tbuckley/cabot-search huggingface dataset:
ARTICLES: Testicular Nonseminoma and Seminoma in Relation to Perinatal Characteristics
Authors: O. Akre, A. Ekbom, C.-C. Hsieh, D. Trichopoulos, H.-O. Adami
Journal: JNCI Journal of the National Cancer Institute (1996)

Testicular cancer incidence peaks during the third decade of life, and an increasing trend in the occurrence of this disease has been seen in many countries. Few risk factors have been established for testicular cancer, but evidence suggests that causal factors operate early in life, perhaps even in utero.We performed a case-control study to evaluate specific perinatal characteristics as risk factors for the two main histopathologic types of testicular cancer: seminomas and nonseminomas.Two hundred thirty-two case patients with invasive testicular cancer and 904 individually matched control subjects (all singleton births), nested in a cohort of men born at 10 hospitals in Sweden from 1920 through 1978, were included in the study. Perinatal information about the study subjects and their parents was obtained from birth records. For the mothers, information was recorded concerning age at menarche, marital status, parity, age at delivery, maternal weight at delivery and at first visit to a maternal-care center, education and/or profession, and any medical problems encountered during pregnancy or after delivery. For the fathers, information was obtained concerning age at delivery and education and/or profession. For the study subjects, information was recorded about the following: gestational age, birth length and weight, placental weight, method of delivery (normal, cesarean section, or with forceps or vacuum extractor), medical problems during hospital stay, presence of jaundice, method of feeding at discharge, and duration of hospital stay after birth. Individuals diagnosed with testicular cancer were identified through the Swedish National Cancer Registry and the Uppsala Regional Cancer Registry. The data were analyzed by use of conditional logistic regression modeling.When testicular cancer was modeled as a single entity, significantly elevated risks were associated with neonatal jaundice (adjusted odds ratio [OR] = 2.30; 95% confidence interval [CI] = 1.07-4.94) and with either low (< 2500 g) or high (> or = 4000 g) birth weight (OR = 2.59; 95% CI = 1.05-6.38 and OR = 1.58; 95% CI = 1.10-2.29, respectively). When seminomas and nonseminomas were analyzed separately, high maternal socioeconomic status (OR = 2.54; 95% CI = 1.05-6.12), neonatal jaundice (OR = 3.96; 95% CI = 1.47-10.69), and low birth weight (OR = 7.62; 95% CI = 1.59-36.60) were associated with nonseminomas, whereas high placental weight (OR = 3.50; 95% CI = 0.97-12.62) suggested increased risk for seminomas.Perinatal exposures appear to influence the risk of testicular cancer, and seminomas and nonseminomas may have somewhat different risk profiles. Future epidemiologic studies should consider the possibility of etiologic heterogeneity in the development of seminomas and nonseminomas.
Importance of Long-Term Follow-Up of Women Receiving Adjuvant Therapy for Breast Cancer in the Community
Authors: Colin McCowan, John A. Dewar, Alastair M. Thompson
Journal: Journal of Clinical Oncology (2011)

read the accompanying editorial with interest, 2 and agree that longterm follow-up of trial participants is important and should be continued because it provides vital information on long-term outcomes, including morbidity.However, this should be extended to include long-term studies of how the medication is used in a community setting outside of clinical trials.Our previous study, 3 referenced by Hackshaw et al, 1 showed that the use of adjuvant therapy in the community is suboptimal compared with adjuvant therapy within trials and that this can have a significant effect on outcomes.Almost half of women who begin receiving adjuvant therapy fail to complete the 5-year course, and patients with low adherence have a higher risk of death.If we are to examine long-term outcomes, it is paramount that this examination is also conducted for women who are managed in the community to evaluate effectiveness in clinical practice.The recommendations of the editorial 2 should be broadened to ensure that the lessons learned from trials are implemented in clinical practice in the community.Where necessary, interventions to support patient adherence to prescribed adjuvant medications should be implemented to ensure that patients obtain the maximum benefit from their medication.
Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo
Authors: Didier Roulin, Yannick Cerantola, Anne Dormond-Meuwly, Nicolas Demartines, Olivier Dormond
Journal: Molecular Cancer (2010)

Abstract The mammalian target of rapamycin (mTOR), which exists in two functionally distinct complexes, mTORC1 and mTORC2 plays an important role in tumor growth. Whereas the role of mTORC1 has been well characterized in this process, little is known about the functions of mTORC2 in cancer progression. In this study, we explored the specific role of mTORC2 in colon cancer using a short hairpin RNA expression system to silence the mTORC2-associated protein rictor. We found that downregulation of rictor in HT29 and LS174T colon cancer cells significantly reduced cell proliferation. Knockdown of rictor also resulted in a G1 arrest as observed by cell cycle analysis. We further observed that LS174T cells deficient for rictor failed to form tumors in a nude mice xenograft model. Taken together, these results show that the inhibition of mTORC2 reduces colon cancer cell proliferation in vitro and tumor xenograft formation in vivo. They also suggest that specifically targeting mTORC2 may provide a novel treatment strategy for colorectal cancer.
Local Chemotherapy as a Curative Measure
Authors: R. V. Jones
Journal: BMJ (1941)

hypertrophy of the adrenals, a positive Ponceau-fuchsin reaction, and clinical improvement following unilateral adrenalectomy.Sterone excretion was reduced following operation.Perhaps these intersexual changes may be diagram- matized like this: y + excessive or altered sterone -virilism d + excessive or altered steronefeminism thus providing a further example of the bisexual properties of the sex hormones when acting on the different biological soils determined by the sex chromosomes.My thanks are due to Mr.
Two-Year Outcomes of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study
Authors: Quan Dong Nguyen, Syed Mahmood Shah, Afsheen A. Khwaja, Roomasa Channa, Elham Hatef, Diana V. Do, David Boyer, Jeffery S. Heier, Prema Abraham, Allen B. Thach, Eugene S. Lit, Bradley S. Foster, Erik Kruger, Pravin Dugel, Thomas Chang, Arup Das, Thomas A. Ciulla, John S. Pollack, Jennifer I. Lim, Dean Eliot, Peter A. Campochiaro
Journal: Ophthalmology (2010)
Combined chemoradiotherapy with gemcitabine in patients with locally advanced inoperable transitional cell carcinoma of the urinary bladder and/or in patients ineligible for surgery: a phase I trial
Authors: M. De Santis, M. Bachner, M. Cerveny, G. Kametriser, T. Steininger, R. Königsberg, A. Schratter-Sehn, F. Sedlmayer, C. Dittrich
Journal: Annals of Oncology (2014)
Bayesian Pharmacokinetically Guided Dosing of Paclitaxel in Patients with Non-Small Cell Lung Cancer
Authors: Milly E. de Jonge, H. J. G. Desirée van den Bongard, Alwin D. R. Huitema, Ron A. A. Mathôt, Hilde Rosing, Paul Baas, Nico van Zandwijk, Jos H. Beijnen, Jan H. M. Schellens
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Paclitaxel is a taxane derivative with a profound antitumor activity against a variety of solid tumors. In a previous clinical study in patients with non-small cell lung cancer (NSCLC) treated with paclitaxel, it was shown that paclitaxel plasma concentrations of 0.1 μmol/liter for ≥15 h were associated with prolonged survival. The purpose of this study was to evaluate the feasibility of Bayesian dose individualization to attain paclitaxel plasma concentrations &amp;gt;0.1 μmol/liter for ≥15 h. Experimental Design: Patients with stage IIIb-IV NSCLC were treated with paclitaxel and carboplatin once every 3 weeks for a maximum of six courses. During the first course, a standard paclitaxel dose of 175 mg/m2 was administered i.v. in 3 h. In subsequent courses, the paclitaxel dose was individualized based on observed paclitaxel concentrations in plasma during the previous course(s) using a Bayesian algorithm. The paclitaxel dose of a subsequent course was increased to the lowest dose for which the predicted time period during which the paclitaxel plasma concentration exceeds 0.1 μmol/liter was &amp;gt;15 h. Results: A total of 25 patients have been included in the study (92 evaluable courses). During the first course, the median time period above the threshold concentration was 16.3 h (range, 7.6–31.6 h), and was &amp;lt;15 h for 9 patients (36%). During subsequent individualized courses, the time period above the threshold concentration was &amp;lt;15 h in 23% (5 of 22), 14% (2 of 14), 23% (3 of 13), 11% (1 of 9), and 11% (1 of 9) of the patients in the second, third, fourth, fifth, and sixth course, respectively. Dose increments, ranging from 5 to 65 mg/m2, were performed in 29 of the 67 individualized courses. Patients with increased individualized doses had similar regimen related toxicities compared with those remaining at a dose of 175 mg/m2. Toxicity was reversible and manageable, and was mainly hematological (granulocytopenia CTC grade 3/4 in 80% of the patients). The objective response rate was 20%. Conclusions: The results indicate that the applied pharmacokinetically guided dosing strategy for paclitaxel is safe and technically feasible. A randomized study is necessary to demonstrate whether dose individualization may result in improved activity and efficacy in patients with NSCLC.
DNA damage–induced transcriptional program in CLL: biological and diagnostic implications for functional p53 testing
Authors: Julia Mohr, Hanne Helfrich, Maxi Fuge, Eric Eldering, Andreas Bühler, Dirk Winkler, Matthias Volden, Arnon P. Kater, Daniel Mertens, Doreen Te Raa, Hartmut Döhner, Stephan Stilgenbauer, Thorsten Zenz
Journal: Blood (2010)
Studies on the purification and characterization of human factor VIII
Authors: Sally L. Marchesi, N. Raphael Shulman, Harvey R. Gralnick
Journal: Journal of Clinical Investigation (1972)

Factor VIII (antihemophilic globulin) has been prepared from Hyland method IV AHG and cryoprecipitate using limited chymotryptic digestion followed by Sepharose gel filtration. The activity of factor VIII is unaffected by the digestion procedure, while fibrinogen in converted to large noncoagulable fragments.
Treatment of heterotopic ossification through remote ATP hydrolysis
Authors: Jonathan R. Peterson, Sara De La Rosa, Oluwatobi Eboda, Katherine E. Cilwa, Shailesh Agarwal, Steven R. Buchman, Paul S. Cederna, Chuanwu Xi, Michael D. Morris, David N. Herndon, Wenzhong Xiao, Ronald G. Tompkins, Paul H. Krebsbach, Stewart C. Wang, Benjamin Levi
Journal: Science Translational Medicine (2014)

Heterotopic ossification induced by injuries and burns is mediated by signaling through the SMAD pathway and can be targeted with topical apyrase.
Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis
Authors: W Katchamart, J Trudeau, V Phumethum, C Bombardier
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To evaluate the efficacy and toxicity of methotrexate (MTX) monotherapy compared with MTX combination with non-biological disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis. <h3>Method:</h3> A systematic review of randomised trials comparing MTX alone and in combination with other non-biological DMARDs was carried out. Trials were identified in Medline, EMBASE, the Cochrane Library and ACR/EULAR meeting abstracts. Primary outcomes were withdrawals for adverse events or lack of efficacy. <h3>Results:</h3> A total of 19 trials (2025 patients) from 6938 citations were grouped by the type of patients randomised. Trials in DMARD naive patients showed no significant advantage of the MTX combination versus monotherapy; withdrawals for lack of efficacy or toxicity were similar in both groups (relative risk (RR) = 1.16; 95% CI 0.70 to 1.93). Trials in MTX or non-MTX DMARD inadequate responder patients also showed no difference in withdrawal rates between the MTX combo versus mono groups (RR = 0.86; 95% CI 0.49 to 1.51 and RR = 0.75; 95% CI 0.41 to 1.35), but in one study the specific combination of MTX with sulfasalazine and hydroxychloroquine showed a better efficacy/toxicity ratio than MTX alone with RR = 0.3 (95% CI 0.14 to 0.65). Adding leflunomide to MTX non-responders improved efficacy but increased the risk of gastrointestinal side effects and liver toxicity. Withdrawals for toxicity were most significant with ciclosporin and azathioprine combinations. <h3>Conclusion:</h3> In DMARD naive patients the balance of efficacy/toxicity favours MTX monotherapy. In DMARD inadequate responders the evidence is inconclusive. Trials are needed that compare currently used MTX doses and combination therapies.
Prediction of Response to Neoadjuvant Chemotherapy by Sequential F-18-Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced-Stage Ovarian Cancer
Authors: Norbert Avril, Stefanie Sassen, Barbara Schmalfeldt, Joerg Naehrig, Stephan Rutke, Wolfgang A. Weber, Martin Werner, Henner Graeff, Markus Schwaiger, Walther Kuhn
Journal: Journal of Clinical Oncology (2005)

Purpose The aim of this study was to evaluate sequential F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) to predict patient outcome after the first and third cycle of neoadjuvant chemotherapy in advanced-stage (International Federation of Gynecology and Obstetrics stages IIIC and IV) ovarian cancer. Patients and Methods Thirty-three patients received three cycles of carboplatin-based chemotherapy, followed by cytoreductive surgery. Quantitative FDG-PET of the abdomen and pelvis was acquired before treatment and after the first and third cycle of chemotherapy. Changes in tumoral FDG uptake, expressed as standardized uptake values (SUV), were compared with clinical and histopathologic response; overall survival served as a reference. Results A significant correlation was observed between FDG-PET metabolic response after the first (P = .008) and third (P = .005) cycle of chemotherapy and overall survival. By using a threshold for decrease in SUV from baseline of 20% after the first cycle, median overall survival was 38.3 months in metabolic responders compared with 23.1 months in metabolic nonresponders. At a threshold of 55% decrease in SUV after the third cycle median overall survival was 38.9 months in metabolic responders compared with 19.7 months in nonresponders. There was no correlation between clinical response criteria (P = .7) or CA125 response criteria (P = .5) and overall survival. There was only a weak correlation (P = .09) between histopathologic response criteria and overall survival. Conclusion Sequential FDG-PET predicted patient outcome as early as after the first cycle of neoadjuvant chemotherapy and was more accurate than clinical or histopathologic response criteria including changes in tumor marker CA125. FDG-PET appears to be a promising tool for early prediction of response to chemotherapy.
Anticoagulation in pulmonary arterial hypertension: a qualitative systematic review
Authors: S. R. Johnson, S. Mehta, J. T. Granton
Journal: European Respiratory Journal (2006)

Thrombotic arteriopathy has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, the role of anticoagulants in the treatment of PAH is uncertain. Through a qualitative systematic review of epidemiological studies, the effectiveness of anticoagulation therapy with warfarin on survival was evaluated in patients with PAH. MEDLINE (1966 to November 2005), EMBASE (1966 to November 2005), bibliographies of included studies and published reviews were searched without language restriction. Epidemiological studies evaluating the effectiveness of warfarin in PAH were included. Studies had to report mortality as an outcome. Seven observational studies evaluating the effectiveness of warfarin comprising 488 patients were identified. Five studies support the effectiveness of anticoagulation therapy, whereas two do not. Data from observational studies suggest that anticoagulation therapy may be an effective intervention in pulmonary arterial hypertension. However, given the methodological limitations and the small number of existing observational studies, a randomised controlled trial is needed in order to definitively address this important clinical issue.
Wheat oral immunotherapy for wheat-induced anaphylaxis
Authors: Sakura Sato, Tomohiro Utsunomiya, Takanori Imai, Noriyuki Yanagida, Tomoyuki Asaumi, Kiyotake Ogura, Yumi Koike, Noriko Hayashi, Yu Okada, Akinori Shukuya, Motohiro Ebisawa
Journal: Journal of Allergy and Clinical Immunology (2015)
Cell Lineage Tracing Reveals a Biliary Origin of Intrahepatic Cholangiocarcinoma
Authors: Rachel V. Guest, Luke Boulter, Timothy J. Kendall, Sarah E. Minnis-Lyons, Robert Walker, Stephen J. Wigmore, Owen J. Sansom, Stuart J. Forbes
Journal: Cancer Research (2013)

Intrahepatic cholangiocarcinoma is a treatment refractory malignancy with a high mortality and an increasing incidence worldwide. Recent studies have observed that activation of Notch and AKT signaling within mature hepatocytes is able to induce the formation of tumors displaying biliary lineage markers, thereby raising the suggestion that it is hepatocytes, rather than cholangiocytes or hepatic progenitor cells that represent the cell of origin of this tumor. Here, we use a cholangiocyte-lineage tracing system to target p53 loss to biliary epithelia and observe the appearance of labeled biliary lineage tumors in response to chronic injury. Consequent to this, upregulation of native functional Notch signaling is observed to occur spontaneously within cholangiocytes and hepatocytes in this model as well as in human intrahepatic cholangiocarcinoma. These data prove that in the context of chronic inflammation and p53 loss, frequent occurrences in human disease, biliary epithelia are a target of transformation and an origin of intrahepatic cholangiocarcinoma.
Human hepatic stem cells from fetal and postnatal donors
Authors: Eva Schmelzer, Lili Zhang, Andrew Bruce, Eliane Wauthier, John Ludlow, Hsin-lei Yao, Nicholas Moss, Alaa Melhem, Randall McClelland, William Turner, Michael Kulik, Sonya Sherwood, Tommi Tallheden, Nancy Cheng, Mark E. Furth, Lola M. Reid
Journal: The Journal of Experimental Medicine (2007)

Human hepatic stem cells (hHpSCs), which are pluripotent precursors of hepatoblasts and thence of hepatocytic and biliary epithelia, are located in ductal plates in fetal livers and in Canals of Hering in adult livers. They can be isolated by immunoselection for epithelial cell adhesion molecule–positive (EpCAM+) cells, and they constitute ∼0.5–2.5% of liver parenchyma of all donor ages. The self-renewal capacity of hHpSCs is indicated by phenotypic stability after expansion for &amp;gt;150 population doublings in a serum-free, defined medium and with a doubling time of ∼36 h. Survival and proliferation of hHpSCs require paracrine signaling by hepatic stellate cells and/or angioblasts that coisolate with them. The hHpSCs are ∼9 μm in diameter, express cytokeratins 8, 18, and 19, CD133/1, telomerase, CD44H, claudin 3, and albumin (weakly). They are negative for α-fetoprotein (AFP), intercellular adhesion molecule (ICAM) 1, and for markers of adult liver cells (cytochrome P450s), hemopoietic cells (CD45), and mesenchymal cells (vascular endothelial growth factor receptor and desmin). If transferred to STO feeders, hHpSCs give rise to hepatoblasts, which are recognizable by cordlike colony morphology and up-regulation of AFP, P4503A7, and ICAM1. Transplantation of freshly isolated EpCAM+ cells or of hHpSCs expanded in culture into NOD/SCID mice results in mature liver tissue expressing human-specific proteins. The hHpSCs are candidates for liver cell therapies.
The Role of microRNA-221 and microRNA-222 in Androgen-Independent Prostate Cancer Cell Lines
Authors: Tong Sun, Qianben Wang, Steven Balk, Myles Brown, Gwo-Shu Mary Lee, Philip Kantoff
Journal: Cancer Research (2009)

Androgen-dependent prostate cancer typically progresses to castration-resistant prostate cancer (CRPC) after the androgen deprivation therapy. MicroRNAs (miR) are noncoding small RNAs (19-25nt) that play an important role in the regulation of gene expression. Recent studies have shown that miR expression patterns are significantly different in normal and neoplastic prostate epithelial cells. However, the importance of miRs in the development of CRPC has not yet been explored. By performing genome-wide expression profiling of miRs, we found that expression levels of several miRs, in particular miR-221 and miR-222, were significantly increased in CRPC cells (the LNCaP-derived cell line LNCaP-Abl), compared with those in the androgen-dependent prostate cancer cell line (LNCaP). Overexpression of miR-221 or miR-222 in LNCaP or another androgen-dependent cell line, LAPC-4, significantly reduced the level of the dihydrotestosterone (DHT) induced up-regulation of prostate-specific antigen (PSA) expression and increased androgen-independent growth of LNCaP cells. Knocking down the expression level of miR-221 and miR-222 with antagonist miRs in the LNCaP-Abl cell line restored the response to the DHT induction of PSA transcription and also increased the growth response of the LNCaP-Abl cells to the androgen treatment. Changing the expression level of p27/kip1, a known target of miR-221 and miR-222, alone in LNCaP cells affected the DHT-independent cell growth but did not significantly influence the response of PSA transcription to the DHT treatment. In conclusion, our data suggest the involvement of miR-221 and miR-222 in the development or maintenance of the CRPC phenotype.
An Open-Label Trial of Evidence-Based Cognitive Behavior Therapy for Nightmares and Insomnia in Crime Victims With PTSD
Authors: Barry Krakow, Lisa Johnston, Dominic Melendrez, Michael Hollifield, Teddy D. Warner, Debie Chavez-Kennedy, Margaret J. Herlan
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Insomnia and nightmares are perceived as secondary phenomena in posttraumatic stress disorder (PTSD). Scant treatment research has targeted these two sleep disturbances. This study reports on an open-label trial of cognitive behavior therapy for insomnia and disturbing dreams in crime victims with PTSD. The relationship among nightmares, sleep disturbances, and PTSD symptoms is discussed. METHOD: Sixty-two participants completed a 10-hour group treatment consisting of imagery rehearsal for nightmares and sleep hygiene, stimulus control, and sleep restriction for insomnia. Nightmare frequency, sleep quality, sleep impairment, and ratings for PTSD, anxiety, and depression symptoms were assessed at baseline and at the 3-month follow-up. RESULTS: All measures demonstrated improvement that was roughly equivalent to changes in clinical severity from severe to moderate for sleep quality, sleep impairment, and nightmare frequency, from borderline severe to borderline moderate for PTSD symptoms, and from extremely severe to borderline severe for anxiety and depression symptoms. CONCLUSIONS: In this uncontrolled study, successful treatment for insomnia and nightmares in crime victims was associated with improvement in symptoms of PTSD, anxiety, and depression. Participants with clinical improvements in PTSD symptoms demonstrated significantly greater improvement in sleep quality and nightmare frequency than those whose PTSD symptoms did not improve.