit in patients with non-small cell lung cancer (NSCLC). Tumoral PD-L1 expression may be important for response to therapy, but the precise mechanism of regulation has yet to be fully elucidated. It is known that PD-L1 expression is elevated in cancers harboring mutations in the RAS family of genes, specifically KRAS. Mutations in the KRAS gene are found in up to 30% of NSCLC tumors, and there are no targeted treatment options available for this subset of patients. The tyrosine phosphatase, SHP-2, has been shown to be a critical regulator of the KRAS signaling cascade. Therefore, genes regulated by the RAS/MAPK signaling cascade, including PD-L1, may be modulated by SHP-2 inhibition. Thus, this study aims to investigate the impact of SHP-2 activity on PD-L1 expression in NSCLC. The allosteric inhibitor of SHP-2, SHP099, was used to ablate SHP-2 activity in KRAS-mutant NSCLC cell lines, H460, A549, H2122, and EGFR-mutant NSCLC cell line PC9. PD-L1 levels were quantified by western blot and flow cytometry analyses. PD-L1 mRNA was measured by quantitative real time PCR (qRT-PCR) analysis. SHP099 activity was confirmed by SHP-2, siRNA transfection in KRAS active cell lines. Inhibition of SHP-2 led to increased levels of PD-L1 expression in the KRAS-mutant cell lines, but not in the EGFR-mutant cells. Analysis of PD-L1 surface expression by flow cytometry confirmed that surface PD-L1 levels increased following exposure to SHP099. To determine whether SHP-2 controlled expression at the transcriptional level, mRNA quantification by qRT-PCR displayed increased levels of PD-L1 mRNA following SHP099 treatment. Together, these results suggest that SHP-2 regulates PD-L1 expression in KRAS-active NSCLC at the level of PD-L1 gene expression. It is presently unclear whether SHP-2 also has a role in controlling protein turnover. Using SHP-2 mutant constructs that mimic a constitutively active phosphatase, we hope to gain further insight into the roles of both SHP-2 catalytic and scaffolding functionality on PD-L1 expression. Citation Format: Keller Toral. The tyrosine phosphatase, SHP-2, is involved in regulating PD-L1 expression in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1773.
Cardiac tamponade and death in a patient receiving total parenteral nutrition
Authors: D. H. Kuiper
Journal: JAMA (1974)

ADMINISTRATION of hypertonic solutions for parenteral nutrition necessitates the use of a central venous catheter, a procedure fraught with complications.<sup>1</sup>We are reporting a case of cardiac perforation, tamponade, and death resulting from this procedure. <h3>Report of a Case</h3> A 63-year-old woman underwent partial gastrectomy and excision of the distal section of the esophagus in December 1970 for an adenocarcinoma of the gastroesophageal junction. Her immediate postoperative course was uneventful. Preoperatively, her weight was 45 kg (99 lb). Her late postoperative course was complicated by severe dumping symptoms, early satiety, and weight loss. During the subsequent 17 months, in spite of numerous attempts to increase the patient's caloric intake with various oral food supplements, her weight declined to 30 kg (66 lb). Repeated esophagoscopy, biopsy, cytologic studies, and barium contrast examinations of the upper gastrointestinal tract failed to disclose any evidence of recurrent neoplasm. We decided to begin total
Infectious Diseases. A Practical Textbook.
Journal: JAMA (1920)

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
NEW INSTRUMENTS.
Journal: JAMA (1891)

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
From the National Institutes of Health
Authors: W. Raub
Journal: JAMA (1990)

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
Manuscripts Approved for JNCI, October 1 to November 1, 1968
Journal: JNCI Journal of the National Cancer Institute (1968)

Manuscripts Approved for JNCI, October 1 to November 1, 1968 JNCI: Journal of the National Cancer Institute, Volume 41, Issue 6, December 1968, Page 1496, https://doi.org/10.1093/jnci/41.6.1496 Published: 01 December 1968
DOMESTIC CORRESPONDENCE.
Authors: G. A. Aschman
Journal: JAMA (1892)

but at the present time there is certainly a strong and grow¬ ing feeling that their employment is not only not necessary, but rather an injury than a benefit to the patient.It may well be questioned if, after all, viewing the subject in its widest aspect, operations for cancer of the stomach have really been or can be of much service.They certainly have
Editorial: Considerations of Risks versus Benefits
Authors: Hans L. Falk
Journal: Environmental Health Perspectives (1975)

An evaluation of risks versus benefits from new products should be encouraged, even when dealing with agents which may cause cancer or malformations in laboratory animals, because there is evidence that safety thresholds exist even for such exposures.However, it is not easy to describe risk and benefit in comparable terms when they may involve generations to come and events in the future.
HLA Class i antigen display on hepatocyte membrane in chronic hepatitis B virus infection: Its role in the pathogenesis of chronic type B hepatitis
Authors: Chia-Ming Chu, Wei-Chue Shyu, Ruey-Wen Kuo, Yun-Fan Liaw
Journal: Hepatology (1987)

It has been suggested that cytotoxic T cells are involved in the recognition and lysis of the infected hepatocytes in chronic hepatitis B virus infection, and that the target antigen is probably HBcAg which is displayed on the hepatocyte membrane during active viral replication. However, studies in other viral infection have demonstrated that cytotoxic T cells recognize viral antigen on the infected cells only in the context of HLA class I antigens. To test whether this mechanism is also operative in chronic hepatitis B virus infection, we studied the expression of HLA class I antigens in livers from 35 patients with chronic hepatitis B virus infection by indirect immunofluorescence using monoclonal antibody against HLA class I antigens. The blocking effect of monoclonal antibody against HLA class I antigens on the in vitro T cell cytotoxicity to autologous hepatocytes was also studied. The results revealed that HLA class I antigen was undetectable on the hepatocyte membrane in all of 10 HBeAg-positive carriers with minor hepatitic activity, whereas it was demonstrated in 15 (88%) of the 17 HBeAg-positive patients with chronic active liver disease and in 7 (87%) of the 8 anti-HBe-positive “normal” carriers. The in vitro T cell cytotoxicity to autologous hepatocytes in six HBeAg-positive patients with chronic active liver disease was significantly inhibited by preincubation of hepatocytes with monoclonal antibody (10 to 40 μg per ml) against HLA class I antigen, but not by monoclonal antibody against HLA class II antigens and non-HLA-associated surface molecules (Leu 11). These findings suggested that HLA class I antigens became detectable on hepatocyte membrane while significant histological activity developed in chronic hepatitis B virus infection, and that the effector cytotoxic T cells required HLA class I antigen as target structure(s).
Natural Born Killers
Authors: Charles W. Schmidt
Journal: Environmental Health Perspectives (1998)

This year, 30 million acres of the corn, cotton, and potatoes planted in the United States will have been genetically engineered to produce an endotoxin normally found in the microbe Bacillus thuringiensis (Bt), a self-contained pesticide that will be toxic only to target insects. Transgenic pest-resistant crops are a cost-effective alternative to chemical pesticides, and may offer a way to help feed the world's growing population with minimal environmental impact.
Missing Middle Initial in Author’s Name
Journal: JAMA Oncology (2016)

Kasmintan A. Schrader, MBBS, PhD, FRCPC, DABMG; Donavan T. Cheng, PhD; Vijai Joseph, PhD; Meera Prasad, MS; Michael Walsh, MD; Ahmet Zehir, PhD; Ai Ni, PhD; Tinu Thomas, MS; Ryma Benayed, PhD; Asad Ashraf, MS; Annie Lincoln, MS; Maria Arcila, MD; Zsofia Stadler, MD; David Solit, MD; David M. Hyman, MD; Liying Zhang, MD, PhD; David Klimstra, MD; Marc Ladanyi, MD; Kenneth Offit, MD; Michael Berger, PhD; Mark Robson, MD
Survival of Patients Treated for Cancer of Breast, Cervix, Lung, and Upper Respiratory Tract at The Ontario Cancer Institute
Journal: JAMA (1963)

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
13th national conference on the Medical Aspects of Sports
Journal: JAMA (1971)

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
A prospective randomized trial comparing 5-fluorouracil (5-FU), mitomycin-C (MMC), and polysaccharide-K (PSK) versus UFT and PSK as adjuvant chemoimmunotherapy (CITX) for patients with locally advanced gastric cancer with curative resection
Authors: H. Lee, J. Choi, S. Kang, S. Jeong, J. Jung, Y. Choi, Y. Cho, S. Han, H. Lim
Journal: Journal of Clinical Oncology (2008)

4581 Background: Adjuvant chemotherapy has demonstrated small but significant survival benefit in locally advanced gastric cancer in several meta-analyses, while adjuvant CITX showed improved outcome of patients (pts) compared to chemotherapy alone in a few trials. However, optimal chemotherapy regimen remains to be determined. We conducted a randomized trial comparing oral (PO) CITX with intravenous (IV) CITX in gastric cancer pts with curative resection. Methods: All enrolled pts underwent radical surgery with at least D2 dissection. After stratification for pathologic stage (IB or II vs. III) and primary tumor size (≤5 cm vs. >5 cm), pts were randomized to IV CITX (5-FU 500 mg/m2 weekly for 24 weeks, MMC 8 mg/m2 every 6 weeks x 4) or PO CITX (UFT 400–600 mg/day for 12 months). Pts in both arms received PSK 3 g/day PO for 4 months. The planned target number of pts was 368 to prove the non-inferiority of PO CITX compared to IV CITX in overall survival. Results: A total of 82 pts (stage IB: 6, II: 29, IIIA: 30, IIIB: 17; 44 in IV arm, 38 in PO arm) were enrolled between May 2002 and October 2005, when the trial was closed due to poor accrual. Pts characteristics were well balanced. With a median follow-up of 51 months (25–68 months) in survivors, there were no significant differences in 4- year disease-free survival (75% vs. 62%, p=0.195) and overall survival (76% vs. 70%, p=0.445) between IV and PO arms. No grade 4 toxicity was observed in both arms. IV arm demonstrated higher incidence of grade 2 or 3 neutropenia (79% vs. 52%, p=0.025), thrombocytopenia (19% vs. 0%, p=0.008), and vomiting (36% vs. 9%, p=0.013). Conclusions: Although accrual was well below that planned, the results of this trial suggest that PO CITX with UFT might have similar efficacy with lower toxicity profile compared with 5-FU and MMC CITX in adjuvant treatment for gastric cancer. No significant financial relationships to disclose.
Trauma Africa
Authors: Ian Roberts
Journal: BMJ (2005)

BBC 1, Thursdays at 9 pm until 21 July Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> A ccording to Noam Chomsky, whom I understand ranks with Karl Marx, Shakespeare, and the Bible as one of the 10 most quoted sources in the humanities, the responsibility of intellectuals is to tell the truth and expose lies. Why not judge a television documentary using the same criteria? So how does the three part series Trauma Africa line up? As someone who was scared witless by a 1970s documentary on climate change (the ice age cometh) that grimly forecast that an ice age was imminent, only to discover years later that global temperatures are heading in the opposite direction, I am sceptical about documentaries. But no problem this time. Trauma rates in Africa are among the highest in the world. According to the World Health Organization, each year there are more than 200 000 road traffic deaths in Africa and perhaps 20 to 30 times as many people seriously injured. And trauma in Africa is definitely getting hotter, with injury rates predicted to increase by around 80% by 2020. Violence—whether every day thuggery (like the man seen in this documentary … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
155P Antitumoral efficacy of dual blockade of EGFR signaling by osimertinib in combination with selumetinib or cetuximab in activated EGFR human NSCLC tumor models
Authors: F. Morgillo, C.M. Della Corte, R. Alfieri, P. Petronini, S. La Monica, F. Papaccio, F. Ciardiello
Journal: Journal of Thoracic Oncology (2018)
Treatment of acute migraine with subcutaneous sumatriptan
Authors: R. K. Cady
Journal: JAMA (1991)

Sumatriptan succinate, a 5-HT<sub>1D</sub>receptor agonist, constricts human cranial arteries. Two parallel-group trials for treatment of acute migraines were conducted in the United States. Adult patients were randomized and given either 6 mg of sumatriptan succinate subcutaneously (n = 734) or placebo (n = 370). At 1 hour, sumatriptan was significantly more effective than placebo in reducing moderate or severe headache pain to mild or no pain (70% vs 22%), in completely relieving headaches (49% vs 9%), and in improving clinical disability (76% vs 34%). Sumatriptan also reduced nausea and photophobia significantly better than placebo. Patients with residual migraines received another injection; those who had originally received sumatriptan received either a second active injection (n = 187) or placebo (n = 178), while those who had received placebo received a second placebo injection (n = 335). Statistical evidence for benefit of second sumatriptan injection is absent. Adverse events associated with sumatriptan were tingling, dizziness, warm-hot sensations, and injection-site reactions. Sumatriptan is effective and well tolerated in patients with acute migraine. (<i>JAMA</i>. 1991;265:2831-2835)
Patterns of second-line chemotherapy for metastatic prostate cancer in the United States.
Authors: Hongwei Wang, Laura Liao, Eliot Obi-Tabot, Robert Sands, Mathieu Rose, Quanwu Zhang
Journal: Journal of Clinical Oncology (2012)

169 Background: Patients with prostate cancer progressing from 1 st line (1L) docetaxel had limited treatment options available. This study is to evaluate patterns of 2 nd line (2L) chemotherapy in US managed care between 2004 and 2010. Methods: Patients with metastatic prostate cancer (mPC) and treated with docetaxel as 1L chemotherapy after July 1, 2004 were ascertained from the OptumInsight database. We evaluated type and timing of chemotherapy and relationships between patient characteristics, physician specialty, healthcare costs and geographic region 6 months prior to 1L docetaxel and choice of 2L chemotherapy. Results: Patients (n=1,173) were on average 71 years old at the onset of 1L docetaxel. During a mean follow-up period of 18 months, 38% patients received 2L treatment. Out of the patients received 2L therapy, 32% received mitoxantrone (MITO), 24% with docetaxel rechallenge (RECH), 14% carboplatin (CARB), and 12% paclitaxel (PAC), plus 11% on combo therapy. An examination of the 2L treatment groups showed that during the 6 months prior to 1L docetaxel, the RECH group (n=101) was older (73yrs), had fewer hospital admissions (12%), lower comorbidity burden (Charlson Comorbidity Index (CCI)=7.4), lower total healthcare costs ($10,083), and 78% patients seeing an oncologist; relative to MITO group (n=143) with 70 years of age, 16% hospital admissions, CCI of 7.5, total healthcare costs of $12,074, and 80% seeing an oncologist. The combo group (n=52) was 66 years old, with 19% hospital admissions, CCI of 8, total healthcare costs of $20, 505, and 92% seeing an oncologist. Median time to MITO from the start of 1L docetaxel was 184 days, 309 days to RECH and 223 days to combo therapy. Midwest (36%) and West (37%) were more frequently using MITO than Northeast (26%) and South (31%), while RECH was more frequently used in Northeast. Conclusions: Patients with mPC in US were most frequently treated with MITO or RECH as 2L chemotherapy after 1L docetaxel. MITO was also given sooner than RECH, hence a valid comparator for comparative effectiveness evaluation on new 2L therapy. Rechallenge with docetaxel increased with time and was given to patients with lower disease burden and healthcare costs than the MITO or Combo group.
Hepatitis B antigenemia in apparently healthy blood donors
Authors: F. M. Griffin
Journal: JAMA (1973)

In an effort to determine the importance of hepatitis B antigenemia in apparently healthy blood donors, 12 asymptomatic male recruit trainees with hepatitis B antigenemia were studied by means of history and physical examination, biochemical tests of hepatic function, and percutaneous hepatic biopsy. All had normal physical examination results. Nine had normal liver function; three had increased enzymes. On biopsy, five had normal hepatic tissue; seven had changes consistent with viral hepatitis. No patient had persistent limiting plate disruption, cirrhosis, or hepatic steatosis. A reasonable approach to apparently healthy hepatitis B antigen carriers may be to observe them clinically and with biochemical tests of hepatic function as long as no evidence of chronic liver disease appears and to reserve liver biopsy for those who have persistent hepatic inflammation. The long-term importance of hepatitis B antigenemia remains unclear.