tbuckley/cabot-search huggingface dataset:
Effects of Diethylnitrosamine on Hepatic Receptor Binding and Autophosphorylation of Epidermal Growth Factor and Insulin in Rats&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: B I Carr, A Roitman, D L Hwang, G Barseghian, A Lev-Ran
Journal: JNCI Journal of the National Cancer Institute (1986)

Carcinogen-mediated alterations in hepatic membrane growth factor receptor activity were investigated with the use of the hepatocarcinogen diethylnitrosamine [(DENA) CAS: 55-18-5]. For the separate assessment of carcinogen-induced acute membrane receptor changes from changes associated with carcinogen- mediated alterations in growth, the receptor activity was measured both acutely after, and several months after, a single ip dose of DENA in male F344 rats. An acute dose-dependent decrease was observed in ligand binding and autophosphorylation of the epidermal growth factor (EGF) and insulin receptor. Binding decreased sharply by 36 hours and recovered by 30 days in Golgi fractions and more slowly in plasma membranes. Scatchard analysis revealed a decrease in receptor number but not affinity. Chronic DENA administration also decreased insulin and EGF binding. Hepatocellular carcinomas, induced by single DENA injections 1 year previously, had decreased EGF receptor binding and autophosphorylation compared to those seen in age-matched controls and also less extensive insulin receptor changes. Single DENA doses thus have two effects: an acute reversible receptor change and a delayed, apparently permanent change associated with altered growth.
Anxiety and affecting factors in pulmonary rehabilitation patients with chronic obstructive pulmonary disease during exacerbation
Authors: Ozden Ozyemisci-Taskiran, Ayca Utkan, Nurdan Kokturk, Gulcin Kaymak Karatas
Journal: European Respiratory Journal (2011)

Aims: To investigate the anxiety prevalence and related factors in COPD patients engaged in the rehabilitation program during exacerbation.

Material and methods: Hospital Anxiety and Depression Scale (HAD) was performed to 75 COPD patients (mean age 69.6±8.8 years). Mean HAD anxiety score was 6.4±5.2.

Results: Patients in both groups had similar age, systemic diseases, social features, disease severity, arterial blood gases, walking distance, heart rate, respiratory rate and saturation during the walk test. However, there were significant differences in some variables between two groups.

View this table:

Clinical and demographic variables of the COPD patients with HAD anxiety scores <11 and ≥11





Conclusion: Despite similar disease severity and walk tests in both groups, patients with high anxiety scores having higher ratio of the inability to complete walk test, more severe symptoms during the test and ADL made us suggest that anxiety levels restricted their participation in physical activity. We think that appropriate psychiatric approach will increase the rehabilitation gains among patients with high HAD anxiety scores.
PTU-296 Evaluation of a regional teaching hospital’s 2 week wait gastrointestinal referral system from primary care against updated national figures:
Authors: JD Chetwood, D Hammersley, M Smith
Journal: Gut (2015)

<h3>Introduction</h3> The 2 week wait (2WW) system implemented in 2000 sought to stratify patients exhibiting high-risk symptoms for cancer, thereby establishing a dedicated pathway for urgent referrals. We audited the quality of GI 2WW referrals and their cancer conversion rate against the published literature. <h3>Method</h3> 1) All 2WW primary care referrals to BSUH gastroenterology over 3 weeks were prospectively analysed and followed up to diagnosis. 2) A 2009 systematic review<sup>1</sup>was updated with more recent literature reports. <b>Inclusion Criteria</b>: All patients referred to our Digestive Disease Department as “2WW”. <h3>Results</h3> <b>Reasons for non-adherence:</b> No PR performed (37, 34%) No duration of symptoms (38, 35%) GI history unanswered (52, 48%) Family history unanswered (56, 52%) Additionally 5 (5%) were referred in an innapropriate age bracket. For UGI: 29 (43%) were referred with &gt;55 and dysphagia, 1 had cancer (3.4% risk from the symptom) 15 (22%) with dyspepsia, 0 had cancer 13 (19%) with unexplained weight loss, 0 had cancer For LGI: 46 (43%) were referred with &gt;60+BHC (bowel habit change), 2 had cancer (4.3% risk from the symptom) 26 (24%) with &gt;40 PR bleed + BHC, 1 had cancer (3.8% risk) 4 (4%) with palp PR mass and 1 had cancer (25% risk) <h3>Conclusion</h3> A published 2009 review<sup>1</sup>indicated average cancer detection from 2WW referrals was 9.5% for LGI and 5.5% for UGI. A pubmed search for relevant GI 2WW articles combined with relevant GUT extracts found 26 later references. By combining total 2WW referrals and conversion rates from all studies, we found similar updated rates of 9.1% from 30237 referrals (LGI) and 6.7% from 10634 referrals (UGI). Our study adds weight to the growing evidence that, despite 2WW guidance stems from level 5 evidence, cancer conversion rates from 2WW referral is poor. In both our data and the literature, no criteria accurately predict cancer.<sup>2</sup> Additionally there is good evidence that lower quality referrals, lead to lower cancer detection rates<sup>3,4 and </sup>a less effective service. The poor adherence to the referral criteria shown in our study may partly explain our particularly poor cancer conversion. We also suspect that historical underinvestment in the service, which led to long waiting times, may have tempted GPs to overstate the urgency of referrals, even though the endoscopy waits are now entirely within target. In an attempt to improve things, we have presented this data to our local clinical reference groups, and are exploring the difficulties encountered with the 2WW process from both sides, alongside ways in which we could improve the service. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Thorne 2009 Padwick 2013 Amin 2009 Jani 2012
Malignancy of Polyoma Virus Infection in Mice in Relation to Stress&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: A. F. Rasmussen, W. H. Hildemann, M. Sellers
Journal: JNCI Journal of the National Cancer Institute (1963)

Stress by avoidance learning and high-frequency sound was applied to weanling Webster-Swiss mice (BRVS) inoculated at birth with polyoma virus by the intracardiac route. The subsequent incidence of tumors and time-mortality distributions were compared with those obtained in unstressed control mice inoculated in the same manner. Palpable tumors initially appeared in some mice of all groups at 48 to 55 days of age, and 96 percent of all animals receiving injections subsequently died with tumors. Eighty-one percent of the mice had multiple tumors at death. Salivary-gland and lung tumors were most frequently seen at the time of death with about equal incidence in 62 to 65 percent of the 195 mice of all groups scored for tumors. Kidney, skeletal, and subcutaneous (including mammary) tumors were observed in 20, 23, and 19 percent of the animals, respectively, whereas overt tumors at other sites were much less frequent. The few survivors at 487 days of age showed no tumors, but possessed hemagglutination-inhibition antibodies in high titers as did the animals that died earlier with tumors. There were no significant differences among the various stressed and control groups in incidence, extent, or location of tumors relative to the times of death. However, there was evidence of a slight diminution in the frequency of overt tumors at all sites in the unstressed control population compared with the stressed populations. The calculated median survival times ranged from 149 to 162 days; there were no statistically significant differences among stressed and control populations in any parameters of the time-mortality distributions. Although the survival times, ranging from 56 to 415 days, reflected a prolonged and variable disease process, the cumulative mortality curves for all groups of mice followed the same log-normal distribution. The polyoma virus-induced malignancies led to a reduction in median lifespan by a factor of at least two thirds. Nevertheless, the stressing procedures used had no substantial effect on either over-all tumor incidence or survival times.
Low frequency of CHEK2 1100delC mutation in breast cancer patients and hereditary breast cancer families in the Czech Republic
Authors: Z. Kleibl, J. Novotny, P. Pohlreich, M. Zikan, P. Cinek, M. Janatova, L. Petruzelka
Journal: Journal of Clinical Oncology (2004)

9538 Background: The 1100delC variant of the cell cycle checkpoint kinase CHEK2 was recently identified as a low-penetrance breast cancer (BC) susceptibility gene. The aim of our study was to examine the frequency of this alteration in the cohort of the 695 Czech BC patients and 135 families and high-risk patients previously screened for mutations in BRCA1 and BRCA2 genes. Methods: DNA from blood samples was analyzed for the presence of the CHEK2 1100delC variant by nested PCR followed by DHPLC (WAVE; Transgenomic). Positive samples were confirmed by sequencing (ABI310, ABI) using independently amplified template. Results: The CHEK2 1100delC variant was identified in 6 out of 695 breast cancer patients (0.85%) and in one out of 135 families and high-risk patients tested for hereditary breast cancer. The subgroup analysis did not show any significant difference of the CHEK2 1100delC prevalence, however one positive BC susceptibility patient belongs to the subgroup 9 BC male patients. In 120 samples of healthy volunteers no mutation was found. Conclusions: Our results suggest that CHEK2 1100delC mutation is very infrequent in our population and its routine investigation should not be recommended. In a role of male breast cancer risk predictor (one positive patient out of nine), evaluation of a larger cohort is necessary. Acknowledgement: The study was supported by the grant of the Czech League against Cancer and First Medical Faculty CU Research Project 111100004 . No significant financial relationships to disclose.
Abstract 4893: High-throughput mutation sequencing of the full exon regions in BRCA1 and BRCA2 genes using nanofluidic-PCR prepared libraries
Authors: Jun Wang, Guoli Li, Ming Chen, Jianfu Heng, Xinwu Guo, Limin Peng, Fan Zhang, Zibo Li, Shouman Wang, Zhi Xiao, Lizhong Dai, Wenjun Yi, Lili Tang
Journal: Cancer Research (2015)

Abstract Breast cancer is one of the most common cancers and also the principal cause of cancer-related death among women in the world. BRCA1 and BRCA2 genes contribute to DNA repair and transcriptional regulation in response to DNA damage. Mutations of BRCA1/2 genes greatly increase lifetime risk to develop breast cancer and these mutations are frequently observed in hereditary breast cancer. In addition, recent studies suggested that breast cancer patients who carry a BRCA1 or BRCA2 germline mutation benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. Therefore, it would be of great interest to develop a high-throughput approach for mutation screening of the full exon regions in BRCA1 and BRCA2 gene. We have developed a targeted gene exon-sequencing approach using a nanofluidic PCR platform, the Access Array™ system, which enables simultaneous amplification of 48 genetic regions (amplicons) from 48 samples in parallel. We have applied this system to generate the libraries of BRCA1 and BRCA2 coding regions. Total 120 target-specific primer pairs were designed covering all 22 exons of BRCA1 and 26 exons of BRCA2. A primer design strategy was applied to incorporate sample-specific barcodes and Illumina sequencing adaptors into each amplicon, allowing direct sequencing without further library preparation. The exon regions of these 2 genes have been amplified on Access Arrays using 48 multiplex mixes of the 120 primer sets in paired tumor/normal tissues from 144 breast cancer patients. We will present the next-generation sequencing data of BRCA1 and BRCA2 mutation screening collected from amplicon libraries generated using the Access Array system. Our results indicate the excellent utilization of this approach in the mutation screening of BRCA1 and BRCA2 in clinical samples. Note: This abstract was not presented at the meeting. Citation Format: Jun Wang, Guoli Li, Ming Chen, Jianfu Heng, Xinwu Guo, Limin Peng, Fan Zhang, Zibo Li, Shouman Wang, Zhi Xiao, Lizhong Dai, Wenjun Yi, Lili Tang. High-throughput mutation sequencing of the full exon regions in BRCA1 and BRCA2 genes using nanofluidic-PCR prepared libraries. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4893. doi:10.1158/1538-7445.AM2015-4893
Correlation between polysialic-neural cell adhesion molecule levels in CSF and medulloblastoma outcomes.
Authors: D Figarella-Branger, C Dubois, P Chauvin, B De Victor, J C Gentet, G Rougon
Journal: Journal of Clinical Oncology (1996)

PURPOSE To quantify CSF levels of polysialic-neural cell adhesion molecule (PSA-NCAM) in patients with medulloblastoma (MB) metastasis, to assess the correlation with other diagnostic techniques (imaging and cytology) and clinical features, and to determine whether it is a suitable marker to monitor response to treatment and subsequent follow-up data. PATIENTS AND METHODS PSA-NCAM levels were measured using a double-site enzyme-linked immunoadsorbant assay (ELISA) in 145 samples from 14 controls and 29 patients with MB. Clinical status of patients, imaging, and cytologic data were available at the time of each lumbar puncture. Medians and ranges for the 131 pooled PSA-NCAM concentrations were calculated for the MB versus the control groups, and for MB patients for normal versus abnormal groups at cytology or imaging, and for four clinical subgroups, respectively. For patients with MB, three PSA-NCAM measurements that corresponded to punctures performed during three time periods following surgery were selected. The kappa measure of agreement was calculated between normal and abnormal groups at cytology or imaging, and between groups of patients in remission and refractory, respectively. For the same phases, sensitivity and specificity of PSA-NCAM and cytology tests and their 95% confidence intervals (95% CIs) were computed. RESULTS PSA-NCAM was never detected in control CSF. PSA-NCAM concentration medians were higher in CSF with metastatic cells or that corresponded to abnormal imaging than in the corresponding normal groups (P &lt; .05). The PSA-NCAM concentration median was significantly higher (P &lt; .05) in CSF from patients refractory to treatment or who relapsed than from patients in remission. Agreements between PSA-NCAM and clinical status and between PSA-NCAM and cytology were excellent during and after treatment. The sensitivity of PSA-NCAM test was always better than that of cytology, whereas its specificity was lower for phases that corresponded to more than 1 month following surgery. However, specificity was 100% for patients refractory to treatment or with relapse. CONCLUSION PSA-NCAM measurement appears to be a new biologic marker of possible use in the management of patients with MB.
Phase II study of biochemical modulation of fluorouracil by low-dose PALA in patients with colorectal cancer.
Authors: P J O'Dwyer, A R Paul, J Walczak, L M Weiner, S Litwin, R L Comis
Journal: Journal of Clinical Oncology (1990)

Higher response rates in colorectal cancer have been observed with regimens that increase the cytotoxicity of fluorouracil (5-FU) by altering the biochemical milieu at its site(s) of action. Phosphonacetyl-L-aspartate (PALA), which inhibits aspartate transcarbamylase and depletes uridine nucleotide pools in vitro and in vivo, selectively potentiates the antitumor activity of 5-FU in preclinical models. In a phase I/II study in patients with advanced colorectal cancer, PALA 250 mg/m2 was given on day 1, followed 24 hours later by 5-FU 2,600 mg/m2 by 24-hour infusion repeated weekly. Through the use of subcutaneous ports and portable infusion pumps, all patients were treated outside the hospital setting. Thirty-nine patients without prior chemotherapy received 884 courses of treatment. The primary site was colon in 31, rectum in eight. Toxicity was generally mild to moderate except among four patients who were escalated to 5-FU 3,250 mg/m2: two developed severe gastrointestinal toxicity and myelosuppression. Among the remaining 35 patients, gastrointestinal and neurologic toxicities predominated, but usually did not develop until the third or fourth month of treatment. Two patients were inevaluable for response. Among the 37 evaluable patients there were three complete and 13 partial remissions for a total response rate of 43% (95% confidence interval [Cl], 27% to 59%). The median duration of response was 5 months (range, 1.5 to 15 months). The projected mean survival is in excess of 17 months. This high response rate is comparable to the best results obtained with other means of modulation of 5-FU. Demonstration of a survival benefit will require larger phase III studies.
Spinal behavior during tidal and deep breathing in healthy male subjects
Authors: Miha Masuda, Hajime Kurosawa, Junichi Ohishi, Daisuke Kobayashi, Masahiro Kohzuki
Journal: European Respiratory Journal (2011)

Spine has joint connections with all ribs and has muscle attachments with a part of diaphragm, suggesting a key role in respiratory mechanics. In this study, we aimed to investigate movement of the spine during tidal and deep breathing at a seated posture in which the spine was free from artificial restriction. Three-dimensional motion analysis using an eight-camera system (60Hz) was performed in fifteen male healthy volunteers (mean age; 27.1±5.7 years). During tidal breathing, the spine moved very little (< 1 mm) while ventral parts of the ribs and the sternum well moved (1.9-5.2mm) as “pump-handle”. Lumber spine moved toward ventral direction with deep inspiration to TLC while upper thoracic spine did with deep expiration to RV. These results suggested that spine was almost fixed during tidal breathing as the pivot of the ribcage. Breathing to RV or TLC recruited varieties of supplemental respiratory muscles, and transformed spine.
Comparison of ERG oncoprotein expression among matched cohorts of African American and Caucasian American patients with prostate cancer.
Authors: David J. K. P. Pfister, Philip Rosen, Denis Young, Gyorgy Petrovics, Youngmei Chen, Albert Dobi, David McLeod, Axel Heidenreich, Shiv Srivastava, Isabell Sesterhenn
Journal: Journal of Clinical Oncology (2012)

52 Background: The ERG proto-oncogene is frequently overexpressed in Prostate Cancer (CaP) following genomic fusion, which places ERG under the control of the TMPRSS2 promoter. Recent studies show higher frequency of ERG rearrangement or ERG oncoprotein expression in CaP of Caucasian-American (CA) patients compared to African-American (AA) patients. The frequency of the ERG oncoprotein expression in prostate tumors of matched CA and AA CaP patients is evaluated to better understand the biological basis for differences in prostate cancer between the two populations. Methods: Ninety-one AA CaP patients were matched for age, Gleason sum and pathologic stage to 91 CA CaP patients. All underwent radical prostatectomy between 1993 and 2010. Whole mount prostate specimens were used for immunohistochemical detection of the ERG oncoprotein by an ERG monoclonal antibody (clone 9FY). Individual foci of tumors were noted as either positive or negative. ERG staining data was linked to dinico-pathologic data. Results: Fifty-nine of 91 CA patients (64.8%) and 41191 (45.0%) AA patients had at least one focus of tumor positive for ERG in a whole-mount prostate section (p = 0.0073). The index tumor was positive for ERG expression in 55/89 (61.8%) CA and 24/85 (28.2%) of AA patients (p &lt;0.001). Seventy-seven of 183 (42.1%) individual foci were positive in CA versus 511196 in AA (26.0%; P &lt;0.001). There was a trend towards increased biochemical recurrence in CA patients with ERG positive index tumors. Conclusions: The prevalence of ERG oncoprotein expression is significantly higher among Caucasian- American patients. Differences in pattern of ERG positivity of index and non-index tumors between Caucasian-American and African-American prostate cancer patients and trends towards decreased biochemical recurrence-free survival suggest a more accelerated growth of ERG-positive tumors in Caucasian-American patients. Differences in ERG expression have the potential to delineate biological distinctions of CaP in these patient populations.
Evaluation of a novel MDM-2 inhibitor with cisplatin/oxalipatin for the treatment of pancreatic cancer independent of p53 mutational status.
Authors: K. Almhanna, A. S. Azmi, F. H. Sarkar, P. A. Philip, D. Yang, S. Wang, R. Mohammad
Journal: Journal of Clinical Oncology (2010)

e13613 Background: p53 mutation (mut-p53) has been reported in over 50% of pancreatic adenocarcinoma (PC). MDM2 inhibitors disrupt the MDM2-p53 interaction and restore p53 function in wild type (wt-p53) tumors but not in tumors with mut-p53. MI-319 is a new small molecule MDM-2 inhibitor (SMI). We tested MI-319 alone and in combination with oxaliplatin or cisplatin in p53 wild and mutant cell lines as well as in tumor bearing mice xenograft models. Methods: Human PC cell lines Capan-2, B×PC-3, Colo-357 and Panc-28 were treated with MI-319 (0 or 15 μM), cisplatin (1 μM), oxaliplatin (15 μM) or the combination of either chemotherapy with SMI for 72 hrs. MTT and colonogenic assay for cell survival were performed. Colo-357 cells were transfected with respective siRNAs using LipofectAMINE 2000. Cell apoptosis was determined using Annexin V FITC apoptosis and ELISA detection kits. Protein was extracted from the cells after 20 hrs of incubation for western blot analysis. Cisplatin/MI 319 combination was tested in mice xenograft models carrying Capan-2 and BxPC-3 tumors treated with MI-319 (200mg/Kg orally BID), cisplatin (4 mg/kg i.v. twice a week) or the combination. Tumor growth was followed and animals were scarified after 2 weeks of treatment. Results: MI-319/cisplatin or MI-319/oxaliplatin combination synergistically suppressed cell growth (MTT CI<1), colony formation, and induced apoptosis in both mut-p53 and wt-p53 cells. Western blot analysis and siRNA silencing studies in mutant as well as p53 null cells demonstrated involvement of p73 which is under the regulation of MDM2, and is rarely mutated in PC. Treatment with cisplatin plus MI-319 effectively reduced tumor growth in both wt-p53 and mut-p53 tumor xenograft models. Residual tumor tissue showed up-regulation of both p73 and p21. Conclusions: MI-319, when administered with either cisplatin or oxaliplatin, induces cell growth inhibition and apoptosis in PC irrespective of p53 mutational status. These combinations warrant further studies for the development of new therapeutic strategies in human pancreatic cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ascenta Therapeutics Ascenta Therapeutics, Bayer, Bristol-Myers Squibb, Curis, Nektar, OSI, Roche, sanofi-aventis Ascenta Therapeutics Amgen, Ascenta Therapeutics, Bayer, Roche Bristol-Myers Squibb, Chugai Pharma, Genentech, Genvec, GlaxoSmithKline, Novartis, sanofi-aventis