tbuckley/cabot-search huggingface dataset:
Abstract P156: IRE1α Activity Is Abbreviated in Myocytes
Authors: DeAnna L Steiger, Yibin Wang
Journal: Circulation Research (2011)

BACKGROUND: A unifying feature of Ischemia/reperfusion injury, myocardial infarction and heart failure is disruption of endo(sarco)plasmic reticulum homeostasis and activation of the intracellular signaling pathway known as “ER Stress” or “Unfolded Protein Response” (UPR). UPR signaling is activated through three ER Stress sensor proteins, including IRE1α. IRE1α can, through direct interaction, induce adaptive or apoptotic signaling programs. Although ER stress signaling is known to be active following various cardiac injuries, it is unknown whether IRE1α contributes to an adaptive or apoptotic program. We sought to characterize the functional impact of IRE1-mediated UPR signaling in cardiomyocytes. HYPOTHESIS: IRE1α-mediated UPR signaling contributes to cardiac hypertrophy or cell death in response to pathological stresses. METHOD: NRVM were treated with adenovirus-mediated IRE1α-myc overexpression. Protein and RNA were harvested two and five days following treatment and IRE1α activation, activity and downstream signaling was monitored by PCR, qPCR, and immunoblot. RESULTS: Ectopic expression led to robust phosphor-IRE1α Ser724 and IRE1α RNase activity toward Xbp-1. BiP and EDEM expression was induced, indicative of adaptive UPR signaling. Apoptotic UPR signaling was not induced (CHOP expression). Surprisingly, IRE1α activity and downstream signaling was transient. After five days, both IRE1α RNase activity and downstream signaling were extinguished, despite continued robust IRE1α protein expression and activation (phospho-Ser724). CONCLUSION: NRVM possess uncharacterized intrinsic mechanisms to protect against unwarranted IRE1α signaling.
Epigenomic and Functional Characterization of Junctophilin 3 (JPH3) as a Novel Tumor Suppressor Being Frequently Inactivated by Promoter CpG Methylation in Digestive Cancers
Authors: Xiaotong Hu, Yeye Kuang, Lili Li, Haimei Tang, Qinglan Shi, Xingsheng Shu, Yanjiao Zhang, Francis KL Chan, Qian Tao, Chao He
Journal: Theranostics (2017)

Junctophilin (JPH) proteins stabilize junctional membrane complexes between plasma membrane and endoplasmic reticulum, also implicated in some human diseases.JPH3 mutations are linked to Huntington's disease-like 2 syndrome.Through epigenomic study of a colon cancer cell line pair (HCT116 and DKO), we identified JPH3 as a methylated novel tumor suppressor gene (TSG) candidate at 16q24.We further studied its epigenetic alterations and functions in digestive tumorigenesis.JPH3 expression at the RNA level was found to be frequently silenced or reduced in colorectal and gastric cancers due to its promoter CpG methylation, which is associated with tumor progression and poor survival of digestive cancer patients.Ectopic expression of JPH3 inhibited tumor cell growth in vitro and in vivo.JPH3 expression upregulated the cytosolic Ca 2+ levels, and unfolded protein response gene expression upon endoplasmic reticulum stress.JPH3 also induced calpain activation and subsequent mitochondrial membrane depolarization and cell apoptosis.Thus, JPH3 was identified as a novel TSG methylated in colorectal and gastric tumors which promotes mitochondrial-mediated apoptosis, also as a potential metastasis and survival biomarker for digestive cancers.
The Italian Multicenter Study of Primary Hyperoxaluria
Authors: Peruzzi Licia, Robbiano Angela, Mandrile Giorgia, Giachino Daniela, Petrarulo Michele, Marangella Martino, Coppo Rosanna, Murer Luisa, Picca Stefano, Berardi Sonia, Mosconi Giovanni, Amoroso Antonio, Marchi Mario De
Journal: Journal of the American Society of Nephrology (2008)
New insights into preventing injuries and illnesses among elite athletics athletes
Authors: Pascal Edouard, Juan-Manuel Alonso, Pedro Branco
Journal: British Journal of Sports Medicine (2017)

For the athletics athlete, ‘injury’ is part of life; either injury and its potential consequences are in his/her mind like the sword of Damocles or injury is present. About two-thirds of athletes will sustain at least one injury during an athletics season.1 Furthermore, it is not uncommon that athletes continue to train despite complaining of pain or injury.2 But this should no longer be considered as the norm! Indeed, the normal condition of athletics practice should be to do so in the absence of any pain or injury. Efforts should be continued to reach this ‘state of peace’ in sports practice. Athletes may also suffer from illnesses, which will also have repercussions on their athletics training and performance.3 4 While medical teams battle to keep their athletes fit and healthy, this is also of major importance to all those who have a stake in the athlete’s performance. To move forward towards the common goal of prevention rather than cure, …
Inhibition of human ovarian cancer cells by troglitazone is mediated via p51A (p63γ)-dependent pathway
Authors: So Yeon Kim, Jae-Jung Lee, Dae Seog Heo
Journal: Cancer Research (2006)

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Peroxisome proliferators-activated receptor-gamma (PPAR-γ) is a member of the nuclear hormone receptor superfamily of ligand-dependent transcription factors and a crucial regulator of cell differentiation and growth. Thiazolidenedione family of the PPAR-γ agonists, such as troglitazone, ciglitazone, and pioglitazone, exhibit antitumor effects in various types of cancer cells. This study shows that the antitumor effect of troglitazone in ovarian cancer cells is independent on PPAR-γ and p53, but dependent on p51A(p63γ). Treatment of human ovarian cancer cells (NIH: OVCAR3, SKOV3, and 2774) with troglitazone induced dose-dependent inhibition of cell growth. But no significant inhibition was induced in normal human cells (normal fibroblast, umbilical vein endothelial cells, and adult epidermal keratinocytes). The growth inhibition was not dependent on the amount of PPAR-γ mRNA and protein. Athough troglitazone (TGZ) binds to PPAR-γ as an agonist, these evidences suggest that TGZ inhibits ovarian cancers independently of PPAR-γ. Cell cycle analysis of TGZ-treated cells revealed the G1-phase arrest in NIH: OVCAR3, SKOV3 and a sub-G1 peak in NIH: OVCAR3, SKOV3, and 2774. Treatment of ovarian cancer cells with the TGZ revealed DNA fragmentation, the hallmark of apoptosis. TGZ increased BAX and p21 protein, the apoptosis and growth arrest related proteins which are responsive to p53. p53 has been implicated in the TZDs-mediated cell-cycle control, differentiation, DNA repair, and apoptosis from previous reports. However, the growth inhibition does not seem to be dependent on p53 in ovarian cancers: NIH: OVCAR3 and 2774 have p53 mutants and SKOV3 is p53-null. The p51A (p63γ) is similar to p53 in structure and function. In particular, p51A (p63γ) protein is capable of inducing p53-respnosive genes and can elicit growth arrest and apoptosis. Treatment of human ovarian cancer cells with TGZ up-regulated the expression of p51A (p63γ) protein. Our study provides that troglitazone induces growth suppression and apoptosis via p51A (p63γ)- dependent pathway in human ovarian cancer cells.
Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations
Authors: Jennifer W. Leiding, Satoshi Okada, David Hagin, Mario Abinun, Anna Shcherbina, Dmitry N. Balashov, Vy H.D. Kim, Adi Ovadia, Stephen L. Guthery, Michael Pulsipher, Desa Lilic, Lisa A. Devlin, Sharon Christie, Mark Depner, Sebastian Fuchs, Annet van Royen-Kerkhof, Caroline Lindemans, Aleksandra Petrovic, Kathleen E. Sullivan, Nancy Bunin, Sara Sebnem Kilic, Fikret Arpaci, Oscar de la Calle-Martin, Laura Martinez-Martinez, Juan Carlos Aldave, Masao Kobayashi, Teppei Ohkawa, Kohsuke Imai, Akihiro Iguchi, Chaim M. Roifman, Andrew R. Gennery, Mary Slatter, Hans D. Ochs, Tomohiro Morio, Troy R. Torgerson
Journal: Journal of Allergy and Clinical Immunology (2017)
Health-related quality of life from a phase 3 randomized trial of fulvestrant 500 mg vs anastrozole for hormone receptor-positive advanced breast cancer (FALCON).
Authors: John Forsyth Russell Robertson, Kwok-Leung Cheung, Shinzaburo Noguchi, Zhimin Shao, Arnold Degboe, Jasmine Lichfield, Jackie Thirlwell, Mehdi Fazal, Matthew J Ellis
Journal: Journal of Clinical Oncology (2017)

1048 Background: The Phase 3 randomized FALCON trial (NCT01602380) demonstrated improved progression-free survival with fulvestrant 500 mg (F) vs anastrozole 1 mg (A) in postmenopausal women with hormone receptor-positive (HR+) locally advanced or metastatic breast cancer (BC) without prior endocrine therapy (hazard ratio [HR] 0.797, 95% confidence interval [CI] 0.637-0.999; p = 0.0486; Robertson et al. Lancet 2016). Overall health-related quality of life (HRQoL) was maintained and similar for F and A. There was no evidence of a detriment with F vs A in time to deterioration for both Trial Outcome Index (TOI; HR 0.90, 95% CI 0.70-1.15; p = 0.4008) and Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) total score (HR 0.84, 95% CI 0.66-1.07; p = 0.1594). We present additional analyses of patient (pt)-reported HRQoL outcomes from FALCON. Methods: Women with HR+ BC were randomized 1:1 to F (Days 0, 14, 28, then every 28 days) or A (daily) until disease progression or discontinuation. HRQoL was assessed by FACT-B questionnaire (TOI [summary of physical and functional well-being and breast cancer subscale scores] and FACT-B total score) at randomization and every 12 weeks during treatment. HRQoL data post-treatment (with or without progression) were also collected. Results: 462 pts were randomized (F, n = 230; A, n = 232). Compliance to FACT-B during treatment ranged from 84.6-100.0%. Mean change from baseline in TOI (scale range 0-92) and FACT-B total score (scale range 0-144) remained broadly stable (approximately ±3 points to Week 132) and similar between arms during treatment. HRQoL was also maintained in FACT-B subscales. Approximately one third of pts had improved TOI (≥ +6 points) and FACT-B (≥ +8 points) total scores from baseline up to Week 144 of treatment with F (ranges 26.4-45.0%, and 20.0-35.8%, respectively) and A (ranges 18.6-32.9%, and 22.7-37.9%, respectively). Conclusions: Compliance to the FACT-B questionnaire on treatment with F and A for HR+ BC in the FALCON trial was good; mean change from baseline in TOI and FACT-B total score was maintained, and similar proportions of pts had improved TOI and FACT-B total score in both arms. Clinical trial information: NCT01602380.
Regulation of tumor suppressor NKX3.1 by ubiquitination
Authors: Bin Guan, Charles Bieberich
Journal: Clinical Cancer Research (2007)

B57  Prostate cancer is the second leading cause of cancer deaths and the most frequently diagnosed malignancy in American men. The NKX3.1 gene located at 8p21.2 encodes a homeodomain-containing transcription factor that has been extensively studied for its prostate-restricted expression and its role in prostate cancer. Diminished expression of NKX3.1 protein has been observed in focal prostatic atrophy, prostatic intraepithelial neoplasia and prostate carcinoma. Nevertheless, the extent of NKX3.1 loss measured by immunostaining in these lesions varies among patient samples, and the correlation between NKX3.1 mRNA and protein level is poor. We identified multiple ubiquitin E3 ligases that target NKX3.1 for degradation in prostate cancer cells. We hypothesize that NKX3.1 and these E3 ligases in combination may be used as biomarkers for prostate cancer.
Proceedings of the British Thoracic Society. 1987 winter meeting. 8-9 December 1987, London. Abstracts.
Authors: R Heaton, M Gille-R, P Snashall, Gdw Crook, R Murdoch, H Todd, Cole Defence, J Devalia, D Grady, Y Harmanyeri, S Tabaqchali, C Kelly, C Ward, F Gould, D Hendrick, E Walters, D Honeybourne, R Lodwick, J Andrews, J Ashby, V Sco1t, G Phillips, R Richards, S Holgate, F Carswell, S Mukherjee, G Parsons, R Milroy, J Douglas, Gdo Lowe, R Carter, C Forbes, S Banham
Journal: Thorax (1988)

In assessment of bronchial responsiveness to inhaled pharmacological agents it is customary to "normal- ise" the concentration-response curve (CRC) so that the baseline measurement of airway calibre is expressed as 100% and responsiveness given as the concentration of agonist causing a given percentage change.This is valid only if the slope of the CRC relates to starting airway calibre in a consistent manner.Increasing use is being made of partial flow-volume loops in bronchial challenge testing, although the influence of starting flow rates on the slope of the CRC so obtained has not been studied.We have investigated this relationship in 20 CRCs from normal subjects and 19 CRCs from asthmatic subjects.Methacholine was administered by the method of Juniper et al (Thorax 1978;33:705-10).Max- imal and partial flow-volume loops were obtained according to the method of Zamel (Clin Respir Physiol 1984;20:471-5).The concentration of methacholine producing a 40% fall in flow at a lung volume 40% above residual volume on the partial loop (V40p) was determined from the log concen- tration-response curve and the slope of the curve determined at that point.Similar assessments were made for a 20% fall in FEV, derived from the maximal loops.In all subjects there was a significant negative correlation between the starting V,P and the slope of the CRC (r = -0 73, p < 0 001).In subgroups of eight asthmatic and six normal subjects whose baseline V40p values overlapped each other's range, there was no significant difference in mean slope between the normal subjects (-16 (055) 1 s-'/mg ml-') and the asthmatic subjects (-199 (1 2) 1 s-'/mg ml-').In contrast, the correla- tion between starting FEV, and slope was much weaker (r = 0-38, p < 0 05).We conclude that "normalisation" of the CRC to methacholine using partial flow-volume loops is a valid procedure.Normal and asthmatic subjects cannot be distinguished on the basis of the slope of such curves.The practice of "normalising" the FEV, concentration-response curve is less justifiable.Rebound increase in bronchial reactivity following regular inhaled terbutaline
A Fluorogenic Probe for Ultrafast and Reversible Detection of Formaldehyde in Neurovascular Tissues
Authors: Xing-Guang Liang, Bo Chen, Ling-Xiao Shao, Juan Cheng, Ming-Zhu Huang, Yu Chen, Yong-Zhou Hu, Yi-Feng Han, Feng Han, Xin Li
Journal: Theranostics (2017)

Formaldehyde (FA) is endogenously produced in live systems and has been implicated in a diverse array of pathophysiological processes.To disentangle the detailed molecular mechanisms of FA biology, a reliable method for monitoring FA changes in live cells would be indispensable.Although there have been several fluorescent probes reported to detect FA, most are limited by the slow detection kinetics and the intrinsic disadvantage of detecting FA in an irreversible manner which may disturb endogenous FA homeostasis.Herein we developed a coumarin-hydrazonate based fluorogenic probe (PFM) based on a finely-tailored stereoelectronic effect.PFM could respond to FA swiftly and reversibly.This, together with its desirable specificity and sensitivity, endows us to track endogenous FA in live neurovascular cells with excellent temporal and spatial resolution.Further study in the brain tissue imaging showed the first direct observation of aberrant FA accumulation in cortex and hippocampus of Alzheimer's mouse model, indicating the potential of PFM as a diagnostic tool.
Identification of CD146 as a novel molecular actor involved in systemic sclerosis
Authors: Elise Kaspi, Xavier Heim, Brigitte Granel, Benjamin Guillet, Jimmy Stalin, Marie Nollet, Alexandrine Bertaud-Foucault, Andrée Robaglia-Schlupp, Patrice Roll, Pierre Cau, Aurélie Leroyer, Richard Bachelier, Audrey Benyamine, Françoise Dignat-George, Marcel Blot-Chabaud, Nathalie Bardin
Journal: Journal of Allergy and Clinical Immunology (2017)
CONCUSSIONS IN JAPANESE HIGH SCHOOL RUGBY PLAYERS: RESEARCH ON INJURIES, SYMPTOMS, AND SIGNS
Authors: Mana Otomo, Shun Torii, Mutsuo Yamada, Toru Fukubayashi
Journal: British Journal of Sports Medicine (2017)

Background In Japan, sports-related concussions have been a subject of active research in recent years. Among sports played in Japan, concussions occur most frequently in rugby football. Objective The purpose of this study was to investigate the status of concussions in high school rugby players, with the intent of prevention. Design Subjects were Japanese high school rugby players. Setting The subjects were evaluated at a clinic in Sugadaira, a revered venue for rugby training in Japan, attended by teams from all over the country. Subjects were 178 high school rugby players who were diagnosed with concussion within 2 hours of injury. Information about the concussion was obtained from the injured player and a witness. Symptoms and disturbances of consciousness after concussion were evaluated using the Sport Concussion Assessment Tool 3 (SCAT3), in an interview format. Results A total of 93% of subjects has been injured during a match, and 43% had a history of concussion. The contact site was the head in more than 90% of cases, with the forehead in 38%, the side of the head in 30%, the back of the head in 21%, the top in 5%, and an unknown site in 6%. The concussion occurred while performing a tackle in 61% cases, and when being tackled in 30%; the cause was uncertain in 9% cases. Symptoms were present in 94% of the subjects on SCAT3 evaluation. The most common symptom was headache (84%). Loss of consciousness occurred in only 15%, but 72% had some loss of memory. Conclusions The most common circumstance of concussion involved head contact was when tackling an opponent. Concussion was associated with subjective symptoms and the loss of memory more often than the loss of consciousness.
One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer
Authors: Kelli M. Luginbuhl, Jeffrey L. Schaal, Bret Umstead, Eric M. Mastria, Xinghai Li, Samagya Banskota, Susan Arnold, Mark Feinglos, David D’Alessio, Ashutosh Chilkoti
Journal: Nature Biomedical Engineering (2017)
A phase II, multicenter, randomized trial of eribulin plus gemcitabine (EG) vs. paclitaxel plus gemcitabine (PG) in patients with HER2-negative metastatic breast cancer (MBC) as first-line chemotherapy (KCSG BR13-11, NCT02263495).
Authors: Kyung Hae Jung, Yeon Hee Park, Seock-Ah Im, Joohyuk Sohn, Keun-Seok Lee, Yee Soo Chae, Ki Hyeong Lee, Jee Hyun Kim, Young-Hyuck Im, Ji-Yeon Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Gun Min Kim, In Hae Park, Soo Jung Lee, Hye Sook Han, Se Hyun Kim
Journal: Journal of Clinical Oncology (2017)

1082 Background: PG chemotherapy is one of the preferred chemotherapeutic regimens for patients with MBC. Eribulin mesylate is a non-taxane inhibitor of microtubule dynamics of the halichondrin class. A recent pooled analysis with eribulin showed improved overall survival (OS) in various patient subgroups. Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Methods: This study was a prospective randomized phase 2, open-label, two-arm, multi-center study comparing EG with PG chemotherapy for patients with HER-2 negative MBC as first-line treatment. Histologically confirmed breast cancer patients, at least 19 years of age, with no prior history of chemotherapy for MBC with evaluable lesions were included. Prior hormonal therapy as a treatment of Hormone Receptor (HR)-positive MBC was allowed. This design was hypothesized that EG chemotherapy would not be inferior to PG chemotherapy. The primary endpoint was Progression-Free Survival (PFS). Estimated 6 mo. PFS rate for each arm was 70%. The secondary endpoints were: Time to Treatment Failure (TTF); OS; neuropathic scale; toxicity; clinical benefit rate. Results: A total of 118 patients (median age: 50, 24-66) were enrolled between 2015 and 2016, and were randomly assigned to PG (n = 59) or EG (n = 59) chemotherapy. Mean number of metastatic sites was 3 (1-8). Six month PFS rates for both arms were 72% for EG and 73% for PG arm (p = 0.457). PFS in PG arm tends to be longer than in EG group (median PFS 12.6 for PG vs. 9.6 months for EG) without statistical significance. In addition, there was no significant difference in OS between the two groups (not reached vs. 21.2 months, p = 0.223). The median numbers of chemotherapy cycles of both groups were 8 for EG and 10 for PG (range 2-32). CBRs were 44% for EG and 45% for PG arm. Major toxicities were neutropenia and neurotoxicity. Grade II or more neurotoxicity was more common in PG than in EG group (40% vs.25%). Conclusions: EG chemotherapy showed similar clinical benefit with PG chemotherapy in terms of PFS but, more favorable neurotoxicity than PG chemotherapy. Clinical trial information: NCT02263495.
Cigarette smoke-induced preneoplastic lung lesions in guinea pigs fed a diet high in ascorbic acid
Authors: Emerich S. Fiala, Ock Soon Sohn, Chung-Xiou Wang, Rama S. Sodum, Joel Reinhardt, Cesar Aliaga, Karam El-Bayoumy
Journal: Cancer Research (2004)

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Lung cancer is the third most common cancer in the U.S., and is the leading cause of cancer death. There are, so far, no effective screening procedures and the cancer has a very high metastatic potential. While cigarette smoking is the most significant cause of lung cancer, more than 50% of new lung cancer cases develop in those smokers who have quit. There is, therefore, an urgent need for new methods of treatment as well as for effective chemopreventive agents for this disease. One serious obstacle to the development of chemopreventive agents for cigarette smoke-induced lung cancer is the lack of realistic animal laboratory models. We have been using the guinea pig in studies to assess the effects of natural antioxidants, such as ascorbic acid, on pulmonary damage due to reactive oxygen and nitrogen species derived from inhaled cigarette smoke. The guinea pig provides a more suitable experimental model for this purpose than other species, such as the mouse, rat, hamster or ferret, which have been used in the past for smoking studies, because the guinea pig, like the human, requires an exogenous source of ascorbic acid. This is not true of the other species, which biosynthesize ascorbic acid according to need. In a 28 day study involving cigarette smoke inhalation by male Hartley guinea pigs twice a day, seven days a week, we found that this treatment induced putative preneoplastic lesions in the lungs. These included hyperplasias, dysplasias and squamous cell metaplasias in the epithelia of bronchi and bronchiolae, and were in every way similar to those found in the lungs of human smokers. No lesions were found in guinea pigs that served as “sham-smoked” controls (i.e., placed in clean inhalation devices without cigarettes, but otherwise treated exactly as the experimental guinea pigs). Because the lesions appeared in the relatively short time of 28 days of cigarette smoke inhalation, it is reasonable to expect that a longer exposure time will lead to the development of frank lung tumors as in the human. To date, this has not been satisfactorily achieved with any animal model. While the appearance of these lesions in the short time span of 28 days was surprising, even more surprising was the fact that most of them occurred in the lungs of guinea pigs consuming a diet high (4000 ppm) rather than low (50 ppm) in ascorbic acid. While some contribution of vitamin E, which was also a variable in this study, cannot be excluded, it would appear that consumption of a diet high in the antioxidant ascorbic acid may facilitate rather than protect from cigarette smoke-induced lung lesions in the guinea pig model. This study was supported by NCI Grant 5 P01 CA 70972.