tbuckley/cabot-search huggingface dataset:
Variation in local treatment of prostate cancer by hospital within New Jersey
Authors: T. R. Blom, R. A. Somer, W. Shih, M. Sarno, D. McNally, M. Todd, S. Yao, G. Lu-Yao, R. Dipaola, M. N. Stein
Journal: Journal of Clinical Oncology (2006)

14551 Background: Although prostate cancer diagnosis and treatment vary through the US, few studies have assessed variations in local therapy between multiple hospitals located within a very narrow geographic region. Methods: To determine the variation of diagnosis and treatment of prostate cancer between hospitals in a local region, data was derived and analyzed from 1,301 patients from fifteen Cancer Institute of New Jersey Oncology Group network hospitals. Tumor registry data from patients with a histological confirmed diagnosis of prostate cancer accessioned over a one-year period between January 1, 2003 and December 31, 2003 was analyzed by a multivariate logistic regression model. Results: Median age of the cohort was 66 and mean number of cases diagnosed at these hospitals for this period was 87 (26–161). When the cohort was assessed overall, 192 cases assessed were African American, 1049 Caucasian, 51 Hispanic, and 32 Asian. Median Gleason score was 6. A total of 463 patients underwent Prostatectomy, and 538 had radiation therapy. Multivariate analysis demonstrated that age and hospital were associated with use of surgery versus no surgery. Race and Gleason score were not associated with use of surgery in this group of hospitals. Multivariate analysis also demonstrated that age and hospital were associated with utilizing radiation therapy versus not utilizing radiation therapy. Again, race and Gleason score were not associated with utilization of radiation therapy in these NJ hospitals. Conclusions: Overall, the most important factors predicting for surgery, and radiation therapy, were age and hospital, which were independent of race and Gleason score. These data support our ongoing assessment of hospital and geographic characteristics that may be responsible for these associations. No significant financial relationships to disclose.
Paclitaxel, carboplatin, and gemcitabine (PCG) versus gemcitabine and vinorelbine (GV) in chemotherapy naïve patients (pts) with advanced non-small cell lung cancer (NSCLC): A phase III trial of the Minnie Pearl Cancer Research Network (MPCRN)
Authors: M. E. Kuzur, D. L. Shipley, D. R. Spigel, J. R. Gray, D. S. Thompson, J. D. Hainsworth, J. E. Bradof, C. D. Webb, J. G. Gandhi, A. Beschorner, F. A. Greco
Journal: Journal of Clinical Oncology (2005)

7056 Background: The MPCRN phase III trial comparing the triplet PCG to the non-platinum doublet GV has been completed for pts with advanced NSCLC. Initially, a four-arm randomized trial was done and PCG and GV were associated with the best median survivals (Cancer 2002; 95:1279–85). GV was significantly less toxic than PCG, providing the rationale for extending the randomized comparison of PCG to GV as a phase III trial. Methods: The primary objective of this randomized phase III study was to compare survival of previously untreated pts with advanced NSCLC treated with PCG versus GV. PCG treatment consisted of P 200mg/m2 IV D1, C (AUC=5) IV D1, G 1000mg/m2 IV D1,8 q 21D. GV treatment was G 1000mg/m2 IV D1,8,15 q 28D and V 25mg/m2 IV D1,8,15 q 28D. Pts were re-evaluated q 2 cycles. Pts without evidence of progression or undue toxicity received a maximum of 6 cycles. Eligibility criteria included: stage IIIB/IV NSCLC, no prior chemotherapy, measurable disease, ECOG PS 0–2, adequate organ function, absence of brain metastases, and informed consent. Study was powered (0.80) to demonstrate an increase in expected 1-year survival from 30% with GV to 45% for PCG, requiring a total of 174 pts on each arm. P-values reported are two sided. Results: 349 pts were enrolled. Baseline pt characteristics were similar in the two groups. Objective response rates were similar for both regimens (PCG 25%; GV 26%). There was less grade 3/4 neutropenia, thrombocytopenia, anemia, alopecia, nausea/vomiting, myalgia/arthralgia and neuropathy (grade 2/3/4) with GV. One-year progression-free survival (PFS) and survival for PCG versus GV were 12% versus 15% (p=NS), and 39% versus 43% ((p=NS), respectively. Conclusions: In the first-line treatment of advanced NSCLC, PCG and GV are equivalent in terms of PFS and survival. Doublet non-platinum therapy with GV is associated with much less toxicity. Further study of GV in early stage NSCLC is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Wilms' Tumor Gene (WT1) Competes With Differentiation-Inducing Signal in Hematopoietic Progenitor Cells
Authors: Kazushi Inoue, Hiroya Tamaki, Hiroyasu Ogawa, Yoshihiro Oka, Toshihiro Soma, Toyoshi Tatekawa, Yusuke Oji, Akihiro Tsuboi, Eui Ho Kim, Manabu Kawakami, Tetsu Akiyama, Tadamitsu Kishimoto, Haruo Sugiyama
Journal: Blood (1998)
Abstract 11870: Development of a Novel Vaccine Against Dipeptidyl Peptidase-4 in Mice
Authors: Zhengda Pang
Journal: Circulation (2014)

Instruction and Hypothesis: The increasing prevalence of type 2 diabetes mellitus (T2DM) is associated with a significant economic burden. We developed and assessed a novel dipeptidyl peptidase-4 (DPP4)-targeted immune therapy to increase glucagon like peptide 1 (GLP-1) hormone levels and improves insulin sensitivity for the prevention and treatment of T2DM.

Methods and Results: We selected 3 suitable regions in DPP4 as candidate targets for a vaccine and conjugated these peptides with keyhole limpet hemocyanin (KLH), which presents a variety of T cell epitopes to induce helper T cell responses. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased the DPP4 titer, inhibited the plasma DPP4 activity, and induced an increase in the plasma GLP-1 level. Moreover, this elevated titer was sustained for 3 months. We then assessed the efficacy of this vaccine in 2 animal models: high fat diet (HFD)-fed C57BL6/J mice and the diabetic kkAy and db/db mouse strains, which are commonly used as rodent models of insulin resistance and early onset T2DM, respectively. In mice fed a high fat diet (HFD), DPP4 vaccination resulted in improved postprandial glucose excursions, insulin sensitivity, and in the diabetic kkAy and db/db mice strains, DPP4 vaccination significantly reduced glucose excursions and increased both the plasma insulin and pancreatic insulin content. Importantly, T cells were not activated following challenge with DPP4 itself, which suggests that this vaccine does not induce cell mediated autoimmunity. Additionally, no significant immune mediated damage was detected in cells and tissues where DPP4 is expressed.

Conclusion: The DPP4 vaccine markedly improved insulin resistance and delayed the development of T2DM by increasing GLP-1 secretion without eliciting an autoimmune response. Thus, the DPP4 vaccine could provide an affordable and effective alternative for T2DM treatment.
Comparison of the association with sleep apnoea of obesity<i>versus</i>insulin resistance
Authors: Alice Liu, Danit Ariel, Cindy Lamendola, Sun H. Kim, Fahim Abbasi, James Cardell, Vanessa Tomasso, Hafasa Mojaddidi, Kaylene Grove, Clete A. Kushida, Gerald M. Reaven
Journal: European Respiratory Journal (2015)

Obesity is considered to be both a risk factor for the development of obstructive sleep apnoea (OSA), and a contributor to the abnormal sleep patterns that characterise this syndrome [1]. Obesity is also associated with insulin resistance [2]. These two phenomena may be unrelated, and represent two untoward effects of excess adiposity. However, the situation is complicated given the apparent association between OSA and insulin resistance [3]. The current study represents an effort to clarify the complex relationships among obesity, OSA, and insulin resistance by defining the extent to which the physiological abnormalities in OSA are independently associated with obesity as compared to insulin resistance. Therefore, we evaluated the relationships of adiposity and insulin-mediated glucose uptake with sleep measurements pertaining to OSA, among overweight/obese men with untreated OSA, without other major comorbidities. Sleep apnoea severity in overweight men may be more closely related to insulin resistance than degree of obesity <http://ow.ly/S1LC5>
In Vivo Selection of Androgen-Insensitive Cells in R3327-G Rat Prostate Tumors: Diethylstilbestrol Diphosphate Treatment Versus Orchiectomy<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: A Pollack, N L Block, B J Stover, G L Irvin, M P Fuentes, A J Claflin, T I Malinin
Journal: JNCI Journal of the National Cancer Institute (1983)

Tumors grown in diethylstilbestrol diphosphate (DES)-treated rats grew significantly more slowly than tumors grown in orchiectomized animals, and tumors grown in orchiectomized animals grew significantly more slowly than tumors grown in controls (intact male rats). When these tumors (phase I) were dispersed and reimplanted into DES-treated, orchiectomized, or control rats in all possible combinations (phase II), a partial selection of androgen-insensitive cells was observed in tumors grown in DES-treated animals. Tumors grown in DES-treated phase I animals responded significantly less to DES treatment or orchiectomy in phase II. In contrast, tumors from phase I orchiectomized animals showed the same responses to orchiectomy in phase II. Since the administration of exogenous testosterone propionate prevented the growth rate inhibitory effects of both DES treatment and orchiectomy, the added effect of DES seemed to be antiandrogenic.
Systemic to pulmonary vascular malformation
Authors: HM Pouwels, BK Janevski, OC Penn, HT Sie, GP ten Velde
Journal: European Respiratory Journal (1992)

A case is reported of life-threatening haemoptysis as a result of an anomalous communication between a bronchial artery and pulmonary vein, demonstrated by angiography. The patient recovered following bilobectomy of the right lower and middle lobes. When a systemic artery is involved in an arteriovenous malformation of the lung, haemodynamics are different compared with those present in malformations fed by the pulmonary artery. This implicates other clinical features, options for surgical intervention and prognosis. In reviewing the literature, a relationship with Rendu-Osler-Weber disease is absent in these specific malformations.
Feasibility Study of a Gemcitabine Combined Regimen in Heavily Pre-Treated Patients with Non-Hodgkin Lymphomas
Authors: Harumi Kato, Kazuhito Yamamoto, Yoshitoyo Kagami, Satsuki Murakami, Daiki Hirano, Hirofumi Taji, Yasuo Morishima, Tomohiro Kinoshita
Journal: Annals of Oncology (2014)
Neo-adjuvant chemotherapy for limb preservation in non-metastatic osteosarcoma of the extremity: AIIMS experience
Authors: M. Malik, P. K. Julka, S. Rastogi, G. K. Rath
Journal: Journal of Clinical Oncology (2005)

9056 Background: Osteosarcoma is the most common primary malignant neoplasm of bone in children and adolescents. The purpose of this study was to determine the optimal therapy and feasibility of limb salvage in patients with localized non metastatic osteosarcoma. Methods: In a prospective single arm study between January 1999 to July 2004 newly diagnosed patients presenting with localized osteosarcoma of the extremity received 3 cycles of neoadjuvant chemotherapy with CAMP i.e. cyclophosphamide (700mg/m2 IV day1), adriamycin (50mg/m2 IV day1), cisplatin (100mg/m2 over 3 days) and methotrexate (175mg/m2 IV day1) with leucovorin rescue followed by definitive surgery. Adjuvant therapy consisted of 3 cycles with CAMP in good responders (>/=90%necrosis) whereas poor responders received ifosfamide, etoposide and cisplatin. Endpoints studied were response to chemotherapy, rate of limb salvage and treatment toxicity. Survival was obtained using Kaplan-Mier estimates. Results: 65 patients were available for analysis. The median age was 18 years (range 9–36 years). Cortical destruction and soft tissue extension of tumor was present in all cases. 35 patients (54%) underwent limb salvage surgery whereas 30 (46%) required amputation. Post surgical margins were positive in 2 cases and the degree of necrosis was >/=90% in 27(42%) cases. The incidence of grade 3 and 4 hematological toxicity was 38% and 9% respectively. Grade 2 GI toxicity was observed in 75% cases. There was no treatment related mortality. 24 patients relapsed, 3 at both local and distant sites and 21 with distant metastasis in the lungs. The 5-year overall and disease free survival were 72% and 63% respectively. The most significant prognostic factors that emerged were the response to neoadjuvant chemotherapy (p=0.003) and the post surgical margin status (p<0.01). Conclusions: Osteosarcoma continues to be a challenge in developing countries with many patients presenting in advanced stages and being unable to afford expensive treatment. Never the less our experience has shown that they can be effectively treated with neoadjuvant and adjuvant chemotherapy with limb sparing surgery. No significant financial relationships to disclose.
Aprepitant as salvage antiemetic therapy in breast cancer patients receiving doxorubicin and cyclophosphamide (AC)
Authors: P. J. Hesketh, J. Younger, R. Sanjay, B. Trainor, P. Sanz-Altamira, M. Krentzin, M. Hayden, A. M. Hesketh
Journal: Journal of Clinical Oncology (2006)

8618 Background: Aprepitant (APR), a neurokinin-1 receptor antagonist, has efficacy in the prevention of nausea and vomiting (NV) in breast cancer (BC) patients (pts) receiving doxorubicin (A) and cyclophosphamide (C) (JCO 2005, 23:2822). Nevertheless, many pts continue to receive only 5-hydroxytryptamine antagonists and dexamethasone (doublet therapy) during cycle 1 of AC. APR is often used as a salvage treatment, with anecdotal reports of improved outcome. We sought to prospectively evaluate this issue in a phase II trial. Methods: Design: multicenter study funded by an unrestricted grant from Merck. Eligibility: BC pts receiving their first cycle of A (≤ 60 mg/m 2 ) and C (≥ 500 mg/m 2 ) on day (d) 1. Antiemetics: ondansetron 8mg IV/PO, or dolasetron 100 mg IV/PO, or granisetron 1 mg IV or 2 mg PO on d 1; and dexamethasone (dex) 8–10 mg IV/PO d 1 and 4 mg PO bid d 2–3. Pts without complete control (no emesis, nausea, or rescue antiemetics) during cycle 1 could continue to cycle 2.During cycle 2, pts again received AC and identical antiemetics (except dex only 4 mg qd d 2–3) plus APR 125 mg PO d 1 and 80 mg PO d 2–3. Data on nausea (4-point scale), emesis and rescue was collected with a pt-report diary. Primary end point: proportion of pts with complete control (CC) during the 120-hours after chemotherapy. Secondary endpoints included acute (&lt; 24 hrs), delayed (24–120 hrs) CC and complete response (no emesis or rescue) Results: Pts: total (47), female (47), eligible (46), analyzed (42), still on study (4). Median age: 49 yrs. CC during cycle 1: 8 pts (19%). Thirty-four pts continued to cycle 2. During cycle 2, 7 pts (21%)(95% CI 9–38%) achieved CC and 13 pts (38 %) complete response (CR) for the 120-hour study period. Acute CR and delayed CR rates for cycles 1 and 2 were 32%(11 pts) vs 68% (23 pts) (p=0.01) and 12%(4 pts) vs 44% (15 pts) (p=0.02) respectively. No emesis rates were 38 vs 79 % during cycles 1 and 2 respectively(p=0.02). The proportion of pts with no nausea or severe nausea for cycles 1 and 2 were 0 vs 21% and 12 vs 3 % respectively. Conclusions: The addition of APR to standard doublet therapy improves antiemetic outcome in BC pts receiving AC who failed to achieve CC during cycle 1 with standard doublet therapy alone. Improvement is seen in the control of emesis and nausea. APR was well tolerated. [Table: see text]
Tumor-penetrating drug delivery for cancer therapy.
Authors: K. N. Sugahara, T. Teesalu, P. P. Karmali, V. R. Kotamraju, L. Agemy, A. M. Lowy, E. Ruoslahti
Journal: Journal of Clinical Oncology (2010)

e13590 Background: Poor drug penetration is a major problem in cancer treatment that leads to ineffective therapy and drug resistance. We have discovered a tumor-specific tissue penetration system that solves this problem. It is based on a tumor-penetrating peptide, iRGD (amino acid sequence: CRGDK/RGPDC), which carries an attached payload specifically to tumors, and subsequently, deep into tumor parenchyma. Two overlapping peptide motifs account for this activity: RGD, which mediates binding to alpha-v integrins on tumor vessels, and RXXR/K (the CendR element), which induces tissue penetration through binding to neuropilin-1. We will report clinical applications of the iRGD tumor targeting system. Methods: Whole body tumor imaging and systemic treatment studies were performed in a panel of mouse xenograft tumors. The applicability of the system to human cancer was evaluated in ex vivo tumor penetrating assays using freshly excised human appediceal tumor samples according to an IRB-approved protocol. Results: iRGD significantly improved the contrast of tumor imaging agents and enhanced the activity of anticancer drugs in mice. Incubating fresh human appendiceal tumors in culture media containing the iRGD peptide or iRGD-coated phage allowed the compounds to penetrate into the tumor tissue up to about 4 mm in 90 min. Conclusions: The tumor homing iRGD peptide penetrates human tumors as well as mouse tumors. The penetration occurs even in the absence of circulation by initiating an active transport pathway. The technology can be used to enhance both systemic and local delivery of drugs into tumor tissue. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ACT, CTI VSB Invitrogen, NCI ICMIC
Abstract 143: An Assessment of Who Dies After Cardiac Arrest in the Era of Therapeutic Hypothermia
Authors: Katherine Zanyk McLean, Julie VanRaemdonck, Diane Capoccia, Carman Turkelson, William Devlin, Robert Swor, Kelly N Sawyer
Journal: Circulation (2014)

Introduction: Much emphasis is placed on who survives after cardiac arrest and how to optimize “good” outcomes. Despite this stress on aggressive post-arrest care and early temperature management, many people still die after admission to the hospital, often with care being withdrawn. The purpose of this study was to assess how and when patients die after undergoing in-hospital post-arrest therapeutic hypothermia (TH). Methods: This was a retrospective chart review of adult patients suffering non-traumatic cardiac arrest who had post-arrest care, including TH, initiated between January 2010 and June 2013 in a large, community academic center. All patients followed the same treatment protocol, with TH induced as soon as possible after arrest, regardless of initial rhythm or arrest location. Demographics, Utstein characteristics, and post-arrest variables, including time to withdrawal of care were collected until death or hospital discharge as part of an on-going quality improvement database. Descriptive statistics and associations are presented. Results: During the study period, 139 patients were included and 92 (66.2%) died prior to discharge (mean age 61.9 (SD 16.31) years, 88 (63.3%) male). Few (12, 13.0%) of these had early termination of the TH protocol or died (8, 10.0%) while intubated. Overall, 72 (78.3%) patients had care withdrawn. The median time from return of spontaneous circulation (ROSC) to withdrawal of care was 96.6 hours (IQR 66.2, 164.1) and 18 (27.3%) patients had care withdrawn &lt;72 hours from ROSC. All patients were referred to the Gift of Life service but only 9 (12.5%) contributed to organ donation. A minority of patients (20, 27.8%) received a formal palliative care consult. Factors associated with withdrawal of care included family wishes, older age, initial non-shockable arrest rhythm, and longer time from arrest to ROSC. Conclusion: More than 75% of this cohort had care withdrawn. Although the majority had care withdrawn more than 72 hours after ROSC, early withdrawal of care was not uncommon. Further study of this group of patients is needed to understand the relationships between pre-arrest predictors of poor prognosis, pre-existing co-morbidities, patient clinical status, and family wishes on the early withdraw of care.
Course features of COPD in women and men
Authors: Mykola Ostrovskyy, Oleksandr Varunkiv, Iryna Savelikhina, Mariana Kulynych-Miskiv
Journal: European Respiratory Journal (2012)

Background. COPD is a leader among the present problems in Pulmonology. Epidemiological data indicate a greater prevalence of this nosology among men. Prevalence of COPD in the world among men is 9.3%, and among women - 7.3%. Given that COPD - a disease mainly of the second half of life, it should be noted that at this period women are characterized by a extinguishing of steroidogenesis function. This factor may be one of those that aggravating the course COPD in women.  Aim: To study the severity of breathlessness on a MMRC scale in women and men with newly diagnosed 2nd stage of COPD.  Materials and methods: The main inclusion criteria were: 1) age of patients ≥ 40 years; 2) Experience smoking ≥ 10 pack / years 3) FEV1 after salbutamol 50% ≤ FEV1 ≤ 70%, FEV1/FVC ≤ 0,7; 4) No other clinically significant disease. There were surveyed 57 patients (including 22 women and 35 men) with newly diagnosed 2nd stage of COPD who were treated at pulmonology department of Ivano-Frankivsk regional center of phthisiology and pulmonology. The average age of women was (58,5 ± 2,8 years) and men - (54,7 ± 3,1 years).  Results. The level of FEV1 on average was 61,2 ± 4,2% in women, and - 58,4 ± 3,9% (p> 0.05) in men. Index of breathlessness on a MMRC scale in women was 3,6 ± 0,4, and 2,9 ± 0,4 - in men. Thus, exploring the clinical course of 2nd stage of COPD among women and men aged 50 to 60 years, we can say that, despite the almost identical clinical manifestations of disease, there is a greater severity of breathlessness on a MMRC scale in women as in men.  Conclusion: The clinical course of COPD in women compared with men characterized with more severe shortness of breath on a MMRC scale with less ventilation violations, according to spirometry.
Abstract 13618: Negative Association of H558r Polymorphism and Ventricular Fibrillation in Patients With Brugada Syndrome
Authors: Hiroya Matsumura, Yukiko Nakano, Masaaki Toshishige, Hidenori Ochi, Takehito Tokuyama, Yoshikazu Watanabe, Hiroshi Kawazoe, Shunsuke Tomomori, Sinji Kishimoto, Kazuaki Chayama, Yasuki Kihara
Journal: Circulation (2014)

BACKGROUND: The common SCN5A polymorphism H558R has been reported as a genetic modulator that improves sodium channel activity in mutated channels by repairing abnormal channel gating kinetics and membrane trafficking. We investigated the possible effects of H558R on the clinical manifestations of Brugada syndrome. METHODS: The study population comprised 95 Brugada syndrome patients (mean age 42 ± 14 years, 91 males and 4 females) and 1,875 normal controls. H558R was genotyped by TaqMan assay in all subjects. The SCN5A gene mutation was screened by resequencing. We evaluated the PR, QRS, and QTc intervals from lead II and the J-point amplitude from leads V1 and V2 of a 12-lead electrocardiogram (ECG). We also evaluated signal-averaged ECG and electrophysiological parameters. RESULTS: H558R was less frequent in patients with Brugada syndrome than normal controls (4.7% vs. 10.3%, P = 0.01). Surprisingly, H558R (minor allele A) was not observed in patients with Brugada syndrome without ventricular fibrillation (VF; n = 60), whereas 7.5% of patients with VF had H558R (n = 35). Nonsynonymous mutation of SCN5A was not detected in patients with H558R. The H558R carriers showed lower J-point elevation in lead V1 than noncarriers (1.8 ± 0.4 vs. 3.3 ± 0.3 mV, P = 0.04). Other parameters in the 12-lead and signal-averaged ECG were similar in patients with and without H558R. CONCLUSION: We demonstrated that the H558R polymorphism was a strong protective genetic modulator even in Brugada syndrome patients without SCN5A mutation.