tbuckley/cabot-search huggingface dataset:
Nutrition and reproduction in women
Journal: Human Reproduction Update (2006)

Malnutrition is a major problem in developing countries, and obesity and eating disorders are increasingly common in developing as well as developed countries. The reproductive axis is closely linked to nutritional status, especially undernutrition in the female, and inhibitory pathways involving detectors in the hind brain suppress ovulation in subjects with weight loss. Recovery may occur after minimal reacquisition of weight because energy balance is more important than body fat mass. Anorexia nervosa and bulimia nervosa affect up to 5% of women of reproductive age causing amenorrhoea, infertility and, in those who do conceive, an increased likelihood of miscarriage. Obesity can affect reproduction through fat cell metabolism, steroids and secretion of proteins such as leptin and adiponectin and through changes induced at the level of important homeostatic factors such as pancreatic secretion of insulin, androgen synthesis by the ovary and sex hormone-binding globulin (SHBG) production by the liver. WHO estimates that 9 to 25% of women in developed countries are severely obese, and obese mothers are much more likely to have obese children, especially if they have gestational diabetes. Obesity-associated anovulation may lead to infertility and to a higher risk of miscarriage. Management of anovulation with obesity involves diet and exercise as well as standard approaches to ovulation induction. Many obese women conceive without assistance, but pregnancies in obese women have increased rates of pregnancy-associated hypertension, gestational diabetes, large babies, Cesarean section and perinatal mortality and morbidity. Among contraceptors, the fear of weight gain affects uptake and continuation of hormonal contraceptives, although existing trials indicate that any such effects are small. For all methods of hormonal contraception, weight above 70 kg is associated with increased failure rates.
Clinical Trial Characteristics and Barriers to Participant Accrual: The MD Anderson Cancer Center Experience over 30 years, a Historical Foundation for Trial Improvement
Authors: Chad Tang, Steven I. Sherman, Mellanie Price, Jun Weng, Suzanne E. Davis, David S. Hong, James C. Yao, Aman Buzdar, George Wilding, J. Jack Lee
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Slow-accruing clinical trials delay the translation of basic biomedical research, contribute to increasing health care costs, and may prohibit trials from reaching their original goals. Experimental Design: We analyzed a prospectively maintained institutional database that tracks all clinical studies at the MD Anderson Cancer Center (Houston, TX). Inclusion criteria were activated phase I–III trials, maximum projected accrual ≥10 participants, and activation prior to March 25, 2011. The primary outcome was slow accrual, defined as &amp;lt;2 participants per year. Correlations of trial characteristics with slow accrual were assessed with logistic regression. Results: A total of 4,269 clinical trials met inclusion criteria. Trials were activated between January 5, 1981, and March 25, 2011, with a total of 145,214 participants enrolled. Median total enrolment was 16 [interquartile range (IQR), 5–34], with an average enrolment rate of 8.7 participants per year (IQR, 3.3–17.7). There were 755 (18%) trials classified as slow accruing. On multivariable analysis, slow accrual exhibited robust associations with national cooperative group trials (OR = 4.16, P &amp;lt; 0.0001 vs. industry sponsored), time from trial activation to first enrolment (OR = 1.13 per month, P &amp;lt; 0.0001), and maximum targeted accrual (OR = 0.16 per log10 increase, P &amp;lt; 0.0001). Recursive partitioning analysis identified trials requiring more than 70 days (2.3 months) between activation and first participant enrolment as having higher odds of slow accrual (23% vs. 5%, OR = 5.56, P &amp;lt; 0.0001). Conclusions: We identified factors associated with slow trial accrual. Given the lack of data on clinical trials at the institutional level, these data will help build a foundation from which targeted initiatives may be developed to improve the clinical trial enterprise. Clin Cancer Res; 23(6); 1414–21. ©2017 AACR.
International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases
Authors: Carmen W. Dessauer, Val J. Watts, Rennolds S. Ostrom, Marco Conti, Stefan Dove, Roland Seifert
Journal: Pharmacological Reviews (2017)

Adenylyl cyclases (ACs) generate the second messenger cAMP from ATP. Mammalian cells express nine transmembrane AC (mAC) isoforms (AC1–9) and a soluble AC (sAC, also referred to as AC10). This review will largely focus on mACs. mACs are activated by the G-protein G<i>α</i><sub>s</sub> and regulated by multiple mechanisms. mACs are differentially expressed in tissues and regulate numerous and diverse cell functions. mACs localize in distinct membrane compartments and form signaling complexes. sAC is activated by bicarbonate with physiologic roles first described in testis. Crystal structures of the catalytic core of a hybrid mAC and sAC are available. These structures provide detailed insights into the catalytic mechanism and constitute the basis for the development of isoform-selective activators and inhibitors. Although potent competitive and noncompetitive mAC inhibitors are available, it is challenging to obtain compounds with high isoform selectivity due to the conservation of the catalytic core. Accordingly, caution must be exerted with the interpretation of intact-cell studies. The development of isoform-selective activators, the plant diterpene forskolin being the starting compound, has been equally challenging. There is no known endogenous ligand for the forskolin binding site. Recently, development of selective sAC inhibitors was reported. An emerging field is the association of AC gene polymorphisms with human diseases. For example, mutations in the AC5 gene (<i>ADCY5</i>) cause hyperkinetic extrapyramidal motor disorders. Overall, in contrast to the guanylyl cyclase field, our understanding of the (patho)physiology of AC isoforms and the development of clinically useful drugs targeting ACs is still in its infancy.
Abstract P2-01-23: Long-term follow-up of persistent breast dermopigmentation after sentinel lymph node identification using superparamagnetic iron oxide particles (SIENNA+®)
Authors: K Hannebicque, L Boulanger, E Bogart, S Giard, MP Chauvet, JL Houpeau
Journal: Cancer Research (2017)

Abstract Background The French Sentimag study evaluated a non-invasive method for the localization of breast cancer sentinel lymph nodes (SLN) using SIENNA+®, a superparamagnetic iron oxide particles (SPIO), in addition to conventional techniques (radiotracer and blue dye). SIENNA+® was injected subcutaneously into the breast and detected by the SENTIMAG® handheld magnetometer probe. The results showed a good SLN identification performance but a skin discoloration was noted during this study after the SIENNA+® injection. This aim of this study was to assess the long-term duration and appearance of this dermopigmentation. Methods: 56 patients had participated in Sentimag study in our Center, 6 patients who had undergone mastectomy were excluded. We selected 50 patients who had undergone breast conservative surgery. For these patients, SLN localization was performed by both the conventional method (radiotracer and /or blue dye) and magnetic tracer, SIENNA+®. 47 patients were reviewed retrospectively from January 2015 to April 2015, 1.5 to 2 years after surgery and were assessed for skin discoloration. Results : Of the 47 patients, a dermopigmentation, from grade 1 (light yellowing) to grade 3 (dark browning) remained visible at the site of injection of SIENNA+® after 20.2 months [14.4-25.9] in 36.1% of the patients (17/47). 6.4% of 47 patients seen had grade 3 skin discoloration and 29.7% had grade 1 or 2 skin discoloration. Interestingly, no patients reported that persistent staining was a cosmetic or psychological problem. Conclusions : The use of SIENNA+® appears as an alternative method to radioisotopes for SLN identification in early breast cancer, but it may result in a prolonged-dermopigmentation at the injection site. To avoid dermopigmentation, it would be interesting to compare different techniques of SIENNA+® injection into the breast (intra-tumoral injection or a deeper periareolar injection) through a randomized trial. Citation Format: Hannebicque K, Boulanger L, Bogart E, Giard S, Chauvet MP, Houpeau JL. Long-term follow-up of persistent breast dermopigmentation after sentinel lymph node identification using superparamagnetic iron oxide particles (SIENNA+®) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-23.
Elderly Patient-Derived Endothelial Cells for Vascularization of Engineered Muscle
Authors: Luba Perry, Moshe Y. Flugelman, Shulamit Levenberg
Journal: Molecular Therapy (2017)

In vitro prevascularization of engineered tissue constructs promises to enhance their clinical applicability. We hypothesize that adult endothelial cells (ECs), isolated from limb veins of elderly patients, bear the vasculogenic properties required to form vascular networks in vitro that can later integrate with the host vasculature upon implantation. Here, we show that adult ECs formed vessel networks that were more developed and complex than those formed by human umbilical vein endothelial cells (HUVECs) seeded with various supporting cells on three-dimensional (3D) biodegradable polymer scaffolds. In parallel, secreted levels of key proangiogenic cytokines were significantly higher in adult EC-bearing scaffolds as compared to HUVEC scaffolds. As a proof of concept for applicability of this model, adult ECs were co-seeded with human myoblasts as well as supporting cells and successfully formed a branched network, which was surrounded by aligned human myotubes. The vascularized engineered muscle tissue implanted into a full-thickness defect in immunodeficient mice remained viable and anastomosed with the host vasculature within 9 days of implantation. Functional "chimeric" blood vessels and various types of anastomosis were observed. These findings provide strong evidence of the applicability of adult ECs in construction of clinically relevant autologous vascularized tissue.
Autologous Stem Cell Transplantation for Elderly Patients with Multiple Myeloma.
Authors: Muzaffar H. Qazilbash, Rima Saliba, Chitra Hosing, Floralyn Mendoza, Suhail R. Qureshi, Donna M. Weber, Michael Wang, Thuy Flosser, Daniel R. Couriel, Marcos De Lima, Partow Kebriaei, Uday Popat, Amin M. Alousi, Richard E. Champlin, Sergio A. Giralt
Journal: Blood (2006)
Alemtuzumab and DHAP (A-DHAP) Is An Effective Salvage Therapy for Peripheral T-Cell Lymphoma, Unspecified: Interim Results of a Phase II Prospective Multicenter Study
Authors: Seok Jin Kim, Kihyun Kim, Byung Soo Kim, Cheolwon Suh, Won Seog Kim
Journal: Blood (2008)
Screening studies of transient elastography and FibroTest in the general population – Authors' reply
Authors: Pere Ginès, Isabel Graupera, Frank Lammert, Paolo Angeli, Llorenç Caballeria, Aleksander Krag, I Nehil Guha, S Darwish Murad, Laurent Castera
Journal: The Lancet. Gastroenterology & hepatology (2017)
A Phase 1 Study of Concomitant High Dose Lenalidomide and 5-Azacytidine Induction in the Treatment of Acute Myeloid Leukemia,
Authors: Giridharan Ramsingh, Peter Westervelt, Amanda Cashen, Geoffrey L. Uy, Keith Stockerl-Goldstein, Camille N. Abboud, Ryan Monahan, John F. DiPersio, Ravi Vij
Journal: Blood (2011)
A composite score associated with spontaneous operational tolerance in kidney transplant recipients
Authors: Richard Danger, Mélanie Chesneau, Chloé Paul, Pierrick Guérif, Maxim Durand, Kenneth A. Newell, Sai Kanaparthi, Laurence A. Turka, Jean-Paul Soulillou, Rémi Houlgatte, Magali Giral, Gérard Ramstein, Sophie Brouard
Journal: Kidney International (2017)
A loss of host-derived MMP-7 promotes myeloma growth and osteolytic bone disease in vivo
Authors: S. T. Lwin, J. A. Fowler, M. T. Drake, J. R. Edwards, C. C. Lynch, C. M. Edwards
Journal: Molecular Cancer (2017)

Matrix metalloproteinases (MMPs) play a critical role in cancer pathogenesis, including tumor growth and osteolysis within the bone marrow microenvironment. However, the anti-tumor effects of MMPs are poorly understood, yet have significant implications for the therapeutic potential of targeting MMPs. Host derived MMP-7 has previously been shown to support the growth of bone metastatic breast and prostate cancer. In contrast and underscoring the complexity of MMP biology, here we identified a tumor-suppressive role for host MMP-7 in the progression of multiple myeloma in vivo. An increase in tumor burden and osteolytic bone disease was observed in myeloma-bearing MMP-7 deficient mice, as compared to wild-type controls. We observed that systemic MMP-7 activity was reduced in tumor-bearing mice and, in patients with multiple myeloma this reduced activity was concomitant with increased levels of the endogenous MMP inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1). Our studies have identified an unexpected tumour-suppressive role for host-derived MMP-7 in myeloma bone disease in vivo, and highlight the importance of elucidating the effect of individual MMPs in a disease-specific context.
Molecular Inhibition of mTOR with Temsirolimus (TORISEL™, CCI-779) Is a Promising Strategy in Relapsed NHL: The University of Chicago Phase II Consortium.
Authors: Sonali M. Smith, Barbara Pro, Scott Smith, Patrick Stiff, Eric Lester, Sanjiv Modi, Janet Dancey, Everett E. Vokes, Koen van Besien
Journal: Blood (2006)
Global Trends in Hematopoietic Cell Transplantation.
Authors: Helen Baldomero, Mahmoud Aljurf, Luis Fernando Bouzas, Alois Gratwohl, Yoshihisa Kodera, Jeff H Lipton, J. Alejandro Madrigal, Lida Minako, Nicolas Novitzky, Marcelo C Pasquini, Jakob R. Passweg, Adriana Seber, Jeffrey Szer, Dietger Niederwieser
Journal: Blood (2012)
Evidence of Stage Shift in Women Diagnosed With Ovarian Cancer During Phase II of the United Kingdom Familial Ovarian Cancer Screening Study
Authors: Adam N. Rosenthal, Lindsay S.M. Fraser, Susan Philpott, Ranjit Manchanda, Matthew Burnell, Philip Badman, Richard Hadwin, Ivana Rizzuto, Elizabeth Benjamin, Naveena Singh, D. Gareth Evans, Diana M. Eccles, Andy Ryan, Robert Liston, Anne Dawnay, Jeremy Ford, Richard Gunu, James Mackay, Steven J. Skates, Usha Menon, Ian J. Jacobs
Journal: Journal of Clinical Oncology (2017)

Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). Patients and Methods Women whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO. Results Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical complexity, P = .16) (CI, 74.0% to 99.9%) compared with 13 (72.2%) of 18 cancers subsequently diagnosed (CI, 46.5% to 90.3%; P = .09). Conclusion ROCA-based screening is an option for women at high risk of OC/FTC who defer or decline RRSO, given its high sensitivity and significant stage shift. However, it remains unknown whether this strategy would improve survival in screened high-risk women.
The association of thymidylate synthase mRNA expression with its three gene polymorphisms in colorectal cancer.
Authors: Kazuyuki Kawakami, Go Watanabe
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2104 

Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU). There have been increasing evidences that TS mRNA expression in colorectal cancer is one of predictive factors for the outcome of the patients treated with 5-FU-based chemotherapy. TS gene has a variable number of tandem repeat (VNTR) in 5’-untranslated region (UTR), which is linked with TS expression. Accordingly, the TS VNTR is a promising predictive factor of 5-FU-based chemotherapy. However, we failed to observe the relation between the TS VNTR and TS mRNA expression in previous study (Clin. Cancer Res. 7: 4096-4101, 2001). Recently, we identified an additional polymorphism, single nucleotide polymorphism (SNP), in the VNTR area (Cancer Res. 63: 6004 - 6007, 2003). In addition, another polymorphism, 6bp-deletion at bp 1494 (TS 1494 del) in the 3’-UTR, was reported. In this study, we analyzed these three polymorphisms and compared them with TS mRNA expression level in human colorectal cancer tissues. The polymorphisms were analyzed by PCR and PCR-RFLP with the template of genomic DNA isolated from 252 colorectal cancer tissues. The polymorphic alleles in 5’-UTR were classified into 2, 3G or 3C according to the combination of VNTR and SNP. Total RNA was isolated from 137 samples and TS mRNA was quantitated by real-time RT-PCR. The frequency of the TS genotypes and the relation between the polymophisms in 5’-UTR and 3’-UTR was summarized in the Table. Sequence disequalibrium was observed between the polymophism in 5’-UTR and TS 1494 del in 3’-UTR. According to previous in vitro study, polymorphic alleles in 5’-UTR were classified into high expression (3G) or low expression allele (2 and 3C). The genotype of the 5’-UTR were then assigned to H/H, H/L or L/L. TS mRNA expression level was significantly higher in colorectal cancer tissues with H/H and H/L than those with L/L genotype. There was no relationship between TS mRNA expression level and the genotype of TS 1494 del. However, TS mRNA expression in cancer tissue with 6(+)/6(+) tended to be higher than 6(−)/6(−) genotype when limited in the samples with 2/2 or 3C/3C genotype in 5’-UTR. These results suggest that the comprehensive genotyping in TS 5’-UTR (VNTR and SNP) can predict the expression level of TS mRNA in colorectal cancer and should be considered for personalized chemotherapy using TS inhibitors. In addition, the polymorphism in 3’-UTR, TS 1494 del, might be affect the TS mRNA expression level in particular genotype of 5’-UTR. Further analysis is needed to clarify the functional significance of the haplotype of TS gene.



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Phase 1, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Intravenous Alvespimycin (KOS-1022) in Patients with Refractory Hematological Malignancies.
Authors: Jeffrey Lancet, Maria R. Baer, Ivana Gojo, M. Burton, M. Quinn, S.M. Tighe, Kapil Bhalla, K. Kersey, S. Wells, Z. Zhong, B. Sadler, Maher Albitar, Robert Johnson, Alison Hannah
Journal: Blood (2006)
Meta-analyses Can Be Credible and Useful
Authors: John P. A. Ioannidis
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Preliminary Clinical Activity in a Phase I Trial of the BCR-ABL/IGF- 1R/Aurora Kinase Inhibitor XL228 in Patients with Ph++ Leukemias with Either Failure to Multiple TKI Therapies or with T315I Mutation
Authors: Jorge Cortes, Ronald Paquette, Moshe Talpaz, Javier Pinilla, Ekatherine Asatiani, Meir Wetzler, Jeffrey H. Lipton, Corynn Kasap, Lynne A. Bui, Douglas O. Clary, Neil Shah
Journal: Blood (2008)
Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies
Authors: Laurie A. Silva, Terence S. Dermody
Journal: Journal of Clinical Investigation (2017)

Chikungunya virus (CHIKV), a reemerging arbovirus, causes a crippling musculoskeletal inflammatory disease in humans characterized by fever, polyarthralgia, myalgia, rash, and headache. CHIKV is transmitted by Aedes species of mosquitoes and is capable of an epidemic, urban transmission cycle with high rates of infection. Since 2004, CHIKV has spread to new areas, causing disease on a global scale, and the potential for CHIKV epidemics remains high. Although CHIKV has caused millions of cases of disease and significant economic burden in affected areas, no licensed vaccines or antiviral therapies are available. In this Review, we describe CHIKV epidemiology, replication cycle, pathogenesis and host immune responses, and prospects for effective vaccines and highlight important questions for future research.