tbuckley/cabot-search huggingface dataset:
For-Profit Medical Schools—A Flexnerian Legacy Upended
Authors: Eli Y. Adashi, Gopika R. Krishna, Philip A. Gruppuso
Journal: JAMA (2017)

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
Abstract P1-02-05: Prognostic role of PIK3CA mutational status in circulating tumor DNA (ctDNA) from HER2-positive metastatic breast cancer patients
Authors: J Lim, K-H Lee, A Min, S-G Kim, J-E Kim, T-Y Kim, S-W Han, D-Y Oh, T-Y Kim, S-A Lim
Journal: Cancer Research (2017)

Abstract Phosphatidylinositol-4, 5-biphosphate 3-kinase, catalytic subunit alpha (PIK3CA) is one of the most commonly mutated genes in breast cancer. But the prognostic and predictive role of PIK3CA mutations remains a matter of debate. It has been suggested that PIK3CA mutations are related to resistance to trastuzumab-based therapies, but they were also related to relatively indolent disease with better progression-free survival. Recently, circulating tumor DNA has been proposed to be a sensitive biomarker for detecting the presence of specific genetic aberrations in various cancer types, providing prognostic and predictive information. In this study, we evaluated prognostic and predictive role of PIK3CA mutations in patients with HER2-positive metastatic breast cancer treated with 1st line trastuzumab and taxane combination chemotherapy. Thirty-four patients with blood samples obtained before 1st line trastuzumab and taxane combination chemotherapy were included in the study. We analyzed two PIK3CA hotspot mutations (E545K, H1047R) in ctDNA by digital droplet PCR (RaindropTM). The samples were collected from April 2005 to December 2011, centrifuged and stored as plasma, and were analyzed in 2015, after 4-10 years of storage period. Median age was 47 years (range: 31 to 75 years), and histologic type of cancer was ductal carcinoma in all cases. PIK3CA mutations were detected in 21 (61.8%) of 34 patients. Patients with mutated PIK3CA in ctDNA had longer progression-free survival (PIK3CA wild type vs mutant, 11.0 months vs 22.0 months; P = 0.013). In hormone receptor positive group, patients with mutated PIK3CA had longer progression-free survival (PIK3CA wild type vs mutant, 12 months vs 18 months, P=0.17). Patients with PIK3CA mutations had a lower objective response rate than patients with wild-type, but there was no statistical significance (CR+PR; PIK3CA wild type vs mutant, 84.6% vs 66.7%, P=0.43). There was no significant difference in response rate (P = 0.48) or PIK3CA mutational status (P = 0.44) according to hormonal receptor status (estrogen receptor and/or progesterone receptor). In conclusion, PIK3CA mutations were frequently detected by digital PCR from ctDNA of patients with HER2-positive breast cancer and they were related to significantly better PFS. We plan to analyze the PIK3CA mutation status in matched tumor tissue. Citation Format: Lim J, Lee K-H, Min A, Kim S-G, Kim J-E, Kim T-Y, Han S-W, Oh D-Y, Kim T-Y, Lim S-A. Prognostic role of PIK3CA mutational status in circulating tumor DNA (ctDNA) from HER2-positive metastatic breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-05.
A Phase I Study of DCDT2980S, an Antibody-Drug Conjugate (ADC) Targeting CD22, in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)
Authors: Ranjana Advani, Daniel Lebovic, Mark Brunvand, Andy I. Chen, Andre Goy, Julie E. Chang, Lauren S Maeda, William Ho, Robert Kahn, Dan Lu, Zheng Su, Yu-Waye Chu, Bruce D. Cheson
Journal: Blood (2012)
Effect of Current Dietary Recommendations on Weight Loss and Cardiovascular Risk Factors
Authors: David J.A. Jenkins, Beatrice A. Boucher, Fredrick D. Ashbury, Margaret Sloan, Patrick Brown, Ahmed El-Sohemy, Anthony J. Hanley, Walter Willett, Melanie Paquette, Russell J. de Souza, Christopher Ireland, Natalie Kwan, Amy Jenkins, Sathish C. Pichika, Nancy Kreiger
Journal: Journal of the American College of Cardiology (2017)

Dietary recommendations emphasize increased consumption of fruit, vegetables, and whole grain cereals for prevention of chronic disease. This study assessed the effect of dietary advice and/or food provision on body weight and cardiovascular disease risk factors. Healthy overweight men (n = 209) and women (n = 710), mean age 44.7 years, body mass index [BMI] 32.4 kg/m2, were randomized between November 2005 and August 2009 to receive Health Canada's food guide (control, n = 486) or 1 of 3 interventions: dietary advice consistent with both Dietary Approaches to Stop Hypertension (DASH) and dietary portfolio principles (n = 145); weekly food provision reflecting this advice (n = 148); or food delivery plus advice (n = 140). Interventions lasted 6 months with 12-month follow-up. Semiquantitative food frequency questionnaires and fasting blood, anthropometric and blood pressure measurements were obtained at baseline, 6 months, and 18 months. Participant retention at 6 and 18 months was 91% and 81%, respectively, after food provision compared to 67% and 57% when no food was provided (p < 0.0001). Test and control treatments showed small reductions in body weight (−0.8 to −1.2 kg), waist circumference (−1.1 to −1.9 cm), and mean arterial pressure (0.0 to −1.1 mm Hg) at 6 months and Framingham coronary heart disease risk score at 18 months (−0.19 to −0.42%), which were significant overall. Outcomes did not differ among test and control groups. Provision of foods increased retention but only modestly increased intake of recommended foods. Current dietary recommendations showed small overall benefits in coronary heart disease risk factors. Additional dietary strategies to maximize these benefits are required. (Fruits, Vegetables, and Whole Grains: A Community-based Intervention; NCT00516620)
Genome-Wide Methylation Analysis of Myeloid Progenitors in Normal Bone Marrow and in Acute Promyelocytic Leukemia At Diagnosis and in Hematological Remission
Authors: Bárbara A Santana-Lemos, Helder H Paiva, Leandro M Colli, Ana Silvia Gouvea-Lima, Eduardo M Rego
Journal: Blood (2012)
Abstract P3-07-17: Squalene epoxidase is a potential metabolic oncogene by amplification with clinical implications in breast carcinoma: An <i>in silico</i> pan-cancer study with <i>i</i> <i>n vitro</i> evidence
Authors: G Zoppoli, D Brown, I Caffa, A Garuti, D Piras, M Gallo, E Isnaldi, A Nencioni, A Ballestrero
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.
Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity <i>In Vitro</i>
Authors: Sandra Rebouissou, Tiziana La Bella, Samia Rekik, Sandrine Imbeaud, Anna-Line Calatayud, Nataliya Rohr-Udilova, Yoann Martin, Gabrielle Couchy, Paulette Bioulac-Sage, Bettina Grasl-Kraupp, Leanne de Koning, Nathalie Ganne-Carrié, Jean-Charles Nault, Marianne Ziol, Jessica Zucman-Rossi
Journal: Clinical Cancer Research (2017)

Purpose: Tivantinib was initially reported as a selective MET inhibitor and is under phase III evaluation in "MET-high" hepatocellular carcinoma (HCC) patients. However, it has been also proposed as an antimitotic agent. We aimed to evaluate the antitumor effect of tivantinib in HCC cells by combining pharmacologic and molecular profiling.Experimental Design: Sensitivity to tivantinib, JNJ-38877605, PHA-665752, vinblastine, and paclitaxel was tested in a panel of 35 liver cancer cell lines analyzed with exome sequencing, mRNA expression of 188 genes, and protein expression. Drug effect was investigated by Western blot analysis and mitotic index quantification. Expression of candidate biomarkers predicting drug response was analyzed in 310 HCCs.Results: Tivantinib sensitivity profiles in the 35 cell lines were similar to those obtained with antimitotic drugs. It induced blockage of cell mitosis, and high cell proliferation was associated with sensitivity to tivantinib, vinblastine, and paclitaxel. In contrast, tivantinib did not suppress MET signaling, and selective MET inhibitors demonstrated an antiproliferative effect only in MHCC97H, the unique cell line displaying MET gene amplification. HCC tumors with high expression of cell proliferation genes defined a group of patients with poor survival. Interestingly, highly proliferative tumors also demonstrated high MET expression, likely explaining better therapeutic response of MET-high HCC patients to tivantinib.Conclusions: Tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. Clin Cancer Res; 23(15); 4364-75. ©2017 AACR.
What Is the Best Combination of First-Line and Salvage Treatments in Follicular Lymphoma? Results of the Multicenter Study “Refoll” by the Fondazione Italiana Linfomi (FIL) On 548 Patients
Authors: Giuseppe Rossi, Luigi Marcheselli, Chiara Bottelli, Alessandra Tucci, Alessandra Dondi, Stefano Luminari, Luca Arcaini, Michele Merli, Alessandro Pulsoni, Carola Boccomini, Benedetta Puccini, Moira Micheletti, Giovanni Martinelli, Andrea Rossi, Vittorio Ruggero Zilioli, Valentina Bozzoli, Monica Balzarotti, Silvia Bolis, Maria Giuseppina Cabras, Massimo Federico
Journal: Blood (2012)
PRAME Protein Is Aberrantly Expressed in Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma.
Authors: Rodrigo Proto-Siqueira, Lorena L. Figueredo-Pontes, Eduardo M. Rego, Edgar G. Rizzatti, Fabio M. Nascimento, Rodrigo S. Abreu e Lima, Roberto P. Falcao, Valery Filonenko, Marco Antonio Zago
Journal: Blood (2004)
Repeated Bone Marrow Aspiration At the End of Induction Therapy: Implications for Treatment Stratification in Paediatric Acute Lymphoblastic Leukaemia
Authors: Jan Zuna, Mari Arens, Rolf Koehler, Renate Panzer-Grümayer, Anja Möricke, Claus R Bartram, Ruth Joas, Eva Fronkova, Gunnar Cario, Martin Stanulla, Martin Zimmermann, Jan Trka, Jan Stary, Andishe Attarbaschi, Georg Mann, Martin Schrappe, André Schrauder
Journal: Blood (2011)
Evaluation of unanticipated 30-day readmission in patients with advanced stage epithelial ovarian cancer.
Authors: Ramez Hassef Eskander, Jenny Chang, Argyrios Ziogas, Hoda Anton-Culver, Robert Bristow
Journal: Journal of Clinical Oncology (2015)

e17684 Background: Unanticipated 30-day hospital readmission is recognized as a quality of care metric and tied to reimbursement. We looked to analyze rate, risk factors and costs associated with readmission in patients with advanced stage ovarian cancer throughout treatment. Methods: The Surveillance, Epidemiology and End Results-Medicare (SEER-Medicare) linked database (1992-2010) was used to evaluate readmission rates within 30-days of discharge for 5 years after the date of diagnosis in patients with stage IIIC/IV ovarian/primary peritoneal/fallopian tube cancer. Multivariate logistic regression was used to identify factors associated with readmission. Results: Of 8,411 eligible subjects, 1,783 (21.2%) were readmitted within 30-days of discharge (2,431 total readmissions). Mean patient age was 75 years. Diagnoses associated with readmission included volume depletion (17.9%), metabolic/electrolyte abnormalities (13.4%), anemia (10.2%), urinary tract infection (9.5%) and ascites (6.6%). In multivariate analysis, year of discharge was significantly associated with 30-day readmission (1996-2000 OR 1.26; 95% CI 1.08-1.48; 2001-2005 OR 1.46 95% CI 1.26-1.68; Referent years 1992-1995), as were Charlson score ≥ 1 (OR 1.23; 95% CI 1.05-1.43), and low median household income (lowest quartile, OR 1.3; 95% CI 1.12-1.52). The median cost of readmission hospital stay was $13,405 in year 2010 dollars, with a total cost of $32.6 million over the study period. Conclusions: Unanticipated 30-day readmission remains a common problem in patients with advanced stage ovarian cancer throughout their disease course. Importantly, modifiable factors are associated with readmission, and may help identify high-risk patients for whom targeted interventions can be developed to reduce readmission and improve quality of life.
Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti‐MicroRNA‐122, RG‐101
Authors: Femke Stelma, Meike H. van der Ree, Marjan J. Sinnige, Anthony Brown, Leo Swadling, J. Marleen L. de Vree, Sophie B. Willemse, Marc van der Valk, Paul Grint, Steven Neben, Paul Klenerman, Eleanor Barnes, Neeltje A. Kootstra, Hendrik W. Reesink
Journal: Hepatology (2017)

MicroRNA‐122 is an important host factor for the hepatitis C virus (HCV). Treatment with RG‐101, an N ‐acetylgalactosamine‐conjugated anti‐microRNA‐122 oligonucleotide, resulted in a significant viral load reduction in patients with chronic HCV infection. Here, we analyzed the effects of RG‐101 therapy on antiviral immunity. Thirty‐two chronic HCV patients infected with HCV genotypes 1, 3, and 4 received a single subcutaneous administration of RG‐101 at 2 mg/kg (n = 14) or 4 mg/kg (n = 14) or received a placebo (n = 2/dosing group). Plasma and peripheral blood mononuclear cells were collected at multiple time points, and comprehensive immunological analyses were performed. Following RG‐101 administration, HCV RNA declined in all patients (mean decline at week 2, 3.27 log10 IU/mL). At week 8 HCV RNA was undetectable in 15/28 patients. Plasma interferon‐γ‐induced protein 10 (IP‐10) levels declined significantly upon dosing with RG‐101. Furthermore, the frequency of natural killer (NK) cells increased, the proportion of NK cells expressing activating receptors normalized, and NK cell interferon‐γ production decreased after RG‐101 dosing. Functional HCV‐specific interferon‐γ T‐cell responses did not significantly change in patients who had undetectable HCV RNA levels by week 8 post–RG‐101 injection. No increase in the magnitude of HCV‐specific T‐cell responses was observed at later time points, including 3 patients who were HCV RNA–negative 76 weeks postdosing. Conclusion : Dosing with RG‐101 is associated with a restoration of NK‐cell proportions and a decrease of NK cells expressing activation receptors; however, the magnitude and functionality of ex vivo HCV‐specific T‐cell responses did not increase following RG‐101 injection, suggesting that NK cells, but not HCV adaptive immunity, may contribute to HCV viral control following RG‐101 therapy. (H epatology 2017;66:57–68).
Abstract P6-07-27: Characterization of neuroendocrine breast carcinomas for biomarkers of therapeutic options
Authors: Z Gatalica, R Feldman, A Ghazalpour, S Vranic
Journal: Cancer Research (2017)

Abstract Introduction: Neuroendocrine breast carcinoma (NBC) is an extremely rare type of cancer, constituting less than 0.1% of all breast tumors, without specific treatment options. We investigated a biomarker database for frequency of molecular markers that may guide personalized treatment choices for these patients. Materials and Methods: Molecular profiles of 40 breast carcinomas with neuroendocrine features [ER/PR+ (n=20), HER2+ (n=1) and TNBC (n=14)] were assessed (all female patients, mean age: 60.3 years, range: 39-83 years). Gene expression (Illumina DASL microarray platform), protein expression (IHC), gene amplification (ISH) and next-generation sequencing (NGS; TruSeq Illumina platform) were performed. Results: 57% of NBCs were positive for hormone receptors (ER/PR), 40% were triple negative TNBC and 3% HER2+ subtypes. Therapeutic biomarkers (IHC) that may guide chemotherapies (and used in other primary sites neuroendocrine tumors) included: high TOP2A (85%) for etoposide or doxorubicin, low TS (57%) for 5-fluorouracil and low ERCC1 (45%) for cisplatin. Additional biomarkers for chemotherapy included: high TOPO1 (60%) for irinotecan, low RRM1 (48%) for gemcitabine and low MGMT (57%) for temozolomide. Biomarkers associated with available targeted therapies included: PTEN loss (39%), positive ALK (33%), cKit (30%), EGFR (29%), AR (26%) and PDGFRA (17%). No gene amplifications were detected in cMET, EGFR, or TOP2A. Targeted sequencing analysis of 47 genes detected variants in TP53, PIK3CA, ERBB4 and APC genes. Gene expression data (included somatostatin receptor gene family- SSTR1/2/3/4/5) was available for 5 patients, for which 3/5 patients exhibited overexpression of at least one SSTR gene. Conclusions: Molecular profiling by a multiplatform approach reveals potential personalized therapy options for this very rare breast cancer subtype. With recent success of somatostatin analogs for other neuroendocrine tumors, the overexpression of SSTR gene family in NBC is worthy of further investigation. Citation Format: Gatalica Z, Feldman R, Ghazalpour A, Vranic S. Characterization of neuroendocrine breast carcinomas for biomarkers of therapeutic options [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-27.
Feasibility analysis of CRS and HIPEC from a single-center experience.
Authors: Luigina Graziosi, Elisabetta Marino, Verena De angelis, Annibale Donini, Anna Marina Liberati
Journal: Journal of Clinical Oncology (2014)

e14023 Background: Peritoneal carcinomatosis (PC) has been considered a rapidly lethal disease and consequently managed by merely palliative option. The clinical interest on this condition has increased for encouraging results reported combing cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Our aim is to analyze treatment related morbidity and safety. Methods: 52 consecutive patients with gastrointestinal PC have been treated from September 2006. A prospective collected database has been created and data were retrospectively analyzed. In 2 cases HIPEC was used as a palliative treatment for malignant ascites. In 38 cases (17 colon cancer, 9 ovaric cancer, 9 gastric cancer, 2 jejunal cancer, 1 peritoneal mesothelioma) HIPEC was used therapeutically. In 12 patients HIPEC was performed as adjuvant treatment for locally advanced gastric cancer. Adverse events were recorded according to Dindo’s classification. Median follow-up was 12 months. Results: Patient’s population average age was 59.2 yo. Average Peritoneal Cancer Index (PCI) was 6.4. CC0 was achieved in 39 patients (77.0%), CC1 in 8 patients (15%), CC2 in 3 patients (8%). We observed adverse events in 13 cases (25%) and among them only 3 cases (5,77%) showed grade III and IV adverse events. There were 3 postoperative deaths (5,77%); two of these patients were older than 70 yo. In our series we also analyzed global 5-year OS and DFS that were respectively 62% and 12%. It’ s important to underline that patients with gastric cancer who underwent prophylactic HIPEC had shown an impressive response to the multimodal treatment with optimal 5-year OS and DFS respectively of 90% and 85%. Conclusions: In our study, overall grade III and IV morbidity and mortality were very low. It could be related to the low median PCI and to the correct patient selection being certainly the procedure’s “achilles heel”. Hipec could be a valid and feasible option for locally advanced gastrointestinal malignancies reporting an acceptable morbidity rate.
Contents, Vol. 61, 1994
Authors: G Fava, H Freyberger, F Pesarin, Padova Zielezny, P Bech, Hillerod Biondi, Roma Cavanaugh, G Christodoulou, Athens Cottraux, P Lyon, Groningen Emmelkamp, Ma Boston, Marburg Florin, Lübeck Freyberger, Bologna Grandi, Trier Hellhammer, Bonn Liedtke, London Marks, M Gent, J Morphy, Nh Nemiah, Isleworth Sensky, Stockholm Theorell
Journal: Psychotherapy and Psychosomatics (1994)
A multicenter, randomized, blinded, phase III study of pasireotide LAR versus octreotide LAR in patients with metastatic neuroendocrine tumors (NET) with disease-related symptoms inadequately controlled by somatostatin analogs.
Authors: Edward M. Wolin, Barbara Jarzab, Barbro Eriksson, Thomas Walter, Christos Toumpanakis, Michael Morse, Paola Tomassetti, Matthias Weber, David R. Fogelman, John Ramage, Donald Poon, Jerry M. Huang, Michelle Hudson, Xin Zhi, Janice L. Pasieka, Abakar Mahamat, Fredrik Swahn, John Newell-Price, Wasat Mansoor, Kjell E. Oberg
Journal: Journal of Clinical Oncology (2013)

4031 Background: The novel somatostatin analog (SSA) pasireotide has a broader binding profile than currently available SSA (octreotide and lanreotide). Results from a phase III study (NCT00690430) of pasireotide LAR (P) vs octreotide LAR (O) in patients (pts) with NET and disease-related symptoms uncontrolled by the maximum approved dose of available SSA are shown. Methods: Pts (N=110) were randomized and stratified by predominant symptom at baseline (diarrhea [D], flushing [F], or D+F) 1:1 to P (60 mg IM) or O (40 mg IM) q28d. Primary objective was symptom response at month (M) 6. Secondary objectives included tumor response and safety. Progression-free survival (PFS) was an exploratory analysis. Results: 53 and 57 pts were enrolled in the P and O arms when the study was halted due to an interim analysis suggesting futility for symptom response. Baseline characteristics were similar between arms. Majority of primary tumor locations were small intestine (72% and 81% in the P and O arms). Symptom response at M6 was 9/43 (21%) and 12/45 (27%) in the P and O arms, odds ratio 0.73 (95% CI, 0.27-1.97; p=0.53). Median numbers of D/day and F/2 weeks and change in symptom from baseline to M6 are in Table. Hyperglycemia (11% vs 0%), diarrhea (9% vs 7%), and abdominal pain (2% vs 9%) were the most common grade 3/4 AEs in the P vs O arms in the core phase, and 7 (13%) and 4 (7%) pts discontinued due to AEs. Median investigator-assessed PFS was 11.8 months and 6.8 months in the P and O arms (HR=0.46; p=0.045). Conclusions: P and O showed a similar safety profile except for the higher frequency of hyperglycemia in P. Pts on P had PFS 5 months longer than pts on O (investigator assessment), despite no differences in symptom response rates. These results warrant a large phase III trial to clarify the role of P as a therapy for NET. Clinical trial information: NCT00690430. [Table: see text]