tbuckley/cabot-search huggingface dataset:
AR-V7 and efficacy of abiraterone (Abi) and enzalutamide (Enza) in castration-resistant prostate cancer (CRPC): Expanded analysis of the Johns Hopkins cohort.
Authors: Emmanuel S. Antonarakis, Changxue Lu, Brandon Luber, Hao Wang, Yan Chen, Yezi Zhu, John L. Silberstein, Maritza N. Taylor, Benjamin Louis Maughan, Channing Judith Paller, Samuel R. Denmeade, Kenneth J. Pienta, Michael Anthony Carducci, Mario A. Eisenberger, Jun Luo
Journal: Journal of Clinical Oncology (2016)

5012 Background: We previously reported an association between ARV7 detection and poor outcomes with Abi/Enza in 62 CRPC pts (NEJM 2014). Here, we expand our analysis to 202 pts, and also report the prognostic significance of CTC detection in addition to ARV7 detection. Methods: We prospectively enrolled CRPC pts starting Abi or Enza, and examined the prognostic value of CTC detection (+ vs -) and ARV7 detection (+ vs -) using a CTC-based ARV7 mRNA assay. We examined ≥50% PSA responses, PSA progression free survival (PSA-PFS), clinical/radiologic PFS (PFS), and overall survival (OS). We constructed multivariable (MVA) models adjusting for PSA, Gleason sum, number of prior hormone therapies, prior Abi/Enza use, prior taxane use, presence of visceral mets, and ECOG score. We also separately examined the 1st-line (Abi/Enza-naïve) and 2nd-line (post-Abi or Enza) novel hormonal therapy (NHT) settings. Results: 202 pts were enrolled (median f/u 12.9 mo, range 1.3–35.8 mo). CTC+/ARV7+ pts were more likely to have Gleason ≥8 (p= .05), M1 disease at diagnosis (p= .01), higher PSA (p< .01), prior Abi/Enza use (p= .03), prior taxane use (p= .02), and ECOG ≥1 (p= .01). Outcomes for the overall cohort, and separately for the 1st-line and 2nd-line NHT cohorts, are shown in the Table. All correlations remained significant in MVA models. Conclusions: The negative prognostic impact of ARV7 in pts receiving Abi/Enza is confirmed in this expanded analysis, and applies to both the 1st-line and 2nd-line NHT settings. This study is the first to suggest that our CTC-based ARV7 assay should be interpreted using 3 separate prognostic categories (CTC–, CTC+/ARV7-, CTC+/ARV7+). N (%) Overall (N = 202) 1st-Line NHT (N = 124) 2nd-Line NHT (N = 78) CTC n = 53 (26.2%) CTC+/ ARV7 n = 113 (56.0%) CTC+/ ARV7+ n = 36 (17.8%) P CTC n = 36 (29.0%) CTC+/ ARV7 n = 73 (58.9%) CTC+/ ARV7+ n = 15 (12.1%) P CTC n = 17 (21.8%) CTC+/ ARV7 n = 40 (51.3%) CTC+/ ARV7+ n = 21 (26.9%) P PSA response 75% 52% 14% < .001 86% 66% 27% < .001 53% 28% 5% .003 PSA-PFS (mo) 11.3 6.2 2.1 < .001 12.7 7.3 2.9 < .001 6.4 4.4 1.1 < .001 PFS (mo) 13.9 7.7 3.1 < .001 21.6 10.1 4.1 < .001 6.2 5.3 2.8 < .001 OS (mo) 28.7 29.5 11.2 < .001 29.7 30.7 21.5 .003 18.8 13.0 8.5 < .001
p53 Mutant Independently Impacts Risk: Analysis of Deletion 5q, Lower-Risk Myelodysplastic Syndromes (MDS) Patients Treated with Lenalidomide (LEN) in the MDS-004 Study
Authors: Leonie Saft, Jack Shiansong Li, Peter L. Greenberg, Mikkael A. Sekeres, Guillermo F. Sanz, François Dreyfus, Pierre Fenaux, Arlene S. Swern, Mary M. Sugrue, Eva Hellstrom-Lindberg
Journal: Blood (2014)
Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors
Authors: Joel G. Turner, Jana L. Dawson, Steven Grant, Kenneth H. Shain, William S. Dalton, Yun Dai, Mark Meads, Rachid Baz, Michael Kauffman, Sharon Shacham, Daniel M. Sullivan
Journal: Journal of Hematology & Oncology (2016)

Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease.We investigated whether the clinical exportin 1 (XPO1) inhibitor selinexor (KPT-330), when combined with pegylated liposomal doxorubicin (PLD) or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients. Mechanistic studies were performed to assess co-localization of topoisomerase II alpha (TOP2A), DNA damage, and siRNA knockdown of drug targets.Selinexor was found to restore sensitivity of multidrug-resistant 8226B25, 8226Dox6, 8226Dox40, and U266PSR human MM cells to doxorubicin to levels found in parental myeloma cell lines. NOD/SCID-γ mice challenged with drug-resistant or parental U266 human MM and treated with selinexor/PLD had significantly decreased tumor growth and increased survival with minimal toxicity. Selinexor/doxorubicin treatment selectively induced apoptosis in CD138/light-chain-positive MM cells without affecting non-myeloma cells in ex vivo-treated bone marrow aspirates from newly diagnosed or relapsed/refractory MM patients. Selinexor inhibited XPO1-TOP2A protein complexes (proximity ligation assay), preventing nuclear export of TOP2A in both parental and multidrug-resistant MM cell lines. Selinexor/doxorubicin treatment significantly increased DNA damage (comet assay/γ-H2AX) in both parental and drug-resistant MM cells. TOP2A knockdown reversed both the anti-tumor effect and significantly reduced DNA damage induced by selinexor/doxorubicin treatment.The combination of an XPO1 inhibitor and liposomal doxorubicin was highly effective against acquired drug resistance in in vitro MM models, in in vivo xenograft studies, and in ex vivo samples obtained from patients with relapsed/refractory myeloma. This drug combination synergistically induced TOP2A-mediated DNA damage and subsequent apoptosis. In addition, based on our preclinical data, we have initiated a phase I/II study with the XPO1 inhibitor selinexor and PLD (ClinicalTrials.gov NCT02186834). Initial results from both preclinical and clinical trials have shown significant promise for this drug combination for the treatment of MM.
Response prediction to neoadjuvant chemotherapy: Comparison between pretherapeutic gene expression profiles and in vitro chemosensitivity assay.
Authors: C. F. Singer, F. Klinglmüller, C. Staudigl, A. Fink-Retter, D. Gschwantler-Kaulich, G. Pfeiler, A. C. Dressler, C. Sartori, M. Bilban
Journal: Journal of Clinical Oncology (2010)

10516 Background: Although the use of (neo-)adjuvant chemotherapy in breast cancer patients has resulted in improved disease-free and overall survival, not all patients benefit equally. Nevertheless, chemotherapy is still applied empirically, since clinical tests for response prediction are not routinely available. We have evaluated the utility of an in vitro chemosensitivity assay (ATP-TCA) and gene expression profiles in predicting response to neoadjuvant chemotherapy. Methods: Pre-therapeutic core biopsies were obtained from 30 breast cancer patients assigned to three cycles of neoadjuvant epirubicin 75 mg/m2 and docetaxel 75 mg/m2 (Epi/Doc) in a prospectively randomized clinical trial (ABCSG 14). Individual tumor samples were subjected to a standardized ATP-based Epi/Doc tumor chemosensitivity assay (ATP-TCA), and to Affymetrix U133 A+B gene expression arrays. Patients then received 3 cycles of chemotherapy, and tumor response was subsequently evaluated by pre-operative ultrasound and Ki67 expression. Results: The efficacy of Epi/Doc in vitro was significantly correlated with differential changes in tumor cell proliferation in response to 3 cycles Epi/Doc in vivo (p = 0.0011; r = 0.73670, Spearmanxs rho), but did not predict for changes in tumor size when measured by ultrasound. While a pre-therapeutic gene expression signature identified tumors with a clinical response to Epi/Doc, no such signature could be found for tumors that responded well to Epi/Doc in vitro, or tumors in which Epi/Doc exerted a strong antiproliferative effect in vivo. Conclusions: This is the first prospective clinical trial to demonstrate the utility of a standardized in vitro chemosensitivity assay in predicting the individual response to chemotherapy in breast cancer patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration DCS Diagnostica GlaxoSmithKline, Novartis, Roche
CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea
Authors: R. Doug McEvoy, Nick A. Antic, Emma Heeley, Yuanming Luo, Qiong Ou, Xilong Zhang, Olga Mediano, Rui Chen, Luciano F. Drager, Zhihong Liu, Guofang Chen, Baoliang Du, Nigel McArdle, Sutapa Mukherjee, Manjari Tripathi, Laurent Billot, Qiang Li, Geraldo Lorenzi-Filho, Ferran Barbe, Susan Redline, Jiguang Wang, Hisatomi Arima, Bruce Neal, David P. White, Ron R. Grunstein, Nanshan Zhong, Craig S. Anderson
Journal: New England Journal of Medicine (2016)

Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain.After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood.Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood.Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).
CD5 expression promotes IL-10 production through activation of the MAPK/Erk pathway and upregulation of TRPC1 channels in B lymphocytes
Authors: Soizic Garaud, Taher E Taher, Marjolaine Debant, Miguel Burgos, Sarra Melayah, Christian Berthou, Kaushal Parikh, Jacques-Olivier Pers, Damien Luque-Paz, Gilles Chiocchia, Maikel Peppelenbosch, David A Isenberg, Pierre Youinou, Olivier Mignen, Yves Renaudineau, Rizgar A Mageed
Journal: Cellular and Molecular Immunology (2016)
Study of quality of life in brain tumor patients treated with three-dimensional conformal radiotherapy.
Authors: V. S. Vankamamidi, V. R. Sunkavalli, K. J. Naidu, M. Malik, S. Pamidighantam
Journal: Journal of Clinical Oncology (2010)

2091 Background: Quality of life (QOL) is becoming universal tool for assessing health outcome measures in clinical arenas including oncology and gaining relevance with advent of novel therapies and better care. This study is an attempt to find answers in the brain tumour population here and their response to RT in terms of HRQOL. Methods: 25 patients with brain tumours, post-op, were enrolled in this study and treated with 3DCRT. The patients took a baseline QOL questionnaire based on the Medical Outcomes Survey SF-36 before RT. The patients were monitored during the course of treatment and assessed 4 weeks following completion of RT and retook QOL questionnaire. The baseline and follow-up QOL SF-36 scores were analysed using paired-samples T test. Results: The median age of the study population was 35. 10 patients had high-grade gliomas, 9 had low-grade gliomas, 6 had non-glial tumours. There was significant improvement (p < 0.001) in physical component summary (PCS), mental component summary (MCS) (p < 0.001) as well as all sub components, physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH),vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH) in the total study group. In patients with high-grade gliomas (n = 10), there was significant improvement in PCS (p < 0.001), MCS (p < 0.011), PF (p < 0.012), RP (p < 0.024), BP (p < 0.004), GH (p < 0.04), VT (p < 0.042), SF (p < 0.001), MH (p < 0.008). There was no significant improvement in RE (p < 0.138). Patients with low-grade gliomas had significant improvement in PCS (p < 0.002), MCS (p < 0.008), PF (p < 0.048), RP (p < 0.001), BP (p < 0.009), GH (p < 0.005), VT (p < 0.012), SF (p < 0.05), RE (0.002), MH (p < 0.003). Patients with non-glial tumours showed significant improvement in RE (0.042), MH (p < 0.03). Conclusions: HRQOL parameters showed statistically significant improvement. Parameters not included in the SF-36 are sleeping adequacy, cognitive functioning, etc though it indirectly analyses all these components. There is a need for prospective, controlled studies to assess baseline and serial QOL studies in brain tumour patients and correlation with factors not included in SF-36 following treatment to plan and modify interventions. No significant financial relationships to disclose.
Primary Prevention of Stroke
Authors: Nathaniel Steiger, Adam S. Cifu
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
Failure to Disclose Conflicts of Interest
Authors: Nader M. Habashi, Penny Andrews, Gary F. Nieman, Micaela Kollisch-Singule, Jason H. T. Bates
Journal: JAMA Surgery (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 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
Reducing blood pressure too low has risks for patients with heart disease, registry finds
Authors: Susan Mayor
Journal: BMJ (2016)

Caution should be exercised when lowering blood pressure (BP) in patients with coronary artery disease, researchers have advised, after an international registry study showed increased risk of cardiovascular death, myocardial infarction, and stroke when BP is below 120 mm Hg systolic and 70 mm Hg diastolic.1

Lowering BP in patients with hypertension has been shown to reduce their risk of cardiovascular events and death, but the optimum target BP is debated. Randomised trials have shown no benefit below 140/90 mm …
United States (US) practices for chronic myelogenous leukemia (CML) management compared to other countries: A worldwide observational registry.
Authors: R. C. Hermann, C. B. Miller, R. Catchatourian, D. Snyder, D. Williams, M. Juma, J. E. Cortes
Journal: Journal of Clinical Oncology (2010)

6585 Background: The WORLD CML Registry is a global registry of the diagnostic and management strategies for CML patients (pts). Pts enrolled from Latin America, US, Asia Pacific, Middle East, Africa, Russia, and Turkey. Differences found in the US vs. Registry overall are reported. Methods: Eligible pts were ≥ 16 yrs of age and entered the Registry within 6 mos of diagnosis (any phase, detectable Ph+ or Bcr-Abl). Demographics, medical history, current disease status and management were collected at baseline and follow-up ( ∼ every 6 mos). Results: 54/148 sites were in the US with fewer academic/university centers and government hospitals. Conversely, more private practices participated in the US. To date, 1,001 pts are entered, with 179 (17.9%) from the US. Males and females (#) in US vs. Registry overall was similar; median ages of 53 (US) and 46 (overall). US cohort had a higher incidence of comorbidities associated with cardiac disorders and diabetes, more pts had no risk score assigned at diagnosis, higher W.H.O. performance status, and lower median spleen size. No difference in CML by phase was observed. US pts were assigned a Sokal score at diagnosis 5.6% of the time; overall assigned 39.1%. Bone marrow, cytogenetic and molecular analyses were performed at similar rates with more biopsies and RT-PCR quantitative in the US. Prior to enrollment, imatinib was used more frequently in the US than overall (64.3% vs. 41.7%). At enrollment, the majority of pts remained on their initial therapy for both US and overall. Majority of US (73.7%) pts were on imatinib vs. 65% for the Registry overall at any time before and after enrollment. Overall, the mean time from diagnosis to response assessment for initial treatment was 1.63 months. Conclusions: There are some regional differences in CML diagnosis and management among the U.S. and overall. Not all pts appear to be treated and monitored per published CML guidelines. Despite regional differences, imatinib is the most commonly prescribed therapy at registry enrollment in both the US and overall pt populations. Long term follow up of patients will allow for meaningful response assessments of patients in the registry. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Bristol-Myers Squibb, Novartis, Wyeth
Leukemia-Specific Ligands Against Childhood Acute Lymphoblastic leukemia
Authors: Noriko Satake, Susmita Sarangi, Astra Chang, Bridget McLaughlin, Ping Zhou, Elaina Kenny, Liliya Kraynov, Sarah Arnott, Jeannine McGee, Jan A. Nolta, Kit Lam
Journal: Blood (2010)
The Perioperative Surgical Home
Authors: David I. Soybel, Kayla Knuf
Journal: JAMA Surgery (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 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
Phase II postoperative adjuvant radiotherapy and erlotinib in patients with stage III cutaneous squamous cell carcinoma.
Authors: S. Spencer, W. Carroll, L. Nabell, R. Meredith, R. Desmond, J. Magnuson, E. Rosenthal
Journal: Journal of Clinical Oncology (2010)

e16007 Background: Cutaneous squamous cell carcinoma is the most common cancer in the United States. Radiotherapy alone is commonly recommended therapy in the adjuvant setting. Stage III cancer is associated with a recurrence rate of 40% at 2 years. Other treatment options are clearly needed. The combination of radiotherapy with targeted EGFR therapy using cetuximab for mucosal squamous cell carcinoma of the head and neck has known efficacy. Preclinical studies have demonstrated potentiation of radiotherapy with erlotinib, but safety and efficacy in the clinical setting remains unknown. We report now the preliminary data of adjuvant radiotherapy and erlotinib used in stage III and recurrent cutaneous squamous cell carcinoma. Methods: Fifteen patients with histologically proven primary T4 and N1 disease or recurrent squamous cell carcinoma arising from the lip, skin of the face, ear, scalp or neck were enrolled. Erlotinib 150mg BID and radiotherapy of 60-66Gy was given after primary surgery. Results: Thirteen males and 2 females were enrolled. The median follow-up time for all patients is 22 months. Toxicity was graded according to the NCI CTC version 3.0 scoring. The most common grade 2/3 toxicity was dermatologic, attributed to erlotinib. The other grade 2/3 toxicities are commonly seen with radiotherapy alone. There were two deaths noted within 30-60 days after completing erlotinib and radiotherapy. One patient suffered a fatal MI and another developed aspirational pneumonia and succumbed. Conclusions: Postoperative erlotinib and radiotherapy is felt to be safe in patients with locally advanced cutaneous squamous cell. The proof of efficacy warrants further confirmation. Toxicity Gr 1 Gr 2 Gr 3 Fatigue 7/15 N/V 4/15 4/15 3/15 Acneiform rash 1/15 4/15 7/15 Mucositis 2/15 6/15 3/15 Esophagitis 8/15 1/15 Hematologic 3/15 Diarrhea 4/15 2/15 Dehydration 4/15 3/15 No significant financial relationships to disclose.