tbuckley/cabot-search huggingface dataset:
Weekly paclitaxel and capecitabine in HER2-negative metastatic breast cancer (MBC): A multicenter GINECO randomized phase II comparing two paclitaxel-capecitabine schedules
Authors: A. Lortholary, A. C. Hardy-Bessard, T. Bachelot, P. Dalivoust, G. de Rauglaudre, J. Alexandre, H. Bourgeois, D. Jaubert, D. Paraiso, R. Largillier
Journal: Journal of Clinical Oncology (2009)

1114 Background: Paclitaxel (Ta) and capecitabine (Xel) are synergistic in vitro. Compared to a continuous weekly Tax combined with a classical 14 days (d)/21 Xel administration (Elza-Brown et al., ASCO 2000), we have explored the combination of Xel 5d/week (wk) and weekly Ta 3 wk out 4 in the objective to increase the efficacy/toxicity ratio of the TaXel combination. Methods: Patients (pts) in first or second-line of MBC, previously treated with anthracyclins + docetaxel were randomized either to A: Ta (60 mg/m 2 /w) + Xel (2000 mg/m 2 /d x 14 d/21) or to B: Ta (80 mg/m 2 /w) + Xel (2000 mg/m 2 /d x 5 d/wk) 3wk out 4. Results: From January 2006 to January 2008, 130 pts were accrued (A 66, B 64). Pts characteristics were well balanced between the two arms including median age (58 yrs), histologic type and grade, hormone receptor-positive tumor (80%), previous treatment, visceral disease (72%), number of sites (&gt;1; 63%), ECOG PS (0; 42%, 1; 58%). Pts received a median of 6 cycles (1–23) with a received/planned mean dose of 89.3% for Ta in both arms and of 74 and 76% for Xel respectively in arm A and B. Haematological toxicity (Tox) was low in both arms with neutropenia Gr 3 in only 8% of cycles, G-CSF support in 2% of cycles, and infection G3 in 5 pts. Alopecia G2 was less frequent in arm A (29 vs 60%). Other Tox were similar in both arms: [G2/3 (%) cutaneous (35/17), pain (36/9), fatigue (26/13), neuropathy (20/3), diarrhea (15/6), mucositis (8/2), vomiting (9/1)] but treatment interruption due to Tox was more frequent in A (A 19, B 7 pts) (p = 0.02). Response rate was 52% (B) versus 44% (A). A progression-free survival advantage was seen for B over A (366 vs 272 days, p = 0,15) including in the triple negative pt subset (n = 26 pts) (197 vs 150 days, p = 0.07). Conclusions: The intermittent regimen (3 wk out 4) of weekly paclitaxel and capecitabine 5 d/week is a well accepted, safe and effective TaXel schedule and might be a chemotherapy regimen of choice in MBC including triple negative patients. No significant financial relationships to disclose.
Abstract 052: Short-acting Hypnotic Drugs Increase Mortality and Obese Patients are Particularly Vulnerable
Authors: Robert D Langer, Daniel F Kripke, Lawrence E Kline
Journal: Circulation (2012)

Background: An estimated 6% – 10% of U.S. adults took a hypnotic drug for poor sleep in 2010. At least 18 studies have reported significant (p&lt;0.05) associations of hypnotic usage with increased mortality. However, most lacked data on newer, supposedly safer, short-acting drugs, and had limited control for confounding by health status. Furthermore, little is known regarding potentially heightened risks in specific vulnerable populations. Objective: The present study was designed to test whether newer short-acting hypnotic drugs were associated with increased mortality after controlling for comorbid conditions, and to assess risks within subgroups of patients with specific medical conditions. Methods: Using electronic medical records from a large U.S. health system the authors conducted a one-to-two matched-cohort survival analysis of associations between hypnotic drug use and mortality. Records were extracted for 10,529 hypnotic users and 23,676 matched controls with no hypnotic prescriptions, mean age 54 years, followed for an average of 2.5 years between 2002 and 2006. Hazard ratios (HR) for death were computed from Cox models controlled for risk factors and stratified on comorbidites. Results: The short-acting drugs zolpidem (41%) and temazapam (20%) accounted for the majority of use. Patients prescribed any hypnotic had substantially elevated hazards of dying compared to non-users. Importantly, the death hazard was evident even in the lowest tertile, 1 to 18 pills per year, HR 3.60 (95% Confidence Interval, 2.92 – 4.44). HRs for the remaining tertiles were 4.43 (3.67 – 5.36) and 5.32 (4.50 – 6.30), demonstrating a dose-response association. HR were robust within subgroups restricted to users and non-users with identical comorbidity, implying that selective use of hypnotics by patients in poor health was an unlikely explanation for the excess mortality. Obesity emerged as a marker of increased vulnerability. Among 2206 patients with a diagnosis of obesity, (mean BMI 38.8), the mortality HRs by hypnotic tertile were 8.07 (3.64 – 17.89), 6.37 (2.73 – 14.88), and 9.34 (4.47 – 19.52). Additional models were fitted for patients with the combination of Obesity + Diabetes + Hypertension to evaluate the possibility that this risk was driven by metabolic syndrome. HRs for that combination were slightly lower than those for obesity alone, suggesting that obesity was the primary factor. Conclusions: Short-acting hypnotics were associated with a more than 3-fold increased hazard of death that, even at low levels of use. Obese patients appear particularly vulnerable, perhaps through interaction with sleep apnea. Emerging evidence for substantial harm, even with limited exposure to hypnotics, should be weighed against any benefits.
Impact of late presentation of HIV infection on short-, mid- and long-term mortality and causes of death in a multicenter national cohort: 2004–2013
Authors: Paz Sobrino-Vegas, Santiago Moreno, Rafael Rubio, Pompeyo Viciana, José Ignacio Bernardino, José Ramón Blanco, Enrique Bernal, Víctor Asensi, Federico Pulido, Julia del Amo, Victoria Hernando, David Dalmau, Maria Luisa Navarro, Maria Isabel González, Jose Luis Blanco, Federico Garcia, Jose Antonio Iribarren, Félix Gutiérrez, Francesc Vidal, Juan Gonzalez-Garcia, Juan Berenguer, Paz Sobrino, Belén Alejos, Débora Álvarez, Susana Monge, Inma Jarrín, Yaiza Rivero, Cristina González, M. Ángeles Muñoz-Fernández, Isabel García-Merino, Coral Gómez Rico, Jorge Gallego de la Fuente, Almudena García Torre
Journal: Journal of Infection (2016)

ObjectivesTo analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004–2013).MethodsCox models and logistic regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 < 350 cells/ml or AIDS.ResultsOf 7165 new HIV diagnoses, 46.9% (CI95%:45.7–48.0) were LP, 240 patients died.First-year mortality was the highest (aHRLP.vs.nLP = 10.3[CI95%:5.5–19.3]); between 1 and 4 years post-diagnosis, aHRLP.vs.nLP = 1.9(1.2–3.0); and >4 years, aHRLP.vs.nLP = 1.5(0.7–3.1).First-year's main cause of death was HIV/AIDS (73%); and malignancies among those surviving >4 years (32%). HIV/AIDS-related deaths were more likely in LP (59.2% vs. 25.0%; p < 0.001). LP declined from 55.9% (2004–05) to 39.4% (2012–13), and reduced in 46.1% in men who have sex with men (MSM) and 37.6% in heterosexual men, but increased in 22.6% in heterosexual women.Factors associated with LP: sex (ORMEN.vs.WOMEN = 1.4[1.2–1.7]); age (OR31–40.vs.<30 = 1.6[1.4–1.8], OR41–50.vs.<30 = 2.2[1.8–2.6], OR>50.vs.<30 = 3.6[2.9–4.4]); behavior (ORInjectedDrugUse.vs.MSM = 2.8[2.0–3.8]; ORHeterosexual.vs.MSM = 2.2[1.7–3.0]); education (ORPrimaryEducation.vs.University = 1.5[1.1–2.0], ORLowerSecondary.vs.University = 1.3[1.1–1.5]); and geographical origin (ORSub-Saharan.vs.Spain = 1.6[1.3–2.0], ORLatin-American.vs.Spain = 1.4[1.2–1.8]).ConclusionsLP is associated with higher mortality, especially short-term- and HIV/AIDS-related mortality. Mid-term-, but not long-term mortality, remained also higher in LP than nLP. LP decreased in MSM and heterosexual men, not in heterosexual women. The groups most affected by LP are low educated, non-Spanish and heterosexual women.
Irreversibility of Liver Tumors in C3H Mice2
Authors: Boris H. Ruebner, M. Eric Gershwin, Earl F. Meierhenry, Lucy S. Hsieh, Patricia L. Dunn
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article Irreversibility of Liver Tumors in C3H Mice Get access Boris H. Ruebner, Boris H. Ruebner Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Eric Gershwin, M. Eric Gershwin Search for other works by this author on: Oxford Academic PubMed Google Scholar Earl F. Meierhenry, Earl F. Meierhenry Search for other works by this author on: Oxford Academic PubMed Google Scholar Lucy S. Hsieh, Lucy S. Hsieh Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia L. Dunn Patricia L. Dunn Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 73, Issue 2, August 1984, Pages 493–498, https://doi.org/10.1093/jnci/73.2.493 Published: 01 August 1984 Article history Received: 01 December 1983 Accepted: 30 March 1984 Published: 01 August 1984
Phase II study of dasatinib in children and adolescents with newly diagnosed chronic phase chronic myelogenous leukemia (CP-CML) or Philadelphia-positive (Ph+) leukemias resistant or intolerant to imatinib.
Authors: J. A. Rosenberg, D. Derreumaux, L. Gore, P. Kearns, A. Baruchel, T. Barrett, M. Zwaan
Journal: Journal of Clinical Oncology (2010)

TPS281 Background: Dasatinib, a highly potent BCR-ABL inhibitor, is safe and effective in adults with Ph+ leukemias. In response to an unmet need for novel agents in childhood diseases with poor outcomes, a comprehensive pediatric drug development program for dasatinib has been initiated. Pediatric studies include one completed phase I study (Aplenc et al. ASCO 2008; 26;3591) in patients (pts) with refractory solid tumors and Ph+ leukemia, and three ongoing studies (one phase I [Zwaan et al. Blood 2008;112:3241] and two phase II) in pts with Ph+ leukemias (1st-line or refractory setting). Although no efficacy was observed in solid tumors, preliminary data show dasatinib is active and tolerable in pts with Ph+ leukemia. In a phase I study in relapsed/refractory Ph+ leukemias resistant/intolerant to imatinib, among 41 evaluable pts, a complete hematologic response (CHR) of 75% was seen in CP-CML, and a major cytogenetic response rate (MCyR) of 88% in CP-CML and 50% in Ph+ CML and ALL/AML2. A phase II study is ongoing to determine the feasibility and toxicity of an intensified chemotherapy backbone + dasatinib in newly diagnosed pts with Ph+ ALL. Methods: A phase II nonrandomized, global study evaluates dasatinib in three cohorts: 1) Ph+ CP-CML ≥ 2nd-line (n=25), 2) Ph+ ALL, AP-CML, or BP-CML ≥ 2nd-line (n=34), and 3) newly diagnosed, treatment-naïve Ph+ CML (n=50). A minimum of 109 pts will be enrolled. Pts (age birth to ≤18 yr) are treated daily with dasatinib 60 mg/m2 (Cohorts 1 and 3) or 80 mg/m2 (Cohort 2) for at least 24 mos. Primary endpoints are MCyR in children with CP-CML resistant/intolerant to imatinib, CHR in Ph+ ALL, AP-CML, and BP-CML resistant/intolerant to or relapsed following imatinib and complete CyR in CP- CML. Secondary endpoints include safety and tolerability; best cytogenetic and hematologic RR; time to and duration of response; disease-free, progression-free, and overall survival; and rates of complete and major molecular response. BCR-ABL mutations will be evaluated at baseline, progression, or end of treatment, and for their potential as predictors of response. The study is actively enrolling pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Putting the Spotlight on Invisible Family Caregivers
Authors: Carol Levine
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Metabotropic Regulation of RhoA/Rho-Associated Kinase by L-type Ca <sup>2+</sup> Channels
Authors: Miguel Fernández-Tenorio, Cristina Porras-González, Antonio Castellano, Alberto del Valle-Rodríguez, José López-Barneo, Juan Ureña
Journal: Circulation Research (2011)

Background: Sustained vascular smooth muscle contraction is mediated by extracellular Ca 2+ influx through L-type voltage-gated Ca 2+ channels (VGCC) and RhoA/Rho-associated kinase (ROCK)-dependent Ca 2+ sensitization of the contractile machinery. VGCC activation can also trigger an ion-independent metabotropic pathway that involves G-protein/phospholipase C activation, inositol 1,4,5-trisphosphate synthesis, and Ca 2+ release from the sarcoplasmic reticulum (calcium channel-induced Ca 2+ release). We have studied the functional role of calcium channel-induced Ca 2+ release and the inter-relations between Ca 2+ channel and RhoA/ROCK activation. Methods and Results: We have used normal and genetically modified animals to study single myocyte electrophysiology and fluorimetry as well as cytosolic Ca 2+ and diameter in intact arteries. These analyses were complemented with measurement of tension and RhoA activity in normal and reversibly permeabilized arterial rings. We have found that, unexpectedly, L-type Ca 2+ channel activation and subsequent metabotropic Ca 2+ release from sarcoplasmic reticulum participate in depolarization-evoked RhoA/ROCK activity and sustained arterial contraction. We show that these phenomena do not depend on the change in the membrane potential itself, or the mere release of Ca 2+ from the sarcoplasmic reticulum, but they require the simultaneous activation of VGCC and the downstream metabotropic pathway with concomitant Ca 2+ release. During protracted depolarizations, refilling of the stores by a residual extracellular Ca 2+ influx through VGCC helps maintaining RhoA activity and sustained arterial contraction. Conclusions: These findings reveal that calcium channel-induced Ca 2+ release has a major role in tonic vascular smooth muscle contractility because it links membrane depolarization and Ca 2+ channel activation with metabotropic Ca 2+ release and sensitization (RhoA/ROCK stimulation).
Adenocarcinoma and Other Lesions of the Glandular Stomach of Mice, Following Intramural Injection of 20-Methylcholanthrene&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Stewart, Harold L., Hare, W. V., Lorenz, Egon, Bennett, J. G.
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article Adenocarcinoma and Other Lesions of the Glandular Stomach of Mice, Following Intramural Injection of 20-Methylcholanthrene Get access Harold L. Stewart, Harold L. Stewart Search for other works by this author on: Oxford Academic PubMed Google Scholar W. V. Hare, W. V. Hare Search for other works by this author on: Oxford Academic PubMed Google Scholar Egon Lorenz, Egon Lorenz Search for other works by this author on: Oxford Academic PubMed Google Scholar J. G. Bennett J. G. Bennett National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 2, October 1949, Pages 359–360, https://doi.org/10.1093/jnci/10.2.359 Published: 01 October 1949
Trastuzumab versus observation in women with early breast cancer and CK-19 mRNA-positive circulating tumor cells (CTCs): A pilot randomized phase II study.
Authors: V. Georgoulias, V. Bozionelou, S. Agelaki, M. Perraki, S. Apostolaki, G. Kallergi, K. Kalbakis, N. E. Androulakis, A. Xyrafas, D. Mavroudis
Journal: Journal of Clinical Oncology (2010)

547 Background: The presence of CK19 mRNA (+) CTCs in women with early breast cancer is associated with increased risk of relapse (JCO 25:5194, 2007; JCO 27:2177, 2009). Trastuzumab, an anti-HER2 antibody, can effectively eliminate CK19 mRNA-positive cells (CCR 10:8185-94, 2004). A pilot randomized phase II study of trastuzumab versus observation was conducted in women with early breast cancer who had CK19 mRNA (+) CTCs. Methods: Sixty eight women with early stage breast cancer and detectable CK19 mRNA (+) CTCs (by RT-PCR) before the initiation and after the completion of adjuvant chemotherapy were randomized to receive trastuzumab 6 mg/kg every 3 weeks for 6 cycles or observation. CK-19 mRNA (+) CTCs were monitored every 3 months. The primary endpoint of the study was disease-free survival (DFS). Results: Thirty-three women received trastuzumab and 35 observation. Of those, 9 (27%) and 10 (28%), respectively, had tumors over-expressing HER2. The two groups had similar clinical and disease-related characteristics. At the end of trastuzumab therapy, 23 of 33 (70%) women had become CK19 mRNA (-) versus 10 of 35 (29%) on the observation arm at the corresponding period (p = 0.001). After a median follow up time of 55 months (range 10-72 months), there was one relapse in the trastuzumab group versus 9 in the observation group (p = 0.014); the median DFS was superior in the trastuzumab group (p = 0.022; log rank test). During the same time, there was one disease-related death in the trastuzumab and 4 in the observation group (p = 0.357). Conclusions: Secondaryadjuvanttrastuzumab administration can reduce the risk of disease recurrence and prolong DFS of women with early breast cancer who have detectable CK-19 mRNA-positive cells. No significant financial relationships to disclose.
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.
Authors: R Turner, C Fox, Matthews, H McElroy, CA Cull, RR Holman, P. A. Neil, D Hadden, D Wright, E Manley, IM Stratton, UK Prospective Diabetes, E. Kohner, Frighi, Michael Gnant
Journal: The Lancet (1998)
Microtubule-associated protein tau and in vitro paclitaxel sensitivity in primary breast cancer
Authors: M. Schmidt, E. Bremer, A. Victor, M. Gehrmann, J. G. Hengstler, H. Koelbl
Journal: Journal of Clinical Oncology (2006)

20088 Background: Paclitaxel has an important role in the adjuvant therapy of primary breast cancer. Recently, microtubule-associated protein tau was described as a marker of paclitaxel sensitivity. We attempted to validate these findings in vitro utilizing the ATP tumorchemosensitivity assay (ATP-TCA). Methods: The in vitro drug sensitivity to paclitaxel was evaluated in 48 fresh primary breast cancer specimens using the ATP-TCA. ATP-TCA results were analysed using the area under the curve (AUC) of growth inhibition. These results were correlated with the expression of tau mRNA measured by quantitative RT-PCR (Spearman’s correlation coefficient). Tau was also compared between progesterone receptor (PgR) positive and negative and estrogen receptor (ER) positive and negative tumors, respectively (Wilcoxon test). Results: The correlation of tau with the AUC for paclitaxel was weak (r = −0.20) and disappeared when considering PgR positive and negative tumors separately (r = −0.004 and r = −0.048, respectively). Tau was found to be differentially expressed between PgR positive and negative as well as between ER positive and negative tumors (p &lt; 0.0005 in both tests). Conclusions: The expression of tau does not show independent predictive value for the in vitro paclitaxel sensitivity in primary breast cancer. No significant financial relationships to disclose.
Phase II study of eribulin mesylate (E7389) halichondrin b analog in patients with refractory breast cancer
Authors: J. L. Blum, B. Pruitt, C. J. Fabian, R. R. Rivera, D. E. Shuster, N. L. Meneses, K. Chandrawansa, F. Fang, S. Z. Fields, L. Vahdat
Journal: Journal of Clinical Oncology (2007)

1034 Background: Eribulin is a structurally simplified analog of halichondrin B, which inhibits microtubule dynamics via a novel mechanism characterized by suppression of microtubule growth, lack of effect on microtubule depolymerization, and sequestration of tubulin into nonfunctional aggregates. This study was designed to assess the activity and tolerance of eribulin in chemotherapy refractory patients with advanced breast cancer. Methods: Eribulin was evaluated in a single-arm Phase II trial in female patients with refractory breast cancer, ECOG performance status of 0–1, measurable disease, and neuropathy ≤ Grade 2. Patients received ≥ 1 prior chemotherapy regimen, including an anthracycline and a taxane. Eribulin was administered as a 2–5 min IV bolus of 1.4 mg/m 2 on Days 1, 8, and 15 of a 28-Day cycle (Group 1). The schedule was modified to Days 1 and 8 of a 21-Day cycle (Group 2), because of dose delays. The primary efficacy endpoint was ORR according to RECIST criteria based upon independent review (IR) of tumor assessment. Results: Of 104 patients enrolled, 103 received eribulin treatment: 70 in Group 1, 33 in Group 2. Median age was 55 yrs (range 32–84). Patients had received a median of 4 prior chemotherapy regimens (range 1–11). Sixty-one percent of tumors were ER+, 14% Her2/neu 3+, and 29% were triple (ER, PR, Her-2) negative. The incidence of dose interruption, delay, or omission during Cycle 1 was 63% (Group 1) and 18% (Group 2). The most common drug related toxicities were neutropenia (75%, Grades 3: 31%, Grade 4: 30%, febrile neutropenia: 3.9%), fatigue (52%, Grade 3: 2.9%, no Grade 4), alopecia (Grade 1/2: 41%), nausea (37%, Grade 3: 1%, no Grade 4), and anemia (36%, Grade 3: 1%, no Grade 4). Peripheral neuropathy occurred in 34% of patients (Grade 3: 3.9%, no Grade 4). Best overall response rate (all PR) by IR was 14.5% and 15.2% in Groups 1 and 2, respectively; the combined ORR was 14.7% (95 % CI: 9–23%). Median PFS was 85 days, and the 6 mo PFS rate was 31%. Conclusions: Eribulin given as a 2–5 min IV infusion on Days 1, 8 of a 21-Day cycle or Days 1, 8, 15 of a 28-Day cycle exhibited a 15% PR rate by IR and a low incidence of Grade 3 neuropathy in this heavily chemotherapy pretreated population. The most common toxicity was neutropenia. The 21-Day schedule had an acceptable toxicity profile. No significant financial relationships to disclose.