tbuckley/cabot-search huggingface dataset:
Primary intermittent chemo-hormonal therapy (CHT) for high risk locally advanced (LAPC) or metastatic prostate cancer (MPC): Preliminary results and quality of life (QOL)
Authors: S. Tucker, R. Leibowitz
Journal: Journal of Clinical Oncology (2005)

4734 Background: Reports of intermittent androgen deprivation (IAD) for PC show equivalence and potential superiority to continuous AD. Failure of IAD results in androgen independent PC (AIPC) for which docetaxel (D) is standard. Given the volume of systemic disease and occult AIPC cells in MPC we have augmented AD with D chemotherapy since 1997 in LAPC and MPC. We report long-term results using a single cycle of CHT for LAPC and MPC. Methods: We have prospectively treated 41 men with PC with CHT. CHT consisted of Triple Androgen Blockade (an LH-RH agonist and antiandrogen or adrenolytic and finasteride 5 MG QD) plus weekly D based chemotherapy. Finasteride 5 MG QD maintenance (FM) was continued in all men when CHT was completed. D was dosed at 25 mg/M2 days 1, 8, and 15 of a 28 day cycle for 4–5 cycles. Estramustine was given as 280 MG TID day of D and day after only. Carboplatin 200 mg weekly was given to 65% of patients. Follow-up QOL has been measured with a validated symptom-based scale for pen-based computers. Results: Median age was 64, mean baseline PSA (bPSA) was 262 ng/mL (range 1–5606); median PSA was 23 ng/mL. Median Gleason score (GS) was 9 (range 6–10). Mean baseline testosterone (T) was 436 ng/dL. Median duration of CHT was 12.6 months. A mean of 13.7 doses of weekly chemotherapy was given. At a median follow-up of 42 months (range 11–76) mean PSA is 11.5 ng/mL. Mean current T is 398 ng/dl. A second cycle of CHT has been initiated in 10/41 men (8 of whom presented with MPC). 3 men with MPC have died from AIPC. Disease specific survival is 92.6%. Detailed QOL data will be presented in full. Conclusions: A single 13 month cycle of CHT provides excellent long-term control and management of poor prognosis LAPC and MPC. D based CHT should be explored further for men with newly diagnosed LAPC or MPC and compared with AD alone. Measurement of time to androgen independence is the appropriate surrogate to measure in this setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Novartis Novartis Self
Artemisinin anti-malarial drugs in China
Authors: Zongru Guo
Journal: Acta Pharmaceutica Sinica B (2016)

Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the "whole nation" system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements.
Abstract 13134: Prevalence of Abnormal Coronary Microcirculatory Resistance Among Patient With Ischemia and Non-Obstructive CAD
Authors: Bina Ahmed, Mark W Sheldon, Mark J Ricciardi
Journal: Circulation (2013)

Background: Registry data indicates that 10-30% of patients undergoing coronary angiography for objective evidence of myocardial ischemia have non-obstructive epicardial CAD. Some patients among th...
Mice Bearing a Targeted Interruption of the Homeobox Gene HOXA9 Have Defects in Myeloid, Erythroid, and Lymphoid Hematopoiesis
Authors: H. Jeffrey Lawrence, Cheryl D. Helgason, Guy Sauvageau, Stephen Fong, David J. Izon, R. Keith Humphries, Corey Largman
Journal: Blood (1997)
Chronic daily administration of oral etoposide--a phase I trial.
Authors: J D Hainsworth, D H Johnson, S R Frazier, F A Greco
Journal: Journal of Clinical Oncology (1989)

In this phase I study, we administered etoposide (VP-16) orally for 21 consecutive days to patients with advanced refractory cancers. All patients had received previous chemotherapy, and 50% of patients had received more than one combination regimen. When given for 21 consecutive days, the maximum-tolerated dose of oral VP-16 was 50 mg/m2/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 21 and 28. In most patients, blood counts had recovered sufficiently by day 35 to begin another 3-week course. WBC count nadirs of less than 1,000/microL occurred in four of 20 courses at this dose, and three patients required hospitalization for treatment of neutropenia and fever. Alopecia occurred in most patients; gastrointestinal (GI) and other toxicities were uncommon. Five of 16 patients with measurable tumor had partial responses of 3 to 4 months duration. Four of these five patients had malignancies that are usually unresponsive to VP-16 when administered by previously investigated schedules. This method of VP-16 administration is well tolerated, convenient, and may optimize antitumor efficacy by exploiting the schedule dependency of this drug. Phase II studies are necessary to define the level of activity of this schedule of VP-16.
Abstract P425: Associations between Physical Activity, Cardiorespiratory Fitness, Abdominal Obesity and Cardiometabolic Risk in Obese Women
Authors: John Clarke, Einat Shalev-Goldman, Ashlee McGuire, Robert Ross
Journal: Circulation (2013)

The independent associations between abdominal obesity, cardiorespiratory fitness (CRF), physical activity (PA) and cardiometabolic risk factors in obese women is unclear. We studied 165 sedentary, abdominally obese women (waist circumference 106.4 ± 10.2 cm, age 51.0 ± 7.8y). Objective measures of PA volume and intensity were obtained by accelerometry and CRF by a maximal treadmill test. Plasma glucose and serum insulin were obtained during a 2-hour glucose tolerance test. The homeostasis model of assessment (HOMA-IR) was used to estimate insulin resistance. Fasting levels for triglycerides, total cholesterol, and high-density lipoproteins were also obtained. Systolic and diastolic blood pressure was measured using the BP True method. With few exceptions PA variables alone were not associated with any cardiometabolic risk factors. WC was associated with all cardiometabolic risk factors except DBP, 1 and 2-hour glucose (p≤0.05). CRF alone was associated with SBP, fasting insulin, and HOMA-IR (p≤0.05). Multivariate analysis revealed associations between WC and HOMA-IR (r2=0.24, p&lt;0.001), fasting insulin (r2=0.25, p&lt;0.001), fasting glucose (r2=0.03, p&lt;0.05), TG (r2=0.05, p&lt;0.05), and HDL (r2=0.06, p&lt;0.05) following adjustment for PA, and CRF. CRF, PA intensity and PA volume were not associated with cardiometabolic risk factors following control for each other and WC. In this study of sedentary, abdominally obese women objective measures of PA intensity and volume were not associated with cardiometabolic risk factors independent of WC and CRF. WC was associated with most of the cardiometabolic risk factors independent of PA and CRF; however, the associations with measures of insulin metabolism were modest whereas the associations with lipid variables and blood pressure were weak.
A prospective study: Hypodermoclysis performed by caregivers in the home setting.
Authors: Marieberta Vidal, David Hui, Janet L. Williams, Gary B. Chisholm, Julio Allo, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

128 Background: Decreased oral intake is very common at the end of life. Dehydration can aggravate symptoms like fatigue, myoclonus, and confusion. Intravenous (iv) hydration at home can be uncomfortable and expensive. Hypodermoclysis (HDC) is a comfortable and inexpensive but rarely used way to provide hydration at the end of life in the home setting. The purpose of this study was to evaluate a program of HDC at home by the caregivers. Methods: All caregivers underwent a 45 minute training session on HDC administration and assessment of infusion site delivered by a specially trained nurse. Caregivers received daily calls and on site evaluation on day 8. Results: A total of 21 patient/caregivers dyads were admitted to this preliminary study: 10 (47%) female patients and 16 (76%) female caregivers. All patients had advanced cancer receiving hospice care at home. All caregivers who received training were able to start the infusion. Side effects were minimal with 1 (5%) care of the needle difficulty and leakage. Conclusions: This preliminary study suggests that subcutaneous hydration can be administered by caregivers at home with minimal burden. It can be easily done by just gravity or weight. It will avoid the use of expensive iv pump devices or need of special technical support. [Table: see text]
Abstract 002: Blinded Head-to-Head Comparison of Intracoronary Allogeneic Cardiosphere-Derived Cells (icCDCs) Versus Allogeneic Mesenchymal Stem Cells (icMSCs) in Swine with Hibernating Myocardium
Authors: Brian R Weil, Gen Suzuki, Merced M Leiker, James A Fallavollita, John M Canty
Journal: Circulation Research (2013)

Background: Autologous icCDCs and icMSCs each improve myocardial function by stimulating endogenous myocyte proliferation. Since few myocytes arise directly from the injected cells, we evaluated the feasibility and comparative efficacy of allogeneic icCDCs vs. icMSCs. Methods: Studies were conducted in a blinded fashion. Immunosuppressed swine (cyclosporine 200 mg/day, N=26) with hibernating myocardium from a chronic LAD stenosis were randomized to receive vehicle, ~35 x 10 6 icMSCs, or ~35 x 10 6 icCDCs. Cells were infused into the 3 major coronary arteries at ~10 6 cells/min under continuous flow conditions. LAD function and pathologic indices of myocyte regeneration and proliferation were assessed 1 month later. Results: Baseline LAD wall thickening (%WT) was reduced in all animals (LAD 38 ± 2% vs. 83 ± 5% in remote, p&lt;0.01) but not different between treatment groups. One month later, LAD %WT remained depressed in vehicle-treated animals but increased to a similar extent following icCDCs and icMSCs (Table). Intracoronary cell therapy also produced large reciprocal increases in nuclear density and reductions in myocyte size with no differences between cell types. Indices of myocyte proliferation (Ki67 and phospho-Histone H3) remained elevated following icCDC treatment but had returned towards control in icMSC-treated animals. Conclusion: Our data demonstrate the feasibility of intracoronary allogeneic icCDC and icMSC infusion to treat viable dysfunctional myocardium without employing the “stop-flow” technique. Both cell types produce an equivalent increase in myocyte number and LAD function after 4-weeks but proliferative indices remain elevated after icCDCs.
Hepatitis C virus-induced hepatocellular carcinoma
Authors: Nicolas Goossens, Yujin Hoshida
Journal: Clinical and Molecular Hepatology (2015)

Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs. Keywords: Carcinogenesis; Hepatitis C; Hepatocellular carcinoma; Prevention
Abstract 115: Video Review and Time-Motion Analysis of the Causes of No-Flow Intervals as Recorded by Accelerometer During Cardiopulmonary Resuscitation
Authors: Yi-Chia Lee, Huang-Fu Yeh, Yen-Pin Chen, Chun-Yi Chang, Wei-Ting Chen, Eric Hao-Chang Chou, Kah-Meng Chong, Hui-Chih Wang, Anna Marie Chang, Patrick Chow-In Ko, Wen-Chu Chiang, Matthew Huei-Ming Ma
Journal: Circulation (2014)

Objectives: Accelerometer (Q-CPR) has been developed and promoted to monitor the quality of cardiopulmonary resuscitation (CPR). Although the device registers the occurrence of no-flow intervals, it does not provide comprehensive information on the causes leading to these no-flow intervals. This study is aimed to analyze causes leading to CPR interruptions registered by Q-CPR by reviewing corresponding video recordings of the resuscitation sessions. Methods: Accelerometer recordings (Q-CPR, Philips) of 20 CPR episodes from December 2010 to April 2014 in a tertiary university ED were obtained. Frequency, timing, duration, and types of no-flow intervals, defined as no-flow duration &gt;= 1.5 seconds, were reviewed. Video recordings of the corresponding CPR sessions were reviewed. Causes leading no flow intervals registered by Q-CPR were categorized and analyzed. Results: The duration of CPR reviewed for the cases averaged 8.59 minutes (range 2.23 - 19.04 minutes). No-flow intervals (pauses &gt;= 1.5 seconds) occurred 122 times (averaged one interruption every 1.27 minutes of CPR) with an average no-flow intervals of 6.45 seconds (range 1.54 - 51.50 seconds). Through detail review of the video-recordings corresponding to the no-flow intervals registered by Q-CPR, the leading causes of no-flow intervals are associated with pulse checks for pulseless electric activity- PEA (19.5%), pre-shock pauses (13.9%), ultrasound exam (11.6%) and intubation (9.6%), as displayed in the following chart. Conclusion: Video recording and time-motion analysis provide detailed information on the causes leading to no-flow intervals registered by QCPR, and could complement information acquired by Q-CPR. Measures should be taken to address leading causes of CPR interruption, especially pulse checks for PEA and pre-shock pauses, to promote quality of CPR.
Bile Diversion in Roux-en-Y Gastric Bypass Modulates Sodium-Dependent Glucose Intestinal Uptake
Authors: Gregory Baud, Mehdi Daoudi, Thomas Hubert, Violeta Raverdy, Marie Pigeyre, Erik Hervieux, Magalie Devienne, Mohamed Ghunaim, Caroline Bonner, Audrey Quenon, Pascal Pigny, André Klein, Julie Kerr-Conte, Valery Gmyr, Robert Caiazzo, François Pattou
Journal: Cell Metabolism (2016)
Grafted-Marrow-Rejection Mortality Contrasted to Homologous Disease in Irradiated Mice Receiving Homologous Bone Marrow&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: J. J. Trentin
Journal: JNCI Journal of the National Cancer Institute (1959)

Bone marrow from the BALB/c and CBA inbred strains of mice and the (BALB/c × CBA)F1 hybrid strain was injected isologously and in various homologous combinations into CBA and (BALB/c × CBA)F1 hybrid mice irradiated with 330 r, 550 r, or 770 r (LD0, 12, and 100 respectively. At the sublethal dose of 330 r, no mortality resulted from any combination of marrow donor and recipient. At the higher doses, two types of mortality were observed in mice receiving bone marrow; (a) “early mortality” (5 to 21 days) after the ordinarily high sublethal dose of 550 r and (b) “delayed mortality” (21 to 60 days) following good, early protection against the otherwise lethal dose of 770 r. Neither type of mortality occurred after administration of isologous marrow, but both types occurred after administration of marrow from an unrelated homologous strain. When F1 marrow was transferred into the parental strain (in which circumstance only the recipient strain is capable of immunologic reaction against the donor, but not vice versa) only “early mortality” was observed. When parental marrow was transferred into the F1 hybrid (in which circumstance only the donor strain is capable of immunologic reaction against the recipient, but not vice versa) only “delayed mortality” was observed. From these observations and other considerations it is concluded that the early mortality, resulting from administration of homologous or heterologous marrow into mice irradiated in the high sublethal or midlethal dose range, is the result of the recovered ability of the host to reject the temporarily grafted marrow, whereas the delayed mortality, following good, early protection against otherwise lethal doses of irradiation with homologous or heterologous marrow, usually results from an immunologic reaction of the grafted marrow derivatives against the tolerant host. The former type of mortality was designated “grafted-marrow-rejection mortality”; the latter, “homologous disease” or “heterologous disease.”
Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes
Authors: Moran Yassour, Mi Young Lim, Hyun Sun Yun, Timothy L. Tickle, Joohon Sung, Yun-Mi Song, Kayoung Lee, Eric A. Franzosa, Xochitl C. Morgan, Dirk Gevers, Eric S. Lander, Ramnik J. Xavier, Bruce W. Birren, GwangPyo Ko, Curtis Huttenhower
Journal: Genome Medicine (2016)

Obesity and type 2 diabetes (T2D) are linked both with host genetics and with environmental factors, including dysbioses of the gut microbiota. However, it is unclear whether these microbial changes precede disease onset. Twin cohorts present a unique genetically-controlled opportunity to study the relationships between lifestyle factors and the microbiome. In particular, we hypothesized that family-independent changes in microbial composition and metabolic function during the sub-clinical state of T2D could be either causal or early biomarkers of progression.We collected fecal samples and clinical metadata from 20 monozygotic Korean twins at up to two time points, resulting in 36 stool shotgun metagenomes. While the participants were neither obese nor diabetic, they spanned the entire range of healthy to near-clinical values and thus enabled the study of microbial associations during sub-clinical disease while accounting for genetic background.We found changes both in composition and in function of the sub-clinical gut microbiome, including a decrease in Akkermansia muciniphila suggesting a role prior to the onset of disease, and functional changes reflecting a response to oxidative stress comparable to that previously observed in chronic T2D and inflammatory bowel diseases. Finally, our unique study design allowed us to examine the strain similarity between twins, and we found that twins demonstrate strain-level differences in composition despite species-level similarities.These changes in the microbiome might be used for the early diagnosis of an inflamed gut and T2D prior to clinical onset of the disease and will help to advance toward microbial interventions.
Loss of Function of The Cell Cycle Regulator Cdh1 Causes Cell Fragility due to Aberrant G2/M Checkpoint and Develops Resistant Disease in a B-ALL/LBL Mouse Model
Authors: Jo Ishizawa, Eiji Sugihara, Norisato Hashimoto, Shinji Kuninaka, Kensuke Kojima, Michael Andreeff, Shinichiro Okamoto, Hideyuki Saya
Journal: Blood (2013)
Liquid biopsies could be superior to tumor biopsy to provide a molecular profile in non-small cell lung cancer (NSCLC) patients
Authors: Jordi Remon, Ludovic Lacroix, David Planchard, Chloe Pannet, Cecile Jovelet, Andrew Lawson, Sarah Smalley, Kevin Howarth, David Gale, Emma Green, Vincent Plagnol, Nicolas Rosenfeld, Jean-Charles Soria, Benjamin Besse
Journal: Journal of Thoracic Oncology (2016)
Treatment patterns of very elderly patients with non-small cell lung cancer
Authors: G. R. Oxnard, P. Fidias, L. V. Sequist
Journal: Journal of Clinical Oncology (2007)

18110 Background: Among patients with non-small cell lung cancer (NSCLC), patients aged 80 or older, termed the ‘very elderly‘, have inferior survival. Treatment patterns within this patient population are poorly described. Methods: A retrospective chart review was performed of 111 outpatients with NSCLC presenting at age 80 or older to an academic referral center over 5.3 years. Based upon available literature regarding elderly patients with NSCLC, a guideline recommended therapy (GRT) was determined for each tumor stage. Each patient’s treatment regimen was evaluated for consistency with the GRT. Particular attention was paid to how patient characteristics and attitudes influenced therapy decisions. Results: Patients characteristics included: median age 82.6 (range 80–92); 50% male; 55% adenocarcinoma, 19% squamous cell; 30% stage I-II, 28% stage III, 39% stage IV; and 59% performance status (PS) 0–1, 25% PS = 2 (PS not available for 15%). 89% of patients received some form of anti-neoplastic therapy and 11% were treated with best supportive care alone. Of 34 patients with localized disease, 53% underwent tumor resection and 38% received definitive radiation. Of 74 patients with stage III or IV disease, 34% received cytotoxic chemotherapy. Radiotherapy (47%) and oral targeted therapy (35%) were the most common treatment modalities overall. 32% of patients received the stage-specific GRT. Multivariable analysis demonstrated that independent predictors for failing to receive GRT included PS = 2 (odds ratio [OR] 17.1, 95% confidence interval [CI] 2.2–135) and age =85 (OR 4.8, 95% CI 1.0–23.4) Of the patients who failed to receive GRT, 19% electively refused GRT that was offered (13% specifically refused chemotherapy), and 76% were not offered GRT (44% due to PS or comorbidities, 32% due to age or unstated reasons). Conclusions: The vast majority of NSCLC patients age 80 or above receive some form of anti-neoplastic therapy, but only one-third of this population receives the stage-specific GRT. The strongest predictor of treatment with GRT is PS 0–1; those with poor PS are 17-fold less likely to receive GRT. A small but clinically significant portion of patients elect against the offered GRT; more data is needed about the attitudes of these patients toward therapy. No significant financial relationships to disclose.
Embrace the Complexity
Authors: Michael Silverstein, Jenny Radesky
Journal: JAMA (2016)

Albert L. Siu, MD, MSPH; and the US Preventive Services Task Force (USPSTF); Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Linda Ciofu Baumann, PhD, RN, APRN; Karina W. Davidson, PhD, MASc; Mark Ebell, MD, MS; Francisco A. R. García, MD, MPH; Matthew Gillman, MD, SM; Jessica Herzstein, MD, MPH; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; Douglas K. Owens, MD, MS; William R. Phillips, MD, MPH; Maureen G. Phipps, MD, MPH; Michael P. Pignone, MD, MPH