tbuckley/cabot-search huggingface dataset:
Randomized phase II study of two cross-over sequences comprising vinorelbine/cyclophosphamide and temozolomide/etoposide in outpatient setting for relapsed or refractory solid tumors in children and young adults.
Authors: M. Saito, H. Kawamoto, A. Ogawa, A. Makimoto
Journal: Journal of Clinical Oncology (2010)

TPS328 Background: Both vinorelbine (VNR) and temozolomide (TMZ), as well as camptotecin derivatives, are regarded as highly promising developmental cytotoxic drugs against pediatric malignancy, so that FDA designated the both drugs as “exclusivity granted,” reported in ASCO 2003. The purpose of this study is to examine safety and efficacy of VNR/cyclophosphamide (CY) (R1) and TMZ/etoposide (VP) (R2), both of which have reported in one adult phase II trial, respectively, in children and young patients (pts) with refractory solid tumors. We also assess which sequence of the two regimens could improve survival with minimum burden. Methods: Eligibility: Pts aged between 3 and 30 years of age with solid tumors (including primary CNS tumors) refractory or relapsed despite disease-specific standard chemotherapies are eligible. Other pts requirements were as follows: PS (ECOG) 0-2; normal organ function; appropriate interval from prior antitumor therapies; no history of either VNR or TMZ use; obtained written informed consent. The study is approved by the local ethical committees of the participating institutions. Treatment plan: In R1, VNR 25mg/m2 intravenously on day1, day8, and day15 and CY orally 25mg/m2 daily in 28 day-cycle. In R2, TMZ 150 mg/m2 orally day 1 to day 5 and VP 50 mg/m2 orally day1 to day 12 in 28 day-cycle. All pts are treated in outpatient setting. Study design: Multi-center, open-label, cross-over randomized phase II. Pts are randomized to group-A or group-B. In group-A, pt receives R1 until progression and then switches to R2 (1st sequence). Pt in group B receives these regimens in reverse order (2nd sequence). Planned sample size is 22 / group (the probability of correct selection is more than 80% when median survivals are 6 months vs. 8 months and survival times are exponentially distributed). Endpoints: Primary endpoint is overall survival. Secondary endpoints includes progression free survival, time to treatment failure, response rate, adverse events, self- reported QOL with face scale, number of days attending school/workplace, and number of days without hospital visit or stay. No significant financial relationships to disclose.
Abstract 17511: Contrast-Enhanced Magnetic Resonance Imaging Allows Identification of Epicardial Substrate of Post-Infarction Ventricular Tachycardias
Authors: Pablo Ávila, Javier Fernández-Portales, Esther Pérez-David, Verónica Crisóstomo, Javier Jiménez-Candil, José Luis Rubio-Guivernau, María Jesús Ledesma-Carbayo, Javier Bermejo, Francisco Fernández-Avilés, Ángel Arenal
Journal: Circulation (2012)

Introduction: Epicardial location of ventricular tachycardia (VT) circuit is a limitation for ablation but its prediction is troublesome. Non invasive identification of epicardial VT substrate coul...
Prophylactic Surgery in Women With a Hereditary Predisposition to Breast and Ovarian Cancer
Authors: Andrea Eisen, Timothy R. Rebbeck, William C. Wood, Barbara L. Weber
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To review the published literature on the efficacy and adverse effects of prophylactic mastectomy (PM) and prophylactic oophorectomy (PO) in women with a hereditary predisposition to breast and ovarian cancer and to provide management recommendations for these women. METHODS: Using the terms “prophylactic,” “preventive,” “bilateral,” “mastectomy,” “oophorectomy,” and “ovariectomy,” a MEDLINE search of the English-language literature for articles related to PM and PO was performed. The bibliographies of these articles were reviewed to identify additional relevant references. RESULTS: There have been no prospective trials of PM or PO for the reduction of breast cancer or ovarian cancer incidence or mortality. Most of the available retrospective studies are composed of women who had surgery for a variety of indications and in whom genetic risk was not well characterized. However, some reports in women at increased risk of breast or ovarian cancer have shown that PM and PO can reduce cancer incidence. CONCLUSION: Interest in and use of PM and PO are high among physicians and high-risk women. PM and PO seem to be associated with considerable reduction in the risk of breast and ovarian cancer, albeit incomplete. The surgical morbidity of PM and PO is low, but the complications of premature menopause may be significant, and few studies address quality-of-life issues in women who have opted for PM and PO. Management recommendations for high-risk individuals are presented on the basis of the available evidence.
LSC 2014 abstract - Influence of a Th2 immune response on airway remodeling in asthma
Authors: Katharina Dietz, Moritz Ulrich, Hoeke Baarsma, Kathrin Suttner, Melanie Königshoff, Carsten Schmidt-Weber, Ulrich Zissler
Journal: European Respiratory Journal (2014)

Background:  The pathological hallmarks of asthma are a Th2 driven chronic inflammation of the airways and airway remodeling. This remodeling process is known to be influenced by several signaling pathways. One of them is the Wnt signaling that is thought to be differentially regulated in asthma patients compared to healthy subjects. As a strong interaction between the epithelium and effector immune cells was previously described, it is likely that the Th2 driven asthmatic immune response is influencing the Wnt signaling in the airway epithelium.   Aim:  To investigate the influence of Th2 immune response on the Wnt signaling in bronchial epithelium.   Methods:  Bronchial epithelial cells were cultured in the presence of IL-4 and RNA was harvested after 6h and subjected to Agilent single color microarray gene expression profiling (60K). Datasets were analyzed under constant significance restrictions (pl0.05). The expression of regulated Wnt genes was validated using SYBR Green based quantitative PCR. Additionally expression of Wnt ligands in sputum supernatants of asthmatic patients versus healthy controls was determined by Western blot.   Results:  Significant gene expression changes of Wnt5a and FZD10 were observed in Th2-subtype specific IL-4 induced bronchial epithelial cells. The mRNA levels of both genes were significantly increased upon stimulation in comparison to a medium control (n=5). Western blot analyses suggest that Wnt5a is expressed in the sputum supernatant of asthma patients, while it is not in healthy controls.   Conclusion:  The results indicate that a Th2 driven immune response enhance the expression of Wnt5a by bronchial epithelial cells, which might affect the global Wnt signaling in the airway.
A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas
Authors: S.J. Kim, D.-Y. Shin, J.S. Kim, D.H. Yoon, W.S. Lee, H. Lee, Y.R. Do, H.J. Kang, H.S. Eom, Y.H. Ko, S.H. Lee, H.Y. Yoo, M. Hong, C. Suh, W.S. Kim
Journal: Annals of Oncology (2016)
Geographic patterns of prostate cancer incidence and mortality - United States, 2001
Authors: R. R. German, T. D. Thompson, S. L. Stewart, C. Friedman, P. Wingo
Journal: Journal of Clinical Oncology (2005)

4650 Background: Except for non-melanoma skin cancer, prostate cancer (PrCA) is the most commonly diagnosed cancer among males, and the second leading cause of cancer-related deaths. To monitor cancer incidence, CDC funds cancer registries in 45 states and D.C. through the National Program of Cancer Registries (NPCR). Methods: Incidence data from 39 NPCR registries and five Surveillance, Epidemiology, and End Results (SEER) registries, and mortality data from CDC’s National Vital Statistics System were used to calculate rates. Cancer incidence data represent 92% of the U.S. population and mortality data represent 100%. Incidence and death rates, age-adjusted to the 2000 U.S. standard, were categorized by state, and expressed per 100,000 men. Aggregate incidence rates were calculated for all U.S. census regions except the South, and death rates were calculated for all regions (Northeast, West, Midwest, and South). Results: In 2001, PrCA incidence rates varied significantly by state, ranging from 119.2 to 213.5 per 100,000 men in Arizona and D.C., respectively. PrCA death rates also varied and ranged from 20.1 in Hawaii to 46.2 in D.C. PrCA incidence varied among the census regions, with incidence significantly higher in the Northeast region compared to the Midwest and West (p<0.0001), and the Midwest higher than the West (p<0.0001). PrCA death rates were significantly lower in the Northeast compared to the South (p=0.03), while death rates in the Northeast, Midwest, and South were significantly higher than in the West (p<0.0001). Conclusions: Data from the NPCR program are an excellent source of local, state, and regional cancer incidence information. When used in conjunction with mortality data, cancer control planners can measure cancer burden to improve and direct practices in their area. Men should periodically consult with their physicians regarding current practices for screening and controlling PrCA, and engage in informed decision making regarding their use. No significant financial relationships to disclose.
Length and quality of survival after hyperfractionated radiotherapy concurrent with low dose gemicitabine for inoperative pancreatic cancer
Authors: K. Maemura, S. Takao, H. Shinchi, T. Aikou
Journal: Journal of Clinical Oncology (2005)

4235 Background: We have developed the chemoradiotherapy by induction of comformal radiation and administration of low dose gemcitabine since 2001 as phase I trial. On the basis of this data, we initiated hyperfractionated radiotherapy (HART) with low dose of twice-weekly gemcitabine in order to achieve shortening of treatment period of, increasing anti-tumor effect and decreasing late complication of radiotherapy. The purpose of this study was to evaluate the survival benefit of HART compared with conventional chemoradiotherapy. Methods: Consecutive thirty one patients with previously untreated, locally advanced, or asymptomatic-metastatic pancreatic adenocarcinoma were enrolled in this study. Reason for unresectability were involvement of superior mesenteric artery, and/or portal vein, paraaortic nodes, distant metastasis and medically inoperable. Twenty six patients were proven adenocarcinoma historogically. Patients were divided into two groups consecutively. First sixteen patients, as conventional group, received confomal RT in conventional manner (50.4Gy/28 fraction, for 6 weeks) with low dose twice weekly gemcitabine (40mg/m2). Next fifteen patients, as HART Group, received HART (50Gy/40Fr, for 4weeks) with gemicitabine in the same manner. The follow-up period ranged from 10 to 36 months. Results: The median survival of 17 months in the HART group was markedly better than the 10.6 in the conventional group. The average hospitalization of the HART group was 90 days, which was less than 115 days in the conventional group. The average monthly Karnofsky score, 77.1 in the conventional group and 83 in the HART group, had no significant deference between two groups. The incidence of Grade 3 or 4 of hematological adeverse effect was 33% in the conventional group and 44% in the HART group. Appetite loss of more than Grade 2 occurred in 72% of patients in the conventional group and 75% in the HART group. Conclusions: HART concurrent with low dose gemcitabine achieved better survival, shortening of hospitalization and comparable toxicity compared with conventional Method: We considered this regimen was one of the crucial therapy for unresectable pancreatic cancer. No significant financial relationships to disclose.
Radium-223 chloride, a first-in-class alpha-pharmaceutical with a benign safety profile for patients with castration-resistant prostate cancer (CRPC) and bone metastases: Combined analysis of phase I and II clinical trials.
Authors: S. Nilsson, C. Parker, I. Haugen, A. Lokna, A. Aksnes, B. Bolstad, G. O'Bryan-Tear, O. S. Bruland
Journal: Journal of Clinical Oncology (2010)

4678 Background: Radium-223 chloride (Alpharadin) is a first-in-class alpha- pharmaceutical which has a potent and highly targeted antitumor effect on bone metastases. Efficacy, safety and tolerability of this agent were evaluated in a combined analysis of phase I/II trials. Methods: Two open-label phase I trials (37 pts) and three double-blind phase II trials (255 pts) were performed in mainly CRPC pts with bone metastases. Doses of radium-223 varied from 5 to 250 kBq/kg b.w. The trials included assessments of safety (haematology and AEs), efficacy (survival, PSA, b-ALP, pain) and dosimetry. Results: Radium-223 wasrapidly eliminated from blood with uptake into bone metastases and excretion into the small intestine with no hepatobiliary excretion, and minimal activity in kidneys, liver or other internal organs. Among 292 pts <1% experienced CTC grade 4 haematological toxicity, about 4% experienced grade 3 anemia, and <3% grade 3 platelets, neutrophils or WBC. Common AEs seen in all studies were nausea (33%), bone pain (30%), fatigue (26%), diarrhea (26%), vomiting (20%) and constipation (20%). No signs of renal or hepatic toxicity were seen. Bone markers and PSA decreased significantly and pain relief was demonstrated. In the placebo-controlled phase II study (placebo n=31 pts; radium-223 n=33 pts) there were more AEs in the placebo group than in the radium-223 group (174 vs 155), and more serious AEs in the placebo group (19 vs 12). Median overall survival improved in the radium-223 group compared to the placebo group (65 vs 46 wks; p=0.017). Conclusions: Radium-223 has shown a promising survival benefit, a benign safety profile and an improvement in pain in CRPC patients with bone metastases. A randomized phase III survival study is ongoing worldwide. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Algeta ASA Algeta ASA Algeta ASA Algeta ASA
Interferon-γ–Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients
Authors: Jing Zhou, Lingfeng Qin, Tai Yi, Rahmat Ali, Qingle Li, Yang Jiao, Guangxin Li, Zuzana Tobiasova, Yan Huang, Jiasheng Zhang, James J. Yun, Mehran M. Sadeghi, Frank J. Giordano, Jordan S. Pober, George Tellides
Journal: Circulation Research (2015)

Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors.To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients.We established an animal model of graft-exacerbated host CVD by combining murine models of atherosclerosis (apolipoprotein E-deficient recipients on standard diet) and of intra-abdominal graft rejection (heterotopic cardiac transplantation without immunosuppression). CVD was absent in normolipidemic hosts receiving allogeneic grafts and varied in severity among hyperlipidemic grafted hosts according to recipient-donor genetic disparities, most strikingly across an isolated major histocompatibility complex class II antigen barrier. Host disease manifested as increased atherosclerosis of the aorta that also involved the native coronary arteries and new findings of decreased cardiac contractility, ventricular dilatation, and diminished aortic compliance. Exacerbated CVD was accompanied by greater levels of circulating cytokines, especially interferon-γ and other Th1-type cytokines, and showed both systemic and intralesional activation of leukocytes, particularly T-helper cells. Serological neutralization of interferon-γ after allotransplantation prevented graft-related atherosclerosis, cardiomyopathy, and aortic stiffening in the host.Our study reveals that sustained activation of the immune system because of chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients.
춘계학술대회 : 구연 ; 비침습적으로 진단된 간문맥압 항진증이 간세포암종 환자의 간절제술 후 합병증 발생과 3년 생존율에 미치는 영향
Authors: 안민, 박중원, 신정아, 박경우, 최준일, 김태현, 이순애, 김영일, 김성훈, 박홍석, 이우진, 박상재, 홍은경, 김창민
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: 절제 가능한 간세포암종의 경우 간기능이 허락하는 한 수술적 절제술이 우선적 치료술이다. 그러나 간세포암종 환자에 동반되는 간경변과 만성 간질환 등으로 인해 낮은 병기의 작은 간세포암종도 절제를 못하거나, 간절제술 후 간부전증이 일어날 수 있다. 그러므로 간절제술 전에 수술 후 합병증을 예측할 수 있는 Child-Pugh 분류와 indocyanine-green (ICG) 청소율검사, 간정맥압기울기(HVPG) 측정 등이 제시되었다. 우리나라의
A straw man on a dead horse: Studying adaptation then and now
Authors: Marlene Zuk
Journal: Behavioral and Brain Sciences (2002)

Although Gould and Lewontin's (1979) paper stimulated an extraordinary response, the current study of adaptation is – and should be – more than a defense against their criticisms. Adaptations are studied by biologists in new and exciting ways, including experimental manipulations of populations in the field and laboratory, comparative analyses of taxa with known evolutionary relationships, and quantitative genetics. These techniques go beyond ascertaining whether or not a trait is an adaptation.
Intrastage Prognostic Heterogeneity: Implications for Adjuvant Chemotherapy of Breast Cancer&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M M Black, B F Hankey, T H Barclay
Journal: JNCI Journal of the National Cancer Institute (1982)

The precise role of the use of adjuvant chemotherapy in the treatment of primary breast cancer has been questioned by some clinicians. One of the most important questions regarding the use of adjuvant chemotherapy is the identification of appropriate patients to receive it. The presence of positive axillary nodes has been the determining factor for the evaluation of chemotherapy in clinical trials. The possibility that other factors should be considered in deciding on the routine use of chemotherapy is discussed here on the basis of data from breast cancer patients diagnosed in the Province of Saskatchewan, Canada, none of whom received chemotherapy as part of their primary treatment. The data illustrate the prognostic heterogeneity that exists among patients with negative axillary nodes and among patients with positive axillary nodes. The implications of such heterogeneity include the possibilities that some patients may not benefit from adjunctive chemotherapy and that some may actually be harmed by it. Specific procedures are described for the analysis of existing clinical trial data to determine whether there is any evidence that some patients may not have benefited from adjunctive chemotherapy. Additional clinical trials would have to be done to substantiate such observations.
Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin-Induced Cardiac Dysfunction
Authors: Hai Ying Fu, Shoji Sanada, Takashi Matsuzaki, Yulin Liao, Keiji Okuda, Masaki Yamato, Shota Tsuchida, Ryo Araki, Yoshihiro Asano, Hiroshi Asanuma, Masanori Asakura, Brent A. French, Yasushi Sakata, Masafumi Kitakaze, Tetsuo Minamino
Journal: Circulation Research (2016)

Rationale: Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. Objective: We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction. Methods and Results: We confirmed that doxorubicin caused ER dilation in mouse hearts, indicating that doxorubicin may affect ER function. Doxorubicin activated an ER transmembrane stress sensor, activating transcription factor 6, in cultured cardiomyocytes and mouse hearts. However, doxorubicin suppressed the expression of genes downstream of activating transcription factor 6, including X-box binding protein 1. The decreased levels of X-box binding protein 1 resulted in a failure to induce the expression of the ER chaperone glucose-regulated protein 78 which plays a major role in adaptive responses to ER stress. In addition, doxorubicin activated caspase-12, an ER membrane–resident apoptotic molecule, which can lead to cardiomyocyte apoptosis and cardiac dysfunction. Cardiac-specific overexpression of glucose-regulated protein 78 by adeno-associated virus 9 or the administration of the chemical ER chaperone 4-phenylbutyrate attenuated caspase-12 cleavage, and alleviated cardiac apoptosis and dysfunction induced by doxorubicin. Conclusions: Doxorubicin activated the ER stress–initiated apoptotic response without inducing the ER chaperone glucose-regulated protein 78, further augmenting ER stress in mouse hearts. Cardiac-specific overexpression of glucose-regulated protein 78 or the administration of the chemical ER chaperone alleviated the cardiac dysfunction induced by doxorubicin and may facilitate the safe use of doxorubicin for cancer treatment.
Abstract P323: The Effect of Smoking Cessation on Weight at 12 Months in Patients Post-Myocardial Infarction
Authors: Sonia M Grandi, Kristian B Filion, Andre Gervais, Lawrence Joseph, Jennifer O'Loughlin, Gilles Paradis, Louise Pilote, Stephane Rinfret, Mark J Eisenberg
Journal: Circulation (2012)

Background: Current guidelines recommend smoking cessation and weight management for secondary prevention in post-myocardial infarction (MI) patients. However, little is known about the effects of smoking cessation on weight change post-MI. Methods: We examined this question using data from a randomized, double-blind, placebo-controlled trial investigating the effect of bupropion on smoking cessation in patients immediately following a MI. Weight change was compared between 3 groups: patients who reported complete abstinence, those who reported intermittent smoking, and those who reported persistent smoking during the 12-month follow-up. Analyses were restricted to patients who attended all follow-up visits (N=179). Weight was collected by research nurses at follow-up. Abstinence was defined by self-report in the previous 7 days and a carbon monoxide level ≤10 ppm. Results: During follow-up, 92 patients were abstinent, 49 were intermittently smoking, and 38 were consistently smoking. At baseline, 68.7% of patients were male, and the mean age was 53.9 years (SD 10.0). The mean weight and BMI at baseline were 78.4 kg (SD 17.7) and 27.3 kg/m 2 (SD 5.0), respectively. Mean body weight increased in all 3 groups during follow-up ( Figure ). However, patients who remained abstinent were more likely to gain weight than those who smoked persistently (difference 3.3 kg, 95% CI 0.9, 5.6). No difference in weight change was present between persistent and intermittent smokers. Both intermittent and persistent smokers reduced their daily cigarette consumption between baseline and 12-month follow-up (mean difference −15.5, 95% CI −19.1, −11.9 and −15.8, 95% CI, −19.9, −11.7, respectively). Conclusions: Patients who remain abstinent are more likely to gain weight 12 months post-MI. Given the importance of weight management in this population, strategies to ensure long-term weight control among patients who quit smoking are needed.