tbuckley/cabot-search huggingface dataset:
Integrin Fibronectin Receptors in Matrix Metalloproteinase-1–Dependent Invasion by Breast Cancer and Mammary Epithelial Cells
Authors: Yifeng Jia, Zhao-Zhu Zeng, Sonja M. Markwart, Korrene F. Rockwood, Kathleen M. Woods Ignatoski, Stephen P. Ethier, Donna L. Livant
Journal: Cancer Research (2004)

Integrins contribute to progression in many cancers, including breast cancer. For example, the interaction of alpha(5)beta(1) with plasma fibronectin causes the constitutive invasiveness of human prostate cancer cells. Inhibition of this process reduces tumorigenesis and prevents metastasis and recurrence. In this study, naturally serum-free basement membranes were used as invasion substrates. Immunoassays were used to compare the roles of alpha(5)beta(1) and alpha(4)beta(1) fibronectin receptors in regulating matrix metalloproteinase (MMP)-1-dependent invasion by human breast cancer and mammary epithelial cells. We found that a peptide consisting of fibronectin PHSRN sequence, Ac-PHSRN-NH(2), induces alpha(5)beta(1)-mediated invasion of basement membranes in vitro by human breast cancer and mammary epithelial cells. PHSRN-induced invasion requires interstitial collagenase MMP-1 activity and is suppressed by an equimolar concentration of a peptide consisting of the LDV sequence of the fibronectin connecting segment, Ac-LHGPEILDVPST-NH(2), in mammary epithelial cells, but not in breast cancer cells. This sequence interacts with alpha(4)beta(1), an integrin that is often down-regulated in breast cancer cells. Immunoblotting shows that the PHSRN peptide stimulates MMP-1 production by serum-free human breast cancer and mammary epithelial cells and that the LDV peptide represses PHSRN-stimulated MMP-1 production only in mammary epithelial cells. Furthermore, PHSRN stimulates MMP-1 activity in breast cancer cells and mammary epithelial cells with a time course that closely parallels invasion induction. Thus, down-regulation of surface alpha(4)beta(1) during oncogenic transformation may be crucial for establishment of the alpha(5)beta(1)-induced, MMP-1-dependent invasive phenotype of breast cancer cells.
Cyclin-Dependent Kinase 5 Decreases in Gastric Cancer and Its Nuclear Accumulation Suppresses Gastric Tumorigenesis
Authors: Longlong Cao, Jiechao Zhou, Junrong Zhang, Sijin Wu, Xintao Yang, Xin Zhao, Huifang Li, Ming Luo, Qian Yu, Guangtan Lin, Huizhong Lin, Jianwei Xie, Ping Li, Xiaoqing Hu, Chaohui Zheng, Guojun Bu, Yun-wu Zhang, Huaxi Xu, Yongliang Yang, Changming Huang, Jie Zhang
Journal: Clinical Cancer Research (2015)

As a cyclin-independent atypical CDK, the role of CDK5 in regulating cell proliferation in gastric cancer remains unknown.
Proangiogenic Effect of Angiotensin-Converting Enzyme Inhibition Is Mediated by the Bradykinin B <sub>2</sub> Receptor Pathway
Authors: Jean-Sébastien Silvestre, Sonia Bergaya, Radia Tamarat, Micheline Duriez, Chantal M. Boulanger, Bernard I. Levy
Journal: Circulation Research (2001)

Recent studies have suggested a proangiogenic effect of angiotensin-converting enzyme (ACE) inhibition. We hypothesized that such a proangiogenic effect of ACE inhibition may be mediated, in part, by bradykinin (BK) B(2)-receptor pathway. This study therefore examined the neovascularization induced by ACE inhibitor treatment in B(2) receptor-deficient mice (B(2)(-/-)) in a model of surgically induced hindlimb ischemia. After artery femoral occlusion, wild-type and B(2)(-/-) mice were treated with or without ACE inhibitor (perindopril, 3 mg/kg/d) for 28 days. Angiogenesis was then quantitated by microangiography, capillary density measurement, and laser Doppler perfusion imaging. The protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were determined by Western blot. In wild-type animals, vessel density and capillary number in the ischemic leg were raised by 1.8- and 1.4-fold, respectively, in mice treated with ACE inhibitor when compared with the nontreated animals (P<0.01). This corresponded to an improved ischemic/nonischemic leg perfusion ratio by 1.5-fold in ACE inhibitor-treated animals when compared with the untreated ones (0.87+/-0.07 versus 0.59+/-0.05, respectively, P<0.01). Activation of the angiogenic process was also associated with a 1.7-fold increase in tissue eNOS protein level in mice treated with ACE inhibitor (P<0.05 versus control) but not with changes in VEGF protein level. Conversely, ACE inhibition did not affect vessel density, blood flow, and eNOS protein level in ischemic hindlimb of B(2)(-/-) mice. Therefore, proangiogenic effect of ACE inhibition is mediated by B(2)-receptor signaling and was associated with upregulation of eNOS content, independently of VEGF expression.
[578] DOES ADJUVANT THERAPY WITH ERYTHROPOIETIN AND GCSF IMPROVE SUSTAINED VIROLOGICAL RESPONSE IN PATIENTS RECEIVING COMBINATION THERAPY WITH PEGYLATED INTERFERON AND RIBAVIRIN FOR CHRONIC HEPATITIS C?
Authors: W.J. Cash, K. Patterson, M.E. Callender, N.I. McDougall
Journal: Journal of Hepatology (2007)
THE REVERSION OF R TO S PNEUMOCOCCI
Authors: Hobart A. Reimann
Journal: The Journal of Experimental Medicine (1929)

A study was made of the behavior of R pneumococcus strains under various experimental conditions. It was found that daughter colonies frequently appeared among the R forms and in some instances tended to replace the typical R forms. The daughter strain produced colonies with shiny surfaces which were morphologically indistinguishable from genuine S colonies although the characteristics of the bacteria comprising them conformed to the R variety. Both R and daughter forms which had resided for long periods of time in vivo have been converted into virulent forms. Strains of R pneumococci which seemed irreversible were apparently converted into S forms by applying the methods of Griffith. A general consideration of the information derived during the recent experimental studies indicates that virulent S pneumococci may dissociate into the R form in vivo, that the R forms may be occasionally found in the sputum of pneumonia patients and also may reside or lie dormant in vivo for a considerable period of time. It has been shown that under favorable circumstances bacteria of the R form may spontaneously revert to the original S form or by special methods may even transform into S forms of another type.
Colon cancer in France: evidence for improvement in management and survival
Authors: C Faivre-Finn, A-M Bouvier-Benhamiche, J M Phelip, S Manfredi, V Dancourt, J Faivre
Journal: Gut (2002)

<b>Background:</b> Cancer registries recording all cases diagnosed in a well defined population represent the only way to assess real changes in the management of colon cancer at the population level. <b>Aims:</b> To determine trends over a 23 year period in treatment, stage at diagnosis, and prognosis of colon cancer in the Côte-d9Or region, France. <b>Patients:</b> A total of 3389 patients with colon cancer diagnosed between 1976 and 1998. <b>Methods:</b> Time trends in clinical presentation, surgical treatment, chemotherapy treatment, stage at diagnosis, postoperative mortality, and survival were studied. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period on prognosis, a relative survival analysis was performed. <b>Results:</b> Between 1976 and 1991, the resection rate increased from 69.3% to 91.9% and then remained stable. This increase was particularly marked in the older age group (56.4% to 90.5%). The proportion of stage III patients treated with adjuvant chemotherapy rose from 4.1% for the 1989–1990 period to 45.7% for the 1997–1998 period. Over the 23 years of the study the proportion of stage I and II patients increased from 39.6% to 56.6%, associated with a corresponding decrease in the proportion of patients with advanced stages. Postoperative mortality decreased from 19.5% to 7.3%. This led to an improvement in five year relative survival (from 33.0% for the 1976–1979 period to 55.3% for the 1992–1995 period). <b>Conclusions:</b> Advances in the management of colon cancer have resulted in improving the prognosis of this disease. However, progress is still possible, particularly in the older age group.
Phase III Study of Efaproxiral As an Adjunct to Whole-Brain Radiation Therapy for Brain Metastases
Authors: John H. Suh, Baldassarre Stea, Abdenour Nabid, John J. Kresl, André Fortin, Jean-Philippe Mercier, Neil Senzer, Eric L. Chang, Adam P. Boyd, Pablo J. Cagnoni, Edward Shaw
Journal: Journal of Clinical Oncology (2005)

To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves survival in patients with brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT).Patients with brain metastases from solid tumors and a Karnofsky performance score of > or = 70 were randomly assigned to receive WBRT with supplemental oxygen and either efaproxiral at 75 or 100 mg/kg (efaproxiral arm) or no efaproxiral (control arm). The primary end point was survival.The study consisted of 515 eligible patients (efaproxiral arm, n = 265; control arm, n = 250). The median survival time (MST) was 5.4 months for the efaproxiral arm versus 4.4 months for the control arm (hazard ratio [HR] = 0.87; P = .16). For the subgroup of patients with non-small-cell lung cancer (NSCLC) or breast cancer, the MST was 6.0 and 4.4 months, respectively (HR = 0.82; P = .07). Cox multiple regression analysis demonstrated a significant reduction in the risk of death for the efaproxiral arm in both primary populations. Further analysis indicated that the benefit may be restricted to the subgroup of patients with breast cancer. Response rates (radiographic complete response plus partial response) improved by 7% (P = .10) and 13% (P = .01) for all patients and for NSCLC and breast cancer patients in the efaproxiral arm, respectively. The most common severe adverse event in patients treated with efaproxiral was hypoxemia, which was reversible and effectively managed with supplemental oxygen in most patients.The addition of efaproxiral, a noncytotoxic radiation sensitizer, to WBRT may improve response rates and survival in patients with brain metastases, particularly metastases from breast cancer. A confirmatory trial for breast cancer patients has been initiated.
VLA Proteins in the Integrin Family: Structures, Functions, and Their Role on Leukocytes
Authors: Martin E. Hemler
Journal: Annual Review of Immunology (1990)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Transition of care and rehospitalization rates for patients who require home oxygen therapy following hospitalization
Authors: Brian Carlin, Kim Wiles, Dan Easley
Journal: European Respiratory Journal (2012)

Objective: To evaluate the effects over the past year of a home care based, respiratory therapist centered transition of care program for patients who require home oxygen therapy following hospital admission for an exacerbation.  Method: The Discharge, Assessment and Summary @ Home (D.A.S.H., Klingensmith HealthCare) program was implemented for patients who require supplemental oxygen use following hospital admission for the last year. This data is a summary of the last year of the program. The program consists of face-to-face visits by a respiratory therapist with the patient in the home environment on days 2, 7, and 30 following hospital discharge. Education, behavior modification, skills training, oxygen titration during performance of activities of daily living, clinical assessment, and adherence data collection are key components of the program. Patients who were discharged from the hospital who required supplemental oxygen were enrolled into the program.  Results: 555 patients from 23 different hospitals in the Western Pennsylvania area were enrolled into the program from March 2010 through February 2012. The primary discharge diagnosis was: COPD 69%; CHF 14%; hypoxemia 6%; pneumonia 4%; and other 7%. The overall readmission rate for the entire group was 5%. The 30 day readmission rate for those with COPD was 3% and for those with CHF was 3%.  Conclusions: With the use of this novel respiratory therapist based transition of care program, the 30 day rehospitalization rate (5%) for those patients who required supplemental oxygen on discharge was significantly lower than the historically observed rates (25%) in the Western Pennsylvania area.
Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 in patients with cirrhosis
Authors: Bashar A. Aqel, Surakit Pungpapong, Michael Leise, K. Tuesday Werner, Amy E. Chervenak, Kymberly D. Watt, Jennifer L. Murphy, Kristen Ryland, Andrew P. Keaveny, Ryan McLemore, Hugo E. Vargas
Journal: Hepatology (2015)

Interferon (IFN)‐free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child‐Pugh‐Turcott [CPT]‐B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12‐58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69‐85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 ( P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. Conclusions: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short‐term impact on MELD score. Long‐term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population. (H epatology 2015;62:1004‐1012)
Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial
Authors: Peter D Gluckman, John S Wyatt, Denis Azzopardi, Roberta Ballard, A David Edwards, Donna M Ferriero, Richard A Polin, Charlene M Robertson, Marianne Thoresen, Andrew Whitelaw, Alistair J Gunn
Journal: The Lancet (2005)
Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus.
Authors: N Hattori, H Kawamoto, S Fujimoto, K Kuno, Y Katsura
Journal: The Journal of Experimental Medicine (1996)

Flow cytometric and immunocytochemical analyses of murine fetal thymus (FT) cells with antibodies to various surface markers and transcription factors reveal that the synthesis of TCF-1 and GATA-3 protein begins simultaneously in a fraction of the most immature population of FT cells, which have the phenotype of CD4-CD8-CD44+CD25-. No TCF-1-producing cells is found in the fetal liver (FL). In CD44+CD25- FT cells, the production of TCF-1 is immediately followed by intracellular expression of CD3 epsilon. It is also found that the T cell development from FL, but not FT, progenitors in the FT organ culture system is severely inhibited by the addition of antisense oligonucleotides for either TCF-1 or GATA-3. These results strongly suggest that TCF-1 and GATA-3 play essential roles in the initiation of the earliest steps of T cell development in the thymus.
Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses
Authors: Zhuzhen Zhang, Fan Zhang, Peng An, Xin Guo, Yuanyuan Shen, Yunlong Tao, Qian Wu, Yuchao Zhang, Yu Yu, Bo Ning, Guangjun Nie, Mitchell D. Knutson, Gregory J. Anderson, Fudi Wang
Journal: Blood (2011)
Basal Insulin Requirement Is ∼30% of the Total Daily Insulin Dose in Type 1 Diabetic Patients Who Use the Insulin Pump
Authors: Akio Kuroda, Hideaki Kaneto, Tetsuyuki Yasuda, Munehide Matsuhisa, Kazuyuki Miyashita, Noritaka Fujiki, Keiko Fujisawa, Tsunehiko Yamamoto, Mitsuyoshi Takahara, Fumie Sakamoto, Taka-aki Matsuoka, Iichiro Shimomura
Journal: Diabetes Care (2011)

To investigate the basal insulin requirement in total daily insulin dose in Japanese type 1 diabetic patients who use the insulin pump.The basal insulin requirement in 35 type 1 diabetic patients without detectable C-peptide using the insulin pump (Paradigm 712) was investigated during 2-3 weeks of hospitalization. The patients were served diabetic diets of 25-30 kcal/kg ideal body weight. Each meal omission was done to confirm stable blood glucose levels within 30 mg/dL variance until the next meal. Target blood glucose level was set at 100 mg/dL before each meal and 150 mg/dL at 2 h after each meal.Total daily insulin dose was 31.6 ± 8.5 units, and total basal insulin requirement was 8.7 ± 2.9 units, which was 27.7 ± 6.9% of the total daily dose.Basal insulin requirement is ~30% of the total daily dose in Japanese type 1 diabetic patients who use the insulin pump.
Dendritic Cells in Irradiated Mice Trigger the Functional Plasticity and Antitumor Activity of Adoptively Transferred Tc17 Cells via IL12 Signaling
Authors: Jacob S. Bowers, Michelle H. Nelson, Sreenath Kundimi, Stefanie R. Bailey, Logan W. Huff, Kristina M. Schwartz, David J. Cole, Mark P. Rubinstein, Chrystal M. Paulos
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The adoptive cell transfer (ACT) of CD8+ T cells is a promising treatment for advanced malignancies. Lymphodepletion before ACT enhances IFNγ+CD8+ T cell (Tc0)–mediated tumor regression. Yet, how lymphodepletion regulates the function and antitumor activity of IL17A+CD8+ T cells (Tc17) is unknown. Experimental Design: To address this question, pmel-1 CD8+ T cells were polarized to secrete either IL17A or IFNγ. These subsets were then infused into mice with B16F10 melanoma that were lymphoreplete [no total body irradiation (TBI)], or lymphodepleted with nonmyeloablative (5 Gy) or myeloablative (9 Gy with hematopoietic stem cell transplantation) TBI. The activation of innate immune cells and function of donor T-cell subsets were monitored in recipient mice. Results: Tc17 cells regress melanoma in myeloablated mice to a greater extent than in lymphoreplete or nonmyeloablated mice. TBI induced functional plasticity in Tc17 cells, causing conversion from IL17A to IFNγ producers. Additional investigation revealed that Tc17 plasticity and antitumor activity were mediated by IL12 secreted by irradiated host dendritic cells (DC). Neutralization of endogenous IL12 reduced the antitumor activity of Tc17 cells in myeloablated mice, whereas ex vivo priming with IL12 enhanced their capacity to regress melanoma in nonmyeloablated animals. This, coupled with exogenous administration of low-dose IL12, obviated the need for host preconditioning, creating curative responses in nonirradiated mice. Conclusions: Our findings indicate that TBI-induced IL12 augments Tc17 cell–mediated tumor immunity and underline the substantial implications of in vitro preparation of antitumor Tc17 cells with IL12 in the design of T-cell immunotherapies. Clin Cancer Res; 21(11); 2546–57. ©2015 AACR.
Gestational Diabetes Mellitus and Life Insurance: What Is the Impact of Gestational Diabetes Mellitus on Life Insurance Premiums?
Authors: Anna S.Y. Zheng, Tony O’Leary, Robert G. Moses
Journal: Diabetes Care (2014)

The diagnosis, management, and implications of gestational diabetes mellitus (GDM) remain areas of controversy. The International Association of the Diabetes and Pregnancy Study Groups (1) suggested new diagnostic criteria based on the results of the Hyperglycemia and Adverse Pregnancy Outcome Study (2). These criteria have been adopted by the World Health Organization (3), but the National Institutes of Health decided there was inadequate evidence for change and has remained with the status quo (4).

A commentary by Ryan in Diabetes Care , among other things, stated that a diagnosis of GDM is “… a medical label of high risk for the future that will influence the mother’s …
Magnesium metabolism in hyperthyroidism and hypothyroidism.
Authors: J E Jones, P C Desper, S R Shane, E B Flink
Journal: Journal of Clinical Investigation (1966)

In 1939, Hueber (1) reported clinical improve- ment in patients with thyrotoxicosis after paren- teral administration of magnesium.Wiswell (2) subsequently was unable to demonstrate any change in the peripheral metabolism of thyroid hormone in hyperthyroid patients given mag- nesium sulfate injections, whereas Neguib (3) reported a decrease in size of both toxic and nontoxic goiters and clinical improvement in three thyrotoxic patients given daily injections of magnesium chloride.Tapley (4) demonstrated that the administration of L-triiodothyronine promptly produced negative magnesium balance in two myxedematous patients and called attention to the similarity between the symptoms of thyrotoxico- sis and magnesium deficiency, as well as between myxedema and magnesium excess.That the se- rum magnesium is elevated in hypothyroidism and decreased in hyperthyroidism has long been known (5-7) but has recently been re-emphasized and as- sociated erythrocyte magnesium alterations re- ported (8).Dempsey and Astwood (9) demonstrated in- creased production of thyroid hormone in ani- mals maintained in the cold.Hegsted, Vitale, and McGrath (10) reported that the magnesium re- quirement to maintain maximal growth rates in animals kept at cold temperatures were four times *
Molecular Diagnosis and Therapy of Kidney Cancer
Authors: W. Marston Linehan, Gennady Bratslavsky, Peter A. Pinto, Laura S. Schmidt, Len Neckers, Donald P. Bottaro, Ramaprasad Srinivasan
Journal: Annual Review of Medicine (2010)

Kidney cancer is not a single disease; it is made up of a number of cancers that occur in the kidney, each having a different histology, following a different clinical course, responding differently to therapy, and caused by a different gene. Study of the genes underlying kidney cancer has revealed that it is fundamentally a metabolic disorder. Understanding the genetic basis of cancer of the kidney has significant implications for diagnosis and management of this disease. VHL is the gene for clear cell kidney cancer. The VHL protein forms a complex that targets the hypoxia-inducible factors for ubiquitin-mediated degradation. Knowledge of this pathway provided the foundation for the development of novel therapeutic approaches now approved for treatment of this disease. MET is the gene for the hereditary form of type 1 papillary renal carcinoma and is mutated in a subset of sporadic type 1 papillary kidney cancers. Clinical trials are currently ongoing with agents targeting the tyrosine kinase domain of MET in sporadic and hereditary forms of papillary kidney cancer. BHD is the gene for the hereditary type of chromophobe kidney cancer. It is thought to be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. Hereditary leiomyomatosis renal cell carcinoma, a hereditary form of type 2 papillary renal carcinoma, is caused by inactivation of a Krebs cycle enzyme due to mutation. Knowledge of these kidney cancer gene pathways has enabled new approaches in the management of this disease and has provided the foundation for the development of targeted therapeutics.