tbuckley/cabot-search huggingface dataset:
Association of changing prostate-specific antigen (PSA) levels on repeat testing with lower risk for Gleason Score (GS) ≥ 7 prostate cancer.
Authors: Tobias Nordström, Jan Adolfsson, Henrik Gronberg, Martin Eklund
Journal: Journal of Clinical Oncology (2016)

284 Background: PSA levels are often verified before recommending a prostate biopsy because of the variability of PSA, We used data from the STHLM3 trial to assess the value of a second PSA test taken prior to biopsy. Methods: STHLM3 is a prospective and population-based prostate cancer diagnostic study performed in Stockholm, Sweden, 2013-2015. 1686 men in STHLM3 with a PSA value 3-10 ng/ml performed a second PSA test within 8 weeks of the first test and then underwent prostate biopsy. We compared proportions of cancer detected in men with stable PSA levels (2 nd PSA within +/-10% of 1 st PSA) to men whose PSA levels increased or decreased at least 10%, respectively. Results: Men with GS ≥ 7 cancer in the biopsy had more stable PSA than men with benign biopsies; the median change was 13.7% (inter-quartile range (IQR) 6.1-26.9) in men with benign biopsies, 13.0% (IQR 6.1-25.6) in men with GS ≤ 6 tumors and 8.2% (IQR 4.5-16.7) in men with GS ≥ 7 tumors. The average risk of having GS ≥ 7 cancer was 15.4% (95% CI 13.7 – 17.1) after the first test (i.e. the entire cohort), 21.6% (95% CI 18.6 – 24.6) in men with stable PSA levels compared with 13.5% (95% CI 10.2 – 16.7) and 9.0% (95% CI 6.6 – 11.4) if PSA levels increased or decreased at least 10%, respectively. There were no significant differences in risk of GS ≤ 6 tumor for men with stable PSA compared to men with increasing/decreasing PSA. Conclusions: As previously shown, the risk of prostate cancer decreases if a repeat PSA test shows decreasing levels. We show that this effect mainly affect GS ≥ 7 tumors, and that the risk of prostate cancer also decreases with increasing PSA values. Our findings need validation, but suggest that PSA is more stable in men with GS ≥ 7 cancer, whereas elevated but fluctuating PSA levels to a higher degree are caused by other processes (e.g. inflammation). Use of decision tools could aid incorporation of complex information such as repeat PSA values in diagnostics.
Correlation of response with overall survival (OS) for nivolumab vs everolimus in advanced renal cell carcinoma (aRCC): Results from the phase III CheckMate 025 study.
Authors: Robert J. Motzer, Padmanee Sharma, Bernard J. Escudier, David F. McDermott, Saby George, Sandy Srinivas, Scott S. Tykodi, Jeffrey Alan Sosman, Elizabeth R. Plimack, Paul D. Nathan, Viktor Gruenwald, Yoshihiko Tomita, Huanyu Zhao, Ian M. Waxman, Hans J. Hammers
Journal: Journal of Clinical Oncology (2016)

4552 Background: In CheckMate 025 (NCT01668784), nivolumab demonstrated superior OS (25.0 mo; 95% CI, 21.8–not estimable [NE]) vs everolimus (19.6 mo; 95% CI, 17.6–23.1) and a higher objective response rate (25% vs 5%, P< 0.001) in previously treated patients with aRCC (N Engl J Med 2015;373:1803–13). Here, we investigated OS benefit with nivolumab vs everolimus by tumor response. Methods: Patients were randomized 1:1 to nivolumab 3 mg/kg intravenously every 2 wk or everolimus 10 mg orally once daily. We conducted a landmark analysis of OS by best response (complete/partial response; responders), stable disease [SD], and progressive disease [PD]) within 4 mo of randomization. OS was assessed using the Kaplan–Meier method. Results: For the 410 and 411 patients randomized to nivolumab and everolimus, median time to response was 3.5 mo (range: 1.4–24.8) and 3.7 mo (1.5–11.2), respectively. By mo 4 with nivolumab, 19% of patients were responders, 30% had SD, and 40% had PD; with everolimus, 3% of patients were responders, 45% had SD, and 31% had PD. The remainder of patients had discontinued, died, or had an unevaluable response by 4 mo. Median (95% CI) OS is shown (table). For nivolumab, OS rates at 12 and 18 mo were 96% and 89% in responders, 91% and 81% in patients with SD, and 70% and 50% in patients with PD by 4 mo. For everolimus, OS rates at 12 and 18 mo were 93% and 77% in responders, 90% and 79% in patients with SD, and 54% and 35% in patients with PD by 4 mo. Analyses of each subgroup by disease features will be presented. Conclusions: Patients who had a best response of SD within 4 mo of starting treatment had a similar survival trajectory compared with responders. Patients with a best response of progression had an improved OS with nivolumab vs everolimus. Clinical trial information: NCT01668784. Responders SD PD Nivolumab, n (%) 77 (19) 121 (30) 164 (40) Median OS (95% CI) NE (24.1–NE) NE (22.7–NE) 14.0 (11.3–16.9) 12-mo rate, % (95% CI) 96 (88–99) 91 (84–95) 70 (63–77) 18-mo rate, % (95% CI) 89 (80–95) 81 (73–87) 50 (42–57) Everolimus, n (%) 14 (3) 186 (45) 127 (31) Median OS (95% CI) NE (12.4–NE) 25.0 (22.9–NE) 9.8 (6.1–12.2) 12-mo rate, % (95% CI) 93 (59–99) 90 (85–93) 54 (45–63) 18-mo rate, % (95% CI) 77 (45–92) 79 (72–84) 35 (27–43)
Abstract 357: Cardiac Fibroblasts as a Support Cell for Endothelial Cell Sprout Formation in Engineered Cardiac Tissue
Authors: Rachel L Twardowski, Lauren D Black
Journal: Circulation Research (2012)

Cardiac tissue engineering offers a promising approach to regenerating post-MI myocardial tissue; however, a primary impediment lies in the inability to adequately vascularize a tissue scaffold. Endothelial cells (ECs) require a support cell to form mature patent lumens and it has been demonstrated that pericytes, vascular smooth muscle cells and mesenchymal stem cells (MSCs) are able to support the formation of mature tubules/vessels. Cardiac fibroblasts (CFs) provide important electrical and mechanical components to the myocardium and are present in the native cardiac cell population, but to date have not been sufficiently studied for their role in angiogenesis in the heart. As a model of myocardial tissue, we co-cultured different concentrations of various cell types in fibrin hemispheres in appropriate combinations of their specific media, to determine the optimal sprout formation through DNA analysis, flow cytometry and immunohistology (IH). For flow cytometry, endothelial cells and mesenchymal stem cells were marked with CD31 and CD90, respectively. The highest total cell count was found in the fetal CF co-cultured populations (Fig 1A p&lt;0.05), but ECs proliferated best with the adult and neonatal CFs (Fig 1B p&lt;0.001). Analysis of IH images (Fig 1C, D) demonstrated that ECs formed the longest (Fig 1E p&lt;0.05) and most numerous sprouts (p&lt;0.002) with CFs as compared to MSCs. However, ECs were able to produce more multicellular sprouts when in culture with the MSCs (Fig 1F p&lt;0.001). In summary, CFs provide a better support system for EC proliferation and sprout formation than MSCs, while MSCs allow for more multicellular sprouts, which is more indicative of the in vivo process.
Early versus delayed autologous stem cell transplant (ASCT) in patients receiving induction therapy with lenalidomide, bortezomib, and dexamethasone (RVD) for newly diagnosed multiple myeloma (MM).
Authors: Ajay K. Nooka, Amelia A. Langston, Edmund K. Waller, Leonard T. Heffner, Charise Gleason, Samatha Muppidi, Melanie Watson, Daniela Casbourne, Lawrence Boise, Jonathan L. Kaufman, Sagar Lonial
Journal: Journal of Clinical Oncology (2013)

8540 Background: Lenalidomide, bortezomib and dexamethasone (RVD) is an active, tolerable induction regimen with superior response rates (≥VGPR rates of 80%) in newly diagnosed MM pts. However, the optimal timing of ASCT with this triplet combination is uncertain. We have evaluated our institutional experience to provide an insight for the best timing of ASCT, where specific patients were offered delayed ASCT based on risk, response and toxicity of therapy. Methods: 222 consecutive transplant-eligible pts with newly diagnosed MM that received at least 3 cycles of RVD and harvested stem cells were included in the analysis from May 2007 until October 2011. Patients underwent early ASCT (received planned ASCT immediately after stem cell harvest, n=136) or delayed transplant (received planned maintenance therapy after collection with intent to proceed with ASCT at first relapse, n=86). Results: Median age of the patients at the time of diagnosis is 60.5 yrs (32-77) vs. 60 yrs (22-73) for early vs. delayed groups. ISS stage 3 disease was seen in 31% patients and 10% patients; high risk cytogenetics were seen in 11% and 7% patients in early vs. delayed groups, respectively. Median time from initiation of induction therapy to ASCT in early group is 5.45 months (range, 3.19-12.68 months). In the delayed SCT group, 28 patients underwent ASCT at a median time of 26.21 months (range, 13.67-41.72 months) from initiation of therapy. At a median follow up of 32 months, 5-year overall survival from diagnosis was 68% and 88% in patients undergoing early and delayed ASCT, respectively (p = 0.106). Conclusions: Transplantation-eligible patients who receive RVD as initial therapy followed by early vs. delayed ASCT result in comparable overall survival. In carefully selected newly diagnosed myeloma patients with lower ISS stage receiving RVD as induction therapy, planned delayed ASCT results in 5-year survival rates close to 90%.
Final results from an open-label, randomised, phase II study of adecatumumab (MT201), a fully human anti-EpCAM antibody, in patients with metastatic breast cancer
Authors: A. H. Awada, M. Schmidt, M. E. Scheulen, P. Obrist, N. Marschner, L. Dirix, C. Dittrich, C. Reinhardt, M. Schuler
Journal: Journal of Clinical Oncology (2007)

3588 Background: High-level expression of the epithelial cell adhesion molecule (EpCAM) has been associated with unfavourable prognosis in various cancers. Adecatumumab was developed as a low-affinity IgG1 antibody targeting EpCAM-positive cancer cells. Methods: EpCAM-positive metastatic breast cancer patients without CNS metastases, with no indication for trastuzumab were eligible; an initial restriction to a maximum of one previous chemotherapy for metastatic disease was subsequently removed. 109 EpCAM- positive patients were enrolled. Patients were stratified into high- and low-level EpCAM expression (n = 74 and 35, respectively) according to immuno-histochemistry testing, and subsequently randomised to receive either high-dose (6 mg/kg/q2w) or low-dose (2 mg/kg/q2w) adecatumumab (n = 54 and 55, respectively). Primary endpoint was clinical benefit rate (CBR = objective response + stable disease) at week 24 with secondary parameters exploring time to progression (TTP) and safety. Results: The primary endpoint (CBR at week 24: &gt;25%) was not met in any of the 4 groups according to central radiological review. Exploratory analyses of the Kaplan-Meier curves, however, showed a lower probability for tumor progression in patients receiving high dose adecatumumab (HR: 0.67 [0.47–0.94]; p=0.047). A similar trend was also observed in patients with high-level EpCAM expression (HR: 0.71 [0.49–1.03]; p=0.116). Further (retrospective) analysis using more stringent criteria for the definition of high-level EpCAM expression indicated an inverse correlation of staining intensity and frequency with probability of progression. An increased incidence of CTC grade 1 and 2 AE was found in the high-dose group with main side effects being gastrointestinal and constitutional symptoms. Conclusions: The observation of dose- and target-dependent activity of adecatumumab warrants further investigation. Definition of the optimum dose and regimen as well as exploration of the predictive value of EpCAM testing will be key in future development. No significant financial relationships to disclose.
Strategies to Develop Inhibitors of Motif-Mediated Protein-Protein Interactions as Drug Leads
Authors: Carles Corbi-Verge, Michael Garton, Satra Nim, Philip M. Kim
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Protein-protein interactions are fundamental for virtually all functions of the cell. A large fraction of these interactions involve short peptide motifs, and there has been increased interest in targeting them using peptide-based therapeutics. Peptides benefit from being specific, relatively safe, and easy to produce. They are also easy to modify using chemical synthesis and molecular biology techniques. However, significant challenges remain regarding the use of peptides as therapeutic agents. Identification of peptide motifs is difficult, and peptides typically display low cell permeability and sensitivity to enzymatic degradation. In this review, we outline the principal high-throughput methodologies for motif discovery and describe current methods for overcoming pharmacokinetic and bioavailability limitations.
A Snapshot of Cancer Spending and Outcomes
Authors: Selena Gonzales, Cynthia Cox, Anne Jankiewicz, David Rousseau
Journal: JAMA (2016)

This Visualizing Health Policy infographic provides details on cancer spending and outcomes in the United States. The US cancer mortality rate, 203 deaths per 100 000 population, was slightly lower than in comparable countries in 2010. Among cancers, lung cancer is the largest contributor to disease burden for both men and women. The United States spent $124 billion to treat cancer in 2012, which accounted for about 7% of the nation’s disease-based health expenditures. However, growth in cancer spending contributed slightly more than 6% to the nation’s medical services expenditure growth between 2000 and 2012, while the top 3 diseases contributed 36%. During that time, per-capita spending on cancer increased 5%, which was slightly lower than the average for all diseases. Cancer medications were among the top 3 for specialty drug spending in 2015, behind medications for inflammatory conditions and multiple sclerosis.
Pembrolizumab (pembro; MK-3475) plus platinum doublet chemotherapy (PDC) as front-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 Cohorts A and C.
Authors: Vassiliki Papadimitrakopoulou, Amita Patnaik, Hossein Borghaei, James Stevenson, Leena Gandhi, Matthew A. Gubens, James Chih-Hsin Yang, Lecia V. Sequist, Joy Yang Ge, Jennifer Bourque, Robert D. Bachman, Ellie Im, Shirish M. Gadgeel
Journal: Journal of Clinical Oncology (2015)

8031 Background: As monotherapy, the anti–PD-1 antibody pembro has shown robust antitumor activity in advanced NSCLC patients (pts). KEYNOTE-021 evaluated the safety, tolerability, and clinical activity of pembro + PDC for treatment-naive advanced NSCLC. Methods: Pts with stage IIIB/IV NSCLC and no prior systemic therapy were randomized 1:1 to pembro 2 or 10 mg/kg Q3W plus carboplatin AUC 6 + paclitaxel 200 mg/m2 (cohort A; any histology) or carboplatin AUC 5 + pemetrexed 500 mg/m2 (cohort C; nonsquamous without EGFR sensitizing mutation or ALK translocation only). Pts received pembro + PDC for 4 cycles followed by pembro maintenance in A and pembro + pemetrexed in C. The dose-limiting toxicity (DLT) observation window was the first 3 wk after initial dosing. Key eligibility criteria included ECOG PS 0-1, measurable disease, and adequate tumor sample for PD-L1 assessment. Response was assessed every 6 wk until confirmed progression (RECIST v1.1, investigator review). Results: As of Dec 2014, 44 pts (20 in cohort A and 24 in cohort C) were treated. One DLT was reported (hospitalization for gr 3 rash, C [pembro 10 mg/kg]). Gr 3-4 treatment-related AE rate was 27% (15% in A, 38% in C); AEs were reversible transaminase elevation (n = 3 in C), anemia (n = 1 in A, 2 in C), rash (n = 1 in A, 1 in C), and colitis (n = 2 in C); no gr 3-4 febrile neutropenia was observed. One patient in C discontinued due to treatment-related gr 3 rash. No treatment-related deaths have occurred. Preliminary ORR (confirmed and unconfirmed) is 30% in A and 58% in C (Table). At the time of analysis, 16 pts in A and 21 pts in C remained on treatment. Conclusions: These data suggest that pembro + PDC has a reasonable safety profile and provides antitumor activity as front-line therapy for stage IIIB/IV NSCLC. Based on the promising ORR observed for pembro + carboplatin and pemetrexed, this combination is being evaluated in a larger cohort. Clinical trial information: NCT02039674. A (carboplatin/paclitaxel) C (carboplatin/pemetrexed) Pembro 10 n = 10 Pembro 2 n = 10 Pembro 10 n = 12 Pembro 2 n = 12 ORR (all PR) 3 (30%) 3 (30%) 8 (67%) 6 (50%) SD 3 (30%) 5 (50%) 4 (33%) 5 (42%) DCR (PR + SD) 6 (60%) 8 (80%) 12 (100%) 11 (92%) PD 3 (30%) 1 (10%) 0 0 No assessment 1 (10%) 1 (10%) 0 1 (8%)
Association of diabetes with perineural invasion and overall survival in surgically resected patients with pancreatic cancer.
Authors: M. A. Shama, M. Tanaka, S. A. Curley, J. L. Abbruzzese, D. Li
Journal: Journal of Clinical Oncology (2010)

4117 Background: Hyperglycemia has been hypothesized to promote perineural invasion through enhanced proliferation of cancer cell and subsequent production of cytokines such as nerve growth factors. Hyperglycemia may also cause demyelinization and axonal degeneration of nerves, which can form defections to make cancer cells enter nerves with deep invasion. The purpose of this study was to test the associations between perineural invasion, diabetes, and survival in patients with pancreatic adenocarcinoma. Methods: We retrospectively reviewed the medical records of 344 patients who underwent resection of pancreatic cancer between 2004 and 2008 at M. D. Anderson Cancer Center. Data recorded included history of diabetes prior to cancer diagnosis, presence of perineural invasion, and AJCC TNM stage. Overall survival time was calculated from the date of pancreatic cancer diagnosis to the date of death. The association between diabetes and perineural invasion was tested using the chi square test. Median survival (MS) was compared using the Kaplan-Meier plot, log-rank test, and Cox proportional hazard model. Results: Ninety-two (26.8%) of 344 patients studied had diabetes. The frequency of perineural invasion was significantly higher in patients with diabetes (94.6%) than in non-diabetics (86.5%) (p = 0.037). The median survival time (MST) was 30.2 versus 20.1 months for non-diabetic and diabetic patients, respectively (p = 0.024), and 27.2 versus 40.3 months for those with or without perineural invasion, respectively (p = 0.002). Both factors remained as significant independent predictor for survival after adjusting for AJCC TNM stage. The hazard ratio (95% confidence interval) was 1.36 (1.03-1.80) for diabetes (p = 0.032) and 1.67 (1.01-2.76) for perineural invasion (p = 0.047). Conclusions: Our finding supports the hypothesis that diabetes promotes perineural invasion in pancreatic cancer, and both diabetes and perineural invasion predict poor survival. Understanding the mechanisms underlying the association between diabetes and perineural invasion could lead to novel therapeutic targets. No significant financial relationships to disclose.
Single Dose of Cholera Vaccine Provides Short-term Protection
Authors: Anita Slomski
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
P0459 : Natural killer cell phenotypic profile in hepatocellular carcinoma (HCC) is predictive of clinical outcome after curative treatment
Authors: E. Cariani, M. Pilli, V. Barili, E. Porro, E. Biasini, A. Olivani, R. Dalla Valle, C. Ferrari, G. Missale
Journal: Journal of Hepatology (2015)
CD4 T-Cell Response to Pandemic H1N1 Specific Vaccine After HSCT In Pediatric Recipients
Authors: Marie-Louise Frémond, Marie Duchamp, Valérie Guérin, Domitille Serraz, Frédérique Duquesne, Marie Ouachée-Chardin, André Baruchel, Ghislaine Sterkers, Jean-Hugues Dalle
Journal: Blood (2010)
Erythroblast morphology in refractory anemia with ring sideroblasts and thrombocytosis
Authors: Giovanni Caocci, Giorgio La Nasa, Barbara J. Bain
Journal: American Journal of Hematology (2016)

The bone marrow karyotype was normal. Molecular analysis showed mutation of SF3B1. JAK2 V617F was not detected and no mutation was detected in CALR or MPL. The patient did not respond to erythropoietin and became transfusion dependent. The presence of two distinct populations of bone marrow erythroblasts, one of which shows a marked defect in hemoglobinization is strongly predictive of acquired sideroblastic erythropoiesis. This cytological abnormality correlates strongly with the presence of an SF3B1 mutation, both in refractory anemia with ring sideroblasts and in RARS-T. In the latter instance, a concomitant mutation that is usually associated with a myeloproliferative neoplasm is often detectable. It is recommended that a Perls' stain for iron is always done on the initial bone marrow aspirate of every patient. Nevertheless, the morphological abnormalities demonstrated in this patient are strongly predictive of sideroblastic erythropoiesis.
An Achilles' Heel for MLL-Rearranged Leukemias: Writers and Readers of H3 Lysine 36 Dimethylation
Authors: Sebastian T. Balbach, Stuart H. Orkin
Journal: Cancer Discovery (2016)

Abstract Summary: Histone H3 lysine 36 dimethylation (H3K36me2), a modification associated with transcriptional activation, is required for mixed-lineage leukemia–dependent transcription and leukemic transformation. In this issue of Cancer Discovery, Zhu and colleagues map the network of readers, writers, and erasers of H3K36me2 and uncover the ASH1L histone methyltransferase as a novel target for therapeutic intervention. Cancer Discov; 6(7); 700–2. ©2016 AACR. See related article by Zhu and colleagues, p. 770.
Elsewhere correspondence
Authors: M. G. Courtney, D. G. Weir, G. S. A. McDonald, Alain G. Lachaux, Bruno P. Descos, Irene C. Loras-Duclaux, Michel R. Hermier, G. Fattovich, A. Alberti, G. Realdi, G. Hoffman
Journal: Hepatology (1988)
Inducing Definitive Erythropoiesis From Human Embryonic Stem Cells Through a Novel Intracellular MPL Dimerization Strategy
Authors: William Sang Kim, Yuhua Zhu, Qiming Deng, Amanda J. Grieco, Gautam G. Dravid, Chintan Parekh, Roger P. Hollis, Timothy Lane, Eric E. Bouhassira, Donald B. Kohn, Gay M. Crooks
Journal: Blood (2013)
Precancerous and Cancerous Lesions of the Forestomach and Dermal-Subcutaneous Tumors in Rats Fed &lt;italic&gt;p&lt;/italic&gt;-Dimethyl-aminobenzene-1-Azo-1-Naphthalene
Authors: Ambadas S. Mulay, Harlan I. Firminger
Journal: JNCI Journal of the National Cancer Institute (1952)

Precancerous and Cancerous Lesions of the Forestomach and Dermal-Subcutaneous Tumors in Rats Fed p-Dimethyl-aminobenzene-1-Azo-1-Naphthalene Ambadas S. Mulay, Ambadas S. Mulay Laboratory of Pathology, National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Harlan I. Firminger Harlan I. Firminger Laboratory of Pathology, National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 1, August 1952, Pages 57–71, https://doi.org/10.1093/jnci/13.1.57 Published: 01 August 1952 Article history Received: 11 March 1952 Published: 01 August 1952