tbuckley/cabot-search huggingface dataset:
Phase II trial of everolimus monotherapy in the palliative treatment of patients with metastatic transitional cell carcinoma (TCC) after failure of platinum-based therapy: Activity and biomarkers.
Authors: E. Seront, B. Sautois, S. Rottey, L. A. D'Hondt, J. Canon, J. Vandenbulcke, N. Whenham, J. C. Goeminne, O. Feron, J. H. Machiels
Journal: Journal of Clinical Oncology (2011)

4622 Background: Dysregulation of mammalian Target of Rapamycin (mTOR) pathway plays a role in TCC development. We assessed the efficacy and toxicity of Everolimus (E), an oral mTOR inhibitor, in patients with palliative TCC in a phase II study and explored potential predictive plasma biomarkers of E activity. Methods: Patients (pts) with metastatic TCC after failure of platinum chemotherapy received E 10 mg/d continuously until progressive disease (PD) or unacceptable toxicity. The primary end point was stable disease (SD) or partial response (PR) at 8 wks according to RECIST criteria (centrally reviewed). A 2-stage design was used (Simon; a=0.15, b=0.1, P0=10%, P1=25%). Plasma samples were collected on day 1 (baseline before treatment), day 28 (during treatment), and at PD. Different angiogenesis-related proteins were analyzed in plasma by cytokine arrays and ELISA. Results: 37 pts were included. 8 pts were not evaluable by imaging at 8 wks due to rapid clinical deterioration (3), death (4), toxicity (1) and were considered in PD. 1 pt was lost at follow-up. Confirmed PR was observed in 2 pts, SD in 8, and PD in 27, resulting in a disease control rate of 27% at 8 wks. In 3 out of these 8 pts with SD, a decrease in the sum of the largest diameters of the target lesions was recorded (1%, 2%, 9%). SD was maintained for 16 weeks in 4 pts, for 24 weeks in 2, and for 52 weeks in 1. Toxicities of E were as reported previously. Plasma analysis showed that E induced changes in angiostatin (+ 114%; p<0.0001) and in PDGF-AB (- 68%; p=0.007) levels. High baseline angiopoietin-1 (Ang-1) levels were correlated to PR/SD (p=0.0057). Pts in SD/PR showed an Ang-1 decrease (- 64%; p=0.02) on day 28 compared to pts in PD (+ 26%; p=0.49). Furthermore, PD was associated with an endoglin increase on day 28 (+ 63%; p=0.0023). Interestingly, in the 2 pts with a PR, an increase in Ang-1, PDGF-AA and PDGF-AB levels was observed at the time of PD compared to those previously detected on day 28. Conclusions: E monotherapy showed moderate activity in advanced TCC. Ang-1, PDGF-AB and endoglin are potential biomarkers that should be investigated further in larger clinical trials.
Phase II trial of docetaxel in non-Hodgkin's lymphomas: a study of the Cancer and Leukemia Group B.
Authors: D R Budman, G R Petroni, J L Johnson, M R Cooper, D M Schlossman, M Barcos, B A Peterson
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate the new anticancer agent, docetaxel, with a novel mechanism of action in patients with non-Hodgkin's lymphoma International Working Formulation (IWF) A through H, to determine the response rate by histologic group and the toxicities of this agent in this population. PATIENTS AND METHODS Sixty-eight patients previously treated for non-Hodgkin's lymphoma with two prior cytotoxic regimens for low-grade and one prior regimen for intermediate-grade lymphoma were entered onto this phase II trial. Central pathologic review was required. Twenty-four IWF A to C and 31 IWF D to H patients with normal hepatic and renal function, performance status (PS) 0 to 2, and adequate hematologic function were eligible. Patients received docetaxel 100 mg/m2 intravenously over 1 hour without corticosteroid premedications every 3 weeks with weekly hematologic monitoring, and tumor assessment every 3 weeks. For grade 3 or 4 hematologic toxicity, the docetaxel dosage was lowered to 75 mg/m2. Patients received a maximum of six cycles of therapy. RESULTS The major response rate was 13% (95% confidence limits, 3% to 32%) for IWF A to C and 16% (95% confidence limits, 5% to 34%) for IWF D to H; response durations ranged from 1.4 to 20 months. Time to response ranged from 1.3 to 2.8 months. Patients refractory to previous chemotherapy were less apt to respond to docetaxel, but the differences were not statistically different in this small sample size. Twelve percent of IWF A to C and 6% of IWF D to H patients discontinued treatment because of toxicity. The major toxicity was granulocytopenia (grade 3 to 4), which occurred in virtually all patients during the first course of therapy. CONCLUSION This study confirms that docetaxel has limited but definite activity in patients with non-Hodgkin's lymphoma and suggests that the previously reported responses with taxanes can not be attributed solely to the use of corticosteroid premedications.
Enteropathy-Type Intestinal T-Cell Lymphoma: Clinical Features and Treatment of 31 Patients in a Single Center
Authors: Joanna Gale, Peter D. Simmonds, Graham M. Mead, John W. Sweetenham, Dennis H. Wright
Journal: Journal of Clinical Oncology (2000)

We report the clinical features and treatment of 31 patients with a diagnosis of enteropathy-type intestinal T-cell lymphoma treated at the Wessex Regional Medical Oncology Unit in Southampton between 1979 and 1996 (23 men, eight women).Patients were identified from our lymphoma database. Details of history, physical examination, staging investigations, treatment, and outcome were taken from patient records.Twelve patients (35%) had a documented clinical history of adult-onset celiac disease, and a further three had histologic features consistent with celiac disease in resected areas of the small bowel not infiltrated with lymphoma. After diagnosis, 24 (77%) of the 31 patients were treated with chemotherapy; the remaining seven had surgical treatment alone. More than half were unable to complete their planned chemotherapy courses, often because of poor nutritional status; 12 patients required enteral or parenteral feeding. A response to initial chemotherapy was observed in 14 patients (complete response, n = 10; partial response, n = 4). Observed complications of treatment were gastrointestinal bleeding, small-bowel perforation, and the development of enterocolic fistulae. Relapses occurred 1 to 60 months from diagnosis in 79% of those who responded to initial therapy. Of the total 31 patients, 26 (84%) have died, all from progressive disease or from complications of the disease and/or its treatment. The actuarial 1- and 5-year survival rates are 38.7% and 19.7%, respectively, with 1- and 5-year failure-free survival rates of 19.4% and 3.2%, respectively.The prognosis for these patients is poor. This, in part, reflects late diagnosis and poor performance status at the time of presentation. The role of salvage treatments and high-dose chemotherapy at relapse is not clear. However, it is encouraging that there are five long-term survivors in our patient population.
Effect of Prolonged Administration of Low Doses of Dietary Retinoids on Cell-Mediated Immunity and the Growth of Transplantable Tumors in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G Forni, S Cerruti Sola, M Giovarelli, A Santoni, P Martinetto, D Vietti
Journal: JNCI Journal of the National Cancer Institute (1986)

A study was conducted on the activity exerted by prolonged dietary supplementation with progressive amounts of retinoids on cell-mediated immune responses and the growth of transplantable tumors in mice. A few groups of BALB/c mice received 0 (group C), 50 (group A 50), 200 (group A 200), 500 (group A 500), and 1,000 (group A 1000) IU retinol palmitate/mouse/day in drinking water for 150 days. At progressive intervals mice from each group were tested for proliferative responses to concanavalin A (Con A), Escherichia coli lipopolysaccharide, interleukin-2, and interferon-gamma release to Con A. Ten mice from each group were also challenged with the 90-100% tumor-inducing dose of 3 distinct transplantable tumors. At the end of the experiment the principal organs were histologically examined, and the accumulation of vitamin A was evaluated. In groups A 200, A 500, and A 1000, an increase in the proliferative responses and production of lymphokines as compared to those in group C occurred after 60-90 days, but vanished after 150 days. The takes of the 3 tumors were impaired when the challenges were performed on days 75 and 150. This enhancement of distinct functions of cellular reactivity and resistance to transplantable tumors showed a linear relationship with the amount of supplemental retinol palmitate for the first 60-90 days. After 150 days, however, these enhancement effects vanished or tended to decrease.
Asphyxia-Induced Bradycardia
Authors: L BERLIN, I WALDMAN
Journal: JAMA (1964)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Exercise intervention for pediatric cancer survivors: Feasibility and preliminary efficacy
Authors: B. Collett, A. Acosta, S. Whitsett, A. McTiernan, D. Friedman
Journal: Journal of Clinical Oncology (2007)

20013 Background: Obesity and diminished physical activity are known sequelae of cancer and its treatment. In medical oncology, data support the efficacy of exercise interventions. We therefore evaluated such an intervention for overweight/inactive adolescent cancer survivors. Methods: Participants were randomized to an exercise or control condition. The intervention group attended exercise sessions for 12-weeks with an exercise physiologist, during which they developed an individualized program emphasizing cardiovascular fitness. Controls received written exercise and nutrition materials. Outcome measures included self-reported health-related quality of life (HRQOL), physical activity, and fatigue; and lab measures of body mass index (BMI) and VO2max. Results: Among the 36 participants (mean age = 18.0 yrs, mean = 12.0 yrs post-diagnosis), at baseline both groups had diminished HRQOL, elevated BMIs, low physical activity, decreased V02max and high levels of fatigue. Post-treatment, there was little change in BMI, while physical activity and fatigue slightly increased in both groups. Study participation among survivors was limited due to the commute and time commitment for center-based sessions. Table 1 . a 7-Day Physical Activity Recall; minutes/week of moderate-intense physical activity b Multidimensional Fatigue Questionnaire; lower scores = increased fatigue Conclusions: Survivors of childhood cancer are at risk for impaired HRQOL, high BMI, decreased physical activity, and fatigue, even 10+ years after diagnosis. Preliminary data are discouraging with respect to the immediate benefits of intervention, but analyses are ongoing to assess other outcomes as well as the impact 3 months following study completion. Feasibility issues of conducting such a study in a tertiary cancer center served by a broad catchment area have been identified. Continued research is required, which includes novel approaches to overcome concerns of time commitment, which limited study participation. [Table: see text] No significant financial relationships to disclose.
Pharmacologically active I.U.D.s.
Authors: S Browne
Journal: BMJ (1972)

only patient experiencing deterioration in sensory function was in the group given dapsone.Again, clofazimine at a higher dos- age did control a necrotizing erythema nodosum leprosum eruption in one patient.These unemphasized findings reflect a general trend in the report indicating the advantages of clofazimine in clinical usage.It may be that had clofazimine been given in a higher dose than 100 mg daily to these South Indian patients-notoriously liable to severe exacerbation in the presence of widespread bacillary breakdown-the reported advantages of clofazimine in preventing erythema nodosum leprosum might have been demonstrated.While the summary may accurately represent the results seen in this limited trial, the authors give little indication of the general tenor of the numerous reports in this field which bring out clearly the advantages of clofazimine that appear only as trends in their report; nor do they take cognizance of the arguments that have in- clined some cost-conscious physicians to prescribe clofazimine in certain circumstances to reaction-prone patients suffering from lepromatous leprosy.The findings of the authors cannot, of course be gainsaid, but the definite and rather sweeping conclusions they draw are not directly derived from the evidence they adduce from a small number of patients treated for an insufficient period of time, and given a fixed (and possibly inadequate) dosage of the drug.-Iam, etc.,
Peritoneal disease in breast cancer: A specific entity with an extremely poor prognosis
Authors: M. H. Tuthill, R. Pell, R. Giuliani, L. Adrian, J. S. Lewis, R. Leonard, C. Coombes, J. Stebbing
Journal: Journal of Clinical Oncology (2009)

e12023 Background: We are observing increasing numbers of patients with advanced breast cancer and peritoneal metastases. There are few published data regarding the prognosis, clinical characteristics, and management of such individuals. Methods: The electronic imaging database at Charing Cross Hospital was searched for the terms ’breast,’ ’cancer or tumor,’ ’peritoneal,’ and ’ascites’ from 2000–2008. Those with confirmed peritoneal disease from breast cancer, as described on ultrasound or staging CT reports with a clinico-pathologic confirmed diagnosis, were included in the study. Results: A total of 1,628 scans were screened and initially 168 patients were identified. A subsequent total of 44 individuals (2.7% of the metastatic cohort) were included in this study, as having breast cancer with peritoneal secondaries. Of these, the majority (77%) had invasive ductal carcinomas (IDC). While the median survival from the diagnosis of metastatic breast cancer measured 20.5 months (range 0.1 -125 months), the median survival of patients with peritoneal disease was 1.56 months (range 0.2 - 27 months). Conclusions: Our data shows that the median survival of patients with peritoneal breast cancer metastasis is surprisingly poor, with only a minority surviving more than six months. A specific association with invasive lobular carcinoma (ILC) was not observed. The dismal outcome of these individuals despite further active therapy merits their inclusion into trials of new treatments. No significant financial relationships to disclose.
A phase I dose finding study of weekly, sequential docetaxel (Doc) followed by flavopiridol (F) in patients with advanced solid tumors
Authors: D. Rathkopf, M. Fornier, M. Shah, J. Kortmansky, E. O'Reilly, A. King, J. Winkelmann, D. P. Kelsen, S. Olsen, G. K. Schwartz
Journal: Journal of Clinical Oncology (2004)

3072 Background: Flavopiridol is a cyclin dependent kinase inhibitor which enhances chemotherapy induced apoptosis. In vitro F enhances Doc-induced apoptosis in a sequence specific manner such that Doc must come before F (Motwani et al. Mol. Cancer Ther. 2:549–555, 2003). In vivoDoc must precede F by at least 4 hours in order to induce this effect. Methods: In view of this finding, we designed a phase I trial of weekly, sequential Doc followed by F in patients with advanced solid tumors. Docetaxel 35 mg/m2 was administered over 30 minutes, followed 4 hours later by escalating doses of F (20, 30, 40, 50, 60, and 70 mg/m2) administered weekly over one hour. This schedule was repeated for 3 weeks out of each 4 week cycle. We used standard eligibility criteria for this phase I trial including normal hepatic, renal, and bone marrow function, and Karnofsky Performance Status (KPS) ≥ 70%. Prior taxane therapy was allowed. Results: Eighteen evaluable patients have been enrolled: median age 56 (range 39–77), median KPS 80%, (range 70–90%), 7 males/11 females, median 3 prior regimens (range 0–10). We have observed no dose limiting toxicity up to a weekly F dose of 60 mg/m2. We observed 2 partial responses in breast (17 weeks) and ovarian cancer (12+ weeks) patients, both of whom had received a prior taxane. Stable disease has been seen in 3 patients with taxane refractory breast cancer (62+, 33, and 18 weeks), 2 patients with pancreas cancer (15 and 17 weeks), and 1 patient with gastric cancer (21 weeks). Conclusion: Our data show that treatment with weekly, sequential Doc followed by F is an effective and safe regimen in patients with advanced solid tumors. Clinical activity is encouraging, even in patients who have received prior taxane therapy. Dose escalation of F continues to the targeted dose of 70 mg/m2. Further dose escalations of F may be possible with a reduced dose of weekly Doc. Phase II trials of weekly, sequential Doc followed by F are planned as second line therapies in patients with metastatic pancreas and gastric cancers. Pharmacokinetic data will be presented. (Sponsored by Aventis Pharmaceuticals) . . Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharmaceuticals Aventis Pharmaceuticals
Potential immune biomarkers of gastrointestinal toxicities and efficacy in patients with advanced melanoma treated with ipilimumab with or without prophylactic budesonide
Authors: D. Berman, S. M. Parker, S. D. Chasalow, J. Siegel, Z. Tsuchihashi, D. Wu, K. Bennett, S. Alaparthy, A. Ronczka, S. Galbraith
Journal: Journal of Clinical Oncology (2008)

3022 Background: The most common adverse events associated with ipilimumab, an anti cytotoxic T-lymphocyte antigen-4 drug for the treatment of advanced melanoma, are immune in nature and primarily gastrointestinal (GI). These immune-related adverse events (irAEs) are likely due to ipilimumab-mediated activation of the immune system. Immune-derived biomarkers that may be associated with response/GI irAEs were explored. Methods: In this randomized, double-blind, placebo-controlled, multicenter, phase II study, eligible patients with stage III (unresectable) or IV melanoma received ipilimumab 10 mg/kg every 3 weeks (Q3W) X 4 induction dosing ± 15 weeks of prophylactic oral budesonide or placebo, followed by maintenance ipilimumab treatment Q12W. Pre-/post-treatment blood, serum, and stool samples were collected to assess: gene polymorphisms, T-cell populations by flow cytometry, humoral response to tumor antigens (TA), and serologic biomarkers of inflammatory bowel disease (IBD). Patients had an endoscopy with biopsy during the first 2 weeks after the first dose and at the onset of ≥Grade 2 diarrhea/colitis. Results: 115 patients were randomized and treated. By Week 4, the mean baseline percentages in peripheral blood of activated CD4+ /CD8+ T cells increased while the mean percentage of naïve CD4+ and CD8+ T cells decreased, indicating immune-system activation. Ipilimumab induced changes in serologic IBD biomarkers that were distinct from classic IBD. Colonic biopsies obtained within the first 2 weeks showed predominantly acute interstitial and crypt inflammation (approximately 13% of subjects) that were histologically distinct from classic IBD or graft-vs-host disease (GVHD). Preliminary analyses suggest no widespread, clinically meaningful changes in humoral response to TA. Conclusions: These data show that the immune system is activated by ipilimumab 10 mg/kg Q3W x 4 induction dosing. The histologic changes in the bowel and the pattern of serologic biomarkers of IBD indicate that ipilimumab-induced colitis is likely distinct from classic IBD and GVHD. The effect of prophylactic budesonide and the associations between biomarkers and efficacy and safety will also be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Abstract 19513: Cystathionine-gamma-lyase/hydrogen Sulfide is Critically Important for Ischemic Revascularization of Aged Mice
Authors: Gopi K Kolluru, Saurabh Rajpal, Sibile Pardue, Xinggui Shen, Christopher G Kevil
Journal: Circulation (2014)

Introduction: Aging is a major risk factor for cardiovascular diseases (CVD) and is associated with complications including oxidative stress and inflammation. Hydrogen sulfide (H2S) and Nitric Oxide (NO) are gaseous signaling molecules implicated in numerous pathophysiological functions of the vasculature. CSE genetic deficiency and subsequent reduction in H2S levels attenuates ischemic vascular remodeling. Additionally, sirtuin1 (Sirt1) critically regulates mechanisms of angiogenesis, inflammation and cardioprotection. However, the importance of CSE/H2S in relation to age-dependent dysfunctions has not been investigated. Objective: To investigate the age-dependent regulation of H2S and NO metabolites in aged mice and the rescue mechanisms mediated upon H2S therapy in aged mice ischemic hind limb model. Methods: Unilateral femoral artery ligation was performed on 52-week-old CSE-/- mice, which were treated with PBS or H2S donor DATS (200μg/kg) administered retro-orbitally twice daily until Day 7. Hind lim...
GW26-e2299 Lifestyle Modification Combined with Perindopril Therapy on hsCRP and MIF Serum Levels in Patients with Stage 1 Hypertension: 1-year Follow-up
Authors: Zhibin Chen, Hao Tang, Zhenyu Li, Yanbing Liang, Zhongfu Ma
Journal: Journal of the American College of Cardiology (2015)
Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation
Authors: Ronit Machtinger, Louise C. Laurent, Andrea A. Baccarelli
Journal: Human Reproduction Update (2015)

BACKGROUNDExtracellular vesicles (EVs) are membrane-bound vesicles, found in biofluids, that carry and transfer regulatory molecules, such as microRNAs (miRNAs) and proteins, and may mediate intercellular communication between cells and tissues. EVs have been isolated from a wide variety of biofluids, including plasma, urine, and, relevant to this review, seminal, follicular and uterine luminal fluid. We conducted a systematic search of the literature to review and present the currently available evidence on the possible roles of EVs in follicular growth, resumption of oocyte development and maturation (meiosis), sperm maturation, fertilization and embryo implantation.