tbuckley/cabot-search huggingface dataset:
Serum Human Telomerase Reverse Transcriptase Messenger RNA as a Novel Tumor Marker for Hepatocellular Carcinoma
Authors: Norimasa Miura, Yoshiko Maeda, Takamasa Kanbe, Hiroaki Yazama, Yohei Takeda, Reina Sato, Tomoe Tsukamoto, Emi Sato, Akira Marumoto, Tomomi Harada, Akiko Sano, Yosuke Kishimoto, Yasuaki Hirooka, Yoshikazu Murawaki, Junichi Hasegawa, Goshi Shiota
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We previously reported the usefulness of a qualified highly sensitive detection method for human telomerase reverse transcriptase (hTERT) mRNA in serum with 89.7% sensitivity for hepatocellular carcinoma (HCC). In this study, we developed a quantitative detection method for serum hTERT mRNA and examined the clinical significance in HCC diagnosis. Experimental Background: In 64 patients with HCC, 20 with liver cirrhosis, 20 with chronic hepatitis, and 50 healthy individuals, we measured serum hTERT mRNA by using the newly developed real-time quantitative reverse transcription-PCR with SYBR Green I. We examined its sensitivity and specificity in HCC diagnosis, clinical significance in comparison with other tumor markers, and its correlations with the clinical variables by using multivariate analyses. Results: Serum hTERT mRNA showed higher values in patients with HCC than those with chronic liver diseases. hTERT mRNA expression was shown to be independently correlated with clinical variables such as tumor size, number, and degree of differentiation (P &amp;lt; 0.001, each). The sensitivity/specificity of hTERT mRNA and alpha;-fetoprotein (AFP) mRNA in HCC diagnosis were 88.2%/70.0% for hTERT and 71.6%/67.5% for AFP, respectively. hTERT mRNA proved to be superior to AFP mRNA, AFP, and des-γ-carboxy prothrombin in HCC diagnosis. Furthermore, hTERT mRNA in serum was associated with that in HCC tissue. Conclusions: The usefulness of hTERT mRNA expression in HCC diagnosis and its superiority to conventional tumor markers were shown. Therefore, serum hTERT mRNA is a novel and available marker for HCC diagnosis.
Studies on the murine Ss protein. I. Purification, molecular weight, and subunit structure.
Authors: J D Capra, E S Vitetta, J Klein
Journal: The Journal of Experimental Medicine (1975)

The murine Ss protein has been isolated and purified. Using specific antisera, the radiolabeled protein has a mol wt of 120,000 in sodium dodecyl sulfate polyacrylamide gels. It is composed of two basic subunits of 23,000 and 14,000 daltons. The smaller molecular weight subunit contains a single disulfide bridge, is devoid of carbohydrate, and may represent the murine equivalent of beta2-microglobulin.
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Authors: Linda Madisen, Theresa A Zwingman, Susan M Sunkin, Seung Wook Oh, Hatim A Zariwala, Hong Gu, Lydia L Ng, Richard D Palmiter, Michael J Hawrylycz, Allan R Jones, Ed S Lein, Hongkui Zeng
Journal: Nature Neuroscience (2009)
Gefitinib (“Iressa”, ZD1839), an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Reverses Breast Cancer Resistance Protein/ABCG2–Mediated Drug Resistance
Authors: Yoichi Nakamura, Mikio Oka, Hiroshi Soda, Ken Shiozawa, Megumi Yoshikawa, Akiko Itoh, Yoji Ikegami, Junji Tsurutani, Katsumi Nakatomi, Takeshi Kitazaki, Seiji Doi, Hisahiro Yoshida, Shigeru Kohno
Journal: Cancer Research (2005)

Abstract Gefitinib (“Iressa”, ZD1839) is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor, and the single agent is clinically effective in non–small cell lung cancer. Although gefitinib combined with various cytotoxic agents has been reported to enhance cytotoxicity in vitro and in mouse models, the mechanism remains undetermined. Here, to explore the mechanism with topoisomerase I inhibitors, we focused on the efflux pump of the breast cancer resistance protein (BCRP/ABCG2), and then examined whether gefitinib restored drug sensitivity in multidrug-resistant cancer cells overexpressing BCRP. We used PC-6 human small cell lung cancer cells and multidrug-resistant PC-6/SN2-5H cells selected with SN-38 of the active metabolite of irinotecan, and BCRP-overexpressing MCF-7/MX cells selected with mitoxantrone and BCRP cDNA transfectant MCF-7/clone 8 cells. Drug sensitivity against anticancer drugs was determined by tetrazolium dye assay, and intracellular topotecan accumulation by FACScan. The topotecan transport study was done using the plasma membrane vesicles of PC-6/SN2-5H cells. The resistant PC-6/SN2-5H cells overexpressed BCRP but not epidermal growth factor receptor mRNA. Ten micromoles of gefitinib reversed topotecan, SN-38, and mitoxantrone resistance, and increased the intracellular topotecan accumulation in the resistant cells but not in the parental cells. Furthermore, gefitinib inhibited the topotecan transport into the vesicles, and the Ki value was 1.01 ± 0.09 μmol/L in the Dixon plot analysis, indicating direct inhibition of BCRP by gefitinib. However, gefitinib was not transported into the vesicles with the high-performance liquid chromatography method. These results indicate that gefitinib reverses BCRP-mediated drug resistance by direct inhibition other than competitive inhibition as a BCRP substrate. Combination of gefitinib and topoisomerase I inhibitors could be clinically effective in cancers expressing BCRP.
The effects of radiotherapy and chemotherapy on female reproduction
Authors: D. Meirow
Journal: Human Reproduction Update (2001)

High dose chemotherapy and radiotherapy have radically increased long-term survival of young cancer patients, but major side effects of these treatments are ovarian failure and infertility. Knowledge of the risks and probabilities of ovarian failure caused by treatment is crucial for patients and physicians in order to make informed choices that will best serve patients’ interests. This review presents data on ovarian damage and failure following exposure to radiotherapy, chemotherapy and ablative therapy. The risk is evaluated from the published literature according to patient’s age, treatment protocol and also according to the diagnosis of some common malignancies. Many of these patients will not be sterilized immediately following treatment, but will suffer from premature menopause. In order to prevent sterilization, ovarian transposition before pelvic irradiation is mandatory. Besides cryopreservation of ovarian tissue and embryos before administration of chemotherapy, the possible protective effect of pituitary–ovarian down-regulation is discussed. The mechanism of primordial follicles damage induced by radio/chemotherapy is presented as well as the role of apoptosis signalling pathways underlying destruction. Increased knowledge of these mechanisms could help to identify potential effective inhibitors that can block the path of primordial follicles destruction and reduce ovarian failure rate.
Selective surgery for peptic ulcer: a review
Authors: I. M. Orr
Journal: Gut (1962)

Peptic ulcer patients do not fall into one secretory pattern and methods are available by which the secretory pattern may be assessed. Provided this assessment is accurate and the operation appropriate to the requirements of the individual patient is carried out, the side-effects are not severe. The mortality from gastric surgery need not be above 1% and even when resection is involved the technical hazards of the operation are rarely the cause of death in experienced hands. Further improvement in immediate and long-term results and protection against recurrence may be expected as the principles of selection become better understood and surgical procedures adequate to each requirement become standardized.
Roles of Phosphatidylinositol 3′-Kinase and Mammalian Target of Rapamycin/p70 Ribosomal Protein S6 Kinase in K-Ras-Mediated Transformation of Intestinal Epithelial Cells
Authors: Jinyi Shao, B. Mark Evers, Hongmiao Sheng
Journal: Cancer Research (2004)

Phosphatidylinositol 3'-kinase (PI3K) activity is required for Ras- mediated transformation of intestinal epithelial cells (IECs). The mammalian target of rapamycin (mTOR) and its downstream pathways control the translation of specific mRNAs that are required for cell proliferation and transformation. Here, we elucidated the roles of PI3K and mTOR in K-Ras-mediated transformation of IECs (IEC-6). Induction of K-Ras activated PI3K and mTOR in IECs. p70 ribosomal protein S6 kinase activity was induced by K-Ras in a PI3K- and mTOR-dependent manner. K-Ras did not significantly alter the phosphorylation of eukaryotic initiation factor 4E-binding protein 1. Treatment with either LY-294002 or rapamycin inhibited IEC proliferation and resulted in G(1) growth arrest. However, it was noted that inhibition of mTOR enhanced K-Ras-mediated morphological transformation and increased invasiveness of IECs in a mitogen-activated protein/extracellular signal-regulated kinase-dependent manner. Furthermore, inhibition of PI3K or mTOR impaired the growth of an array of colon cancer cells. Spindle transformation, reduced E-cadherin, and increased invasiveness were observed in LY-294002-treated Moser cells. Thus, our results suggest that K-Ras-mediated transformation of IECs involves activation of the PI3K/mTOR pathway. Inhibition of PI3K/mTOR activity leads to G(1) growth arrest of transformed IECs. On the other hand, inhibition of PI3K or mTOR may induce the epithelial to mesenchymal transdifferentiation of IECs under certain circumstances.
The Belgian PCB and dioxin incident of January-June 1999: exposure data and potential impact on health.
Authors: N van Larebeke, L Hens, P Schepens, A Covaci, J Baeyens, K Everaert, J L Bernheim, R Vlietinck, G De Poorter
Journal: Environmental Health Perspectives (2001)

In January 1999, 500 tons of feed contaminated with approximately 50 kg of polychlorinated biphenyls (PCBs) and 1 g of dioxins were distributed to animal farms in Belgium, and to a lesser extent in the Netherlands, France, and Germany. This study was based on 20,491 samples collected in the database of the Belgian federal ministries from animal feed, cattle, pork, poultry, eggs, milk, and various fat-containing food items analyzed for their PCB and/or dioxin content. Dioxin measurements showed a clear predominance of polychlorinated dibenzofuran over polychlorinated dibenzodioxin congeners, a dioxin/PCB ratio of approximately 1:50,000 and a PCB fingerprint resembling that of an Aroclor mixture, thus confirming contamination by transformer oil rather than by other environmental sources. In this case the PCBs contribute significantly more to toxic equivalents (TEQ) than dioxins. The respective means +/- SDs and the maximum concentrations of dioxin (expressed in TEQ) and PCB observed per gram of fat in contaminated food were 170.3 +/- 487.7 pg, 2613.4 pg, 240.7 +/- 2036.9 ng, and 51059.0 ng in chicken; 1.9 +/- 0.8 pg, 4.3 pg, 34.2 +/- 30.5 ng, and 314.0 ng in milk; and 32.0 +/- 104.4 pg, 713.3 pg, 392.7 +/- 2883.5 ng, and 46000.0 ng in eggs. Assuming that as a consequence of this incident between 10 and 15 kg PCBs and from 200 to 300 mg dioxins were ingested by 10 million Belgians, the mean intake per kilogram of body weight is calculated to maximally 25,000 ng PCBs and 500 pg international TEQ dioxins. Estimates of the total number of cancers resulting from this incident range between 40 and 8,000. Neurotoxic and behavioral effects in neonates are also to be expected but cannot be quantified. Because food items differed widely (more than 50-fold) in the ratio of PCBs to dioxins, other significant sources of contamination and a high background contamination are likely to contribute substantially to the exposure of the Belgian population.
Association of Environmental Toxicants and Conduct Disorder in U.S. Children: NHANES 2001–2004
Authors: Joseph M. Braun, Tanya E. Froehlich, Julie L. Daniels, Kim N. Dietrich, Richard Hornung, Peggy Auinger, Bruce P. Lanphear
Journal: Environmental Health Perspectives (2008)

The purpose of this study was to examine the association of tobacco smoke and environmental lead exposure with conduct disorder (CD).The National Health and Nutrition Examination Survey (NHANES) 2001-2004 is a nationally representative cross-sectional sample of the noninstitutionalized U.S. population. We examined the association of prenatal tobacco, postnatal tobacco, and environmental lead exposure with CD in children 8-15 years of age (n = 3,081). We measured prenatal tobacco exposure by parent report of cigarette use during pregnancy, and postnatal tobacco using serum cotinine levels. We assessed lead exposure using current blood lead concentration. Parents completed the Diagnostic Interview Schedule for Children to determine whether their children met criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV ) for CD.Overall, 2.06% of children met DSM-IV criteria for CD in the past year, equivalent to 560,000 U.S. children 8-15 years of age. After adjustment, prenatal tobacco exposure was associated with increased odds for CD [odds ratio (OR) = 3.00; 95% confidence interval (CI), 1.36-6.63]. Increased blood lead levels (fourth vs. first quartile) and serum cotinine levels (fifth vs. first quintile) were associated with an 8.64-fold (95% CI, 1.87-40.04) and 9.15-fold (95% CI, 1.47-6.90) increased odds of meeting DSM-IV CD criteria. Increasing serum cotinine levels and blood lead levels were also associated with increased prevalence of CD symptoms (symptom count ratio, lead: 1.73; 95% CI, 1.23-2.43; symptom count ratio, cotinine: 1.97; 95% CI, 1.15-3.40).These results suggest that prenatal tobacco exposure and environmental lead exposure contribute substantially to CD in U.S. children.
Haplotype-specific suppression of cytotoxic T cell induction by antigen inappropriately presented on T cells.
Authors: P J Fink, I L Weissman, M J Bevan
Journal: The Journal of Experimental Medicine (1983)

To detect a strong cytotoxic T lymphocyte (CTL) response to minor histocompatibility (H) antigens in a 5-d mixed lymphocyte culture, it is necessary to use a responder that has been primed in vivo with antigen-bearing cells. It has previously been shown that minor-H-specific CTL can be primed in vivo both directly by foreign spleen cells and by presentation of foreign minor H antigens on host antigen-presenting cells. This latter route is evident in the phenomenon of cross-priming, in which H-2 heterozygous (A x B)F1 mice injected 2 wk previously with minor H-different H-2A (A') spleen cells generate both H-2A- and H-2B-restricted minor-H-specific CTL. In a study of the kinetics of direct- vs. cross-priming to minors in F1 mice, we have found that minor H-different T cells actually suppress the induction of virgin CTL capable of recognizing them. CTL activity measured from F1 mice 3-6 d after injection with viable A' spleen cells is largely H-2B restricted. The H-2A-restricted response recovers such that roughly equal A- and B-restricted activity is detected in mice as early as 8-10 d postinjection. This temporary hyporeactivity does not result from generalized immunosuppression--it is specific for those CTL that recognize the foreign minor H antigen in the context of the H-2 antigens on the injected spleen cells. The injected spleen cells that mediate this suppression are radiosensitive T cells; Lyt-2+ T cells are highly efficient at suppressing the induction of CTL in vivo. No graft vs. host reaction by the injected T cells appears to be required, as suppression of direct primed CTL can be mediated by spleen cells that are wholly tolerant of both host H-2 and minor H antigens. Suppression cannot be demonstrated by in vitro mixing experiments. Several possible mechanisms for haplotype-specific suppression are discussed, including inactivation of responding CTL by veto cells and in vivo sequestration of responding CTL by the injected spleen cells.
Prevention and management of duodenal polyps in familial adenomatous polyposis
Authors: L A A Brosens
Journal: Gut (2005)

amilial adenomatous polyposis (FAP) is one of two well described forms of hereditary colorectal cancer.The primary cause of death from this syndrome is colorectal cancer which inevitably develops usually by the fifth decade of life.Screening by genetic testing and endoscopy in concert with prophylactic surgery has significantly improved the overall survival of FAP patients.However, less well appreciated by medical providers is the second leading cause of death in FAP, duodenal adenocarcinoma.This review will discuss the clinicopathological features, management, and prevention of duodenal neoplasia in patients with familial adenomatous polyposis. FAMILIAL ADENOMATOUS POLYPOSIS cFAP is an autosomal dominant disorder caused by a germline mutation in the adenomatous polyposis coli (APC) gene.FAP is characterised by the development of multiple (>100) adenomas in the colorectum.Colorectal polyposis develops by age 15 years in 50% and age 35 years in 95% of patients.The lifetime risk of colorectal carcinoma is virtually 100% if patients are not treated by colectomy. 1atients with FAP can also develop a wide variety of extraintestinal findings.These include cutaneous lesions (lipomas, fibromas, and sebaceous and epidermoid cysts), desmoid tumours, osteomas, occult radio-opaque jaw lesions, dental abnormalities, congenital hypertrophy of the retinal pigment epithelium, and nasopharyngeal angiofibroma.In addition, FAP patients are at increased risk for several malignancies, such as hepatoblastoma, pancreatic, thyroid, biliary-tree, and brain tumours. 1 Other gastrointestinal manifestations commonly found in FAP patients are duodenal adenomas, and gastric fundic gland and adenomatous polyps.Of concern, duodenal cancer is the second leading cause of death after colorectal cancer in these individuals.
Cigarette Smoking, Alcohol Drinking, Hepatitis B, and Risk for Hepatocellular Carcinoma in Korea
Authors: S. H. Jee, H. Ohrr, J. W. Sull, J. M. Samet
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Liver cancer is one of the most common cancers worldwide, particularly in Asia and Africa, where infectious hepatitis and aflatoxin exposures are common. We conducted a prospective cohort study of liver cancer in Korea to assess the independent effects and interactions of smoking, alcohol consumption, and hepatitis B on risk of mortality from hepatocellular carcinoma. Methods: From a total of 1 283 112 men and women free of cancer at baseline, 3807 died from liver cancer during follow-up from 1993 to 2002. All participants reported their smoking and alcohol consumption, and hepatitis B surface antigen (HBsAg) status was documented for 47.2% of the participants. Relative risk and 95% confidence intervals (CIs) of mortality from hepatocellular carcinoma were calculated using proportional hazards models adjusted for age, alcohol drinking, diabetes, and HBsAg status. Results: Current smoking was associated with increased risk of mortality from hepatocellular carcinoma in men (RR = 1.4; 95% CI = 1.3 to 1.6) but not women (RR = 1.1; CI = 0.8 to1.7). The relative risk of mortality from hepatocellular carcinoma for male HBsAg carriers was 24.3 (95% CI = 21.9 to 26.9) times that in HBsAg-negative males; the relative risk for HBsAg-positive women was 54.4 (95% CI = 24.8 to119.5). Heavy alcohol drinking was associated with hepatocellular carcinoma mortality risk in the subgroup of men who were tested for HBsAg (RR =1.5; 95% CI = 1.2 to 2.0). There was no interaction among smoking, alcohol drinking, and HBsAg in terms of hepatocellular carcinoma mortality. Conclusion: Cigarette smoking, heavy alcohol consumption, and HBsAg were independently associated with increased risk of mortality from hepatocellular carcinoma but did not interact synergistically. The relatively higher increase in mortality from hepatocellular carcinoma in HBsAg-seropositive women compared with men merits further research.
A Century of Deciphering the Control Mechanisms of Sex Steroid Action in Breast and Prostate Cancer: The Origins of Targeted Therapy and Chemoprevention
Authors: V. Craig Jordan
Journal: Cancer Research (2009)

Abstract The origins of the story to decipher the mechanisms that control the growth of sex hormone–dependent cancers started more than 100 years ago. Clinical observations of the apparently random responsiveness of breast cancer to endocrine ablation (hormonal withdrawal) provoked scientific inquiries in the laboratory that resulted in the development of effective strategies for targeting therapy to the estrogen receptor (ER; or androgen receptor in the case of prostate cancer), the development of antihormonal treatments that dramatically enhanced patient survival, and the first successful testing of agents to reduce the risk of developing any cancer. Most importantly, elucidating the receptor-mediated mechanisms of sex steroid–dependent growth and the clinical success of antihormones has had broad implication in medicinal chemistry with the synthesis of new selective hormone receptor modulators for numerous clinical applications. Indeed, the successful translational research on the ER was the catalyst for the current strategy for developing targeted therapies to the tumor and the start of “individualized medicine.” During the past 50 years, ideas about the value of antihormones translated effectively from the laboratory to improve clinical care, improve national survival rates, and significantly reduced the burden of cancer. [Cancer Res 2009;69(4):1243–54]
Should the NHS work at weekends as it does in the week? No
Authors: P. Flynn
Journal: BMJ (2013)

Some royal colleges recently advised that patients should get the same consultant led care at weekends as they do on weekdays. <b>Bruce Keogh</b> (doi:10.1136/bmj.f621) agrees that this would benefit patients, but <b>Paul Flynn</b> sees little justification for elective care at weekends and asks who’s going to pay
Changes in the peritoneal equilibration test in selected chronic peritoneal dialysis patients.
Authors: W K Lo, A Brendolan, B F Prowant, H L Moore, R Khanna, Z J Twardowski, K D Nolph
Journal: Journal of the American Society of Nephrology (1994)

Fifty-five patients on chronic peritoneal dialysis with two or more peritoneal equilibration tests (PET) performed between 1983 and 1992 with a mean interval of 21.9 +/- 22.7 months were studied retrospectively. Repeated PET were performed when transport changes were suspected rather than routinely. According to the initial PET, there were 16 high (HI), 17 high-average (HA), 15 low-average (LA), and 7 low (LO) transporters. There was a significant decrease in the mean creatinine dialysate to plasma ratio (D/P creatinine) in the HI transporters and an increase in the LA and LO transporters. The mean dialysate to instilled glucose ratio (D/Do) significantly increased in the HI transporters. The change in both the D/P creatinine and the D/Do of an individual strongly and inversely correlated to their respective initial values. The change in D/P creatinine and D/Do were significantly and inversely correlated to each other, indicating an actual transport change. No correlation was found between the change in transport with peritonitis episodes or frequencies. The centripetal [corrected] change of transport toward average described here may explain why low clearances or low ultrafiltration rates due to rapid transport are infrequent causes of peritoneal dialysis technique failure, and why patients who have been dialyzed for a long period are usually HA transporters.