tbuckley/cabot-search huggingface dataset:
Staging Procedures, Clinical Management, and Survival Outcome for Ovarian Carcinoma
Authors: Roger Hand
Journal: JAMA (1993)

To evaluate the relationship between survival and patterns of clinical management for ovarian carcinoma.Retrospective analysis of cancer registry data including follow-up, operative reports, and pathology reports.Seventy-seven Illinois hospitals with active cancer registries.A total of 2669 women with newly diagnosed ovarian carcinoma from 1983 through 1988.Frequency of use of specific staging procedures and treatment options. Survival was estimated using the Kaplan-Meier product-limit method.Thirty percent of 632 stage I patients, 31% of 233 stage II patients, and 45% of 516 stage III patients underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, sampled peritoneal washings, and node biopsy. Five-year survival for those receiving this extensive surgery (who were therefore pathologically staged) was as follows: stage I, 80%; stage II, 63%; and stage III, 28%. For those not receiving this extensive surgery (who were therefore clinically staged), the 5-year survival at these stages was 76%, 62%, and 21%, respectively. The overall survival curves were not significantly different between those who were pathologically staged and those who were clinically staged for stage I patients (P = .27) or stage II patients (P = .47), but were for stage III patients (P = .01). Platinum-based combination chemotherapy was given to 76% of 221 patients with pathological stage III disease. Their 5-year survival--50% for the group with no residual disease and 20% for the group with residual disease--was better than for those receiving regimens without platinum--37% and 5%, respectively, for the two groups--and the overall survival curves were significantly better for those receiving platinum (P < .0005 for both groups). The groups receiving platinum had younger patients.Extensive surgery for pathological staging was not usually done for management of ovarian cancer, while platinum-based chemotherapy was commonly used. Failure to undergo extensive surgery had little impact on survival for stage I and II patients. However, use of extensive surgery and platinum-based chemotherapy improved survival for stage III patients. The improved survival for this group receiving platinum-based chemotherapy may be explained in part by selection of younger patients for this treatment.
Abnormal Carbohydrate Metabolism During Pregnancy
Authors: Giancarlo Paradisi, Arabella Biaggi, Sergio Ferrazzani, Sara De Carolis, Alessandro Caruso
Journal: Diabetes Care (2002)

To evaluate whether abnormal endothelial function, a common finding in premenopausal women with type 2 diabetes, is present in early states of diabetes during pregnancy, such as impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM).Brachial artery flow-mediated dilatation (FMD) (endothelium-dependent) and nitrate-induced dilatation (NID) (endothelium-independent) were measured in 23 pregnant subjects with carbohydrate abnormalities (10 IGT, 13 GDM) and in 15 pregnant control subjects during the third trimester of gestation. High-resolution vascular ultrasonography was used to perform these investigations. A fasting lipid panel was obtained, and glucose and insulin values in response to a 100-g oral glucose load were also measured.FMD was significantly reduced in both groups of women with abnormal carbohydrate metabolism compared with control subjects (7.6 +/- 1.1% in the IGT group and 4.1 +/- 0.9% in the GDM group vs. 10.9 +/- 1.1% in control subjects, P < 0.04 and P < 0.0001, respectively). Significant difference in FMD was also observed between IGT and GDM groups (P < 0.04). NID was comparable in the three groups. Among all subjects, FMD showed a strong independent negative correlation with glycemic area (r=-0.60, P < 0.0001).Endothelial dysfunction, an early marker of macrovascular disease, is present in pregnancies complicated by IGT and GDM. This alteration, which seems to be directly related to glycemic levels, could explain, at least in part, the increased risk for concurrent hypertensive disorders during pregnancy in these women.
Surgical treatment of granuloma inguinale
Authors: None Bozbora, None Erbil, None Berber, None OzarmaGan, None OzarmaGan
Journal: British Journal of Dermatology (1998)

Granuloma inguinale is an indolent, progressive, ulcerative and granulomatous skin disease caused by Calymmatobacterium granulomatosis. It is generally treated with antibiotics. However, long‐standing and complicated disease requires surgical treatment. Two patients with extensive and multiple perianal fistulas and abscesses unresponsive to medical treatment were managed with radical surgical resection. The first patient healed by primary intention, but a diverting colostomy was made for the second patient and the tissue defect was closed with a rotation flap. Follow‐up at 4 years revealed the disappearance of the symptoms and the absence of recurrence in both patients.
Metastases of Human Melanomas Transplanted in “Nude” Mice2
Authors: B. C. Giovanella, S. O. Yim, A. C. Morgan, J. S. Stehlin, L. J. Williams
Journal: JNCI Journal of the National Cancer Institute (1973)

Three human melanomas grown in tissue culture were injected intradermally or subcutaneously into thymus-deficient “nude” mice. Invasive tumors were induced by 2 melanomas at the site of injection. All 3 metastasized to the cervical or inguinal lymph nodes and 1 to the lungs. Karyotypic analysis of the 3 metastatic tumors identified them as human.
The Role of Cyclooxygenase Inhibition in the Antineoplastic Effects of Nonsteroidal Antiinflammatory Drugs (Nsaids)
Authors: Steven J. Shiff, Basil Rigas
Journal: The Journal of Experimental Medicine (1999)

According to WHO statistics, in 1996 875,000 new cases of colorectal cancer were diagnosed and 495,000 deaths were attributed to it worldwide ([1][1]). It is the third most common cause of cancer deaths and its incidence and mortality rates continue to rise.

Most colorectal cancers develop via a
Extension of Increased Atherosclerotic Wall Thickness Into High Shear Stress Regions Is Associated With Loss of Compensatory Remodeling
Authors: Jolanda J. Wentzel, Elbert Janssen, Jeroen Vos, Johan C.H. Schuurbiers, Rob Krams, Patrick W. Serruys, Pim J. de Feyter, Cornelis J. Slager
Journal: Circulation (2003)

Atherosclerosis preferentially develops at average low shear stress (SS) locations. SS-related signaling maintains lumen dimensions by inducing outward arterial remodeling. Prolonged plaque accumulation at low SS predilection locations explains an inverse relation between wall thickness (WT) and SS. No data exist on WT-SS relations when lumen narrowing and loss of compensatory remodeling commence.In 14 patients, an angiographically normal artery (stenosis <50%) was investigated with ANGiography and ivUS (ANGUS) to provide 3D lumen and wall geometry. Selection of segments >5 mm in length, in between side branches, yielded 25 segments in 12 patients. SS at the wall was calculated by computational fluid dynamics. WT smaller than 0.2*lumen diameter was defined as normal. Largest arc of normal WT defined reference cross sections. Lumen area relative to the reference cross sections defined area stenosis (AS). Average segmental AS smaller or greater than 10% defined preserved or narrowed lumen, respectively. Total vessel area relative to the reference defined vascular remodeling (VR). For the preserved lumens (n=11, AS=1.7+/-5.6%, P=NS), axially averaged WT and SS were inversely related (slope, -0.46+/-0.55 mm/Pa, P<0.05) and VR was positive (7+/-9%, P<0.05). Narrowed segments (n=13, 1 excluded, AS=18+/-6%, P<0.05) showed no relation between WT and SS or vascular remodeling.In patient coronary arteries, the often-reported inverse WT-SS relationship appears restricted to lumen preservation and positive vascular remodeling. Its disappearance with lumen narrowing suggests a growing importance of non-SS-related plaque progression.
Cigarette smoke modulates rhinovirus-induced airway epithelial cell chemokine production
Authors: M. H. Hudy, S. L. Traves, S. Wiehler, D. Proud
Journal: European Respiratory Journal (2009)

Human rhinovirus (HRV) infections induce epithelial cell production of chemokines that may contribute to the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. Cigarette smoking is the predominant risk factor for the development of COPD and also aggravates asthma symptoms. We examined whether cigarette smoke extract (CSE) modulates viral inflammation by altering the profile of HRV-induced epithelial chemokine production. Purified HRV-16, and CSE were used to examine the effects on CXC chemokine ligand (CXCL)8 and CXCL10 production from both primary human bronchial epithelial cells and the BEAS-2B epithelial cell line. Both CSE and HRV-16 induced CXCL8 production and, when used in combination, induced at least an additive production of CXCL8 compared with either stimulus alone. In contrast, CSE did not induce CXCL10 and markedly inhibited HRV-16-induced CXCL10 production. Inhibition of HRV-16-induced CXCL10 by CSE was mediated, at least in part, via transcriptional regulation. The increased CXCL8 production seen with the combination of CSE and HRV-16 was not due to transcriptional regulation but was associated with CXCL8 mRNA stabilisation. Thus, CSE differentially modulates HRV-16-induced chemokine production from human airway epithelial cells in a manner that might be expected to alter inflammatory cell profiles.
Signal transducer and activator of transcription 3 promotes angiogenesis and drives malignant progression in glioma
Authors: Tiffany A. Doucette, Ling-Yuan Kong, Yuhui Yang, Sherise D. Ferguson, Jinbo Yang, Jun Wei, Wei Qiao, Gregory N. Fuller, Krishna P. Bhat, Kenneth Aldape, Waldemar Priebe, Oliver Bögler, Amy B. Heimberger, Ganesh Rao
Journal: Neuro-Oncology (2012)

Signal transducer and activator of transcription (STAT) 3 has been described as a "master regulator" of signaling pathways involved in the transition from low-grade glioma (LGG) to high-grade glioma (HGG). Although STAT3 is overexpressed in HGGs, it remains unclear whether its overexpression is sufficient to induce or promote the malignant progression of glioma. To characterize the effect of STAT3 expression on tumor progression in vivo, we expressed the STAT3 gene in glioneuronal progenitor cells in mice. STAT3 was expressed alone or concurrently with platelet-derived growth factor B (PDGFB), a well-described initiator of LGG. STAT3 alone was insufficient to induce tumor formation; however, coexpression of STAT3 with PDGFB in mice resulted in a significantly higher incidence of HGGs than PDGFB alone. The median symptomatic tumor latency in mice coexpressing STAT3 and PDGFB was significantly shorter, and mice that developed symptomatic tumors demonstrated significantly higher expression of phosphorylated STAT3 intratumorally. In HGGs, expression of STAT3 was associated with suppression of apoptosis and an increase in tumor cell proliferation. HGGs induced by STAT3 and PDGFB also displayed frequent foci of necrosis and microvascular proliferation. The expression of CD31 (a marker of endothelial proliferation) was significantly higher in tumors induced by coexpression of STAT3 and PDGFB. When mice injected with PDGFB and STAT3 were treated with a STAT3 inhibitor, median survival increased and the incidence of HGG and CD31 expression decreased significantly. These results demonstrate that STAT3 promotes the malignant progression of glioma. Inhibiting STAT3 expression mitigates tumor progression and improves survival, validating it as a therapeutic target.
Combined Vascular Endothelial Growth Factor Receptor/Epidermal Growth Factor Receptor Blockade with Chemotherapy for Treatment of Local, Uterine, and Metastatic Soft Tissue Sarcoma
Authors: Wenhong Ren, Borys Korchin, Guy Lahat, Caimiao Wei, Svetlana Bolshakov, Theresa Nguyen, William Merritt, Adam Dicker, Alexander Lazar, Anil Sood, Raphael E. Pollock, Dina Lev
Journal: Clinical Cancer Research (2008)

Soft tissue sarcoma (STS) is a rare heterogeneous malignancy. Overall survival has been stagnant for decades, primarily because systemic therapies are ineffective versus metastases, the leading cause of STS lethality. Consequently, we examined whether tyrosine kinase receptors active in STS growth signaling might be blockable and whether multireceptor blockade might synergize with low-dose STS chemotherapy by therapeutically affecting STS cells and their associated microenvironment.Vandetanib (AstraZenca), a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, was evaluated alone and with chemotherapy in vitro and in vivo in three human STS nude mouse xenograft models of different STS locations (muscle, uterus, lung), stages (primary, metastatic), and subtypes (leiomyosarcoma, fibrosarcoma, uterine sarcoma: luciferase-expressing MES-SA human uterine sarcoma cells surgically implanted into uterine muscularis with bioluminescence tumor growth assessment; developed by us).In vitro, human STS cells were sensitive to vandetanib. Vandetanib alone and with chemotherapy statistically significantly inhibited leiomyosarcoma local growth and fibrosarcoma lung metastasis. Direct injection of MES-SA into nude mice uterine muscularis resulted in high tumor take (88%), whereas s.c. injection resulted in no growth, suggesting microenvironmental tumor growth modulation. Vandetanib alone and with chemotherapy statistically significantly inhibited uterine sarcoma growth. In all models, vandetanib induced increased apoptosis, decreased tumor cell proliferation, and decreased angiogenesis.Vandetanib has antitumor effects against human STS subtypes in vitro and in vivo, where it also affects the tumor-associated microenvironment. Given the urgent need for better systemic approaches to STS, clinical trials evaluating vandetanib, perhaps with low-dose chemotherapy, seem warranted.
Multiple Coronary Arteriovenous Fistulas to the Coronary Sinus With an Unruptured Coronary Sinus Aneurysm and Restrictive Coronary Sinus Opening to the Right Atrium
Authors: Sung-Ho Jung, Won-Chul Cho, Suk Jung Choo, Hyun Song, Cheol Hyun Chung, Joon-Won Kang, Jae-Kwan Song, Jae Won Lee
Journal: Circulation (2009)
Liver disease in rheumatoid arthritis and Sjogren's syndrome. Prospective study using biochemical and serological markers of hepatic dysfunction.
Authors: J Webb, K Whaley, R N MacSween, G Nuki, W C Dick, W W Buchanan
Journal: Annals of the Rheumatic Diseases (1975)

Inter-relationships of biochemical and immunological tests of liver function have been studied in a prospective study of 216 patients with rheumatoid arthritis (RA), 32 patients with Sjogren's syndrome, and 27 patients with the sicca syndrome, and these results have been compared with those obtained 289 patients with osteoarthrosis or with a form of seronegative polyarthropathy. In general the prevalence of abnormalities in serum alkaline phosphatase, bromsulphthalein excretion, smooth muscle antibody, and mitochondrial antibody in the former three groups was higher than in patients with osteoarthrosis. Patients with Sjogren's syndrome with RA had a higher prevalence of abnormalities of bromsulphthalein excretion, salivary duct antibody than patients with the sicca syndrome. Patients with RA had a higher pervalence of rheumatoid factor than those with the sicca syndrome. Patients with a positive smooth muscle or mitochondrial antibody were found to have a higher prevalence of hepatomegaly and splenomegaly, of abnormal liver function tests, of other autoantibodies, and of histological abnromalitis of liver than those in whom these tests were negative.
A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/- γc-/- double-mutant mice
Authors: Rozemarijn S. van Rijn, Elles R. Simonetti, Anton Hagenbeek, Marieke C. H. Hogenes, Roel A. de Weger, Marijke R. Canninga-van Dijk, Kees Weijer, Hergen Spits, Gert Storm, Louis van Bloois, Ger Rijkers, Anton C. M. Martens, Saskia B. Ebeling
Journal: Blood (2003)
Impact of Psychotherapeutic Support for Patients With Gastrointestinal Cancer Undergoing Surgery: 10-Year Survival Results of a Randomized Trial
Authors: Thomas Küchler, Beate Bestmann, Stefanie Rappat, Doris Henne-Bruns, Sharon Wood-Dauphinee
Journal: Journal of Clinical Oncology (2007)

The impact of psychotherapeutic support on survival for patients with gastrointestinal cancer undergoing surgery was studied.A randomized controlled trial was conducted in cooperation with the Departments of General Surgery and Medical Psychology, University Hospital of Hamburg, Germany, from January 1991 to January 1993. Consenting patients (N = 271) with a preliminary diagnosis of cancer of the esophagus, stomach, liver/gallbladder, pancreas, or colon/rectum were stratified by sex and randomly assigned to a control group that received standard care as provided on the surgical wards, or to an experimental group that received formal psychotherapeutic support in addition to routine care during the hospital stay. From June 2003 to December 2003, the 10-year follow-up was conducted. Survival status for all patients was determined from our own records and from three external sources: the Hamburg cancer registry, family doctors, and the general citizen registration offices.Kaplan-Meier survival curves demonstrated better survival for the experimental group than the control group. The unadjusted significance level for group differences was P = .0006 for survival to 10 years. Cox regression models that took TNM staging or the residual tumor classification and tumor site into account also found significant differences at 10 years. Secondary analyses found that differences in favor of the experimental group occurred in patients with stomach, pancreatic, primary liver, or colorectal cancer.The results of this study indicate that patients with gastrointestinal cancer, who undergo surgery for stomach, pancreatic, primary liver, or colorectal cancer, benefit from a formal program of psychotherapeutic support during the inpatient hospital stay in terms of long-term survival.
Individualizing Follow-Up for Patients With Early-Stage Melanoma
Authors: Vernon K. Sondak, Sancy A. Leachman
Journal: Journal of Clinical Oncology (2011)

In this era of personalized medicine, in which every patient is sup- posed to be treated using a therapeutic plan that is tailored to provide the right care at the right time and in the right place, it is surprising how little attention has been paid to personalizing follow-up for patients after curative treatment of cancer. This is certainly true in localized cutane- ous melanoma, for which there is little if any consensus with regard to standard follow-up strategies and virtually no guidance with regard to how to individualize follow-up on the basis of a patient's estimated risk of requiring additional interventions. Should we (and our pa- tients) care about this deficiency? Absolutely— given the time, effort, and expense that are involved in the follow-up of patients with local- ized melanoma when weighed against the relatively limited value derived per clinic visit, and the challenges that patients in many loca- tions face with regard to obtaining appointments with dermatologists who are willing to perform comprehensive skin examinations and
Family correlations of arsenic methylation patterns in children and parents exposed to high concentrations of arsenic in drinking water.
Authors: Joyce S Chung, David A Kalman, Lee E Moore, Michael J Kosnett, Alex P Arroyo, Martin Beeris, D N Guha Mazumder, Alexandra L Hernandez, Allan H Smith
Journal: Environmental Health Perspectives (2002)

We investigated the evidence of a familial contribution to urinary methylation patterns in families ingesting arsenic in drinking water. Arsenic methylation can be assessed by measuring urinary levels of inorganic arsenic (InAs) and its methylated metabolites, monomethylarsonate (MMA), and dimethylarsinate (DMA). Methylation activity is reflected in the ratios: InAs/methylated arsenic (InAs/metAs) and MMA/DMA. Eleven families from Chile were selected because of their long-term exposure to very high levels of arsenic in drinking water (735-762 microg/L). Each family consisted of a father, a mother, and two children. We measured urinary arsenic and its methylated metabolites for each participant (n = 44). The intraclass correlation coefficients showed that 13-52% of the variations in the methylation patterns were from being a member of a specific family. Family correlations were calculated for father-mother, parent-child, and sibling-sibling pairs. Methylation patterns correlated strongly between siblings [r = 0.78 for InAs/metAs, 95% confidence interval (CI), 0.34-0.94; r = 0.82 for MMA/DMA, 95%CI, 0.43-0.95] compared to lower correlations in father-mother pairs (r = 0.18, r = -0.01, respectively), after adjustment for total urinary arsenic, age, and sex. Family correlations were not notably altered when adjustments were made for specific blood micronutrients (methionine, homocysteine, folate, vitamin B6, selenium, and vitamin B12 potentially related to methylation. We also report on a family pedigree with high prevalence of arsenic-induced effects. Participants from this family had low InAs/metAs values, which is consistent with increased toxicity of trivalent methylated arsenic species. Despite our small sample size, we observed that methylation patterns aggregate in families and are correlated in siblings, providing evidence of a genetic basis for the variation in arsenic methylation. Larger studies with more extensive pedigrees will need to be conducted to confirm these findings.
Large-scale identification of human genes implicated in epidermal barrier function
Authors: Eve Toulza, Nicolas R Mattiuzzo, Marie-Florence Galliano, Nathalie Jonca, Carole Dossat, Daniel Jacob, Antoine de Daruvar, Patrick Wincker, Guy Serre, Marina Guerrin
Journal: Genome biology (2007)

Abstract Background During epidermal differentiation, keratinocytes progressing through the suprabasal layers undergo complex and tightly regulated biochemical modifications leading to cornification and desquamation. The last living cells, the granular keratinocytes (GKs), produce almost all of the proteins and lipids required for the protective barrier function before their programmed cell death gives rise to corneocytes. We present here the first analysis of the transcriptome of human GKs, purified from healthy epidermis by an original approach. Results Using the ORESTES method, 22,585 expressed sequence tags (ESTs) were produced that matched 3,387 genes. Despite normalization provided by this method (mean 4.6 ORESTES per gene), some highly transcribed genes, including that encoding dermokine, were overrepresented. About 330 expressed genes displayed less than 100 ESTs in UniGene clusters and are most likely to be specific for GKs and potentially involved in barrier function. This hypothesis was tested by comparing the relative expression of 73 genes in the basal and granular layers of epidermis by quantitative RT-PCR. Among these, 33 were identified as new, highly specific markers of GKs, including those encoding a protease, protease inhibitors and proteins involved in lipid metabolism and transport. We identified filaggrin 2 (also called ifapsoriasin), a poorly characterized member of the epidermal differentiation complex, as well as three new lipase genes clustered with paralogous genes on chromosome 10q23.31. A new gene of unknown function, C1orf81 , is specifically disrupted in the human genome by a frameshift mutation. Conclusion These data increase the present knowledge of genes responsible for the formation of the skin barrier and suggest new candidates for genodermatoses of unknown origin.