tbuckley/cabot-search huggingface dataset:
Selective Estrogen Receptor Modulation and Reduction in Risk of Breast Cancer, Osteoporosis, and Coronary Heart Disease
Authors: V C Jordan, S Gapstur, M Morrow
Journal: JNCI Journal of the National Cancer Institute (2001)

The recognition of selective estrogen receptor modulation in the laboratory has resulted in the development of two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, for clinical application in healthy women. SERMs are antiestrogenic in the breast but estrogen-like in the bones and reduce circulating cholesterol levels. SERMs also have different degrees of estrogenicity in the uterus. Tamoxifen is used specifically to reduce the incidence of breast cancer in premenopausal and postmenopausal women at risk for the disease. In contrast, raloxifene is used specifically to reduce the risk of osteoporosis in postmenopausal women at high risk for osteoporosis. The study of tamoxifen and raloxifene (STAR) trial is currently comparing the ability of these SERMs to reduce breast cancer incidence in high-risk postmenopausal women. There is intense interest in understanding the molecular mechanism(s) of action of SERMs at target sites in a woman's body. An understanding of the targeted actions of this novel drug group will potentially result in the introduction of new multifunctional medicines with applications as preventive agents or treatments of breast cancer and endometrial cancer, coronary heart disease, and osteoporosis.
microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway
Authors: Takashi Mitamura, Hidemichi Watari, Lei Wang, Hiromi Kanno, Makiko Kitagawa, Mohamed Kamel Hassan, Taichi Kimura, Mishie Tanino, Hiroshi Nishihara, Shinya Tanaka, Noriaki Sakuragi
Journal: Molecular Cancer (2014)

We aimed to investigate whether MIR31 is an oncogene in human endometrial cancer and identify the target molecules associated with the malignant phenotype. We investigated the growth potentials of MIR31-overexpressing HEC-50B cells in vitro and in vivo. In order to identify the target molecule of MIR31, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human endometrial cancer tissues. We also investigated the MIR31 expression in 34 patients according to the postoperative risk of recurrence. The overexpression of MIR31 significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo. MIR31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3'-UTR and consequently promoted the translocation of YAP1, a key molecule in the Hippo pathway, into the nucleus. Meanwhile, the nuclear localization of YAP1 increased the transcription of CCND1. Furthermore, the expression levels of MIR31 were significantly increased (10.7-fold) in the patients (n = 27) with a high risk of recurrence compared to that observed in the low-risk patients (n = 7), and this higher expression correlated with a poor survival. MIR31 functions as an oncogene in endometrial cancer by repressing the Hippo pathway. MIR31 is a potential new molecular marker for predicting the risk of recurrence and prognosis of endometrial cancer.
Soluble CD36 and Risk Markers of Insulin Resistance and Atherosclerosis Are Elevated in Polycystic Ovary Syndrome and Significantly Reduced During Pioglitazone Treatment
Authors: Dorte Glintborg, Kurt Højlund, Marianne Andersen, Jan Erik Henriksen, Henning Beck-Nielsen, Aase Handberg
Journal: Diabetes Care (2008)

OBJECTIVE—We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS—Thirty PCOS patients were randomized to 30 mg/day pioglitazone or placebo for 16 weeks. Fourteen weight-matched healthy female subjects were included as control subjects. sCD36, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, euglycemic-hyperinsulinemic clamps, and whole-body dual-energy X-ray absorptiometry scans were performed. RESULTS—sCD36 (2.87 relative units [0.88–9.36] vs. 1.67 relative units [0.72–3.89]), oxLDL (44.9 units/l [26.9–75.1] vs. 36.1 units/l [23.4–55.5]), and hsCRP (0.26 mg/dl [0.03–2.41] vs. 0.12 mg/dl [0.02–0.81]) were significantly increased in PCOS patients versus control subjects (geometric mean ± 2 SD). In PCOS, positive correlations were found between central fat mass and sCD36 (r = 0.43), hsCRP (r = 0.43), and IL-6 (r = 0.42) (all P &amp;lt; 0.05). After adjusting for fat mass, sCD36 and oxLDL correlated inversely with measures of insulin-stimulated glucose metabolism and positively with lipid oxidation during insulin stimulation in PCOS patients and control subjects (n = 44). sCD36 and oxLDL were significant independent predictors of glucose and lipid metabolism, whereas hsCRP and IL-6 showed no significant contribution. Following pioglitazone treatment, insulin sensitivity increased, whereas sCD36 (3.21 relative units [0.76–13.6] vs. 2.33 relative units [0.84–6.46]) and hsCRP decreased (P &amp;lt; 0.05). No significant changes were measured in body composition. CONCLUSIONS—sCD36 and oxLDL correlated with measures of insulin sensitivity independent of central fat mass. Pioglitazone treatment reduced sCD36 while improving insulin-stimulated glucose metabolism, further supporting the association between sCD36 and insulin resistance in PCOS.
Cancer Mortality in the United States by Education Level and Race
Authors: Jessica D. Albano, Elizabeth Ward, Ahmedin Jemal, Robert Anderson, Vilma E. Cokkinides, Taylor Murray, Jane Henley, Jonathan Liff, Michael J. Thun
Journal: JNCI Journal of the National Cancer Institute (2007)

Although both race and socioeconomic status are well known to influence mortality patterns in the United States, few studies have examined the simultaneous influence of these factors on cancer incidence and mortality. We examined relationships among race, education level, and mortality from cancers of the lung, breast, prostate, colon and rectum, and all sites combined in contemporary US vital statistics.Age-adjusted cancer death rates (with 95% confidence intervals [CIs]) were calculated for 137,708 deaths among 119,376,196 individuals aged 25-64 years, using race and education information from death certificates and population denominator data from the US Bureau of the Census, for 47 states and Washington, DC, in 2001. Relative risk (RR) estimates were used to compare cancer death rates in persons with 12 or fewer years of education with those in persons with more than 12 years of education.Educational attainment was strongly and inversely associated with mortality from all cancers combined in black and white men and in white women. The all-cancer death rates were nearly identical for black men and white men with 0-8 years of education (224.2 and 223.6 per 100,000, respectively). The estimated relative risk for all-cancer mortality comparing the three lowest (< or = 12 years) with the three highest (> 12 years) education categories was 2.38 (95% CI = 2.33 to 2.43) for black men, 2.24 (95% CI = 2.23 to 2.26) for white men, 1.43 (95% CI = 1.41 to 1.46) for black women, and 1.76 (95% CI = 1.75 to 1.78) for white women. For both men and women, the magnitude of the relative risks comparing the three lowest educational levels with the three highest within each race for all cancers combined and for lung and colorectal cancers was higher than the magnitude of the relative risks associated with race within each level of education, whereas for breast and prostate cancer the magnitude of the relative risks associated with race was higher than the magnitude of the relative risks associated with level of education within each racial group. Among the most important and novel findings were that black men who completed 12 or fewer years of education had a prostate cancer death rate that was more than double that of black men with more schooling (10.5 versus 4.8 per 100,000 men; RR = 2.17, 95% CI = 1.82 to 2.58) and that, in contrast with studies of mortality rates in earlier time periods, breast cancer mortality rates were higher among women with less education than among women with more education (37.0 and 31.1 per 100,000, respectively, for black women and 25.2 versus 18.6 per 100,000, respectively, for white women).Cancer death rates vary considerably by level of education. Identifying groups at high risk of death from cancer by level of education as well as by race may be useful in targeting interventions and tracking cancer disparities.
EGFR Gene Mutations: A Call for Global x Global Views of Cancer
Authors: W. R. Sellers, M. Meyerson
Journal: JNCI Journal of the National Cancer Institute (2005)

Successful medical therapy depends largely on penetrating the molecular underpinnings of pathogenic processes. Gradually, we have begun to link pathogenesis to alterations in the genome. The completed human genome sequence coupled with the development of technology capable of high-resolution genome interrogation holds special promise for cancer therapeutics because, unlike most medical illness, cancer presents with a separate genome that can be readily isolated. Thus, comparative analysis of the diseased and normal genomes may in theory identify the pathogenic genome alterations. Indeed, identifi cation of genetic alterations leading to the inactivation of tumor suppressor genes and/or activation of oncogenes has revealed many of the regulatory pathways deregulated during cancer initiation
DOES THE GONADOTROPIC HORMONE INDUCE ANTIBODIES OR ANTIHORMONES?
Authors: Felix Sulman
Journal: The Journal of Experimental Medicine (1937)

1. It is shown in 52 experiments upon rabbits that the purified gonadotropic hormone has no antigenic function—as an antigen or a haptene—either in the form of prolan derived from the urine of pregnant women or in the form of prosylan, derived from the blood of pregnant mares. 2. The experiments reported elsewhere which ascribe an antigenic structure to prolan, are due to confusion with the so called non-specific urine antigen (urine colloid). 3. Sera of rabbits which are abundant in prolan antihormone (Collip) also contain no antibodies against prolan. The antihormones against the gonadotropic substances must accordingly be considered as protective ferments (Abderhalden). 4. The employment of castrated animals has no influence upon the above results. 5. The lack of immunizingly effective components in pure prolan and prosylan (a) inhibits the possibility of serological diagnosis of pregnancy for the diagnostician; (b) protects the therapeutist against undesirable toxic and allergic secondary effects in intensive prolan treatment. The latter also is valid for pure prosylan preparations. 6. No prolan antibodies could be found in the blood of pregnant women in the 2nd and 4th month of pregnancy, or 1 day and 1 month postpartum. 7. Antihormone against prolan of human origin has no paralysing effect upon a prosylan preparation derived from the blood of pregnant mares (antex); there exists therefore a species specificity.
Cutaneous Infection Caused by Plant Pathogen<i>Colletotrichum gloeosporioides</i>
Authors: Li-Yu Lin, Chao-Chun Yang, Jau-Yn Wan, Tsung Chain Chang, Julia Yu-Yun Lee
Journal: JAMA Dermatology (2015)

oped persistent lip plaques despite successful oncological treatment. 5Others report the use of retinoids for its keratolytic effects, but with varying outcomes due to the underlying cancer. 3Only 1 other case has described improvement in oral lesions with systemic retinoids. 6This patient had metastatic gastric carcinoma but was eventually lost to follow-up.To our knowledge, this is the first report of oral malignant AN and tripe palms occurring in association with invasive renal urothelial carcinoma.Despite palliative chemotherapy, the patient's oral symptoms persisted and only improved after 8 weeks of acitretin treatment.A palliative approach was adopted with the aim of improving her eating ability and nutritional status.In malignant AN, successful treatment of the underlying cancer results in improvement of cutaneous or oral signs.We wish to highlight that systemic retinoids can be considered for symptomatic relief in patients with metastatic or late-stage carcinomas, thereby improving nutritional status and quality of life.
Somatic<i>NLRP3</i>mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes
Authors: Kenji Nakagawa, Eva Gonzalez-Roca, Alejandro Souto, Toshinao Kawai, Hiroaki Umebayashi, Josep María Campistol, Jeronima Cañellas, Syuji Takei, Norimoto Kobayashi, Jose Luis Callejas-Rubio, Norberto Ortego-Centeno, Estíbaliz Ruiz-Ortiz, Fina Rius, Jordi Anton, Estibaliz Iglesias, Santiago Jimenez-Treviño, Carmen Vargas, Julian Fernandez-Martin, Inmaculada Calvo, José Hernández-Rodríguez, María Mendez, María Teresa Dordal, Maria Basagaña, Segundo Bujan, Masato Yashiro, Tetsuo Kubota, Ryuji Koike, Naoko Akuta, Kumiko Shimoyama, Naomi Iwata, Megumu K Saito, Osamu Ohara, Naotomo Kambe, Takahiro Yasumi, Kazushi Izawa, Tomoki Kawai, Toshio Heike, Jordi Yagüe, Ryuta Nishikomori, Juan I Aróstegui
Journal: Annals of the Rheumatic Diseases (2013)

: Familial cold autoinflammatory syndrome, Muckle-Wells syndrome (MWS), and chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome are dominantly inherited autoinflammatory diseases associated to gain-of-function NLRP3 mutations and included in the cryopyrin-associated periodic syndromes (CAPS). A variable degree of somatic NLRP3 mosaicism has been detected in ≈35% of patients with CINCA. However, no data are currently available regarding the relevance of this mechanism in other CAPS phenotypes.To evaluate somatic NLRP3 mosaicism as the disease-causing mechanism in patients with clinical CAPS phenotypes other than CINCA and NLRP3 mutation-negative.NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. Apoptosis-associated Speck-like protein containing a CARD (ASC)-dependent nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants.A variable degree (5.5-34.9%) of somatic NLRP3 mosaicism was detected in 12.5% of enrolled patients, all of them with a MWS phenotype. Six different missense variants, three novel (p.D303A, p.K355T and p.L411F), were identified. Bioinformatics and functional analyses confirmed that they were disease-causing, gain-of-function NLRP3 mutations. All patients treated with anti-interleukin1 drugs showed long-lasting positive responses.We herein show somatic NLRP3 mosaicism underlying MWS, probably representing a shared genetic mechanism in CAPS not restricted to CINCA syndrome. The data here described allowed definitive diagnoses of these patients, which had serious implications for gaining access to anti-interleukin 1 treatments under legal indication and for genetic counselling. The detection of somatic mosaicism is difficult when using conventional methods. Potential candidates should benefit from the use of modern genetic tools.
Intercellular Communication in the Anterior Pituitary*
Authors: Jeffrey Schwartz
Journal: Endocrine Reviews (2000)

In addition to hypothalamic and feedback inputs, the secretory cells of the anterior pituitary are influenced by the activity of factors secreted within the gland. The list of putative intrapituitary factors has been expanding steadily over the past decade, although until recently much of the work was limited to descriptions of potential interactions. This took the form of evidence of production within the pituitary of factors already known to influence activity of secretory cells, or further descriptions of actions on pituitary cells by such factors when added exogenously. A new phase of discovery has been entered, with extensive efforts being made to delineate the control of the synthesis and secretion of the pituitary factors within the gland, regulation of the receptors and response mechanisms for the factors in pituitary cells, and measurements of the endogenous actions of the factors through the use of specific immunoneutralization, receptor blockade, tissue from transgenic animals, and other means. Taken together, these findings are producing blueprints of the intrapituitary interactions that influence each of the individual types of secretory cells, leading toward an understanding of the physiological significance of the interactions. The purpose of this article is to review the recent literature on many of the factors acting as intrapituitary signals and to present such finding in the context of the physiology of the secretory cells.
Chris T. Bolliger: keep him in your mind
Authors: F. J. F. Herth
Journal: European Respiratory Journal (2012)

The community of respiratory medicine is shocked and saddened by the unexpected and untimely death of Chris Bolliger who died on November 2, 2012, in Cape Town, South Africa. Up until his death he was the Director and Head of the Respiratory Research Unit and Co-head of the Division of Pulmonology of the Department of Medicine at the University of Stellenbosch, Cape Town, South Africa.

We have lost a good friend, an experienced researcher, a caring doctor, an excellent teacher and the most wonderful mentor that you could ask for. A complete representation of the life and achievements of Chris Bolliger is not possible. I have highlighted a couple of benchmarks as a reminder.

Chris was born and grew up in Switzerland and attended school in Basel. After graduating from high school he went to medical schools in Basel and Lausanne. In 1976 he completed medical school and began his training in internal and pulmonary medicine in Switzerland. In the early1980s he moved to South Africa and in 1989 became an …
Assessment of atopic dermatitis using self-report and caregiver report: a multicentre validation study
Authors: J.I. Silverberg, N. Patel, S. Immaneni, B. Rusniak, N.B. Silverberg, R. Debashis, N. Fewkes, E.L. Simpson
Journal: British Journal of Dermatology (2015)

Journal Article Assessment of atopic dermatitis using self‐report and caregiver report: a multicentre validation study Get access J.I. Silverberg, J.I. Silverberg Departments of Dermatology, Preventive Medicine and Medical Social Sciences Feinberg School of Medicine at Northwestern University Chicago IL U.S.ANorthwestern Medicine Multidisciplinary Eczema Center Chicago IL U.S.A Correspondence Jonathan I. Silverberg. E‐mail: jonathanisilverberg@gmail.com Search for other works by this author on: Oxford Academic Google Scholar N. Patel, N. Patel Department of Dermatology Feinberg School of Medicine at Northwestern University Chicago IL U.S.A Search for other works by this author on: Oxford Academic Google Scholar S. Immaneni, S. Immaneni Department of Dermatology Feinberg School of Medicine at Northwestern University Chicago IL U.S.A Search for other works by this author on: Oxford Academic Google Scholar B. Rusniak, B. Rusniak Northwestern Medicine Multidisciplinary Eczema Center Chicago IL U.S.A Search for other works by this author on: Oxford Academic Google Scholar N.B. Silverberg, N.B. Silverberg Department of Dermatology Mount Sinai St Luke's–Roosevelt Hospital and Beth Israel Medical Centers New York NY U.S.A Search for other works by this author on: Oxford Academic Google Scholar R. Debashis, R. Debashis Department of Dermatology Mount Sinai St Luke's–Roosevelt Hospital and Beth Israel Medical Centers New York NY U.S.A Search for other works by this author on: Oxford Academic Google Scholar N. Fewkes, N. Fewkes Department of Dermatology Oregon Health Science University Portland ORU.S.A Search for other works by this author on: Oxford Academic Google Scholar E.L. Simpson E.L. Simpson Department of Dermatology Oregon Health Science University Portland ORU.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 6, 1 December 2015, Pages 1400–1404, https://doi.org/10.1111/bjd.14031 Published: 01 December 2015
Lymphedema: A primer on the identification and management of a chronic condition in oncologic treatment
Authors: Brian D Lawenda, Tammy E Mondry, Peter A S Johnstone
Journal: CA A Cancer Journal for Clinicians (2009)

The primary goals of oncologic therapy are the compassionate care of cancer patients, eradication of disease, and palliation of symptoms. Advances in various targeted therapies such as highly conformal and image-guided radiotherapy techniques, sentinel lymph node dissection, and molecularly targeted agents hold the promise of allowing those goals to be reached with fewer treatment-related complications. Unfortunately, certain side effects remain problematic due to the inability to completely avoid injuring normal tissues. Lymphedema, a chronic condition that occurs as a result of the body's inability to drain lymph fluid from the tissues, is a common treatment-related side effect experienced by cancer patients. In this review, many of the important aspects of lymphedema with which clinicians who treat cancer patients should be familiar are outlined, including the anatomy, pathophysiology, diagnosis, and management of this condition. The authors also identify some of the resources available both to cancer patients with lymphedema and to the clinicians who treat them. It is hoped that this review will convey the importance of the early identification and management of this incurable disorder because this is essential to minimizing its complications.
Peroxisome Proliferator–Activated Receptor α Gene Regulates Left Ventricular Growth in Response to Exercise and Hypertension
Authors: Yalda Jamshidi, Hugh E. Montgomery, Hans-Werner Hense, Saul G. Myerson, Ines Pineda Torra, Bart Staels, Michael J. World, Angela Doering, Jeanette Erdmann, Christian Hengstenberg, Steve E. Humphries, Heribert Schunkert, David M. Flavell
Journal: Circulation (2002)

Background — Left ventricular hypertrophy (LVH) occurs as an adaptive response to a physiological (such as exercise) or pathological (valvular disease, hypertension, or obesity) increase in cardiac work. The molecular mechanisms regulating the LVH response are poorly understood. However, inherited defects in fatty acid oxidation are known to cause severe early-onset cardiac hypertrophy. Peroxisome proliferator–activated receptor α (PPARα) regulates genes responsible for myocardial fatty acid oxidation and is downregulated during cardiac hypertrophy, concomitant with the switch from fatty acid to glucose utilization. Methods and Results — The role of PPARα in left ventricular growth was investigated in 144 young male British Army recruits undergoing a 10-week physical training program and in 1148 men and women participating in the echocardiographic substudy of the Third Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Augsburg study. A G/C polymorphism in intron 7 of the PPARα gene significantly influenced left ventricular (LV) growth in response to exercise ( P =0.009). LV mass increased by 6.7±1.5 g in G allele homozygotes but was significantly greater in heterozygotes for the C allele (11.8±1.9 g) and in CC homozygotes (19.4±4.2 g). Likewise, C allele homozygotes had significantly higher LV mass, which was greater still in hypertensive subjects, and a higher prevalence of LVH in the Third MONICA Augsburg study. Conclusions — We demonstrate that variation in the PPARα gene influences human left ventricular growth in response to exercise and hypertension, indicating that maladaptive cardiac substrate utilization can play a causative role in the pathogenesis of LVH.