tbuckley/cabot-search huggingface dataset:
Abstract 13469: A Detailed Family History of Myocardial Infarction Provides Detailed Information on Risk of Myocardial Infarction, a Nationwide Cohort Study
Authors: Mattis F Ranthe, Jonathan A Petersen, Henning Bundgaard, Jan Wohlfahrt, Mads Melbye, Heather A Boyd
Journal: Circulation (2012)

Background:  Ischemic heart disease clusters in families, but most cardiovascular risk score systems (e.g. HeartScore) are not taking the potential risk associated with a positive family history into account. The weight of this risk factor may depend on the relatedness to the affected relative. To elucidate on this we aimed to examine the effect of a detailed family history of myocardial infarction (MI) on the risk of MI in a nationwide cohort.   Methods:  In Danish national registers, we established a cohort of persons born from 1930 with identifiable first- (parents, children or siblings) or second- (grandparents/children and half-siblings) degree relatives. We registered incident MIs in persons aged ≥20 years. In cohort members we registered diagnoses of diabetes mellitus and arteriel hypertension, and use of cardiovascular medication. We used Poisson regression to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for MI by family history of MI. All IRRs were adjusted for age, sex, calendar period, hypertension, diabetes and use of diuretics, calcium-antagonists, beta-blockers, lipid-lowering drugs, and drugs affecting the renin-angiotensin system.   Results:  In 3.6 million cohort-members followed for 48 million person-years, we identified 70,536 incident MIs. Fully adjusted IRRs (95% CI) for MI by family history of MI in one, two or three first degree relatives were 1.47 (1.42-1.60), 2.42 (2.20-2.66) and 3.40 (2.24-5.17), respectively. Corresponding estimates for second degree relatives were 1.15 (0.99-1.33), 1.89 (1.35-2.65) and 2.26 (0.85-6.03). For MI in a same-sex twin the IRR was 10.27 (5.02-21.02), MIs in opposite-sex twins or full-siblings conferred risks of 2.62 (0.36-18.87) and 2.74 (2.43-3.09). The IRRs by MI in parents and grandparents were 1.77 (1.71-1.84) and 1.18 (0.99-1.41), respectively. IRRs increased with younger age of cohort member and of relative at time of MI.   Conclusion:  Lower risks in parents as compared to siblings suggests gene-environment interactions. A dose-response pattern was evident when comparing first and second degree relatives and examining number of relatives with MI. This supports inclusion of a detailed family history in risk-assessment in patients with a family history of MI.
Effect and safety of FOLFOXIRI+b-mab as preoperative chemotherapy for multiple liver metastases of colorectal cancer.
Authors: Yasushi Ichikawa, Ayumu Goto, Takeshi Shimamura, Takashi Ishikawa, Jun Watanabe, Kazuteru Watanabe, Mitsuyoshi Ota, Shoichi Fujii, Hirotoshi Akiyama, Kuniya Tanaka, Itaru Endo
Journal: Journal of Clinical Oncology (2012)

e14047 Background: R0 resection for liver metastases of colorectal cancer is one of the promising treatment to improve prognosis of advanced colorectal cancer. Recently, effective anti-cancer drugs and various regimens using them were created and some advanced inoperable liver metastases were converted to operable by these chemotherapy. Therefore, development of powerful regimens to shrink liver metastases strongly is an important issue. In our department phase I/II study of FOLFOXIRI+B-mab including fluoroiuracil/oxaliplatin/irinotecan/bevacizumab for advanced liver metastases of colorectal cancer as pre-operative chemotherapy has been conducted now. Methods: The study was designed as a single-arm, open-label phase I/II trial. Phase I was conducted as sequential dose escalation to define the maximum-tolerated dose (MTD) of irinotecan. Patients who are colorectal cancer with 4 or more liver metastases and no other distant metastases are included. The regimen includes bevacizumab; 5 mg/kg, oxaliplatin; 85 mg/m 2 , l-LV; 200 mg/m 2 , 5FU; 400 mg/m 2 administered on day 1, followed by 5FU; 2400 mg/m 2 continuously administered for 46 hours. Dose escalation of Irinotecan was planned from level 1; 150 mg/m 2 , level 2; 180 mg/m2 and level 0; 125 mg/m 2 . In phase II, R0 resection rate of liver metastases as primary endpoint will be evaluated using MTD of irinotecan estimated in phase I. Results: Currently, 6 patients were studied. One patient showed grade 3 diarrhea as dose-limiting toxicity. For the other 5 patients, the study was accomplished. Grade 4 neutropenia was detected in 60%, however no patient showed febrile neutropenia. Excluding hematological toxicity, grade 3 or worse adverse event was only one grade 3 diarrhea described above. All 5 patients were performed R0 resection. All 5 patients showed PR and average of reduction rate was 62.7%. There was no pathological CR in the 5 patients who was performed R0 resection. There was no severe postoperative complication in them. Conclusions: This regimen is safe and shows high PR rate. So, the regimen is effective and improve R0 resection rate for multiple liver metastases of colorectal cancer. Further investigation of this study is still ongoing now.
A randomized double-blind phase III study of efficacy of <i>lactobacillus CD2</i> lozenges in preventing radiation- and chemotherapy-induced oral mucositis in head and neck cancer patients: Interim analysis
Authors: A. Sharma, G. K. Rath, S. P. Choudhary, A. Thakar, B. K. Mohanti, S. Bahadur, A. R. Sahu, A. Johar, A. Dwary
Journal: Journal of Clinical Oncology (2009)

6008 Background: Oral mucositis is major toxicity in patients receiving RT with or without chemotherapy (CTRT) for squamous cell carcinoma of head and neck (SCCHN). This compromises ones ability to tolerate and complete treatment. Interventions available till date to limit and restrict mucositis are unsatisfactory. This study was undertaken to test the efficacy of lactobacillus CD2 in rendering patients more tolerant to the anticancer therapy. Methods: Prospective randomized double blind phase III study. Inclusion criteria were: resectable SCCHN patients suitable for CTRT or radical RT, age group 18–70 years, KPS&gt;70%, normal hematological and biochemical functions. Eligible patients were randomized to receive total of 6 lozenges (to be dissolved by itself in the mouth) of either study product or placebo daily from the day anticancer treatment was started until one week after completion of anticancer therapy. Randomization was done in block of 10 patients. Initially it was planned to enroll 150 evaluable patients but protocol was amended to have total of 200 patients, to have interim analysis after 150 evaluable patients. This would have α and β error of 0.05 and 0.20, respectively. RT was given as 70 Gy/ 35# over 7 weeks with cisplatin 40 mg/m2 weekly x 7. Study was started in January 2007. Primary end points are: percentage of patients able to complete anticancer treatment and incidence of grade 3 and 4 mucositis. Results: This analysis was carried out on first 150 evaluable patients (75 in each arm). 135 were stage III or IV. Forty one (54.7%) in study arm and 36 (48%) in placebo arm took lozenges as planned (p = 0.414). Sixty seven (89.3%) in study arm and 56 (74.7%) in placebo arm could complete anticancer treatment (two sided p = 0.023). Grade 3 and 4 mucositis was seen in 40 (55.6%) and 44 (58.9%) patients respectively in study product and placebo arms (two sided p = 0.062). Conclusions: Study met one of its primary endpoint. Significantly more patients could complete anticancer treatment in study product arm and there was reduction in incidence of grade III and IV mucositis. We expect final results to be available before meeting. [Table: see text]
Clinicopathological features in correlation with epidermal growth factor receptor gene mutations in non-small cell lung cancer (NSCLC)
Authors: F. Tanaka, S. Matsumoto, T. Takuwa, N. Kondo, Y. Okumura, K. Fukuoka, T. Nakano, S. Hasegawa
Journal: Journal of Clinical Oncology (2007)

21148 Background: Mutations in the epidermal growth factor receptor (EGFR) gene are found in 10–30% of non-small cell lung cancer, and are useful to predict the efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib and erlotinib. However, it is sometimes difficult to examine such mutations. Thus, prediction of presence or absence of EGFR mutations, correlated with clinical response to EGFR-TKIs, based on clinicopathological characteristics may be important in clinical practice. Methods: We retrospectively assessed EGFR-mutation status in correlation with clinical features including FDG-PET findings and pathological features including presence or absence of bronchioalveolar component (BAC) in adenocarcinoma (Ad) case. A total of 72 consecutive patients (24 females; mean age, 65 years; 40 Ad cases) who received thoracotomy from August 2005 through October 2006 were reviewed Results: Sixteen cases (22%) had EGFR-mutations (8 cases each in exon 19 and exon 21). The incidence of EGFR-mutation was significantly higher in female (42%) or never-smoker (60%) than in male (13%) or smoker (15%). EGFR-mutation was almost exclusively found in Ad; among Ad cases, there was no significant difference in the incidence of EGFR-mutation between BAC-positive (47%) and BAC-negative cases (29%; p=0.33). Among 61 cases who received FDG-PET scan prior to thoracotomy, only 15% of EGFR- mutated cases had higher FDG-uptake, whereas 47% of EGFR-wild cases had higher FDG-uptake (p=0.36); the sensitivity and specificity of lower FDG-uptake to predict the presence of EGFR-mutations were 71% and 53%, respectively. The positive predictive value (PPV) of lower- FDG-uptake for the presence of EGFR-mutations was only 29%, but the negative predictive value (NPV) was as high as 85%. The mean standardized uptake value (SUV) of FDG for EGFR-wild patients and EGFR-mutated patients were 5.7 and 3.3, respectively (p=0.11). The mean SUV for tumors mutated in exon 19 seemed to be lower than that for tumors mutated in exon 21 (1.8 versus4.6). Conclusions: Higher FDG-uptake combined with clinical features (male and smoker) may help to exclude patients with EGFR-wild tumors who may not respond to EGFR-TKIs treatment. No significant financial relationships to disclose.
Lung cancer resection does not change characteristic serum proteomic profiles
Authors: D. G. Ward, A. Alzetani, J. Starczynski, G. Kaur, S. Trotter, N. James, M. J. Wakelam, W. Wei, L. J. Billingham, P. J. Johnson, A. Martin
Journal: Journal of Clinical Oncology (2006)

10051 Background: Surface-enhanced laser desorption/ionisation time of flight mass spectrometry (SELDI-TOF-MS) has been proposed as a method for determining characteristic serum proteomic profiles that permit discrimination between cancer and non-cancer patients. The aim of this study was to test in a group of lung cancer patients the hypothesis, that these profiles ‘return to normal’ following tumour resection, as would be expected if they behave as conventional serological tumour makers. Methods: Serum samples were collected from 39 patients with non-small cell lung cancer, 1 day pre-surgery, 1 day post-surgery and, for 17 of these, approximately three months later; samples were also obtained from 38 non-cancer control subjects. All samples were subjected to SELDI-TOF-MS analysis on CM10 chips. Students t-tests were used to identify differentially expressed peaks in the profiles. Results: The SELDI profiles of the lung cancer sera compared to non-lung-cancer controls showed 19 significantly differentially expressed peaks (p&lt;0.01), 14 of which were used to develop a neural network capable of discriminating between the two groups. Analysis of proteomic features showed that despite the absence of cancer in patients 3-months post-surgery, no statistically significant differences could be detected between the pre-treatment and 3-month post-operative samples from the same patients, including the 19 features that were found to discriminate between lung and non-lung cancer. One of the proteins significantly decreased in the serum of lung cancer patients was identified as transthyretin. Conclusions: SELDI can detect differentially expressed protein peaks characteristic of lung cancer compared to non-lung cancer patients but following surgical resection of the cancer, neither the pattern nor the individual peaks revert to the levels observed in non-lung cancer patients. The hypothesis that such differences would revert to normal after tumour removal was not supported. Work funded by Cancer Research UK No significant financial relationships to disclose.
Does gefitinib aggravate radiation induced respiratory dysfunction?
Authors: T. Mekhail, D. J. Adelstein, T. W. Rice, L. A. Rybicki, J. P. Saxton, M. M. Decamp, S. C. Murthy, G. Videtic, M. A. Carroll
Journal: Journal of Clinical Oncology (2004)

3116 Background: Significant concern has been expressed about the potential for gefitinib to produce interstitial pneumonitis, particularly in association with pulmonary radiation therapy. This possibility is being assessed in an ongoing study of neoadjuvant chemoradiotherapy and gefitinib for patients with locoregionally advanced esophageal cancer. Methods: Patients on this study are treated with 30 Gy of preoperative radiation (150 cGy bid) and a single concurrent chemotherapy course using 5-fluorouracil (1000 mg/m2/day) and cisplatin (20 mg/m2/day), both given as 4-day continuous infusions beginning on the first day of radiation therapy. Gefitinib, 250 mg daily, is given for 28 days, also beginning on day 1 of radiation therapy. Pre-treatment and post-treatment pulmonary function testing, including spirometry and carbon monoxide diffusion capacity (DLCO), is performed in all patients in preparation for surgical resection, which is scheduled no sooner than two weeks after completing the gefitinib. Results: Thus far, 9 patients have been entered on this study, ranging in age from 38–68 (median 59) years. All patients are men; 8 of 9 patients are white and have an adenocarcinoma. All patients had at least T3N0 disease. The mean pre-treatment FEV1 was 92% predicted (range 50%–133%). After chemoradiotherapy the mean FEV1 was 93% predicted (range 61% - 132%). The mean pre-treatment DLCO was 114% predicted (range 81%–138%) and fell to 102% (range 71%–130%) after treatment. This did not represent a clinically meaningful (>20%) reduction in DLCO (P=0.98). After surgery only one patient experienced any pulmonary complication; a post-operative pneumonia which resolved with antibiotic therapy. Conclusion: Limited experience suggests that this gefitinib containing induction regimen does not contribute to the early development of radiation-induced respiratory dysfunction. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Arterial blood carboxyhemoglobin as a predictor for response after chemotherapy in patients with lung cancer
Authors: K. Nakayama, H. Yasuda, T. Sasaki, T. Suzuki, M. Asada, S. Okinaga, M. Yamaya
Journal: Journal of Clinical Oncology (2006)

20029 Background: It is desirable to predict the response to chemotherapy in patients with lung cancer using a simple and reliable method. Arterial blood carboxyhemoglobin concentration (Hb-CO) is a useful biomarker for severity in inflammatory pulmonary diseases and is associated with cancer tissue volume in operable NSCLC. However, arterial Hb-CO as a predictor for response to chemotherapy in advanced lung cancer has not been reported. Methods: We enrolled 35 patients with SCLC and 66 ones with NSCLC in stage III or stage IV, treated with chemotherapy between October 2000 and December 2002. All patients with SCLC were treated with PE (cisplatin 80 mg/m 2 , day 1 and etoposide 100 mg/m 2 , day 1-day 3) every 3 weeks. The patients with NSCLC were treated with either VC (vinorelbine 25 mg/m 2 , day 1 and 8 plus cisplatin 80 mg/m 2 , day 1) or DG (gemcitabine 1100 mg/m 2 , day 1 and day 8 plus docetaxel 60 mg/m 2 , day 1) every 3 weeks. Arterial Hb-CO were examined before and at during chemotherapy and the response rate were studied. The patients with either a partial response (PR) or a complete response (CR) were categorized as responder, whereas patients with no change (NC) or progressive disease (PD) were as non-responders. According to the analysis in aterial Hb-CO, the patients were divided into two subgroups, patients with high (≥0.3%) or low (&lt;0.3%) maximum changes in the Hb-CO (ΔHb-CO) during chemotherapy. Results: The response rate was 80% in SCLC and 38% in NSCLC. In responder patients with SCLC or NSCLC, the arterial Hb-CO significantly increased and reached maximum at day 4 of the 1st cycle of chemotherapy. In contrast, in non-responder patients, the Hb-CO did not increase during the chemotherapy. The response rate in patients with high ΔHb-CO was significantly higher than that with low ΔHb-CO in SCLC (26/26 vs 2/9, P &lt; .001) and NSCLC (24/24 vs 1/42, P &lt; .001). The high ΔHb-CO at day 4 of the 1st chemotherapy cycle was significantly associated with the response to the chemotherapy in SCLC (Odd ratio, OR = 12.5 [95% CI: 3.13–50, P &lt; .001]) and in NSCLC (OR = 25 [95% CI: 3.23–100, P &lt; .01]) (logistic regression analysis). Conclusions: Increases in arterial Hb-CO at day 4 of the 1st chemotherapy cycle in SCLC and SCLC may be a predictor of response to chemotherapy. No significant financial relationships to disclose.
Virus Production in Cultures of Simian Virus 40-Transformed Human Amnion Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Jorgen Fogh, James Loveless, Edwin Gaffney
Journal: JNCI Journal of the National Cancer Institute (1970)

Cultures of epithelial human amnion cells, infected and transformed by simian virus 40 (SV40), produced virus at all stages of cultivation before and during the period of “crisis,” as reported for human fibroblasts. The virus production pattern was tri phasic, including an initial period of high virus production (phase 1), a period of low yields (phase 2), and a subsequent increase in yields before “crisis” (phase 3). Variation of the multiplicity of the initial virus exposure and culture age, and of the transfer dilutions, did not change this pattern. However, the time of phase 3 was related to approaching “crisis” and therefore depended on the multiplicity of exposure and transfer dilution factors. Shortly after infection the number of virus-producing cells (infectious centers or V-antigen-containing cells) was high, as reported for fibroblasts, but a subsequent period with nearly all cells producing virus was not observed for the amnion cultures. During the next period (phase 2 for amnion cells) very few cells (amnion: 0.01–0.3%) were virus producers in both systems; the output per amnion cell, however, was relatively higher (up to 2500 ID 50/cell). Before “crisis,” virus-producing cells increased significantly in the amnion cultures, in contrast to a decrease reported for fibroblasts. Inclusion-body-containing amnion cells were observed both initially and during serial cultivation, even after many culture passages; their frequency was correlated with the virus titers in the culture supernatant. Virus production and cell recovery at culture transfer were inversely related, and, as previously reported for chromosome changes, the morphology and growth pattern of the transformed cells differed in the three virus phases. The triphasic virus production pattern in the present system is interpreted as the results of a series of shifts in the balance between the amount of virus available and the degree of susceptibility of the transformed cells to reinfection. “Crisis” is correlated with a cellular change toward a decreased resistance to SV40. Since premature “crisis” could not be induced by superinfection with SV40 during the period of low virus production, it is apparent that “crisis” requires a certain number of cell divisions.
PD-L1 and PD-L2 Protect The Heart In a T-Cell Receptor Transgenic Model Of Graft-Versus Host Disease
Authors: Kathryn W Juchem, Britt Anderson, Cuiling Zhang, Arlene Sharpe, Jennifer McNiff, Anthony Demetris, Mark J Shlomchik, Warren D Shlomchik
Journal: Blood (2013)
Efficacy of orally available selective melanocortin-4 receptor antagonists in a murine model of cancer cachexia
Authors: R. Dallmann, P. Weyermann, J. P. Magyar, C. Anklin, M. Hufschmid, S. Nordhoff, M. Henneböhle, J. Dubach- Powell, I. Courdier-Fruh, C. Mondadori
Journal: Journal of Clinical Oncology (2009)

e20668 Background: Cachexia is among the most debilitating and life-threatening aspects of cancer. It represents a metabolic syndrome affecting essential functional circuits involved in the regulation of homeostasis, and includes anorexia, fat and muscle tissue wasting. The anorexigenic peptide alpha-MSH is believed to be crucially involved in the normal and pathologic regulation of food intake. It was speculated that blockade of its central physiological target, the melanocortin (MC)-4 receptor, might provide a promising anti-cachexia treatment strategy. This idea is supported by the fact that in animal studies, agouti-related protein (AgRP), the endogenous inverse agonist at the MC-4 receptor, was found to affect two hallmark features of cachexia, i.e. to increase food intake and to reduce energy expenditure. Methods: Two recently discovered, non peptidic, chemically unrelated, orally active MC-4 receptor antagonists penetrating the blood brain barrier were studied. Specifically, the influence on food intake in healthy mice, and effects in the murine C26 cancer-cachexia model were investigated. Results: Both compounds were found to distinctly increase food intake in healthy mice. Moreover, in mice subcutaneously implanted with C26 adenocarcinoma cells, repeated oral administration (starting the day after tumor implantation) of each of the two compounds almost completely prevented tumor induced weight loss, and diminished loss of lean body mass and fat mass. Conclusions: In contrast to the previously reported peptidic and small molecule MC-4 antagonists, the compounds described here work by the oral administration route. In the light of patient care, orally active compounds might offer a considerable advantage for the treatment of cancer cachexia. [Table: see text]
Combination Of Regulatory T Cells and Rapamycin As Treatment For Experimental Chronic Graft-Versus-Host Disease
Authors: Ludovic Belle, Gregory Ehx, Joan Somja, Marilene Binsfeld, Muriel Hannon, Jo Caers, Gilles Fransolet, Yves Beguin, Stephanie Humblet, Frederic Baron
Journal: Blood (2013)