tbuckley/cabot-search huggingface dataset:
Genetic architecture of colorectal cancer
Authors: Ulrike Peters, Stephanie Bien, Niha Zubair
Journal: Gut (2015)

Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3–5%) of cases arise from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well defined genes. In contrast, CRC is predominantly a late onset 'sporadic' disease, developing in individuals with no obvious hereditary syndrome. In recent years, genome wide association studies have discovered that over 40 genetic regions are associated with weak effects on sporadic CRC, and it has been estimated that increasingly large genome wide scans will identify many additional novel genetic regions. Subsequent experimental validations have identified the causally related variant(s) in a limited number of these genetic regions. Further biological insight could be obtained through ethnically diverse study populations, larger genetic sequencing studies and development of higher throughput functional experiments. Along with inherited variation, integration of the tumour genome may shed light on the carcinogenic processes in CRC. In addition to summarising the genetic architecture of CRC, this review discusses genetic factors that modify environmental predictors of CRC, as well as examples of how genetic insight has improved clinical surveillance, prevention and treatment strategies. In summary, substantial progress has been made in uncovering the genetic architecture of CRC, and continued research efforts are expected to identify additional genetic risk factors that further our biological understanding of this disease. Subsequently these new insights will lead to improved treatment and prevention of colorectal cancer.
Prospective Evaluation of Early Cardiac Damage Induced by Epirubicin-Containing Adjuvant Chemotherapy and Locoregional Radiotherapy in Breast Cancer Patients
Authors: M.T. Meinardi, D.J. van Veldhuisen, J.A. Gietema, W.V. Dolsma, F. Boomsma, M.P. van den Berg, C. Volkers, J. Haaksma, E.G.E. de Vries, D.Th. Sleijfer, W.T.A. van der Graaf
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients. PATIENTS AND METHODS: Patients (median age, 46 years; range, 28 to 55 years) were treated with five cycles of fluorouracil, epirubicin (90 mg/m 2 ), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction. RESULTS: No patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P = .001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P &lt; .01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P = .04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P &lt; .01). No persistent alterations were found in diastolic function and HRV. CONCLUSION: Relatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.
The risk of hepatocellular carcinoma in patients with previous malignancy
Authors: A. B. Siegel, R. B. McBride, H. El-Serag, D. Hershman, L. Zablotska, R. Brown, A. I. Neugut
Journal: Journal of Clinical Oncology (2007)

17075 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Its incidence has doubled over the past 20 years in the United States. Determination of the pattern of occurrence of HCC as a second primary malignancy might give clues for new risk factors for HCC, or may reveal common genetic or environmental risks. Methods: We identified patients with a diagnosis of a second primary HCC between 1973 and 2002 using the Surveillance, Epidemiology, and End-Results Program (SEER) a compilation of population-based cancer registries in the United States, to calculate the observed to expected (O/E) frequency of second primary HCC after a different primary cancer. We stratified by ethnicity, latency from the year of diagnosis of primary cancer to HCC diagnosis, and period of diagnosis of primary cancer as early (1973–1987) or late (1987–2002). Results: We reviewed 1,931,911 subjects with cancer, and identified 1,185 second primary HCC cases. Overall, a second primary HCC after any primary cancer was less frequent than expected (O/E=0.82, 95% CI=0.77–0.87). We found positive associations with head and neck cancers (oral cavity/pharynx O/E=2.1, 95% CI=1.7–2.5), Kaposi's sarcoma (O/E=3.3, 95% CI=1.2–7.1) and Hodgkin's disease (O/E=2.3, 95% CI=1.2–4.0). Negative associations were seen for breast cancer (O/E=0.7, 95% CI=0.6–0.8), colorectal cancer (O/E=0.6, 95% CI=0.6–0.8), and prostate cancer (O/E=0.7, 95%CI=0.6–0.8). Overall, lower O/E ratios were seen in whites, while in African Americans and those of other races, the O/E ratios were close to one. Latency times were relatively short for head and neck cancers and Kaposi's sarcoma (most within 12–59 months), and greater than 120 months for most cases of HCC after Hodgkin's disease. All cases of Kaposi's sarcoma were seen in the later time period. Conclusions: These results highlight possible shared risk factors of alcohol ingestion and viral exposures which may predispose to second primary HCC after other primary malignancies. Providers should maintain heightened alertness for second primary HCC in these patients, especially those with head and neck cancers and HIV. No significant financial relationships to disclose.
De novo <scp>CD</scp>5+ diffuse large <scp>B</scp>‐cell lymphoma: Adverse outcomes with and without stem cell transplantation in a large, multicenter, rituximab treated cohort
Authors: Lapo Alinari, Alejandro Gru, Carl Quinion, Ying Huang, Arletta Lozanski, Gerard Lozanski, Jacqueline Poston, Girish Venkataraman, Eunhye Oak, Friederike Kreisel, Steven I. Park, Stephanie Matthews, Jeremy S. Abramson, Hana Iris Lim, Peter Martin, Jonathon B. Cohen, Andrew Evens, Zeina Al‐Mansour, Arun Singavi, Timothy S. Fenske, Kristie A. Blum
Journal: American Journal of Hematology (2016)

De novo CD5+ diffuse large B-cell lymphomas (DLBCL) are a distinct subgroup of DLBCL with poor prognosis. However the role of rituximab-containing therapy and salvage stem cell transplantation in this patients' population remain to be defined. We retrospectively reviewed clinical features and outcomes of 102 patients with de novo CD5+ DLBCL treated with rituximab-containing therapy at nine different institutions. By Hans' criteria, 64 patients had activated B-cell (ABC) subtype, 24 germinal center B-cell (GCB) subtype, and 14 were not evaluated. No patients had a myc translocation. Eighty-three patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), 7 with rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone (R-EPOCH), and 6 with R-CHOP with methotrexate, 3 g/m(2) . The overall response rate to front-line therapy was 85%. The 3-year progression free survival (PFS) and overall survival (OS) for all patients were 40 and 65%, respectively. The 3-year PFS for ABC- and GCB-subtypes was 34 and 45%, respectively. The 3-year OS for ABC- and GCB-subtypes was 62 and 67%, respectively. The median time to second treatment failure was 3 months and 1 month for ABC- and GCB-subtypes, respectively. Twenty of 28 (71%) transplanted patients with autologous, allogeneic, or both, relapsed. This study confirms the poor prognosis of de novo CD5+ DLBCL in a large multi-center cohort despite initial rituximab-containing chemotherapy and suggests that stem cell transplantation fails to salvage the majority of these patients. Approaches to prevent recurrence and/or novel therapies for relapsed disease are needed for this subgroup of DLBCL patients.
Sentinel node biopsy in Asian breast cancer patients: An observation study of 1,000 consecutive patients treated at a single institute
Authors: H. Kawaguchi, H. Shigematsu, C. Koga, E. Mori, S. Nishimura, Y. Nakamura, K. Nishiyama, T. Esaki, S. Ohno
Journal: Journal of Clinical Oncology (2009)

e11584 Background: In woman with breast cancer, sentinel lymph node (SLN) biopsy (SLNB) provides staging information and a favorable effect on quality of life if the SLN does not have metastasis. While many reports already showed safety and reliability about SLNB for breast cancer patients in Western countries, few reports have published from Asian countries. Our purpose of this study is to prove the technical success, accuracy and safety of this method for Asian population. Methods: We did feasibility study of 183 patients from 2000 to 2002. After that, we evaluated detection rate, positive rate, axillary relapse rate in 1,000 consecutive patients who underwent sentinel lymph node biopsy for breast cancer at a single institute in Japan from 2002 to August 2008. In this series, both radioactive agent (technetium) and vital blue die (indigocarmine) were used to investigate the SLNs. Results: We could accurately predict SLNs in 994 (99.4%) of the 1,000 patients. The proportion of technical success was high regardless of surgeon's experience. Intraoperative frozen section histology showed that positive SLNs were found in 176 (17.7%) patients (13 micrometastasis and 163 macrometastasis). Defenitive histology found metastasis in 24 cases who defined as negative by the frozen section examination. 15 of 24 (62.5%) cases underwent delayed axillary lymph node dissection (ALND) after definitive histology. The histological concordance between frozen section and permanent sections of SLNs was 97.6%. Finally, 796 patients were followed up without ALND. With a median follow-up time of 3.5 years (0.5–5.2), axillary lymph node recurrence were occurred in 5 patients (5 of 796, 0.6%). The relapse time since SLNB ranged from 16 to 33 months. There were not any patients with allergic reactions. Conclusions: This is the report about observation study including more than 1,000 patients from Asian country. SLNB is seemed to be a safe and acceptably accurate method for Asian early breast cancer patients. No significant financial relationships to disclose.
Influence of Dietary Fat on the Induction of Mammary Tumors by N -Nitrosomethylurea: Associated Hormone Changes and Differences Between Sprague-Dawley and F344 Rats 2
Authors: Po-Chuen Chan, Jonathan F. Head, Leonard A. Cohen, Ernst L. Wynder
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Influence of Dietary Fat on the Induction of Mammary Tumors by N-Nitrosomethylurea: Associated Hormone Changes and Differences Between Sprague-Dawley and F344 Rats Get access Po-Chuen Chan, Po-Chuen Chan 3Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, N.Y. 10595. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jonathan F. Head, Jonathan F. Head 3Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, N.Y. 10595. Search for other works by this author on: Oxford Academic PubMed Google Scholar Leonard A. Cohen, Leonard A. Cohen 3Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, N.Y. 10595. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ernst L. Wynder Ernst L. Wynder 3Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, N.Y. 10595. 4We thank Dr. P. Hill, Dr. J. Silverman, and Mr. C. Choi for technical assistance, Dr. S. Stellman for statistical evaluation, and Dr. John H. Weisburger for critical review of the manuscript. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 4, October 1977, Pages 1279–1283, https://doi.org/10.1093/jnci/59.4.1279 Published: 01 October 1977 Article history Received: 07 February 1977 Accepted: 30 April 1977 Published: 01 October 1977
Good prescribing: benefits, hazards, harms, and risks
Authors: Jeff Aronson
Journal: BMJ (2016)

<h3>Introduction</h3> Women of reproductive age (WRA) are a high-risk population for anaemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of adverse pregnancy complications. However, in India, there are limited population-based data to guide evidence-based recommendations and priority setting. The objective of this study is to conduct a population-based biomarker survey of anaemia and vitamin B<sub>12</sub> and folate status in WRA as part of a periconceptional surveillance programme in Southern India. <h3>Methods</h3> WRA (15–40 years) who are not pregnant or lactating and reside within 50 km<sup>2</sup> of our community research site in Southern India will be screened and invited to participate in the biomarker survey at our research facility at Arogyavaram Medical Centre. After informed consent/assent, structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, dietary, anthropometry, health and reproductive history data. Venous blood samples will be collected at enrolment; whole blood will be analysed for haemoglobin. Plasma, serum and red blood cells (RBCs) will be processed and stored &lt;−80°C until batch analysis. Vitamin B<sub>12</sub> concentrations will be measured via chemiluminescence, and RBC and serum folate concentrations will be evaluated using the World Health Organisation (WHO)-recommended microbiological assay at our laboratory in Bangalore. A WHO surveillance system will also be established to determine the baseline prevalence of birth defects in this setting. <h3>Ethics and dissemination</h3> This study has obtained clearance from the Health Ministry Screening Committee of the Indian Council of Medical Research. The study protocol was reviewed and approved by the Institutional Review Board at Cornell University and the Institutional Ethics Committees at Arogyavaram Medical Centre and St. John’s Research Institute. Findings from this biomarker survey will establish the burden of anaemia and micronutrient deficiencies in WRA and directly inform a randomised trial for anaemia and birth defects prevention in Southern India. The results of this study will be disseminated at international research conferences and as published articles in peer-reviewed journals. <h3>Trial registration numbers</h3> Clinical trials registration number NCT04048330, NCT03853304 and Clinical Trials Registry of India (CTRI) registration number REF/2019/03/024479.
Allogeneic Inhibition Between Two Human Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Nelda B. Holmgren, Donald J. Merchant
Journal: JNCI Journal of the National Cancer Institute (1968)

The indirect immunofluorescence method was used to analyze cell interaction in population mixtures of two cultured human cells, HEp-2 and amnion (RP Am 1), during growth in vitro. A specific antiserum containing antibodies for antigen on amnion cells but none for antigens on HEp-2 cells made it possible to follow the fate of each cell type under optimal conditions of growth and without the use of aggregating agents. Population analysis revealed that inhibition or death of the amnion cells occurred and the degree appeared to depend on factors influencing cell contact. In contrast, the HEp-2 cells were relatively unaffected or markedly stimulated. Cell homogenates of the HEp-2 and RP Am 1 cells did not inhibit either the isogeneic or allogeneic cells. Partial protection of the amnion cells was afforded by exposure to antibody before growth in mixed culture, and the degree showed some correlation with antibody concentration.
P104 Serum ferritin concentration may predict waiting list mortality but not independent of model for end-stage liver disease score: evaluation of a cohort of 422 patients
Authors: M Al-Freah, M Foxton, W Bernal, G Auzinger, V Aluvihare, A Suddle, K Agarwal, N Heaton, J Wendon, J O'Grady, M Heneghan
Journal: Gut (2010)

Introduction  Recent data suggest that serum ferritin (SF) concentration predicts mortality in patients awaiting liver transplantation (LT).  Aim  To test SF concentration as a predictor of waiting list (WL) mortality.  Method  Retrospective analysis of all patients assessed at our centre for LT over a 4-year period.  Results  Patients with acute liver failure (138), amyloid (15), multiple organ transplants (14) and re transplantation (18) were excluded. Of the remaining 422 listed patients for LT, 45 died on the wait list (11%), 26 (6%) were de-listed and 350 (83%) transplanted. Men comprised 64%. SF was analyzed as a continuous and categorical variable. Patients were classified into 3-groups according to assessment SF ( 400 ug/l), (Walker et al Hepatology 2010;15:1683). There was a significant difference in gender distribution (p=0001), listing model for end-stage liver disease (MELD) (p=0.0001), etiology of cirrhosis (p=0001) between groups, with alcoholic cirrhosis and HCV representing 45% and 35% respectively of SF >400ug/l group. Univariate analysis demonstrated age at listing (HR 0.97, p=0.013), listing MELD (HR 0.86, p=0.0001), listing Na (HR 1.10, p=0.0001), SF (HR 1.0,p=0.002), SF 200-400 (HR2.86, p=0.001) as predictors of WL mortality; whilst SF>400 was insignificant (HR 2.14,p=0.078). On multivariate analysis, only MELD score (p=00001), age at listing (p=0.002) and serum Na (0.011) were significant predictors of listing outcome. Serum Ferritin analyzed as continuous or categorical variable failed to predict WL mortality. ROC curve analysis showed AUROC for MELD of 0.73 whilst that for SF of 0.65. This analysis determined a cut-off for SF of 266ug/l as significant predictor of WL mortality. Interestingly, SF 200–400 (HR 3.9, p=0.002) and SF >266 ug/l (as determined by ROC curve analysis, HR 2.9, p=0.006) were significant indicators of 1-year post-LT survival. However, age, gender, presence of HCC, MELD score and Na level at transplant failed to predict 1-year post-LT survival.  Conclusion  Although SF may appear to predict listing outcome, it failed to do so independent of established predictors of outcome such as age, MELD and serum Na in this cohort. However, SF predicted 1-year post-LT mortality. SF merits further study in larger cohorts of patients.
CD62L Expression Is Associated With Chronic Lymphocytic Leukemia (CLL) Cell Survival In Vitro and Represents a Novel Therapeutic Target In CLL
Authors: Melinda Burgess, Peter Mollee, Richa Singhania, Catherine Cheung, Lynne Chambers, Reynolds Brent, Louise Smith, Nicholas Saunders, Nigel McMillan, Devinder S Gill
Journal: Blood (2013)
Abstract 13153: Long-Term Results of Cell-Free Biodegradable Scaffolds for In Situ Tissue-Engineering Pulmonary Artery in a Canine Model
Authors: Goki Matsumura, Shojiro Matsuda, Noriko Isayama, Yuki Sakamoto, Yoshito Ikada, Kenji Yamazaki
Journal: Circulation (2012)

We have previously developed a new biodegradable scaffold that does not require any cell seeding to create an in-situ tissue-engineering vasculature (iTEV) in a canine IVC model. We assessed the hy...
Abstract 18507: Impact of Sleep Disordered Breathing on Long-term Outcome in Patients with Acute Coronary Syndrome
Authors: Toru Mazaki, Hiroyoshi Yokoi, Masashi Iwabuchi, Masakiyo Nobuyoshi
Journal: Circulation (2012)

Background: There has been growing evidence associating sleep disordered breathing (SDB) with cardiovascular events. However, the impact of SDB on long-term outcome in patients with acute coronary syndrome (ACS) has not been fully evaluated. Methods: We performed an overnight cardio-respiratory monitoring in 361 patients with ACS who were successfully treated with percutaneous coronary intervention between December 2004 and November 2009. Patients with an apnea-hypopnea index≥5/hour were considered to have SDB. We defined major adverse cardiovascular events (MACE) as cardiovascular death, non-fetal myocardial infarction, stroke and admission for congestive heart failure. Patients were followed for a mean period of 3.8 years. Results: Comorbidity of SDB with ACS was found in 195 patients (54%). MACE-free survival rate was significantly lower in patients with SDB (76% vs. 89%, p=0.0084). Multivariate logistic regression analysis identified SDB (hazard ratio: 2.03, 95% CI: 1.02 to 4.06, p=0.045) and reduced cardiac systolic function (Ejection fraction &lt; 45%) (hazard ratio: 3.42, 95% CI: 1.80 to 6.49, p&lt;0.001) as independent predictors of MACE. Conclusions: Our study showed a high prevalence of SDB among patients with ACS and SDB appeared to be a valuable predictor for clinical outcome in them. This suggests that earlier diagnosis and intervention for SDB should be considered in patients with ACS.
Low paediatric tuberculosis case detection rate in Southern Mozambique
Authors: Elisa López-Varela, Orvalho Joaquim Augusto, Luis Guerra, Durval Respeito, Charfudin Sacoor, Jahit Sacarlal, Giovanni Battista Migliori, Giovanni Sotgiu, Pedro L. Alonso, Alberto L. García-Basteiro
Journal: European Respiratory Journal (2015)

Two core indicators adopted for evaluating tuberculosis (TB) control programmes are treatment outcome and case detection rate (CDR). While the former is easy to report, the CDR can only be estimated (calculated as notifications of new and relapse cases divided by estimated incidence). According to the World Health Organization (WHO), Mozambique has one of the lowest CDRs among the high TB burden countries (HBCs), with 37% in 2013 [1]. In children, calculating CDR is even more challenging, given the difficulty in diagnosing TB and the lack of accurate estimates for paediatric incidence [2]. Several paediatric TB incidence estimates have been published recently [3–5], showing higher figures than those provided by WHO. The large variation in estimates and the lack of population-based data from HBCs (particularly from Sub-Saharan Africa) highlights the urgent need for new data to inform predictive models necessary to implement the "End TB Strategy" and achieve elimination [6]. The objective of this study was to calculate the paediatric CDR in Mozambique and to provide reference methodology and evidence for other countries. In this study, the case detection rate of TB in children <3 years in Manhiça, Mozambique was estimated to be 40.8% <http://ow.ly/UQg0g> The authors thank the participants and their families. The authors are grateful to the National TB Program (Maputo, Mozambique), Denise Naniche (ISGLOBAL, Barcelona, Spain), Alberto Bila Junior (CISM, Manhiça, Mozambique), health staff at the Manhiça District Hospital (Manhiça, Mozambique) and peripheral health centres for their contribution.
Molecular staging of the sentinel lymph node in melanoma patients: correlation with clinical outcome
Authors: A. Romanini, G. Manca, D. Pellegrino, R. Murr, S. Sarti, F. Bianchi, A. AlSharif, C. Orlandini, V. Zucchi, M. Castagna, D. Gandini, G. Salimbeni, F. Ghiara, P. Barachini, G. Mariani
Journal: Annals of Oncology (2005)