tbuckley/cabot-search huggingface dataset:
Phase II study of docetaxel plus epirubicin versus docetaxel plus cisplatin as first-line chemotherapy for treatment of advanced breast cancer (CHN TAX-618)
Authors: Y. J. Wang, Q. Fu, Q. Wu, F. X. Su, L. Z. Zhou, Z. B. Ye, J. Q. Yang
Journal: Journal of Clinical Oncology (2006)

10535 Background: The combination of docetaxel plus epirubicin (TE) have demonstrated a significant activity in advance breast cancer (ABC) as first-line chemotherapy. In the meantime, some emerging literatures suggest that docetaxel-cisplatin (TP) combination has a powerful synergistic interaction with less cardiotoxicity. The main objectives of this multicenter study are to evaluate the efficacy and safety of TE versus TP. Methods: From August 2003 to February 2005, 80 patients with at least one measurable lesion were randomized with ratio of 2:1 to receive TE or TP as as first-line chemotherapy. Dosages were as follows: docetaxel 75 mg/m 2 plus epirubicin 60 mg/m 2 or docetaxel 75 mg/m 2 plus cisplatin 75 mg/m 2 intravenously once every 3 weeks for a maximum of 6 cycles. Baseline characteristics were well balanced. Results: A total of 55 patients were assigned to TE (median age 48 yearas) and 25 patients were treated with TP (median age 50 yearas). The same of median 4 cycles treatment were administered for two arms. A complete clinical response was observed in 3.6% and 4.0% of patients treated with TE and TP, respectively (P = 1.00). Overall (complete and partial) clinical response rates for TE and TP were 48% and 56%, respectively (P =0.469). Disease control rates (CR + PR + SD) for TE and TP were 83.6% and 80%, respectively (P = 0.755). The median TTP were TE: 10.8months,TP: 11.2 months days (P = 0.247). Grade 3/4 toxicities included: nausea/vomiting (16.3% TE; 12.0% TP); diarrhea (1.8% TE; 0% TP); alopecia (32.7% TE; 12.0% TP); anemia (1.8% TE; 4.0%TP); neutropenia (65.5% TE; 4.8% TP); febrile neutropenia (3.6% TE; 0% TP). Conclusions: Both TE and TP were active and tolerant regimens for ABC. While there may have been a trend toward lower toxicities in favor of the docetaxel/cisplatin combination, although no significant difference was observed during our study. No significant financial relationships to disclose.
Thrombotic Thrombocytopenic Purpura and Sporadic Hemolytic-Uremic Syndrome Plasmas Induce Apoptosis in Restricted Lineages of Human Microvascular Endothelial Cells
Authors: Debashis Mitra, Eric A. Jaffe, Babette Weksler, Katherine A. Hajjar, Carl Soderland, Jeffrey Laurence
Journal: Blood (1997)
Abstract B14: Cisplatin induced activation of the epidermal growth factor receptor as a mechanism for epigenetic silencing in ovarian cancer cell platinum resistance
Authors: Michaela Lee Granados, Laurie G. Hudson, Sabrina Leigh Samudio-Ruiz
Journal: Clinical Cancer Research (2015)

Abstract The 5-year survival rate for women diagnosed with ovarian cancer remains dismally unchanged at 44%. Resistance to platinum compounds in ovarian cancer imparts a major obstacle to increasing patient survival. The epidermal growth factor receptor (EGFR) plays a role in the regulation of growth and differentiation in normal cells, and proliferation in malignant cells. It is known that disregulation of the EGFR pathway, including prolonged receptor activation, is associated with platinum resistance in cellular models and our lab revealed a novel mechanism by which constitutive EGFR activation regulates DNA methyltransferase (DNMT) activity and DNA methylation. Platinum resistance is associated with epigenetic downregulation (via DNA methylation) of genes involved in platinum drug response, particularly genes important for drug uptake. Given the established link between platinum resistance and alterations to DNA methylation, our studies investigated the effects of acute cisplatin treatment on EGFR activation and DNMT activity. We hypothesized that acquired chemoresistance resulting from cisplatin treatment is initially triggered by cisplatin-induced EGFR activation and subsequent alterations to DNMT activity. We show activation of EGFR upon treatment of OVCA433 cells with cisplatin. Functional EGFR activation following cisplatin treatment was also observed by evaluating activation of downstream targets, Jak2 and Akt. Hence, cisplatin facilitates activation of EGFR and its downstream signaling pathways. Moreover, there was also a significant increase in DNMT activity in cisplatin treated cells when compared to untreated passage controls. These observations unmask a potential mechanism by which initial exposure to cisplatin can activate EGFR signaling and cause epigenetic alterations that may contribute to the development of platinum resistance. By understanding the underlying mechanism for development of platinum resistance and discovering targets of methylation, we may be able to enhance sensitivity to platinum based chemotherapeutics. Citation Format: Michaela Lee Granados, Laurie G. Hudson, Sabrina Leigh Samudio-Ruiz. Cisplatin induced activation of the epidermal growth factor receptor as a mechanism for epigenetic silencing in ovarian cancer cell platinum resistance. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B14.
High cholesterol diet is not linked to increased heart risk, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Nineteen patients, representing a spectrum of thyroid function, were studied. The mean 24-hr thyroid <sup>131</sup>I uptakes determined by a standard counting procedure and by our scintillation camera counting method were 15.0% and 16.4%, respectively, for the entire patient population. The 24-hr <sup>131</sup>I uptakes from these two methods correlated with a coefficient of 0.99. A high degree of correlation between the two methods was found in evaluating euthyroid and hypothyroid patients and a similar finding was noted in the one hyperthyroid patient studied.
Prognostic significance of HPV and p16 status in patients with oropharyngeal cancer treated on a large international phase III trial
Authors: D. Rischin, R. Young, R. Fisher, S. Fox, Q. Le, L. Peters, J. Choi, B. O'Sullivan, J. Giralt, G. McArthur
Journal: Journal of Clinical Oncology (2009)

6004 Background: Previous studies have reported that in patients with oropharyngeal cancer (OPC) the presence of human papilloma virus (HPV) is associated with an improved prognosis. We sought to determine the prognostic importance of HPV and p16 in patients with OPC treated with concurrent chemoradiation on a large international phase III trial. Methods: Patients with previously untreated Stage III or IV head and neck squamous cell cancer were randomized to receive definitive radiotherapy concurrently with either cisplatin or cisplatin plus tirapazamine. In this substudy, analyses were restricted to patients with OPC who received &gt; 60 Gy and did not have major radiation deviations predicted to impact on tumor control. HPV 16/18 were detected by in situ hybridization and scored as detected or undetected. p16 was detected by immunohistochemistry. Nuclear and cytoplasmic staining intensity of tumor cells was scored as grade 0–3, with grade 2 and 3 called positive. Log rank and Cox regression used for survival analyses. p values were 2-sided . Results: 384 out of 861 patients had OPC and met the eligibility criteria. Slides were available for HPV assay in 195 and for p16 in 186, and for both in 173. 54/195 (28%) were HPV positive, 107/186 (58%) were p16 positive. HPV pos tumors were associated with better 2-year overall survival (OS) (94 v 77%, p = 0.007) and better failure-free survival (FFS) (86 v 75%, p = 0.035) compared to HPV neg tumors. Similarly p16 pos tumors were associated with better 2-year OS (92 v 75%, p = 0.004) and FFS (87 v 72%, p = 0.003) compared to p16 neg . After adjustment for stage, Hb and ECOG PS, HPV pos had better OS than HPV neg (HR 0.29, p = 0.018), and p16 pos had better OS than p16 neg (HR 0.39, p = 0.013). When the HPV and p16 results were combined the relative HRs for OS were: HPVpos/p16pos 0.35 (45 patients, 26% of cases), HPVpos/p16neg 0 (3pts, 2%), HPVneg/p16pos 0.73 (58pts, 33%), HPVneg/p16neg 1.79 (67 pts, 39%). Conclusions: Our results confirm the prognostic significance of tumor HPV status in oropharyngeal cancer treated with chemoradiation, but also show that p16 identifies a larger group with an improved prognosis. The HPV neg/p16 pos population has a better prognosis compared to patients with HPV neg/p16 neg tumors. No significant financial relationships to disclose.
Monitoring children's growth
Authors: P C Hindmarsh
Journal: BMJ (1996)

The safety profile and observed high acceptability of products containing desogestrel or gestodene allow their continued use, subject to thorough, unbiased counselling in the context of all the recent studies and the letter from the Committee on Safety of Medicines.10The faculty is committed to developing evidence based guidelines, and until further data are available it endorses the guidelines given in the box.
Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo
Authors: Ryo Hotta, Lily S. Cheng, Hannah K. Graham, Nandor Nagy, Jaime Belkind-Gerson, George Mattheolabakis, Mansoor M. Amiji, Allan M. Goldstein
Journal: Biomaterials (2016)
Stimulation of Na+/H+ exchange is not required for induction of hypertrophy of renal cells in vitro.
Authors: M Mackovic-Basic, L G Fine, J T Norman, E J Cragoe, I Kurtz
Journal: Journal of the American Society of Nephrology (1992)

Hypertrophy of renal proximal tubular cells is associated with an early increase in Na+/H+ antiport activity both in vivo and in vitro. The purpose of the study presented here was to determine whether functioning Na+/H+ antiport activity is required for hypertrophy to occur. LLC-PK1 cells deficient in Na+/H+ antiport activity were prepared by the "proton-suicide" method. Mutant cells had 28 to 40% of the normal Na+/H+ antiport activity. The addition of 50 nM methylisobutylamiloride to these cells decreased the antiport activity to less than 5% of the control value. In the mutant cells, steady-state intracellular pH was normal as was the protein content. After exposure of the wild-type cells for 72 h to 10(-6) M insulin and 10(-9) M insulin-like growth factor 1, cell protein content increased significantly. The increase in protein content induced by these growth factors in the mutant cells did not differ significantly from the response of the wild-type cells. Lowering the Na+/H+ exchange further by the addition of methylisobutylamiloride (50 nM) to less than 5% of the control value did not blunt the hypertrophic response in the mutant cells. These studies indicate that hypertrophy can be induced in LLC-PK1 cells by growth factors when basal Na+/H+ antiport activity is reduced to low levels by selective mutation or by competitive inhibition. The results suggest that stimulation of the Na+/H+ antiporter is not an essential prerequisite for the induction of hypertrophy in renal cells.
Pharmacodynamic response in phase I combination study of ABT-888 and topotecan in adults with refractory solid tumors and lymphomas.
Authors: J. J. Ji, S. Kummar, A. P. Chen, Y. Zhang, R. Putvtana, R. J. Kinders, L. Rubinstein, R. E. Parchment, J. E. Tomaszewski, J. H. Doroshow
Journal: Journal of Clinical Oncology (2010)

2514 Background: Poly(ADP-ribose) (PAR) polymerase (PARP) inhibitors such as ABT-888 may prevent efficient repair of DNA damage induced by topoisomerase 1 inhibitors and lead to double-strand breaks, which activate DNA-damage signaling pathways through phosphorylation of histone H2AX (γH2AX). We evaluated the pharmacodynamics (PD) of ABT-888 and topotecan alone and in combination through quantitative detection of PARP activity and γH2AX foci in peripheral blood mononuclear cells (PBMCs) and tumor samples. Methods: PBMCs and tumor biopsies (optional) were collected, and validated assays were used to compare pre- and post-treatment levels of γH2AX and PAR, a product of PARP. PAR was measured by ELISA and γH2AX by immunofluorescence assay. Results: We enrolled 24 patients (pts) with refractory solid tumors and lymphomas. The dose of topotecan was reduced and administration schedule changed due to myelosuppression (Table). PARP was modulated by the various administration schedules. In PBMCs, >50% reduction in PAR was observed in 13 of 18 pts. When ABT-888 was given on D1 only, PAR levels in PBMCs returned to baseline levels by D2 in 3 of 5 pts. In the 3 pts for whom paired tumor biopsies were available, PAR reduction was 89.3% (pt on dose level [DL] 1), 98.7% (pt on DL-2), and 75.5% (pt on DL-3). Topotecan did not appear to alter the ability of ABT-888 to inhibit PARP. Elevated levels of γH2AX were detected in PBMCs after doses of 0.9 and 1.2 mg/m2/day topotecan alone but not lower doses. However, when given with ABT-888, 3 of 7 pts on DL-3 and all 3 pts on DL-2 had significant increases in γH2AX. γH2AX upregulation was associated with PARP inhibition; mean PAR reduction ± SD in PBMCs 2 h post-dose in pts on DL −3 was 97.8% ± 5.5% for γH2AX responders vs. 52.3% ± 28.1% for nonresponders. Conclusions: The PARP inhibitor ABT-888 potentiated DNA damage caused by topotecan as indicated by the increase in γH2AX foci. Funded by NCI Contract HHSN261200800001E. Dose and days (D) of administration Dose level Topotecan IV (mg/m2/day) ABT-888 (10 mg q12h PO) No. of patients 1 1.2 (D-8, 2-5) D1-7 6 −1 0.9 (D-8, 2-5) D1-7 3 −2 0.75 (D1-5) D2-5 3 −3 0.6 (D1-5) D2-5 7 1A 0.75 (D1-5) D1 only 5 No significant financial relationships to disclose.
Phase II study of irofulven in recurrent or metastatic gastric cancer: A Cancer Therapeutic Research Group (CTRG) study
Authors: H. C. Chung, W. Yeo, S. Y. Rha, M. Boyer, S. Y. Ong, R. Lim, B. Zee, J. K. Roh, B. C. Goh, A. T. Chan
Journal: Journal of Clinical Oncology (2006)

14105 Background: Cytotoxic chemotherapy has been widely used in patients (pts) with advanced or metastatic gastric cancer, but the reported high response rates in phase II settings have not been confirmed by randomized trials. Moreover, the therapeutic impact on survival has been modest. The purpose of this study was to evaluate Irofulven, a DNA interacting acylfulvene analog, as first line therapy for pts with recurrent or metastatic gastric cancer. Methods: The main eligibility criteria were: Histologically or cytologically confirmed disease; age &gt; 18 yrs; ECOG ≤ 2; measurable disease; no prior chemotherapy for recurrent or metastatic disease; life expectancy &gt; 3 months. Irofulven was given at 0.45 mg/kg i.v. over 30-min infusion (max. 50 mg), on Day 1 and 8, every 3 weeks. The primary endpoint was treatment response and toxicity; the secondary end-point was survival. A 2-stage phase II design was used. In the first stage, the target enrollment was 20, if ≤ 2 responses were observed, the study would be stopped and the treatment concluded to be ineffective; if ≥ 6 responses were observed, the study drug would be concluded to be active. Otherwise, another 15 pts would be entered into the second stage. Survival was constructed using the Kaplan-Meier method. All patients entering the trial were included in the survival analysis. Results: 23 pts were entered into the first stage. The median no. of cycles per pt was 2 (range: 1–6). 2 pts (9%) had ≥ 1 week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, 7 pts (30%) required dose reductions; 5 (22%) had dose omitted. 22% and 17% pts developed grade 3/4 anemia and neutropenia respectively. There was no grade 4 thrombocytopenia or neutropenic fever. Of the 20 evaluable pts, no responses was observed, 3 pts had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55–9.39). Conclusions: Irofulven was tolerated at the described dose but showed no evidence of antitumor activity in patients with advanced gastric cancer. Acknowledgement: The study was sponsored by the Division of Cancer Treatment and Diagnosis, National Cancer Institute, U.S.A, and its collaborator MGI Pharma, Inc. No significant financial relationships to disclose.
Listening to the voices of abused older people: should we classify system abuse?
Authors: Y. Mysyuk, R. G. J. Westendorp, S. Biggs, J. Lindenberg
Journal: BMJ (2015)

Elder abuse is often the result of the organisation of health systems rather than the fault of individuals, argue <b>Yuliya Mysyuk and colleagues</b>. They call for system abuse to be acknowledged and addressed by incorporating older people’s views when designing health services
Abstract 4189: Evaluation of Coronary Plaque Rupture in Patients With Chronic Coronary Artery Disease: Optical Coherence Tomography Study
Authors: Tetsuya Fusazaki, Tomonori Itoh, Hiroki Matsui, Tatsuhiko Koeda, Takumi Kimura, Iwao Gotoh, Shoma Sugawara, Yoshinobu Ogino, Kentarou Komuro, Yuji Takahashi, Yujirou Naganuma, Motoyuki Nakamura
Journal: Circulation (2009)
Abstract 12547: Lowest Left Ventricular Mass (LVM) Confers Survival Benefit in Patients with Severe Isolated Aortic Stenosis (AS) and Normal Left Ventricular Ejection Fraction (EF)
Authors: Eddy Barasch, Florentina Petillo, Simcha Pollack, Peter D-Y Rhee, Jeanna Kahn, Wendy Stovold, Nathanie Reichek
Journal: Circulation (2012)

Objective: Left ventricular hypertrophy (LVH) in patients (pts) with severe AS is regarded as an adaptative mechanism that normalizes wall stress and myocardial oxygen demand. Recent data cast doub...
A pilot study of SP versus FP chemotherapy in postoperative setting for histologically stage IIIb-IV(M0) gastric cancer.
Authors: S. Lee, H. Jeung, H. C. Chung, S. Noh, W. Hyung, J. Ahn, S. Y. Rha
Journal: Journal of Clinical Oncology (2010)

e14630 Background: Although FP efficacy has not been proven, it has been used for the prevention of relapse in post-operative gastric cancer. This pilot study was conducted to investigate the safety and efficacy of SP vs FP in post-operative setting for stage IIIB-IV(M0) gastric cancer. Methods: After curative resection, stage IIIB-IV (M0) gastric cancer patients were assigned to postoperative SP or FP. Eight cycles of S-1 (40 mg/m2 two times daily, D1-14) plus cisplatin (60 mg/m2 on day 1) were administered every 3 weeks or 6 cycles of FU (1g/m2 per day, D 1-4) plus cisplatin (80 mg/m2 on day 1) were administered every 4 weeks. Results: A total of 41 patients were recruited from January 2009 to December 2009. In total, 91 cycles of SP (n = 20) and 93 cycles of FP (n = 21) were administered, with a median of five (range 1-8) in the SP arm and four (range 1-6) in the FP arm. The median relative dose intensity per patient was 75% (range, 20.08-100) for S-1, 100% (range, 50-125) for P and 100% (range, 64-100) for 5-FU, 100% (range, 66.65-100) for P. Although the relative dose intensity for FP remained stable, there was a steady decrease in relative dose intensity for SP during treatment. After a median follow-up of 4.7 months (range 0.56-11.32), the median RFS is not reached in both arms. Relapses occurred in 0 of 20 (0%) SP arm and in 4 of 21 (19%) FP arm (p = 0.0459). The incidence of grade 3-4 granulocytopenia was 36.8% with SP and 14.3% with FP. Grade 3-4 nonhaematologic toxicities were: fatigue (5.2% with SP vs. 4.8% with FP), vomiting (10.5% with SP vs. 0 % with FP), and infection (5.2% with SP vs. 0% FP). Conclusions: These results indicated that SP was active and tolerable as an adjuvant treatment for curatively resected stage IIIB-IV(M0) gastric cancer. But, considering a steady decrease in the relative dose intensity of S-1 during treatment, further study is warranted to determine the optimal dose and combination. No significant financial relationships to disclose.
Two-Year Survey of Hematologic Malignancies in Uganda
Authors: S. Amsel, J. S. Nabembezi
Journal: JNCI Journal of the National Cancer Institute (1974)

All cases of leukemia, lymphosarcoma, Burkitt's lymphoma, Hodgkin's disease, multiple myeloma, and histiocytic medullary reticulosis reported in Uganda during a 2-year period were analyzed with regard to sex, incidence, and regional variations in incidence. In Kyadondo County, the incidence of these diseases was similar to that found in other African populations, but lower than the rates found in Western countries. In the age-specific incidence curves for Uganda, a marked decrease in incidence in the older age group was evident at a point where the rate in Western countries increases geometrically. An exception was Hodgkin's disease, for which the rate and bimodal shape of the age-specific incidence curve were similar to those of Western countries. There was a low rate of leukemia of all cytologic types. In the Northern Province of Uganda, the high rate of Burkitt's lymphoma was confirmed, and the incidence of Hodgkin's disease and lymphosarcoma was higher than expected. Eleven cases of histiocytic medullary reticulosis were recorded.
Bone Marrow Colony-Forming Cells in Mice With Virus-Induced Lymphoid Leukemia: Relation to Serum Colony-Stimulating Activity and Blood Granulocytes 2
Authors: Roger S. Foster
Journal: JNCI Journal of the National Cancer Institute (1977)

Mice with advanced lymphoid leukemia have elevated peripheral blood granulocytes and elevated serum colony-stimulating activity, which promotes the in vitro growth of granulocyte and/or macrophage colonies. The number of bone marrow precursor cells of the in vitro granulocyte and/or macrophage colonies varied from normal to 10% of normal. The elevation of colony-stimulating activity correlated best with a combination of increased blood granulocytes and a deficiency of bone marrow precursor cells, which suggested that colony-stimulating activity is a leukopoietin that increases the efficiency and rate of production of granulocytes.
Feasibility study of adjuvant vinorelbine and cisplatin in Japanese patients with completely resected stage II-IIIA non-small cell lung cancer.
Authors: N. Yoshimura, S. Kudoh, S. Mitsuoka, T. Kimura, K. Hirata
Journal: Journal of Clinical Oncology (2010)

e17514 Background: Recent clinical trials have shown that adjuvant cisplatin (CDDP)-based chemotherapy improved survival for patients with completely resected stage II-IIIA non-small cell lung cancer (NSCLC). In combination with CDDP, vinorelbine (VNR) was the only third generation drug to demonstrate survival benefits. In this study the feasibility of postoperative CDDP and VNR was prospectively examined in Japanese patients. Methods: Patients with completely resected stage II-IIIA NSCLC were received CDDP 40 mg/m2 and VNR 25 mg/m2 on days 1 and 8, every 3-week, 4 cycles. The primary end point was completion rate (CR) of the therapy and the secondary end point was safety and toxicity. This study, with a planned sample size of 20, had 80% power to support the hypothesis that the true CR was >80%, and 5% significance to deny the hypothesis that the true CR was <50%. Results: Between May 2007 and February 2008, 20 patients with completely resected stage II-IIIA NSCLC were enrolled in the study and all patients were treated. Demographics: Male/Female 9/11; ECOG PS 0/1 8/12; median age 63 (range 35-74); p- stage IIA/IIB/IIIA 2/6/12; histological type adenocarcinoma/squamous cell carcinoma/large cell carcinoma 13/6/1; type of surgery lobectomy/neumonectomy 20/0. Twenty patients were enrolled, and the CR for the 4 cycles was 90% (18/20). Grade 3 or 4 hematology toxicities were observed neutropenia in 90%, leukopenia in 65%, anemia in 30%, and febrile neutropenia in 5%. Grade 3 or 4 non-hematology toxicities were not observed. Conclusions: Postoperative adjuvant chemotherapy consisting of CDDP 40 mg/m2 and VNR 25 mg/m2 on days 1 and 8 was shown to be well tolerable in Japanese patients with completely resected stage II-IIIA NSCLC. No significant financial relationships to disclose.