tbuckley/cabot-search huggingface dataset:
Expression of cyclin D1 and its relation with ER, PgR, C-erbB2, Ki-67, and p53 in breast cancer.
Authors: A. Haydaroglu, S. Demirci, D. Demir, B. Aydin, Y. Bolukbasi, O. Zekioglu, L. Yeniay, N. Ozdemir, E. Gokmen, R. Ylmaz
Journal: Journal of Clinical Oncology (2010)

e11084 Background: To evaluate the cyclin D1 expression in breast cancer patients and to investigate its correlation with other prognostic factors ([ER], progesterone receptor [PgR], C-erbB2, Ki-67, and p53). Methods: The study included 85 ER (+) breast cancer patients who were treated with postoperative radiotherapy (RT). Expressions of ER, PgR, C-erbB2, cyclin D1 protein, Ki-67, and p53 were determined by immunohistochemistry. A cut off point of 10% was used to distinguish between the categories of negative and positive staining for PgR, cyclin D1 protein, Ki- 67, and p53. Overexpression of C-erbB2 was defined as tumors with 2 (+) and 3 (+) C-erbB2 expression. Results: Patients' median age was 49 (range: 27-83). Approximately two-thirds of the patients were stage II and III and invasive ductal carcinoma was the most common histopathology. All patients were ER (+) and 56.5% of the patients were PgR positive. Ki-67 was positive in 61.2% and p53 was positive in 21.8% of the patients. In 6.3% of the patients C-erbB2 was overexpressed. Cyclin D1 expression was positive in 90.6% of the patients. Five-year disease free (DFS) and overall survival (OS) rate of the patients with ≤ 10 expression of cyclin D1 is nonsignificantly lower than the cases with > 10 expression of cyclin D1 (79% vs. 81%; 87% vs. 93%, p = 0.8 and 0.4 respectively). Cyclin D1 expression is positively correlated with the rate of ER positivity and Ki-67 expression (r = 0.4, p < 0.0001 and r = 0.3, p = 0.001 respectively). On univariate analysis, c-erbB2 expression was the significant prognostic factor for DFS (p = 0.03); and modified Bloom and Richardson grade (p = 0.04), nuclear grade (p = 0.021) and C-erbB2 expression (p = 0.03) were significant prognostic factors for OS. Conclusions: In the literature, the prognostic value of cyclin D1 is controversial. In this study, cyclin D1 was not found as a prognostic factor however it is correlated with the rate of ER positivity and Ki 67 expression. No significant financial relationships to disclose.
US drug labels to warn of risks of combining opioids and benzodiazepines
Authors: Michael McCarthy
Journal: BMJ (2016)

The US Food and Drug Administration is demanding changes to the labels for prescription opioid and benzodiazepine products to include warnings of the risks of profound sedation, respiratory suppression, coma, and death when these drugs are used in combination.1

FDA commissioner Robert Califf said that the agency was taking the action in response to the substantial increase in overdoses seen in patients taking opioids and benzodiazepines together. He said, “We implore healthcare professionals to heed these new warnings and more …
Relationship between ERCC1 C8092A and Mad1 G558A polymorphism with disease progression, and survival in patients with advanced epithelial ovarian cancer treated with induction chemotherapy with carboplatine paclitaxel (PC).
Authors: L. H. Montalvo, F. M. Vasquez, D. G. Rincon, C. C. Hernandez, M. S. Andrade, P. F. Martinez, C. D. Romero
Journal: Journal of Clinical Oncology (2010)

5101 Background: Platinum and taxane are active drugs in the treatment of ovarian cancer.The polymorphism C8092A of ERCC1 is involved in NER pathway of platinum-induced damage DNA.Mad1 G558A with modulation of the chromosomal segregation. As primary aim we evaluated the influence of these polymorphisms with progression-free survival (PSF) and survival (OS) in women with ovarian cancer treated with induction chemotherapy (PC). Methods: ERCC1 C8092A and Mad1 G558A polymorphism were determined on DNA isolated from blood samples by PCR in 73 patients with ovarian cancer who received induction chemotherapy with 3 courses of paclitaxel 175 mg/m2 and AUC6 carboplatin every 3 weeks. Informed consent was obtained for all subjects. Results: Between 01/08 to 07/09 73 women were evaluated, age media was 52 years, stages III (52.8 %) and IV (37.2 %), histology papillary (87.2%) high grade (77.9%).The genotype distribution at C8092A was: C/C 42 %(n = 31), 45% (n = 33) with C/A, and 13% (n = 9) with A/A.Mad1 G558A normal genotype G/G was observed in 20% (n= 14) A/A 41% (n = 30) and G/A in 39% (29). 67.7% women of A/A or G/A genotypes had an increased risk of disease progression (HR 3.7;95% CI, 1.1- 12.8; p = 0 .026) and 35% for G/G. Median PFS were 20 and 27 months with the G558A G/A or A/A genotypes versus the G/G genotype, respectively. All women with G/G are life at this time (p = 0.71).Women with ERCC1 C8092A C/A or A/A genotypes compared with the C/C genotype had a minor risk of disease progression 66.7% y 54.8% (p = 0.590).Median PFS were 11 and 8 months for C/A or A/A versus the C/C genotype, respectively (p = 0.017). OS in women with the C/A or A/A genotype in 28.3 months compared with 17 months for C/C (p = 0.020). Conclusions: ERCC1 C8092A polymorphism was an independent predictor of PFS and OS.Although Mad1 G558A polymorphism does seem to be associated only with PSF, this study suggesting to Mad1 G558A polymorphism might be prognostic biomarker. No significant financial relationships to disclose.
CAST: a new score for early prediction of neurological outcomes after cardiac arrest before therapeutic hypothermia with high accuracy
Authors: Mitsuaki Nishikimi, Naoyuki Matsuda, Kota Matsui, Kunihiko Takahashi, Tadashi Ejima, Keibun Liu, Takayuki Ogura, Michiko Higashi, Hitoshi Umino, Go Makishi, Atsushi Numaguchi, Satoru Matsushima, Hideki Tokuyama, Mitsunobu Nakamura, Shigeyuki Matsui
Journal: Intensive Care Medicine (2016)
Phase II trial alternating mFOLFOX 6 and FOLFIRI (FIREFOX) regimens in first-line treatment of advanced colorectal cancer in Japanese patients (KSCC 0701).
Authors: Y. Akagi, S. Tokunaga, Y. Emi, Y. Kakeji, T. Kusumoto, H. Baba, Y. Ogata, T. Tanaka, K. Shirouzu, Y. Maehara
Journal: Journal of Clinical Oncology (2010)

3553 Background: The aim of this study was to explore the efficacy and safety of an alternating regimen of mFOLFOX6 and FOLFIRI in the first-line treatment of advanced colorectal cancer. Specifically, we wanted to evaluate the impact of scheduling on the dose-limiting neurotoxicity and diarrhea associated with oxaliplatin and irinotecan. Methods: Eligibility criteria included histologically confirmed advanced colorectal cancer, ECOG PS 0-2 and adequate bone marrow, renal and hepatic function. Patients (pts) received an alternating regimen of 4 cycles of mFOLFOX-6 (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) followed by 4 cycles of FOLFIRI (oxaliplatin replaced with irinotecan 150 mg/m2 d1). This schedule was repeated until unacceptable toxicity or disease progression occurred. Results: Of the 48 pts enrolled from July 2007 to June 2008. Two of the patients did not fulfill the eligibility criteria. M/F, 34/12; median age, 66 years (range 43-75); ECOG PS 0/1/2, 37/9/0. The median number of administration cycles was 12 (range, 1–31). Response for CR, PR, SD, PD and NE were 1 (2.1%), 26 (56.5%), 14 (30.4%), 2 (4.3%) and 3 (6.5%), respectively. An overall response rate was 58.7% (95% CI: 43.9 %–73.5 %). Median progression-free survival was 10.3M (95% CI: 7.5 M–11.9 M) and median overall survival was not determined. The 2-year survival rate was 57.1%. Of the 47 pts evaluated for toxicity. The most common grade 3-4 adverse events were leucopenia (26%), neutropenia (55%), anemia (4%), neurotoxicity (0%), diarrhea (2%), febrile neutropenia (4%), nausea (4%), vomiting (2%) and hypersensitivity (0%). Conclusions: The results of this phase II study show that this FIREFOX alternating schedule is effective and well tolerated in the first-line treatment of advanced colorectal cancer. The low rate of grade 3 neurotoxicity/paresthesia is also promising. Now we finished the enrollment of pts of KSCC 0801 study (KSCC 0701 + bevacizumab) and are following the patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Yakult Honsha Co., Ltd. Yakult Honsha Co., Ltd.
Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling
Authors: Shouji Matsushima, Junya Kuroda, Peiyong Zhai, Tong Liu, Shohei Ikeda, Narayani Nagarajan, Shin-ichi Oka, Takashi Yokota, Shintaro Kinugawa, Chiao-Po Hsu, Hong Li, Hiroyuki Tsutsui, Junichi Sadoshima
Journal: Journal of Clinical Investigation (2016)

NADPH oxidases (Noxes) produce ROS that regulate cell growth and death. NOX4 expression in cardiomyocytes (CMs) plays an important role in cardiac remodeling and injury, but the posttranslational mechanisms that modulate this enzyme are poorly understood. Here, we determined that FYN, a Src family tyrosine kinase, interacts with the C-terminal domain of NOX4. FYN and NOX4 colocalized in perinuclear mitochondria, ER, and nuclear fractions in CMs, and FYN expression negatively regulated NOX4-induced O2– production and apoptosis in CMs. Mechanistically, we found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. Transverse aortic constriction activated FYN in the left ventricle (LV), and FYN-deficient mice displayed exacerbated cardiac hypertrophy and dysfunction and increased ROS production and apoptosis. Deletion of Nox4 rescued the exaggerated LV remodeling in FYN-deficient mice. Furthermore, FYN expression was markedly decreased in failing human hearts, corroborating its role as a regulator of cardiac cell death and ROS production. In conclusion, FYN is activated by oxidative stress and serves as a negative feedback regulator of NOX4 in CMs during cardiac remodeling.
Implementation of the Ten Steps to Successful Breastfeeding Saves Lives
Authors: Joan Younger Meek, Lawrence Noble
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Asthma Trajectories in a Population-based Birth Cohort. Impacts of Air Pollution and Greenness
Authors: Hind Sbihi, Mieke Koehoorn, Lillian Tamburic, Michael Brauer
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

The heterogeneity of asthma phenotypes may explain inconsistencies in observed associations with environmental exposures.To identify trajectories of childhood asthma and to characterize the potential impact of residential greenness and air pollution on asthma trajectory subgroups.Linked administrative databases of medical visits were used to define the occurrence and recurrence of asthma over a 10-year follow-up period within a population-based birth cohort of more than 65,000 children. Group-based trajectory modeling was used to identify unique asthma trajectories. Weighted multinomial regression was used to assess the relationship between asthma trajectories and risk factors, including environmental exposures.Group-based trajectory modeling distinguished four trajectories: one with no asthma representing 88.8% of the cohort, one with transient asthma (5.6% of the cohort), and two trajectories with chronic asthma with early (<1 yr; 1.5%) and late (<3 yr; 4.1%) onset during early childhood. These trajectories differed with respect to socioeconomic markers and modifiable risk factors, including maternal smoking and breastfeeding initiation. After accounting for sex, parity, breastfeeding, term birth weight, household income, maternal education, delivery mode, and smoking, an interquartile increase in nitrogen dioxide exposure increased the risk of membership in the early and late-onset chronic asthma trajectories, relative to subjects without asthma, by 50% and 20%, respectively (weighted risk ratio, 1.5 and 1.2; 95% confidence interval, 1.2-1.9 and 1.0-1.4). Greenness was not associated with any of the asthma trajectories.Traffic-related air pollution increased the probability of a chronic asthma trajectory.
In support of Fatty Acid Synthase (FAS) as a metabolic oncogene in breast cancer: Extracellular acidosis acts in an epigenetic fashion activating Fatty Acid Synthase (FAS) gene expression in non-cancerous human breast epithelial MCF10A and breast cancer MCF-7 cells
Authors: Javier A. Menendez, Josiah P. Decker, Susan K. Peirce, Ivan Horak, Ruth Lupu
Journal: Cancer Research (2005)

2784   Relatively little information exists on the ultimate molecular mechanisms by which the lipogenic enzyme Fatty Acid Synthase (FAS) is differentially overexpressed in a biologically aggressive subset of human malignancies. Since the microenvironment of solid tumors contains regions of poor oxygenation and high acidity, it has recently been suggested that cancer-associated FAS is a novel metabolic oncogene conferring a selective growth advantage upon stresses such as hypoxia and/or low pH. Here, we performed transient transfection studies with a 178-bp FAS promoter fragment harboring a complex Sterol Regulatory Element Binding Proteins (SREBP)-binding site to evaluate whether extracellular low pH and/or hypoxia may act in an epigenetic fashion by inducing changes in the transcriptional activation of FAS gene in cancer cells. First, non-cancerous human breast epithelial MCF10A and breast cancer MCF-7 cells cultured in acidosis (pH 6.5), but not under hypoxia or in the presence of hypoxia mimetics, demonstrated a more than two-fold increase in the transcriptional activity of FAS promoter-reporter constructs compared with control cells grown under standard culture conditions (pH 7.4). Second, the up-regulatory effect of extracellular acidosis on the transcriptional activation of FAS gene was not observed when the FAS promoter was truncated at the SREBP-binding site. Third, MCF10A and MCF-7 cells engineered to overexpress the Her-2/ neu  ( erb B-2) oncogene exhibited a SREBP-dependent activation of the FAS promoter-reporter construct up to six-fold higher than that found in wild-type MCF10A or MCF-7 cells, while extracellular acidosis resulted only in a marginal increase of Her-2/ neu -promoted activation of FAS gene. This study reveals for the first time that extracellular acidosis can work in an epigenetic fashion by up-regulating the transcriptional expression of FAS gene in non-cancerous and cancerous breast epithelial cells, a stimulatory effect that is equally mimicked by well-characterized oncogenic stimuli such as Her-2/ neu . Therefore, it is reasonable to suggest that activation of FAS gene expression is a very early and necessary molecular event of the malignant cell phenotype, thus supporting the role of FAS as a novel metabolic oncogene in breast cancer cells.
Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered
Authors: Ellen S. de Morrée, Nicholas J. Vogelzang, Daniel P. Petrylak, Nikolay Budnik, Pawel J. Wiechno, Cora N. Sternberg, Kevin Doner, Joaquim Bellmunt, John M. Burke, Maria Ochoa de Olza, Ananya Choudhury, Juergen E. Gschwend, Evgeny Kopyltsov, Aude Flechon, Nicolas van As, Nadine Houede, Debora Barton, Abderrahim Fandi, Ulf Jungnelius, Shaoyi Li, Jack Shiansong Li, Ronald de Wit
Journal: JAMA Oncology (2016)

The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles.To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the Mainsail trial.The Mainsail trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors.Total number of docetaxel cycles delivered as an independent factor for OS.Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660-2.194; P < .001), irrespective of lenalidomide treatment (HR, 1.060; 95% CI, 0.924-1.215; P = .41). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received more than 10 cycles had a median OS of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median OS of 22.8 months (P < .001).These findings suggest that continuation of docetaxel chemotherapy contributes to the survival benefit. Prospective validation is warranted.
Phase I study of sorafenib plus ifosfamide in patients with advanced soft tissue and bone sarcoma: A Spanish Group for Research on Sarcomas (GEIS) study.
Authors: X. Garcia del Muro, A. Lopez-Pousa, J. Martin Broto, R. Cubedo, L. Jimenez Colomo, O. Gallego, M. Provencio-Pulla
Journal: Journal of Clinical Oncology (2010)

10024 Background: Sorafenib is a multi-kinase inhibitor of VEGFR, PDGFR and RAF that showed activity against some sarcoma subtypes. Preclinical studies suggest that the combination of sorafenib with cytotoxic agents could result in additive activity. Methods: Patients with advanced soft tissue or bone sarcoma, previously treated with doxorubicin, no prior ifosfamide, ECOG PS 0-2, and adequate hematological, renal and hepatic function, were enrolled in this phase I study to assess safety, tolerability, pharmacokinetics (PK), and to identify the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of the combination of sorafenib and ifosfamide. A 3+3 dose escalation design with cohorts of 3-6 patients was used. Sorafenib was given po continuously. Ifosfamide was given iv over 4 hours on 3 consecutive days every 3 weeks. Dose levels 1, 2, 3 and 4 corresponded to sorafenib 200, 400, 400 and 400 mg, bid, plus ifosfamide 6, 6, 7.5 and 9 gr/m2, with concurrent administration of mesna 400, 400, 500 and 600 mg/m2 iv, at 0, 4 and 8 hours after ifosfamide administration. Results: Twelve patients were enrolled: median age 58 years (23-70); gender 6M: 6F; 3 lipo, 2 leio, 2 chondro, 5 other. The median number of cycles was 4. Patients were treated at 3 dose levels, the MTD was reached at level 3 and the RD was: sorafenib 400 mg bid and ifosfamide 6 g/m2, together with,esna 400 mg/m2. Three DLTs occurred, one at the second dose level and two at the third: fatigue grade 4, encephalopathy grade 3 and emesis grade 3. Other toxicities included rash, hand-foot syndrome, neutropenia, thrombocytopenia, anemia and deep vein thrombosis. Eight patients achieved stable disease lasting more than 5 months. Progression-free survival rate at 3 months was 64%. Concomitant treatment with sorafenib and ifosfamide showed no relevant effect on PK of both drugs. Conclusions: The combination of sorafenib and ifosfamide appears to be feasible and safe allowing the administration of active doses of both agents. A phase II study to assess the activity of this combination is ongoing. No significant financial relationships to disclose.
Crispr Sgrnas Genome-Wide Screen Identifies the Proteasome Regulatory Subunit PSMC6 As a Bortezomib Resistance Gene in Human Multiple Myeloma Cells
Authors: Chang-Xin Shi, Klaus M Kortum, Yuan Xiao Zhu, Patrick Jedlowski, Esteban Braggio, Laura Ann Bruins, Patrick G. Votruba, Moulun Luo, Robert A. Stewart, Jonathan M. Ahmann, A. Keith Stewart
Journal: Blood (2015)
Beta-blockers and COPD: the show must go on
Authors: Jose Luis Lopez-Campos, Eduardo Márquez-Martín, Ciro Casanova
Journal: European Respiratory Journal (2016)

Identification of comorbidities is now recognised as one of the pillars for a comprehensive clinical evaluation in chronic obstructive pulmonary disease (COPD) [1]. Specifically, the burden of coexisting cardiovascular disease in COPD has gained significant attention, with specific algorithms being developed for its clinical detection [2]. The relationship between the heart and COPD is of clinical relevance not only for the well-documented relationship between the two organs [3], but also for the potential mutual influence of treatments. The interactions between oral beta-blockers and inhaled β-adrenergic drugs pose significant challenges for clinicians involved in the management of patients with chronic cardiorespiratory conditions. In particular, the use of beta-blockers in COPD remains the subject of ongoing controversy [4]. Current evidence on beta-blockers efficacy and safety in COPD is encouraging but limited with future studies needed <http://ow.ly/IaNL301YANI>
Combination of the glycoengineered Type II CD20 antibody obinutuzumab (GA101) and The novel Bcl-2 selective Inhibitor GDC-0199 Results in superior In Vitro and In Vivo Anti-tumor activity in models Of B-Cell Malignancies
Authors: Deepak Sampath, Sylvia Herter, Frank Herting, Ellen Ingalla, Michelle Nannini, Marina Bacac, Wayne J. Fairbrother, Christian Klein
Journal: Blood (2013)
Whole-Genome Sequencing Results From 30 Patients with Waldenstrom's Macroglobulinemia
Authors: Zachary Hunter, Lian Xu, Yangsheng Zhou, Guang Yang, Xia Liu, Yang Cao, Christina Hanzis, Patricia Sheehy, Robert Manning, Christopher J Patterson, Jason M Laramie, Donald A Skifter, Stephen E Lincoln, Steven P Treon
Journal: Blood (2011)
Severity of renal impairment in patients with heart failure and atrial fibrillation: implications for non‐vitamin K antagonist oral anticoagulant dose adjustment
Authors: Nathaniel M. Hawkins, Pardeep S. Jhund, Andrea Pozzi, Eileen O'Meara, Scott D. Solomon, Christopher B. Granger, Salim Yusuf, Marc A. Pfeffer, Karl Swedberg, Mark C. Petrie, Sean Virani, John J.V. McMurray
Journal: European Journal of Heart Failure (2016)