tbuckley/cabot-search huggingface dataset:
Phase III study comparing vinorelbine/gemcitabine with vinorelbine/carboplatin as first-line chemotherapy of advanced NSCLC: A Norwegian Lung Cancer Study Group trial.
Authors: Ø. Fløtten, R. M. Bremnes, B. H. Grønberg, S. Sundstrøm, T. Amundsen, H. Rolke, U. Aasebø, K. Hornslien, T. Wentzel-Larsen, C. von Plessen
Journal: Journal of Clinical Oncology (2010)

7597 Background: Platinum based chemotherapy is the standard first line treatment for advanced non- small cell lung cancer (NSCLC). However, side-effects are common and earlier studies have suggested that non-platinum combinations are equally effective but less toxic. This may improve health related quality of life (HRQoL) during the treatment. Methods: Eligible patients had stage IIIB (ineligible for curative radiotherapy) or stage IV, performance status (PS) 0-2 and adequate bone marrow/kidney/liver function. They were randomized to receive up to three courses of vinorelbine 60 mg/m2 PO + gemcitabine 1,000 mg/m2 IV day 1 and day 8 (VG) or vinorelbine 60 mg/m2 PO day 1 + 8 + carboplatin AUC = 5 (Calvert's formula) IV day 1 (VC). Patients > 75 years received 75% of the dose. The primary endpoint was overall survival. Secondary endpoints were HRQoL (global health status, pain, nausea/vomiting, dyspnea and fatigue) reported on the EORTC QLQ-C30 + LC13 at week 9, toxicity and use of palliative radiotherapy. Results: 444 patients from 35 Norwegian hospitals were randomized from September 07 until April 09. Their median age was 65 years, 254 (58%) were men and 112 (25%) had PS 2. There were no differences in median overall survival (VG: 6.3 months, VC: 7.0 months; log rank p = 0.89) or in HRQoL. Preliminary toxicity analyses of 414 patients showed more grade IV neutropenia and need for blood transfusions in the VC arm, but no differences in numbers of infections or hospitalisations. Conclusions: The two regimens yielded similar results with respect to survival and HRQoL. Complete data on toxicity/adverse events and use of palliative radiotherapy will be presented at the annual meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pierre Fabre Pharma Norden A/S Pierre Fabre Pharma Norden A/S
Evidence for independent recruitment of zeta-crystallin/quinone reductase (CRYZ) as a crystallin in camelids and hystricomorph rodents.
Authors: P Gonzalez, P V Rao, S B Nuñez, J S Zigler
Journal: Molecular Biology and Evolution (1995)

Zeta-crystallin/quinone reductase (CRYZ) is an NADPH oxidoreductase expressed at very high levels in the lenses of two groups of mammals: camelids and some hystricomorph rodents. It is also expressed at very low levels in all other species tested. Comparative analysis of the mechanisms mediating the high expression of this enzyme/crystallin in the lens of the Ilama (Lama guanacoe) and the guinea pig (Cavia porcellus) provided evidence for independent recruitment of this enzyme as a lens crystallin in both species and allowed us to elucidate for the first time the mechanism of lens recruitment of an enzyme-crystallin. The data presented here show that in both species such recruitment most likely occurred through the generation of new lens promoters from nonfunctional intron sequences by the accumulation of point mutations and/or small deletions and insertions. These results further support the idea that recruitment of CRYZ resulted from an adaptive process in which the high expression of CRYZ in the lens provides some selective advantage rather than from a purely neutral evolutionary process.
Merkel cell carcinoma: value of sentinel lymph-node status and adjuvant radiation therapy
Authors: A. Servy, E. Maubec, P.E. Sugier, F. Grange, S. Mansard, T. Lesimple, E. Marinho, B. Couturaud, A. Girod, S. Albert, R. Dendale, E. Calitchi, L. Sarda, J. Chanal, L. Deschamps, X. Sastre-Garau, L. Laroche, B. Crickx, M.F. Avril
Journal: Annals of Oncology (2016)
An Epizootic in Hamsters of Lymphomas of Undetermined Origin and Mode of Transmission&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: K R Ambrose, J H Coggin
Journal: JNCI Journal of the National Cancer Institute (1975)

An epizootic of lymphomas arose spontaneously on three occasions in a facility containing both inbred and randombred Syrian hamsters. These tumors developed in approximately half the colony-born hamsters and were horizontally transmissible to those brought into the colony.
Authors’ reply to Gøtzsche and Hamilton
Authors: Halle R Amick, Gerald Gartlehner, Bradley N Gaynes, Kathleen N Lohr
Journal: BMJ (2016)

We thank Gotzsche and Hamilton for their thoughtful responses.1 2 3

Gotzsche raises an important problem: the risk of dependence in people taking second generation antidepressants. The evidence for this is mixed, and the discussion of the balance between harm and benefit remains an active one.4 Careful consideration of what dependence is and how it overlaps with symptoms of drug discontinuation is key. Withdrawal symptoms are associated with discontinuation of many second generation antidepressants, but they are …
Wet or dry: translatable “water mazes” for mice and humans
Authors: Kerin K. Higa, Jared W. Young, Mark A. Geyer
Journal: Journal of Clinical Investigation (2016)

Although the cognitive and biological characteristics of Alzheimer's disease (AD) are well known and mouse models of AD are available, current treatments for AD-related cognitive deficits have quite limited efficacy. The development of tasks with cross-species validity may enable better prediction of the efficacy of potential new treatments. In this issue of the JCI, Possin et al. present a virtual version of the Morris water maze (a common test of spatial learning and memory for rodents) that is designed for use with humans. The authors tested a mouse model of AD (transgenic mice expressing human amyloid precursor protein [hAPP]) and patients in the earlier mild cognitive impairment (MCI) stage of AD in their respective versions of the maze. Using novel statistical methods, they detected similar deficits across species, providing support for the hAPP model and use of the virtual water maze. Importantly, this work enabled recommendations for appropriate sample sizes when developing potential therapeutics for AD.
Palliative radiotherapy in pediatric malignancies
Authors: S. Bhasker, A. Turaka, B. K. Mohanti, V. Bajpai
Journal: Journal of Clinical Oncology (2006)

9050 Background: To evaluate the role of palliative radiotherapy in the management of incurable pediatric malignancies. Methods: Records of 40 pediatric patients treated between Jan’ 2003 and Nov’ 2005 were reviewed and analyzed retrospectively. All of theses 40 children received palliative external beam radiotherapy for symptom control. Palliative radiotherapy was given either as single modality or in addition to surgery, chemotherapy and symptom relief drugs. Information recorded for each patient included age, sex, and extent of disease, histological types, symptomatology, treatment methods and symptom relief. Results: There were 28 boys and 12 girls in the age group of 1 to 18 years, with a median age of 14 years (range of 1–18 years). Predominant symptoms were swelling with or without pain, bleeding, and weakness of limbs. The median duration of symptoms was 90 days (range of 4–50 days). The diagnosis of these children varied with different histologies, most in the group of malignant round cell tumors (11), retinoblastoma (4), neuroblastoma (4), AML with chloromas (3), Ewing’s sarcoma (4). All patients presented with advanced stages of disease. Out of 40 patients 18 (45%) had disseminated disease at presentation. Nine patients underwent surgery while 32 patients received chemotherapy and all but two patients received symptom relief drugs in addition to palliative radiotherapy. The various dose schedules were either 5 Gy or 8 Gy for single fraction treatment while the dose schedules for fractionated radiotherapy ranged from 20 Gy in 5 fractions to 30 Gy in 10 fractions. Four patients showed complete resolution, 20 patients showed good, while 15 patients had little, 1did not have any relief in their symptoms. At the completion of multimodality treatment, 18 patients had partial response, 8 patients had progressive disease, 8 had stable disease and two patients had complete response. The disease status of 4 patients could not be known. Conclusions: The role of radiotherapy as palliative modality in children with locally advanced lesions provides better symptom relief in combination with other modalities of treatment. No significant financial relationships to disclose.
춘계학술대회 : 포스터발표 ; 바이러스성 간염, B형 : Multiplex RFMP 방법을 이용한 B형간염바이러스의 라미부딘, 아데포비어 내성 돌연변이 분석
Authors: 지승일, 박영민, 정현재, 박상종, 정종렬, 신수경, 홍선표, 유왕돈, 김수옥
Journal: Clinical and Molecular Hepatology (2007)
US panel recommends depression screening for all adults
Authors: Michael McCarthy
Journal: BMJ (2016)

The US Preventive Services Task Force has recommended that all adults aged 18 years and older be screened for depression, including pregnant and postpartum women.

The task force said that depression was the leading cause of disability among adults in high income countries and imposed a substantial burden of disease, affecting individuals, their families, and society as a whole.

The independent, volunteer panel of experts in preventive care and evidence based medicine was asked to make recommendations for preventive care services, such as counseling and preventive drugs, while weighing the potential benefits and risks, but not the …
Effect of 3-Methylcholanthrene on Hyperplastic and Early Neoplastic Hepatic Lesions Induced in Rats by Carbon Tetrachloride&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1970)

Buffalo male and Female rats 5, 8, 12, 24, 52, and 76 weeks old, with hepatic lesions induced by carbon tetrachloride, were fed 3-methylcholanthrene to study the effect on hepatic lesions induced by CCI4. This chemical increased the incidence of hyperplastic nodules and small hepatocellular carcinomas in animals of all ages. The difference was greater in animals 12 weeks of age and older. Females were more susceptible to the development of hyperplastic nodules and carcinomas than were males. Multiple nodules and carcinomas were observed in the livers of animals given both chemicals, whereas animals receiving CCI4 had fewer lesions per liver. Cirrhosis of the liver was more advanced in the animals given methylcholanthrene and carbon tetrachloride simultaneously.
Final results of a combination study between trabectedin and pegylated liposomal doxorubicin (PLD) in patients with advanced malignancies
Authors: R. B. Cohen, R. J. Schilder, J. Cheng, J. W. Lee, T. Cardosa, O. Trifan, L. Ding, M. von Mehren
Journal: Journal of Clinical Oncology (2005)

3074 Background: Trabectedin (Yondelis, ET-743) is a marine-derived compound, which binds to the minor groove of DNA and is active at nM concentrations. Trabectedin is thought to act through the transcription-coupled nucleotide excision repair system. In clinical studies trabectedin has demonstrated activity in soft tissue sarcoma, ovarian and breast cancer. Methods: Eligibility criteria included normal liver function tests, limited prior doxorubicin exposure (≤ 250 mg/m2), and normal cardiac function. PLD 30 mg/m2 was administered i.v. over one hour followed immediately by one of six trabectedin doses (0.4, 0.6, 0.75, 0.9, 1.1, and 1.3 mg/m2) i.v. over 3 hours every 21 days. The effect of the combination on the liver morphology was evaluated in biopsies obtained from consenting patients. Results: Six dose levels of trabectedin were evaluated. The DLTs were one grade 3 AST and two grade 4 ALT elevations observed at a trabectedin dose of 1.3 mg/m2. The recommended dose is trabectedin 1.1 mg/m2 plus PLD 30 mg/m2. The thirty patients treated in this study were heavily pretreated: 23 had received 1–5 prior chemotherapies (median 3), 15 received prior radiotherapy, and 27 had prior tumor related surgery. Grade 3 and 4 toxicities in pooled cycles were: ALT elevation (4%), neutropenia (3%), hand-foot syndrome (2%), AST elevation (1%) and nausea/vomiting (1%). One subject terminated treatment after 6 cycles due to adverse events. Six patients had a partial response and 14 patients have had stable disease for > 3 months. Images of the liver morphology from patients treated with this drug combination will be presented. Conclusions: Trabectedin and PLD can be combined at near full single agent therapeutic doses. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Johnson & Johnson
Abstract 14783: Cyclophilin a and Basigin Promotes Pulmonary Hypertension by Inducing Inflammation and Vascular Smooth Muscle Cell Proliferation
Authors: Kimio Satoh, Kota Suzuki, Junichi Omura, Nobuhiro Kikuchi, Satoshi Miyata, Tatsuro Minami, Koichiro Sugimura, Tatsuo Aoki, Kotaro Nochioka, Shunsuke Tatebe, Masanobu Miura, Saori Yamamoto, Toru Shimizu, Shohei Ikeda, Nobuhiro Yaoita, Yoshihiro Fukumoto, Kazufumi Nakamura, Hiroshi Ito, Kenji Kadomatsu, Hiroaki Shimokawa
Journal: Circulation (2014)

Introduction: Cyclophilin A (CyPA) is secreted from VSMCs by oxidative stress and promotes VSMC proliferation. However, the role of CyPA and its extracellular receptor Basigin (Bsg) in the pathogenesis of pulmonary hypertension (PH) remains to be elucidated.

Methods & Results: To determine the role of CyPA/Bsg signaling in PH development, CyPA+/- and Bsg+/- mice were exposed to hypoxia (O2 10%) for 4 weeks. The pulmonary arteries (PA) of CyPA+/- and Bsg+/- mice exposed to normoxia did not differ in morphology compared with their littermate controls. In contrast, CyPA+/- (n=12) and Bsg+/- mice (n=15) exposed to hypoxia revealed significantly reduced right ventricular systolic pressure (RVSP), PA remodeling and RV hypertrophy compared with their littermate controls (all P<0.01). Importantly, after transplantation of bone marrow, the severity of PH was still exacerbated in Bsg+/+ recipient mice compared with Bsg+/- recipient mice regardless of the source of bone marrow (Bsg+/+ or Bsg+/-), suggesting the crucial role of Bsg in PA. To further evaluate the role of Bsg, we harvested VSMCs from Bsg+/+ and Bsg+/- mice. Bsg expression in Bsg+/+ VSMCs was induced by extracellular CyPA, and was further augmented by hypoxia (O2 2%). The expression of NADPH oxidases (e.g. NOX2 and p47phox) was lower in Bsg+/- than in Bsg+/+ VSMCs. In contrast, Nrf2 and its downstream HO-1 were induced in Bsg+/- as compared with Bsg+/+ VSMCs. Additionally, the expression of BMPR2, which negatively regulates PDGF-BB and EGF in patients with PH, was induced in Bsg+/- VSMCs. Mechanistic studies demonstrated that Bsg+/- VSMCs revealed less secretion of cytokines/chemokines and growth factors (e.g. PDGF-BB). VSMC proliferation was significantly reduced in Bsg+/- compared with Bsg+/+ in response to 2% FBS, suggesting the crucial role of Bsg in VSMC proliferation. Finally, we examined CyPA-induced secretion of growth factors from VSMCs harvested from the PA of PH patients. Extracellular CyPA induced secretion of growth factors and chemokines (e.g. PDGF-BB, SDF-1, and FGF-2) and inflammatory cytokines (e.g. IL-1β, IL-2, and TNF-α) and this effect was enhanced by hypoxia (O2 2%).

Conclusions: These results indicate the crucial role of extracellular CyPA and vascular Bsg in the pathogenesis of PH.
Assessment of the restrictive allograft syndrome in patients after lung transplantation
Authors: Vasiliki Bessa, Bjoern E. Kleibrink, Gerhard Weinreich, Markus Kamler, Helmut Teschler, Urte Sommerwerck
Journal: European Respiratory Journal (2012)

Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of long term mortality after lung transplantation. The rare but constant finding of fibrotic changes has led to the hypothesis that bronchiolitis obliterans syndrome (BOS) is not the only manifestation of chronic rejection after lung transplantation.

Aims: The purpose of our study was to evaluate the recently reported criteria for the diagnosis of Restrictive Allograft Syndrome (RAS) in our post-lung transplantation population.

Methods: We retrospectively analyzed the lung function tests from 162 patients after lung transplantation from 2000 to 2011 with a conditional survival of 180 days. Established criteria for BOS were used for the definition of CLAD. RAS was defined as a detectable, irreversible decline of more than 10% of the best post-transplant total lung capacity (TLC). CT-scans were evaluated for the detection of possible causes for the TLC-decline.

Results : In our study 68 (42%) patients were diagnosed with CLAD, and 22 (14%) of these patients met the criteria for RAS after exclusion of 13 patients with other causes for a TLC-decline. Mean post-transplant survival was 2873±198 days in patients with no CLAD, 2583±261 days in patients with BOS and 2624±318 days for RAS patients (p=n.s.). In the subgroup of RAS patients CT-scans showed no alterations in 8 patients, honeycombing or reticular pattern in 3 patients and consolidations or infiltrates in 8 patients.

Conclusions: The percentage of restrictive lung function patterns in CLAD patients was comparable to the previously published data. In our study mortality of patients that developed RAS was not different from the BOS group.
Cancers of the Gallbladder and Biliary Tract in Alaskan Natives: 1970–791&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: L P Boss, A P Lanier, P H Dohan, T R Bender
Journal: JNCI Journal of the National Cancer Institute (1982)

The records of Alaskan Native patients with gallbladder and extrahepatic bile duct cancers diagnosed during 1970--79 were reviewed. Of 34 cases identified, the primary cancer was in the gallbladder in 29, resulting in age-adjusted incidence rates for gallbladder cancer of 4.4 for males and 17.6 for females. On the basis of calculations applying cancer incidence rates for U.S. whites to the Alaska Native population, a greater than expected number of both Eskimo and Indian patients were diagnosed. A 5-year review of cholecystectomies indicated that nonmalignant gallbladder disease was also elevated in both Indians and Eskimos.
Cardiovascular Health in Brazil
Authors: Antonio Luiz P. Ribeiro, Bruce B. Duncan, Luisa C. C. Brant, Paulo A. Lotufo, José Geraldo Mill, Sandhi M. Barreto
Journal: Circulation (2016)

Brazil is a large country, with an evolving economy, but marked social inequalities. The population is formed by an admixture of native Brazilians, Europeans, and Africans; is predominantly urban; and faces rapid aging. Time trends related to health behaviors show a substantial reduction in smoking rates, but a rising prevalence of overweight and obesity, unhealthy eating habits, and insufficient physical activity. The high prevalence of hypertension and the increasing prevalence of diabetes mellitus are also causes for concern. Cardiovascular disease (CVD) has been the leading cause of mortality since the 1960s and has accounted for a substantial percentage of all hospitalizations. In 2011, CVD was responsible for 31% of all deaths, with ischemic heart disease (31%) and cerebrovascular diseases (30%) being the leading CVD causes. Despite an increase in the overall number of CVD deaths, the age-adjusted mortality rates for CVD declined 24% between 2000 and 2011. Health care delivered by Brazil’s universal public health system, which focuses on primary prevention, has contributed to this achievement. However, the decline in age-adjusted mortality differs according to race, sex, and socioeconomic status with black individuals and lower-income populations sustaining the greatest impact of CVD, especially at younger ages. With one of the world’s largest public health systems in terms of population coverage, Brazil has the means to implement actions to confront the high burden of CVD, focusing on health promotion and comprehensive care. Insufficient funding, low education levels, and social inequalities remain as the main barriers to be overcome.
Abstract 1768: Chloroquine potentiates carfilzomib but not bortezomib effects on myeloma cells
Authors: Kristine Misund, Katarzyna Anna Baranowska, Toril Holien, Kristian Starheim, Ida Johansson, Glenn Buene, Anders Waage, Geir Bjørkøy, Anders Sundan
Journal: Cancer Research (2015)

Abstract Proteasomal inhibition has proven good clinical effect in Multiple Myeloma; however, some patients are resistant to treatment and most patients acquire resistance during the disease course. It is well known that cells degrade proteins by two distinct but interconnected pathways; one is protein degradation by proteasomes, which may be clinically targeted by proteasome inhibitors, the other is by formation of autophagosomes and lysosomal degradation, which can be inhibited by hydroxychloroquine (HCQ). Assuming that the two arms of protein degradation may compensate for each other, there is a rationale to simultaneously target both arms. We tested the combined effects of HCQ and the reversible proteasome inhibitor bortezomib or the irreversible inhibitor carfilzomib on myeloma cell lines and primary cells. As expected, HCQ potentiated carfilzomib-induced myeloma cell death, but surprisingly, HCQ had little or no effect on bortezomib activity. We also found that HCQ potentiated the effect of the irreversible proteasome inhibitor oprozomib, but not the effect of the reversible inhibitor ixazomib. Thus, the sensitivity towards the irreversible proteasome inhibitors carfilzomib or oprozomib is to a larger extent affected by the autophagic system than the reversible inhibitors bortezomib and ixazomib. In conclusion, we here suggest that in attempts to increase the clinical efficacy of proteasome inhibitors, inhibitors of autophagy and lysosomal degradation such as HCQ should be combined with an irreversible proteasome inhibitor such as carfilzomib, and not with bortezomib. Citation Format: Kristine Misund, Katarzyna Anna Baranowska, Toril Holien, Kristian Starheim, Ida Johansson, Glenn Buene, Anders Waage, Geir Bjørkøy, Anders Sundan. Chloroquine potentiates carfilzomib but not bortezomib effects on myeloma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1768. doi:10.1158/1538-7445.AM2015-1768