tbuckley/cabot-search huggingface dataset:
Abstract 4883: A novel target capture approach for next generation sequencing and its application to oncogenic mutation detection
Authors: Yanxia Bei, Brendan Galvin, Cynthia Richard
Journal: Cancer Research (2015)

Abstract Due to the complexity and heterogeneity of cancer genetics, next generation sequencing has played an increasingly important role in cancer diagnosis, prognosis and therapeutics. An effective target enrichment strategy further simplifies data analysis associated with NGS and further reduces costs. We have developed a novel target capture technique that offers advantages over traditional in-solution hybridization and multiplex PCR protocols. With this method, genomic DNA is first enzymatically nicked to generate single stranded DNA of desirable length, in a sequence independent manner. The DNA fragments are then rapidly hybridized to short probes that can be captured by beads. The off target sequence of the captured DNA, defined by the probes, is subsequently removed via enzymatic digestion. The resulting targeted sequence are ligated with NGS platform specific adaptors and amplified by PCR. With our method, genomic DNA can be converted into libraries ready for sequencing within 6 hours; and the procedure is easily scalable for automation. To demonstrate the efficacy of this method, we have designed a cancer panel to interrogate 50 genes that are commonly mutated in cancer, and tested it on various DNA samples including FFPE. The results demonstrate that our approach captures targeted sequence with high specificity and uniformity, and detects variants with great accuracy and sensitivity. Citation Format: Yanxia Bei, Brendan Galvin, Cynthia Richard. A novel target capture approach for next generation sequencing and its application to oncogenic mutation detection. [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 4883. doi:10.1158/1538-7445.AM2015-4883
Wide-field radiation therapy alone or with chemotherapy for Hodgkin's disease in relapse from combination chemotherapy.
Authors: P Mauch, N Tarbell, A Skarin, D Rosenthal, H Weinstein
Journal: Journal of Clinical Oncology (1987)

Nineteen patients with Hodgkin's disease who relapsed primarily in nodal sites after intensive combination chemotherapy were retreated with wide-field radiation therapy alone or with additional chemotherapy between January 1971 and December 1984. Six patients presented in second relapse and 13 patients in first relapse. Seven patients were treated with combination chemotherapy and radiation therapy and twelve patients were treated with radiation therapy alone. Radiation therapy field sizes and doses were similar to those recommended for early-stage Hodgkin's disease patients treated with radiation therapy alone. The 5-year actuarial freedom from relapse (FFR) and survival following retreatment were 48% and 69%, respectively. Twelve patients are currently disease-free 12 to 172 months following retreatment. Wide-field radiation therapy alone or with additional chemotherapy should be considered for patients with advanced Hodgkin's disease who relapse in nodal sites after initial combination chemotherapy.
A Follow-up Study of a Ten-Percent Sample of the Canadian Labor Force. I. Cancer Mortality in Males, 1965–73&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G R Howe, J P Lindsay
Journal: JNCI Journal of the National Cancer Institute (1983)

Journal Article A Follow-up Study of a Ten-Percent Sample of the Canadian Labor Force. I. Cancer Mortality in Males, 1965–73 Get access Geoffrey R. Howe, Geoffrey R. Howe Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan P. Lindsay Joan P. Lindsay Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 70, Issue 1, January 1983, Pages 37–44, https://doi.org/10.1093/jnci/70.1.37 Published: 01 January 1983 Article history Received: 16 March 1982 Accepted: 04 August 1982 Published: 01 January 1983
Comment on Nunley et al. Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes. Diabetes Care 2015;38:1768–1776
Authors: Kiki van Broekhoven, Giesje Nefs
Journal: Diabetes Care (2016)

Nunley et al. (1) examined the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes as compared with adults without type 1 diabetes. The authors concluded that the prevalence of cognitive impairment was five times higher in adults with type 1 diabetes as compared with participants without type 1 diabetes (28% vs. 5%), independent of age, education, or blood pressure. Diabetes-specific factors related to cognitive impairment were chronic hyperglycemia and prevalent microvascular disease.

While the current study provides us …
Deoxynucleotidase Activity in Rat Liver and Certain Tumors&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: S FIALA, A FIALA, G TOBAR, H McQUILLA
Journal: JNCI Journal of the National Cancer Institute (1962)

The deoxynucleotidase activity in the liver tissue of the adult rat is shown by enzymes distinct from 5′-nucleotidase and resides primarily in the cytoplasmic structures. The “mitochondrial” deoxynucleotidase has an activity optimum at pH 5.5 and dephosphorylates 5′-deoxycytidylic acid (dCMP), 5′-deoxyadenylic acid (dAMP), and 5′-deoxyguanylic acid (dGMP); the ergastoplasm-bound deoxynucleotidase acts on thymidylic acid (TMP) and 5′-deoxyuridylic acid (dUMP) with optima at pH 6.0 and 8.0, respectively. The mitochondrial deoxynucleotidase is low in embryonal liver cells, increases in the postnatal life, is high in adult rat liver, but decreases during regeneration. Its course of activity during the embryonic and postnatal period is reversed to that of dCMP deaminase. On the other hand, dCMPase is low in proliferating tissues, e.g., lymphatic organs. During experimental carcinogenesis in rat liver and resulting tumors, the scarcity of cytoplasmic structures depletes the dCMPase activity. In such tumors as the Novikoff rat tumor, mouse Sarcoma 180, and Ehrlich ascites tumor cells, dCMPase is low. Inorganic phosphate inhibits mitochondrial deoxynucleotidase, which can be extracted by water from fresh and acetone-powdered tissue and is found in the “albumin” fraction of these extracts. It is concluded that the deoxynucleotides may be the natural substrates of certain “acid phosphatases” in liver and that these deoxynucleotidases may regulate the content of deoxynucleotides in the cell and participate in the regulation of cell proliferation.
Multiple Primary Neoplasms in Blacks Compared to Whites. II. Further Cancers in Patients With Cancer of the Buccal Cavity and Pharynx2
Authors: Guy R. Newell, Edward T. Krementz, Jane D. Roberts
Journal: JNCI Journal of the National Cancer Institute (1974)

Incidence of multiple primary neoplasms in patients with an index cancer of the buccal cavity and pharynx was determined from 23 years' experience of the Charity Hospital Tumor Registry. Expected cancers were calculated by the application of age-, sex-, and racespecific incidence rates to the person-years experience in the registry; these rates were compared to observed cancers. White males with primary cancers of the lip and mouth had a significantly increased risk of developing further cancer of the skin and lung. Black males with primary cancer of the salivary gland had a threefold increased risk which was accounted for by subsequent cancer of the lung and prostate. Black males with primary cancer of the mouth had a threefold increased risk, which was explained by subsequent additional cancers of the buccal cavity and pharynx and lung. The fivefold increased risk among black males with primary cancer of the pharynx was accounted for by subsequent cancers of the esophagus, lung, and prostate. White females with cancer of the lip and mouth had an increased risk of further skin cancer. Black females had no increased risk for subsequent cancers.
A phase I dose escalation study of AGS-8M4 (ASP6183), an anti-AGS-8 fully human antibody, in advanced ovarian cancer.
Authors: D. K. Armstrong, T. J. Herzog, L. M. Reyno, M. Vincent, L. Jackson, P. Sabbatini
Journal: Journal of Clinical Oncology (2010)

5059 Background: AGS-8M4 (ASP6183) is an IgG1k fully human monoclonal antibody (MAb) directed to AGS-8, a novel cell surface protein expressed on tumor cells in patients with ovarian cancer. In xenograft mouse models, AGS-8M4 inhibited tumor growth and prolonged survival. Methods: Women with recurrent disease or stage III/IV advanced ovarian cancer who had received at least one prior platinum containing regimen were treated. AGS-8M4 was administered by IV infusion over 1 hour every 2 weeks (Q2W) for four doses in cohorts of 3-6 subjects at doses of 1, 5, 10 and 20 mg/kg. Disease assessments were performed every 8 weeks. Subjects with stable disease (SD) were eligible to receive 4 additional doses of AGS-8M4 in extended treatment at the same dose and schedule. SD was defined as no new onset or worsening of symptoms or measureable disease (per RECIST). The primary endpoints of the study were safety and pharmacokinetics (PK). Secondary endpoints included immunogenicity and anti-tumor activity. Results: Of the 15 women who received AGS-8M4, 11 completed the 4 planned treatment doses, 2 withdrew early and 2 are still receiving treatment. One subject (10 mg/kg) with a history of thrombocytopenia had a dose-limiting toxicity (DLT) due to thrombocytopenia; however, the cohort was expanded and no further DLTs were experienced. One subject in the 20 mg/kg cohort who had SD is receiving AGS-8M4 extended therapy. No deaths, infusion-related toxicities, or anti-AGS-8M4 antibodies have been reported. PK results from doses up to 20 mg/kg indicate linear PK. Decline in serum concentration of AGS-8M4 was biphasic. The terminal half-life of AGS-8M4 (t1/2lz) ranged from 2 to 3 weeks. The median accumulation ratio for AGS-8M4 Q2W dosing ranged from 1.5 to 1.9 weeks. AUC and Cmax increased proportionally with increase in doses from 1 to 20 mg/kg. Conclusions: AGS-8M4 was well tolerated at all dose levels. Based on the results of this study, a phase Ib study of AGS-8M4 in combination with two different chemotherapy regimens has been initiated and phase II combination studies are planned. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agensys, Inc., Astellas Pharma Agensys, Inc. Agensys, Inc., Astellas Pharma Agensys, Inc.
The increased comorbidities in obese asthmatics
Authors: Nejdiye Mazican, Sermin Börekçi, Bilun Gemicioglu
Journal: European Respiratory Journal (2011)

Aim:  Many studies have demonstrated an association between obesity and asthma, also the affects of obesity with airway inflammation were investigated. The aim of this study was to investigate the difference of age, sex, atopy, comorbid diseses and pulmonary function test parameters between obese and non obese asthmatics.   Method:  The data files of 210 asthmatic patients who admitted to our outpatient clinic in 2010 were evaluated.169 patients without attact, with asthma control test over 20 and accessed BMI (body mass index) value enrolled in this study. The patients were divided in to two groups; BMI>30 kg/m 2  (obese) and BMI≤ 30 kg/m 2  (normal). The two groups were compared to age, gender, smoking history, comorbidities (gastroezafageal reflux, hypertension, diabetes mellitus, glaucoma, psychiatric disease, hipertirodi), allergy skin test positivity and pulmonary function test parameters by using statistical program SPSS 15.0 software.   Results:  The mean age of the 169 patients was 39.5±15%, 32% were male and 68% were women.The obese group included 31 patients. The two groups were compared. In the group with normal weight FEV1 and FVC values were significantly higher (p 0.05).   Conclusion:  The gastroesophageal reflux and hypertension comorbidities were more commonly seen in obese asthmatic than non obese asthmatics.
The effect of bevacizumab on wound healing after resection of colorectal liver metastases despite persistent VEGF inactivation at wound sites.
Authors: P. Starlinger, L. Alidzanovic, D. Schauer, T. Maier, C. Nemeth, B. Herberger, L. Pop, B. Gruenberger, T. Gruenberger, C. Brostjan
Journal: Journal of Clinical Oncology (2011)

e14005 Background: The antibody bevacizumab (Bev) has proven a promising tool for anti-angiogenic cancer therapy by neutralizing vascular endothelial growth factor A (VEGF). Although VEGF is known as a major regulator of wound healing and liver regeneration, the incidence of postoperative complications at these sites is unexpectedly low in patients after neoadjuvant therapy including Bev. Mechanistic studies evaluating this discrepancy are limited. Methods: 40 patients with stage IV colorectal cancer received chemotherapy with (n = 31) or without (n = 9) Bev prior to resection of liver metastases. Plasma samples were taken before and 1-3 days after surgery. Additionally, intraabdominal (abd) and subcutaneous (sc) drainage samples were collected in 24 patients. The percentage of Bevacizumab bound vs. free VEGF was evaluated by immunoprecipitation. Results: No increased incidence of wound healing complications or postoperative liver failure was observed in Bev treated patients as compared to chemotherapy controls. As previously reported, a significant rise in VEGF blood levels was recorded in response to neoadjuvant treatment with bevacizumab (P < 0.001). Postoperative plasma VEGF levels were also found to be significantly higher in Bev treated patients (p<0.01). In contrast, VEGF was significantly lower in abd and sc fluid of Bev treated as opposed to control patients without Bev (p<0.05). Despite this discrepancy in systemic versus local VEGF concentrations, VEGF was mostly bound by Bev in both, plasma and wound fluid. With respect to the other angiogenesis factors investigated in wound fluid, Bev treated patients had substantially elevated PD-ECGF levels as compared to controls. Conclusions: VEGF feedback production in response to neoadjuvant Bev therapy was detectable by an increase in circulating (systemic) VEGF in patient plasma prior to surgery and in the postoperative period. However, at the actual site of wound healing, we found significantly reduced VEGF values in Bev patients, and the remaining VEGF was inactivated by Bev. Therefore, wound healing seems to proceed independent of VEGF and might be supported by other, compensatory growth factors such as PD-ECGF.
Drug Screening Reveals That Ibrutinib (PCI-32765) Exhibits Synergy With BCL-2 and Proteasome Inhibitors In Models Of Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL)
Authors: Mark Axelrod, Zhishuo Ou, Liang Zhang, Vicki Gordon, Elyse R Lopez, Archito T. Tamayo, Richard J. Ford, Lan V Pham, Michael J. Weber, Michael E. Williams, Michael Wang
Journal: Blood (2013)
Relationship between epidermal growth factor receptor (EGFR) gene copy number, p16 status, and outcome in locally advanced squamous cell carcinoma of the head and neck (LASCCHN).
Authors: B. J. Solomon, R. J. Young, R. Fisher, S. B. Fox, G. A. McArthur, D. Rischin
Journal: Journal of Clinical Oncology (2010)

5528 Background: Human papilloma virus infection (HPV) is a powerful prognostic biomarker in LASCCHN and can be indirectly identified by p16 immunohistochemistry (IHC). Increased EGFR gene copy number has been reported to be a negative predictor of outcome in LASCCHN. In this study the relationship of p16 to EGFR gene copy number in patients treated with chemoradiation was assessed. Methods: Formalin-fixed paraffin embedded tissue was obtained from 110 patients with LASCCHN treated on three clinical trials with conventional chemoradiation or with a tirapazamine containing regimen. EGFR gene copy number was assessed by Fluorescence in situ hybridization (FISH) using LSI EGFR SpectrumOrange/CEP 7 SpectrumGreen probes (Vysis/Abbott). Tumors with high polysomy or amplification of EGFR were scored as positive. p16 was assessed by IHC using a validated antibody (Neomarkers). Markers were correlated with outcome i.e., failure-free survival (FFS) and overall survival (OS) using Cox regression, adjusting for trial. Results: Results for both EGFR FISH and p16 IHC were obtained in 97 patients. EGFR FISH was positive in 21/97 (22%) tumors including 12/66 (18%) oropharyngeal tumors. p16 was positive in 40/97 (41%) tumors including 36/66 (55%) oropharyngeal tumours. Only 1/40 p16 positive tumors were EGFR FISH positive compared with 20/57 p16 negative tumors (p<0.001). EGFR FISH positivity was associated with inferior FFS (HR 2.48 (95%CI 1.14 to 5.38), p = 0.022) and OS (HR 2.33 (95%CI 0.98 to 5.57), p = 0.057). p16 positivity was associated with improved FFS (HR 0.19 (95%CI 0.07 to 0.56), p = 0.002) and OS (HR 0.18 (95%CI 0.05 to 0.62), p = 0.006). On multivariable Cox regression analysis only p16 was independently predictive of outcome (p = 0.007 and 0.0014 for FFS and OS respectively). Conclusions: EGFR FISH positivity and p16 expression were found to be almost mutually exclusive in LASCCHN with only 1 of 97 tumors positive for both markers suggesting that increased EGFR copy number is largely restricted to HPV-negative LASCCHN. EGFR FISH and p16 were predictive of outcome in univariate analyses, but only p16 remained predictive on multivariable analysis. No significant financial relationships to disclose.
Tumor Development in Mice Bearing a Plastic Cylinder and Inoculated With Human Neoplastic Cells 2
Authors: Christiane Dosne Pasqualini, Luisa Sen, Fortuna Saal, Laura Schwartz, Lidia Z. Tkaczevski
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Tumor Development in Mice Bearing a Plastic Cylinder and Inoculated With Human Neoplastic Cells Get access Christiane Dosne Pasqualini, Christiane Dosne Pasqualini Instituto de Investigaciones Hematológicas, Academia National de Medicina and Catedra de Microbiologia y Parasitologia, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina Search for other works by this author on: Oxford Academic PubMed Google Scholar Luisa Sen, Luisa Sen Instituto de Investigaciones Hematológicas, Academia National de Medicina and Catedra de Microbiologia y Parasitologia, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina Search for other works by this author on: Oxford Academic PubMed Google Scholar Fortuna Saal, Fortuna Saal Instituto de Investigaciones Hematológicas, Academia National de Medicina and Catedra de Microbiologia y Parasitologia, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina Search for other works by this author on: Oxford Academic PubMed Google Scholar Laura Schwartz, Laura Schwartz Instituto de Investigaciones Hematológicas, Academia National de Medicina and Catedra de Microbiologia y Parasitologia, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina Search for other works by this author on: Oxford Academic PubMed Google Scholar Lidia Z. Tkaczevski Lidia Z. Tkaczevski Instituto de Investigaciones Hematológicas, Academia National de Medicina and Catedra de Microbiologia y Parasitologia, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 283–286, https://doi.org/10.1093/jnci/51.1.283 Published: 01 July 1973 Article history Received: 09 January 1973 Accepted: 14 March 1973 Published: 01 July 1973
Activity of Neoadjuvant Lapatinib (L) Plus Trastuzumab (T) for Early Breast Cancer (Ebc) According to Pik3Ca Mutations: Pathological Complete Response (Pcr) Rate in the Cherlob Study and Pooled Analysis of Randomized Trials
Authors: V. Guarneri, M.V. Dieci, L. Carbognin, A. Maiorana, S. Bettelli, G. Tortora, P.F. Conte, E. Bria
Journal: Annals of Oncology (2014)
Chimerism Induction Without GVHD Following Low Intensity Conditioning In MHC Disparate Recipients: Combining The Benefit Of Cyclophosphamide Post Transplant With The Tolerogenicity Of Megadose T Cell Depleted HSCT
Authors: Esther Bachar-Lustig, Noga Or-Geva, Yael Zlotnikov Klionsky, Yair Reisner
Journal: Blood (2013)
Safety of capecitabine (X) compared to fluorouracil/leucovorin (5-FU/LV) for the adjuvant treatment of elderly colon cancer patients (pts)
Authors: E. Díaz-Rubio, H. Burris, J. Y. Douillard, F. Y. Coxon, T. Maughan, O. Bertetto, J. Schueller, F. Husseini, N. Marschner, W. Scheithauer
Journal: Journal of Clinical Oncology (2004)

3737 Background: The improved safety profile of the oral fluoropyrimidine X (Xeloda) versus bolus 5-FU/LV has been demonstrated in over 3000 pts in 3 large randomized trials in 1st line metastatic and adjuvant colon cancer (Twelves EJC 2002, Scheithauer Ann Oncol 2003). In addition, the safety advantage over 5-FU/LV in the adjuvant setting was maintained in older pts (≥65 years) and also in terms of less early severe toxicity with X. The median age of pts at diagnosis of colon cancer is increasing in developed countries. Therefore we examined whether there is enough evidence to support the safe use of X in an elderly population, i.e. pts 70 years and older. Methods: We performed retrospective analyses on the safety database of the X-ACT adjuvant colon cancer trial, which compared X (993 pts) to 5-FU/LV Mayo Clinic Regimen (974 pts) in Dukes' C colon cancer pts. Adverse events (AEs) in the two arms were analyzed by age: <40, 41–69 and ≥70 years. P-values are not calculated due to the retrospective nature of analysis. Results: Sufficient patient numbers enable comparisons between X and 5-FU/LV for the 41–69 age group (763 vs 738, not shown) and ≥70 group (186 vs 205, table), whereas there were few pts aged <40 (44 vs 31, not shown). Hyperbilirubinemia was minimal in both arms when graded by NCI CTCAE. Conclusions: The improved safety profile of X vs 5-FU/LV is not only maintained in pts over 65, but also in the elderly over 70 years of age. It would be of interest to compare this dataset to that of the INT 0089 trial (Mayo Clinic regimen vs Roswell Park weekly bolus regimen). Pending the final results of the X-ACT study, capecitabine could provide a convenient and effective new option for an aging population. Study sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. No significant financial relationships to disclose.