tbuckley/cabot-search huggingface dataset:
The concomitant occurrence of multiple epidermal cysts, osteomas and thyroid gland nodules is not diagnostic for Gardner syndrome in the absence of intestinal polyposis: a clinical and genetic report
Authors: S.-M. Herrmann, Y.D. Adler, K. Schmidt-Petersen, V. Nicaud, C. Morrison, M. Paul, Ch.C. Zouboulis
Journal: British Journal of Dermatology (2003)

Gardner syndrome, a phenotypic variant of familial adenomatous polyposis, is characterized by the classical clinical triad of skin and soft tissue tumours, osteomas and intestinal polyposis, but disease patterns with pairs of these findings have also been reported. Different mutations in the adenomatous polyposis coli (APC) gene have been shown to be associated with Gardner syndrome disease phenotypes. A 36-year-old patient presented with multiple epidermal cysts on the face, left ear lobe and neck, and the possible diagnosis of Gardner syndrome was based on the additional findings of two classical osteomas in the left radius and ulna and a cold non-malignant nodule of the thyroid gland. Intestinal polyposis was lacking at the time of examination. Major deletions but not microdeletions were excluded by a cytogenetic analysis with 650 chromosomal bands per haploid set. Systematic sequencing of the entire coding region of the APC gene (> 8500 bp) of the patient and five healthy controls was also performed. As a results, new APC gene polymorphisms were identified in exons 13 [A545A (A/G)] and 15 [G1678G (A/G), S1756S (G/T), P1960P (A/G)]. We also detected D1822V (A/T) which has recently been reported to be potentially related to colorectal carcinoma, and genotyped 194 randomly chosen healthy individuals from the Glasgow area for this as well as for the above variants in exons 13 and 15. Interestingly, of the 194 controls, 112 carried the DD (57.7%), 71 the DV (36.6%), and the remaining 11 (5.7%), including our patient, the VV genotype. It is therefore unlikely that APC D1822V serves as an important marker for colorectal carcinoma. In conclusion, we failed to identify obvious germline candidate mutations in > 8500 bp of the coding region of the APC gene in a patient with multiple epidermal cysts, osteomas and a thyroid gland nodule; major chromosomal deletions were excluded. Therefore, we assume that only the presence of intestinal polyposis is a marker for Gardner syndrome.
Oxidized LDL promotes the mitogenic actions of Chlamydia pneumoniae in vascular smooth muscle cells
Authors: M. N. Chahine, J. Deniset, E. Dibrov, S. Hirono, D. P. Blackwood, J. A. Austria, G. N. Pierce
Journal: Cardiovascular Research (2011)

The atherogenic actions of Chlamydia pneumoniae (C. pneumoniae), a common respiratory pathogen, are dependent upon a high-cholesterol environment in vivo. It is possible that oxidized low-density lipoprotein (oxLDL) is responsible for promoting the atherogenic effects of C. pneumoniae through a stimulation of cell proliferation. This study determined whether oxLDL can enhance the mitogenic action of C. pneumoniae in vascular smooth muscle cells (VSMCs) and the involvement of mitogen-activated protein kinase (MAPK) pathways and heat shock protein 60 (HSP60) in these mechanisms.Primary rabbit VSMCs were treated with live C. pneumoniae, heat-inactivated C. pneumoniae or infection medium, and subsequently incubated for up to 48 h in the presence or absence of oxLDL. Chlamydia pneumoniae infection alone stimulated cell proliferation and the addition of oxLDL significantly amplified this proliferative effect. This proliferation was accompanied by extracellular signal-regulated kinase-1 and -2 (ERK1/2) activation and an up-regulation of HSP60 expression. Changes in proliferation and HSP60 expression were attenuated by the inhibition of ERK1/2.These results indicate a novel role for oxLDL in promoting the mitogenic actions of C. pneumoniae in the vasculature. ERK1/2 is an important factor in the stress-mediated response and HSP60 up-regulation in VSMC. These data provide mechanistic evidence that C. pneumoniae may stimulate atherogenesis.
Genetic Susceptibility Loci for Breast Cancer by Estrogen Receptor Status
Authors: Montserrat Garcia-Closas, Stephen Chanock
Journal: Clinical Cancer Research (2008)

Abstract Breast cancer is a heterogeneous disease, and risk factors could be differentially associated with the development of distinct tumor subtypes that manifest different biological behavior and progression. In support of this view, there is growing evidence that known breast cancer risk factors vary by hormone receptor status and perhaps other pathologic characteristics of disease. Recent work from large consortial studies has led to the discovery of novel breast cancer susceptibility loci in genic (CASP8, FGFR2, TNRC9, MAP3K1, LSP1) and nongenic regions (8q24, 2q35, 5p12) of the genome, and to the finding of substantial heterogeneity by tumor characteristics. In particular, susceptibility loci in FGFR2, TNRC9, 8q24, 2q35, and 5p12 have stronger associations for estrogen receptor–positive (ER+) disease than estrogen receptor–negative (ER−) disease. These findings suggest that common genetic variants can influence the pathologic subtype of breast cancer, and provide further support for the hypothesis that ER+ and ER− disease result from different etiologic pathways. Current studies had limited power to detect susceptibility loci for less common tumor subtypes, such as ER− disease including triple-negative and basal-like tumors. Ongoing work targeting uncommon subtypes is likely to identify additional tumor-specific susceptibility loci in the near future. Characterization of etiologic heterogeneity of breast cancer may lead to improvements in the understanding of the biological mechanisms for breast cancer, and ultimately result in improvements in prevention, early detection, and treatment.
A Phase 2 Trial of Sunitinib in Patients with Advanced Non–clear Cell Renal Cell Carcinoma
Authors: Nizar M. Tannir, Elizabeth Plimack, Chaan Ng, Pheroze Tamboli, Nebiyou B. Bekele, Lianchun Xiao, Lisa Smith, Zita Lim, Lance Pagliaro, John Araujo, Ana Aparicio, Surena Matin, Christopher G. Wood, Eric Jonasch
Journal: European Urology (2012)
Cytokine production in whole blood cell cultures of patients with rheumatoid arthritis
Authors: A J G Swaak, H G van den Brink, L A Aarden
Journal: Annals of the Rheumatic Diseases (1997)

The measurement of cytokine production of activated lymphocytes and monocytes in the whole blood cell (WBC) culture system may provide a sensitive tool for evaluating the actual ongoing immune response of patients with rheumatoid arthritis (RA).Lipopolysaccharide (LPS) up to 250 pg/ml was used for the stimulation of monocytes for measuring the production of tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL6) and IL12, while the anti-CD3 (1 microgram/ml) and anti-CD28 (5 micrograms/ml) combination was used for T cell stimulation with the measuring of IL4 and interferon gamma (INF gamma) production. Twenty seven patients with RA and 23 healthy controls were studied.The results showed a decreased IL6 (LPS stimulus 4-6 pg/ml) and IL-12 (LPS stimulus 16-62 pg/ml) production in the RA patients. The maximal production of both cytokines was comparable with the normal controls. T cell stimulation showed a significant decreased INF gamma production in the RA patients.These findings obtained in the WBC culture system are highly suggestive for a decreased TH-1 derived cytokine production by a diminished IL12 production in RA patients. Another possibility is that both IL12 and INF gamma production in WBCs are inhibited by eventual circulating serum factors.
Both Dietary Protein and Fat Increase Postprandial Glucose Excursions in Children With Type 1 Diabetes, and the Effect Is Additive
Authors: Carmel E.M. Smart, Megan Evans, Susan M. O’Connell, Patrick McElduff, Prudence E. Lopez, Timothy W. Jones, Elizabeth A. Davis, Bruce R. King
Journal: Diabetes Care (2013)

To determine the separate and combined effects of high-protein (HP) and high-fat (HF) meals, with the same carbohydrate content, on postprandial glycemia in children using intensive insulin therapy (IIT).Thirty-three subjects aged 8-17 years were given 4 test breakfasts with the same carbohydrate amount but varying protein and fat quantities: low fat (LF)/low protein (LP), LF/HP, HF/LP, and HF/HP. LF and HF meals contained 4 g and 35 g fat. LP and HP meals contained 5 g and 40 g protein. An individually standardized insulin dose was given for each meal. Postprandial glycemia was assessed by 5-h continuous glucose monitoring.Compared with the LF/LP meal, mean glucose excursions were greater from 180 min after the LF/HP meal (2.4 mmol/L [95% CI 1.1-3.7] vs. 0.5 mmol/L [-0.8 to 1.8]; P = 0.02) and from 210 min after the HF/LP meal (1.8 mmol/L [0.3-3.2] vs. -0.5 mmol/L [-1.9 to 0.8]; P = 0.01). The HF/HP meal resulted in higher glucose excursions from 180 min to 300 min (P < 0.04) compared with all other meals. There was a reduction in the risk of hypoglycemia after the HP meals (odds ratio 0.16 [95% CI 0.06-0.41]; P < 0.001).Meals high in protein or fat increase glucose excursions in youth using IIT from 3 h to 5 h postmeal. Protein and fat have an additive impact on the delayed postprandial glycemic rise. Protein had a protective effect on the development of hypoglycemia.
Factors relating to the severity of symptoms at 5 yrs in children with severe wheeze in the first 2 yrs of life
Authors: NM Wilson, CJ Dore, M Silverman
Journal: European Respiratory Journal (1997)

Wheezing in early childhood covers a wide spectrum of morbidity. Since little is known about the factors determining either the pattern or the severity of this range of symptoms, 51 children, admitted to hospital with acute wheeze in the first 2 yrs of life, were monitored prospectively between the ages of 4.5-5.5 yrs. Our hypothesis was that the predictors of severe episodes and of interval symptoms in 5 year olds would differ. Symptom diaries were kept, from which the symptom pattern and severity was assessed. The frequency and severity of acute episodes were analysed separately from day-to-day (interval) symptoms. A physiological assessment was made at 5 yrs. During the 12 month study period, 11 children were symptom-free, 15 were reported to wheeze only in response to viral infections, and 25 wheezed from multiple triggers. Bronchial responsiveness was significantly increased in those with a family history of asthma but was unrelated to any index of atopy. In a multiple logistic regression analysis, a family history of asthma and a personal history of allergy (but not results of skin-prick testing or serum immunoglobulin E (IgE) significantly predicted both attack severity and interval symptoms. An additive effect of two factors (atopy plus a family history of asthma or bronchial responsiveness) on symptom severity was suggested, without any evidence of an interaction. It is concluded that in this population of 5 year olds, with an early history of severe wheezing, familial bronchial responsiveness and atopy of operated independently to determine both interval symptoms and attack severity.
Amenorrhoea in women with non-alcoholic chronic liver disease.
Authors: T F Cundy, J Butler, R M Pope, A K Saggar-Malik, M J Wheeler, R Williams
Journal: Gut (1991)

Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage. The hormonal findings in amenorrhoeic chronic live disease patients are not uniform. In some, hypogonadotrophic hypogonadism is related to undernutrition whereas others have normal to high values of luteinising hormone and sex steroids. Prolonged oestrogen deficiency can be a risk factor for osteoporosis in women with chronic liver disease.
S1.02 * SUBLETHAL IRRADIATION ENHANCES INVASIVENESS OF MALIGNANT GLIOMA CELLS; IMPLICATIONS FOR RADIOTHERAPY OF HUMAN GLIOBLASTOMA
Authors: S. Jung, J. Pei, H. H. Ryu, I. H. Park, M. Wen, W. Y. Jang, T. Y. Jung, K. S. Moon, I. Y. Kim
Journal: Neuro-Oncology (2014)

PURPOSE: This study explored the effect of irradiation on glioma invasion and also established relation between the infiltrative phenotype of glioma and the expression of p53 and MMP-2. METHODS: Human glioma cell line, U87MG (p53+) was prepared. U2OS (p53+) and SAOS2 (p53-) from osteosarcoma were used as control for p53 positive or negative. Each cell lines received single dose (2-8Gy) of irradiation, and then were analyzed the expression of p53, TIMP-1, 2 by western blot and MMP-2 activity by zymography. In order to confirm p53-MMP2 association, RNAi of p53 was treated into U87MG. The effect of irradiation on malignant glioma invasion was investigated by bioluminescence imaging after implantation U87-Fluc cell line in nude mouse brain, and then immunohistochemistry for p53, MMP-2 and in situ zymography were performed. RESULTS: MMP-2 activity and p53 expression were increased in proportional to irradiation dose in U87-MG and U2OS. TIMP-1, 2 was not changed in u87MG, but was increased in U2OS. In SAOS, TIMP-1, not TIMP-2 was increased after irradiation. Interestingly, MMP-2 began to express in 8 Gy-induced SAOS cells and expression of p53 and TIMP-1 were simultaneously increased. In vivo experiment, tumor margin of irradiated group was changed infiltrative phenotype, while control group was clear. MMP-2 and p53 was highly expressed in marginal area. And also, p53 knockdown decrease MMP-2 activity in irradiation induced u87MG cells. CONCLUSION: Irradiation could enhance glioma invasion, p53 expression and MMP-2 activities. Consequently p53 may regulate MMP-2 activity and high level of MMP-2 activation may play important roles in alteration to invasive growth pattern of U87MG by irradiation. These data suggest that the current involved-field radiotherapy for malignant glioma may need to be reconsidered and that future trials should consider pharmacologic therapies inhibiting invasion concurrently with radiotherapy.
Human Disease Associated with Exposure to Light
Authors: James H. Herndon, Robert G. Freeman
Journal: Annual Review of Medicine (1976)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Interleukin-21: Basic Biology and Implications for Cancer and Autoimmunity
Authors: Rosanne Spolski, Warren J. Leonard
Journal: Annual Review of Immunology (2007)

Interleukin-21 (IL-21), a potent immunomodulatory four-α-helical-bundle type I cytokine, is produced by NKT and CD4 + T cells and has pleiotropic effects on both innate and adaptive immune responses. These actions include positive effects such as enhanced proliferation of lymphoid cells, increased cytotoxicity of CD8 + T cells and natural killer (NK) cells, and differentiation of B cells into plasma cells. Conversely, IL-21 also has direct inhibitory effects on the antigen-presenting function of dendritic cells and can be proapoptotic for B cells and NK cells. IL-21 is also produced by Th17 cells and is a critical regulator of Th17 development. The regulatory activity of IL-21 is modulated by the differentiation state of its target cells as well as by other cytokines or costimulatory molecules. IL-21 has potent antitumor activity but is also associated with the development of autoimmune disease. IL-21 transcription is dependent on a calcium signal and NFAT sites, and IL-21 requires Stat3 for its signaling. The key to harnessing the power of IL-21 will depend on better understanding its range of biological actions, its mechanism of action, and the molecular basis of regulation of expression of IL-21 and its receptor.
Mucosal damage mediated by clostridial toxin in experimental clindamycin-associated colitis.
Authors: G D Abrams, M Allo, G D Rifkin, R Fekety, J Silva
Journal: Gut (1980)

Panretinal cryotherapy (PRC) was used to treat 15 eyes with rubeosis, nine of which had established neovascular glaucoma, and seven eyes with proliferative diabetic retinopathy. The rubeosis regressed, with preservation of vision and return to normal of intraocular pressure, in all but one eye. With one exception all eyes with proliferative retinopathy also showed new vessel regression after treatment. PRC may be considered an effective alternative to retinal photocoagulation in the treatment of advanced rubeosis, early rubeotic glaucoma, and in certain circumstances proliferative diabetic retinopathy.
Targeted Therapy with a<i>Salmonella Typhimurium</i>Leucine-Arginine Auxotroph Cures Orthotopic Human Breast Tumors in Nude Mice
Authors: Ming Zhao, Meng Yang, Huaiyu Ma, Xiaoming Li, Xiuying Tan, Shukuan Li, Zhijian Yang, Robert M. Hoffman
Journal: Cancer Research (2006)

Abstract We report here a modified auxotrophic strain of Salmonella typhimurium that can target and cure breast tumors in orthotopic mouse models. We have previously reported development of a genetically modified strain of S. typhimurium, selected for prostate tumor targeting and therapy in vivo. The strain, termed S. typhimurium A1, selectively grew in prostate tumors in xenograft models causing tumor regression. In contrast, normal tissue was cleared of these bacteria even in immunodeficient athymic mice with no apparent side effects. A1 is auxotrophic (leucine-arginine dependent) but apparently receives sufficient nutritional support only from tumor tissue. The ability to grow in viable tumor tissue may account, in part, for the unique antitumor efficacy of the strain. In the present report, to increase tumor-targeting capability of A1, the strain was reisolated after infection of a human colon tumor growing in nude mice. The tumor-isolated strain, termed A1-R, had increased targeting for tumor cells in vivo as well as in vitro compared with A1. Treatment with A1-R resulted in highly effective tumor targeting, including viable tumor tissue and significant tumor shrinkage in mice with s.c. or orthotopic human breast cancer xerographs. Survival of the treated animals was significantly prolonged. Forty percent of treated mice were cured completely and survived as long as non–tumor-bearing mice. These results suggest that amino acid auxotrophic virulent bacteria, which selectively infect and attack viable tumor tissue, are a promising approach to cancer therapy. (Cancer Res 2006; 66(15): 7647-52)
A Novel Synthetic Inhibitor of CDC25 Phosphatases
Authors: Marie-Christine Brezak, Muriel Quaranta, Odile Mondésert, Marie-Odile Galcera, Olivier Lavergne, Frédéric Alby, Martine Cazales, Véronique Baldin, Christophe Thurieau, Jeremiath Harnett, Christophe Lanco, Philip G. Kasprzyk, Gregoire P. Prevost, Bernard Ducommun
Journal: Cancer Research (2004)

Abstract CDC25 dual-specificity phosphatases are essential regulators that dephosphorylate and activate cyclin-dependent kinase/cyclin complexes at key transitions of the cell cycle. CDC25 activity is currently considered to be an interesting target for the development of new antiproliferative agents. Here we report the identification of a new CDC25 inhibitor and the characterization of its effects at the molecular and cellular levels, and in animal models. BN82002 inhibits the phosphatase activity of recombinant human CDC25A, B, and C in vitro. It impairs the proliferation of tumoral cell lines and increases cyclin-dependent kinase 1 inhibitory tyrosine phosphorylation. In synchronized HeLa cells, BN82002 delays cell cycle progression at G1-S, in S phase and at the G2-M transition. In contrast, BN82002 arrests U2OS cell cycle mostly in the G1 phase. Selectivity of this inhibitor is demonstrated: (a) by the reversion of the mitotic-inducing effect observed in HeLa cells upon CDC25B overexpression; and (b) by the partial reversion of cell cycle arrest in U2OS expressing CDC25. We also show that BN82002 reduces growth rate of human tumor xenografts in athymic nude mice. BN82002 is a original CDC25 inhibitor that is active both in cell and animal models. This greatly reinforces the interest in CDC25 as an anticancer target.
The Bcl-2 Family Protein Inhibitor, ABT-737, Has Substantial Antimyeloma Activity and Shows Synergistic Effect with Dexamethasone and Melphalan
Authors: Suzanne Trudel, A. Keith Stewart, Zhihua Li, Yanjun Shu, Sheng-Ben Liang, Young Trieu, Donna Reece, Josh Paterson, Dingyan Wang, Xiao-Yan Wen
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The aim of this study is to investigate the antimyeloma activity of a novel Bcl-2 family inhibitor, ABT-737, in preclinical treatment of multiple myeloma. Experimental Design: The antimyeloma activity of ABT-737 was evaluated in cultured myeloma cell lines and patient myeloma samples, and in a xenograft mouse myeloma model. Drug combination therapy using ABT-737 with other commonly used myeloma drugs was also investigated. Results: MY5 and JJN3 cell lines exhibited the most sensitivity to ABT-737 with an EC50 of 0.2 and 0.5 μmol/L, respectively, with increased cell apoptosis and elevated activated caspase-3. We identified two distinct groups of myeloma patient samples that were either sensitive or resistant to the drug. Four of 15 patient bone marrow samples (27%) were highly sensitive to ABT-737 at doses of 0.25 and 0.5 μmol/L, which eliminated 80% to 90% of myeloma cells as a result of cellular apoptosis 3 days after drug treatment. ABT-737 showed a synergistic effect when combined with dexamethasone or melphalan in inducing myeloma cell death. Furthermore, the dexamethasone-resistant MM1(Dex)R myeloma cell line was highly sensitive to 0.2 μmol/L ABT-737. As determined by colony assay, little or no detectable toxicity to patient hematologic progenitor cells was observed at 1 μmol/L ABT-737. ABT-737 dose dependently suppressed tumor growth in a xenograft MY5 mouse model. Conclusions: These studies show substantial antimyeloma activity of ABT-737 as a single agent or in combination with dexamethasone or melphalan and suggest a rationale for future clinical trials.