tbuckley/cabot-search huggingface dataset:
Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study
Authors: Robert Scragg, Alistair W. Stewart, Debbie Waayer, Carlene M. M. Lawes, Les Toop, John Sluyter, Judy Murphy, Kay-Tee Khaw, Carlos A. Camargo
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D. <h3>Objective</h3> To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population. <h3>Design, Setting, and Participants</h3> The Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D<sub>3</sub>(n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis. <h3>Interventions</h3> Oral vitamin D<sub>3</sub>in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). <h3>Main Outcomes and Measures</h3> The primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels &lt;20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis. <h3>Results</h3> Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes. <h3>Conclusions and Relevance</h3> Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:ACTRN12611000402943
Small Airway Hyperresponsiveness In Precision-Cut Lung Slices Of Patients With Mild To Moderate COPD: Relationship Between Tissue Structure And Function
Authors: Herman Meurs, Annet B. Zuidhof, Carolina R.S. Elzinga, Marieke Smit, Anouk Oldenburger, Cécile M. Bidan, Reinoud Gosens, Wim Timens, Harm Maarsingh
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Standard CHOP therapy for low (L) or low-intermediate (L-I) risk patients (pts) with aggressive non-Hodgkin's lymphoma (NHL): A multicenter phase II study by Japan Clinical Oncology Group (JCOG 9508)
Authors: M. Ogura, Y. Kagami, K. Itoh, K. Tobinai, T. Chou, K. Aikawa, N. Ishizuka, T. Hotta, M. Shimoyama
Journal: Journal of Clinical Oncology (2004)

6703 Background: To confirm the efficacy and safety of standard CHOP therapy in Japanese pts with L or L-I risk aggressive NHL, we conducted a multicenter phase II study with overall survival (OS) as primary endpoint. Methods: Eligibility criteria were as follows: newly-diagnosed, intermediate or high grade NHL by Working Formulation; L or L-I risk by International Prognostic Index (IPI); clinical stage of II, III, IV or bulky I; ages less than 70; PS 0–3. Eight courses of standard CHOP therapy were given every 3 weeks. Involved-field radiotherapy (30 to 40 Gy) was added after chemotherapy for bulky disease at baseline, and was optional for residual tumors. Results: Between June 1995 and May 1999, a total of 213 pts were enrolled, and 173 pts were pathologically eligible (diffuse large B; 68%) by the central review according to WHO classification. Out of 173 pts, 87 and 80 pts were of L and L-I risk, respectively. Three pts with high-intermediate IPI risk, 1 high IPI risk, 1 stage I without bulky disease, and 1 prior radiotherapy were ineligible. % complete response of L and L-I risk pts was 83% (95% CI; 74–90%) and 74% (95% CI; 63–83%), respectively. Five-year OS was 73% (95% CI; 64–83%) and 64% (95% CI; 53–74%), and 5-year progression-free survival (PFS) was 63% (95% CI; 52–73%) and 38% (95% CI; 27–59%). Major toxicity by JCOG toxicity criteria in all treated pts (212 pts) was grade 4 neutropenia (64%). Non-hematologic toxicities were acceptable; the most frequent grade 3 toxicity was nausea/vomiting (3%), and grade 4 toxicity was observed in one who developed paralytic ileus. One treatment-related death was observed due to hepatitis B virus reactivation. Conclusions: CHOP was confirmed to be a standard therapy in Japanese pts with L or L-I risk aggressive NHL. However, the relatively low %PFS suggests the necessity of further investigations to find more effective first-line therapy for L-I risk pts. No significant financial relationships to disclose.
Prognostic value of plasma vascular endothelial growth factor in hormone-sensitive advanced stage prostate cancer: An exploratory analysis
Authors: M. A. Alikhan, V. Kaushal, P. Mehta, H. J. Spencer, M. Kohli
Journal: Journal of Clinical Oncology (2004)

4683 Background: We report an exploratory analysis on the prognostic value of plasma vascular endothelial growth factor (pVEGF) in hormone sensitive advanced prostate cancer patients undergoing androgen deprivation therapy (ADT). Methods: Patients (n=40) on clinical trials with measurements of angiogenesis markers were followed till radiological progression and/or death (events). All pVEGF and basic fibroblast growth factor (bFGF) measurements were performed in platelet poor plasma using commercially available ELISA kits. bFGF was also measured in urine. Wilcoxon rank sum test was used to compare median VEGF levels in patient groups with and without above events. Results: At 18 months follow-up (range 18–24 months), 40% (15/40) patients have experienced events (6 radiological progression, 6 deaths following a radiological progression, and 3 deaths with no radiological progression). Median pVEGF levels of all patients and comparison between patients with and without events are shown in table 1. 30/40 patients with advanced hormone-sensitive disease received ADT as primary prostate treatment without any preceding definitive prostate therapy. Median pVEGF of these patients during ADT with and without events is also shown and compared in table 1. Plasma and urine bFGF was measurable in four patients, none of whom has had an event. Conclusions: We found limited prognostic value of pVEGF in hormone sensitive prostate cancer in this exploratory analysis. A larger study population in this stage may identify subgroups of hormone sensitive prostate cancer patients in whom circulatory angiogenesis markers may have prognostic or predictive value, which could assist in guiding therapeutic interventions with anti angiogenic agents during this stage. No significant financial relationships to disclose.
Preferences for breast cancer prevention among BRCA mutation carriers
Authors: J. Jacobson, P. Patel, A. Bharthuar, D. Hershman, K. Hill, E. Warner, D. Plewes, S. Messner, R. Erichson, V. Grann
Journal: Journal of Clinical Oncology (2007)

17018 Purpose: Breast cancer screening with MRI is a new option available to patients with BRCA 1/2 mutations. We analyzed preferences for this modality and 10 other breast cancer- related health states and preventive measures among women without cancer or known high risk and women with BRCA mutations. Methods: Following IRB approval, we administered a time trade-off questionnaire to mutation carriers and to women without breast cancer or known high risk. We used Kruskal-Wallis test to compare the two groups with respect to continuous variables, chi-square tests to compare proportions, and the Wilcoxon signed rank test for pairwise comparisons. We then developed logistic regression models to analyze the association of mutation carrier status and demographic factors with willingness to trade time for each of the 11 health states. Results: Two-hundred-four women (44 mutation carriers and 160 without breast cancer or known high risk) responded to the questionnaire. Both groups assigned the highest preference rating to mammography and the next-highest to MRI, but the differences in ratings were not statistically significant. Both groups assigned the lowest preference ratings to having a child with a mutation and the next lowest to ovarian cancer. In pairwise comparisons, both groups ranked oophorectomy higher than ovarian cancer (p &lt;0.01), but mutation carriers did not rank prophylactic mastectomy significantly differently from breast cancer (p=0.38). In the logistic regression models, mutation carrier status was not a statistically significant predictor of willingness to trade time for any health state, but younger age, lower income, and nonwhite race/ethnicity were associated with willingness to trade time for certain health states. Conclusion: Our data indicate that MRI is as acceptable as mammography to respondents, and that the preferences of BRCA 1/2 mutation carriers are similar to those of other women. Age and other demographic factors may be more important than mutation status in determining preferences. The preference ratings of individuals should not be inferred from demographic characteristics or mutation status. However, such ratings can help to clarify the quality of life implications of clinical decision-making and health care policy regarding breast cancer prevention. No significant financial relationships to disclose.
Pilot study: Second-line carboplatin and docetaxel combination chemotherapy in the patients with advanced non-small-cell lung cancer(NSCLC) pretreated with cisplatin-based regimens
Authors: S. Y. Park, K. W. Kim, M. S. Kim, S. C. Kim
Journal: Journal of Clinical Oncology (2004)

7307 Background: Several chemotherapy agents have been evaluated in the second-line setting, but standard treatment remains controversial. The combination of carboplatin and docetaxel as the first-line treatment has showed promising results in the treatment of advanced NSCLC with 40–60% response rates in chemotherapy naïve-patients. Single docetaxel as the second-line treatment was reported to show promising activity leading to the improved survival and quality of life. Methods: In this pilot study we tried to evaluate the efficacy of second-line carboplatin and docetaxel in the patients with advanced NSCLC pretreated with cisplatin-based regimens. Results: From 1999 to 2003, total 22 patients (male:female = 15:7, median age 59.5) with advanced NSCLC (squamous cell carcinoma : adenocarcinoma : poorly differentiated carcinoma = 10:8:4, III:IV = 13:9) who showed the progression (13) or relapse (9) during or after cisplatin-based chemotherapy (cisplatin/vinorelbine : cisplatin/gemcitabine = 15:7), were treated with carboplatin AUC 5 mg/ml min and docetaxel 75 mg/ml on Day 1 in a 21-day cycle. Median number of cycles was 2 (1–6) and total 58 cycles were given. Myelosuppressions (netropenia grade III (%/cycle) 17.2/10, IV 3.4/2, thrombocytopenia III 1.7/1) were major side effects and other toxicities were acceptable. There was no treatment-related death. 1 partial response (4.5%), 7 (31.8%) stable disease, and 14 (63.6%) progression were observed. Median survival was 5 months. Conclusions: As compared with other regimen in the second-line treatment, the response rate in this study was discouraging. Given its toxicity and cost, we concluded, the second-line carboplatin and docetaxel in the patients with advanced NSCLC pretreated with cisplatin-based regimen seems to be not advisable. No significant financial relationships to disclose.
Long-term use of antibiotics and risk of colorectal adenoma
Authors: Yin Cao, Kana Wu, Raaj Mehta, David A Drew, Mingyang Song, Paul Lochhead, Long H Nguyen, Jacques Izard, Charles S Fuchs, Wendy S Garrett, Curtis Huttenhower, Shuji Ogino, Edward L Giovannucci, Andrew T Chan
Journal: Gut (2017)

<h3>Objective</h3> Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated. <h3>Design</h3> We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16 642 women aged ≥60 enrolled in the Nurses9 Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic regression to calculate ORs and 95% CIs. <h3>Results</h3> We documented 1195 cases of adenoma. Increasing duration of antibiotic use at age 20–39 (p<sub>trend</sub>=0.002) and 40–59 (p<sub>trend</sub>=0.001) was significantly associated with an increased risk of colorectal adenoma. Compared with non-users, women who used antibiotics for ≥2 months between age 20 and 39 had a multivariable OR of 1.36 (95% CI 1.03 to 1.79). Women who used ≥2 months of antibiotics between age 40 and 59 had a multivariable OR of 1.69 (95% CI 1.24 to 2.31). The associations were similar for low-risk versus high-risk adenomas (size ≥1 cm, or with tubulovillous/villous histology, or ≥3 detected lesions), but appeared modestly stronger for proximal compared with distal adenomas. In contrast, recent antibiotic use within the past four years was not associated with risk of adenoma (p<sub>trend</sub>=0.44). <h3>Conclusions</h3> Long-term antibiotic use in early-to-middle adulthood was associated with increased risk of colorectal adenoma.
Tumor profiling on 1245 gliomas and paired tumor study on 19 high grade gliomas.
Authors: Joanne Xiu, David Spetzler, Ryan Bender, Anatole Ghazalpour, Zoran Gatalica, Sandeep K. Reddy, David Eric Piccioni, Jethro Lisien Hu, Michael J. Glantz, Santosh Kesari
Journal: Journal of Clinical Oncology (2015)

2058 Background: Gliomas are molecularly heterogeneous with genetic alterations driving the growth of recurrences different from the initial tumor. Previous reports showed molecular changes during progression of lower grade gliomas to GBM, driving tumor growth and treatment resistance; however changes during progression of high-grade gliomas have not been systematically reported. Methods: 1245 glioma tumors (934 GBM) were tested with multiple platforms including sequencing (SEQ), immunohistochemistry (IHC), fluorescent/chromogenic in-situ hybridization (FISH/CISH), fragment analysis (FA) and promoter methylation (Me) assay. Metachronous paired tumors from 19 patients (pts) were assessed for biomarker changes over time. Results: EGFRvIII was seen exclusively in GBM (16% of GBM) while amplification was more common in GBM than grade II-III tumors (56% vs. 20%, p < 0.001). MGMT Me was seen in 47% of all, and was more common in grade II-III (64% vs. 42%, p < 0.001). PD-L1 expression on tumor cells was seen in 27% and was more common in tumors without MGMT Me (36% vs. 18%, p = 0.01). PD-1 expression on tumor-infiltrating lymphocytes was seen in 48% and was higher in GBM than grade II-III(54% vs. 30%, p = 0.005). 38 of 48 sequenced genes had mutations, including BRCA1 (8%) and BRCA2 (6%). 1p19q co-deletion was seen in 26% of grade II-III and 2.9% of GBM. Paired tumors from 19 pts (18 GBM and 1 grade III in both samples) taken at an average of 469 days apart (91-1400) showed that 17 pairs (89%) had one or more biomarker changes over time. 3 of 13 (23%) pairs lost MGMT Me, potentially indicating acquired resistance to temozolomide. EGFR aberrations including amplification (N = 1), mutations on the extracellular (EGFRvIII, N = 1) and intracellular domains (T790M, N = 1; Exon 20 insertion N = 1) were acquired in 3 pairs. One pt, presenting with a PTEN mutation, acquired three additional mutations: cKIT (E583K), PTPN11 (A72T) and PIK3CA (D434N). Conclusions: Multiplatform tumor profiling on a large cohort of gliomas confirms tumor heterogeneity. Changes in MGMT Me and EGFR of potential therapeutic importance are frequently observed in high grade gliomas at the time of recurrence, suggesting the need for a re-biopsy for tumor profiling to direct the next line of therapy.
Impact of cancer on the productivity of American Families
Authors: Y.-C. T. Shih, L. Zhao
Journal: Journal of Clinical Oncology (2004)

6058 Background: Studies of disease burden of cancer usually focused on individuals who suffered from cancer, but neglected the spillover effect of cancer on the productivity of family members of cancer patients (pts). This study examines the overall impact of cancer on the productivity using families as the unit of analysis. Methods: A sample of cancer pts was extracted from the 2000 Medical Expenditure Panel Survey (MEPS) data. Cancer was identified from the ICD-9-CM and the Clinical Classification Codes. Productivity-loss at family-level was measured by total work-loss days for all employed family members, those diagnosed with cancer, and those having work-loss days due to caring for illness of others. We used a two-part model to examine the likelihood of having productivity loss from employed family caregivers (a logit model) and the quantity of work-loss between cancer and non-cancer families (a Least Square model). Results: The 2000 MEPS contained 8,849 families; 7.6% had one or more family member had a cancer diagnosis. Among family members who were employed, the average number of work-loss days was 10.7 and 7.2 days for cancer and non-cancer families, respectively (P=0.007). Employed family caregivers (defined as employed family members who reported having work-loss days to care for others) were found in 20.6% and 18.1% of the cancer and non-cancer families (P=0.189), with 7.7 and 3.7 work-loss days (P=0.09), respectively. Results from the two-part model (Table 1) showed no significant difference in the likelihood of having productivity loss from employed family caregivers. However, among families with employed family caregivers, cancer families had a significant higher number of work-loss days. Conclusions: Cancer affects the productivity of American families through work-loss of cancer pts and their family caregivers. Failure to incorporate the effect of cancer on family caregivers may underestimate the economic burden of cancer. No significant financial relationships to disclose.
Home hospice care in Nepal: a low-cost service in a low-income country through collaboration between non-profit organisations
Authors: Binay K Shah, Tara Shah
Journal: The Lancet Global Health (2017)

BackgroundNepal is a low-income country in south Asia with a population of more than 27 million people. Because of late diagnosis and poor access to care, almost 90% of approximately 60 000 people diagnosed with cancer in Nepal annually will die within 1 year of diagnosis. Here, we describe our experience in successfully establishing a home hospice programme in Kathmandu, Nepal.MethodsIn 2015, Binaytara Foundation, a US-based non-profit organisation, collaborated with a Nepal-based non-profit organisation, Cancer Care Nepal, to develop a home hospice programme in Kathmandu. We interviewed 150 terminally ill patients and their family to investigate the need for a hospice programme. A project leader (a Nepali physician) was appointed. In the second phase of the programme, we trained health-care providers and implemented electronic medical records. A hospice nurse practitioner from Idaho, USA, travelled to Nepal to train 15 Nepali nurses. A motorbike was provided for the hospice nurse to travel to patients' homes.FindingsThe hospice programme was launched in January, 2016. By September, 2016, 65 patients had been enrolled in home hospice care. The service is provided free of charge to the patients and their family. The cost of running the hospice programme is US$17 per day. All costs, including equipment, salary, staff training, electronic medical records, fuel, and other monthly expenses have been paid for by Binaytara Foundation.InterpretationHome hospice programmes are very important in low-income countries like Nepal where most patients with cancer are diagnosed at late stages, and many patients do not have access to cancer centres. To make a home hospice project successful, several factors, such as the selection of an appropriate local partner organisation, training, and financial support are necessary and the project should respect local cultural contexts.FundingNone
Insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 is active in breast cancer cells and enhances growth inhibition by herceptin through an increase in cell cycle arrest
Authors: A. Esparís-Ogando, R. Rodríguez-Barrueco, J. Borges, L. Ferreira, A. Pandiella, A. Ocana
Journal: Journal of Clinical Oncology (2007)

21077 Background: Targeting ErbB2 with the monoclonal antibody trastuzumab (Herceptin) has shown to be active in breast cancer. However, a proportion of patients do not benefit from this treatment due to primary resistance. Mechanisms proposed for this resistance include activation of other receptors involved in proliferation as is the case of the insulin-like growth factor receptor (IGF-1R).Different strategies have been proposed for the inhibition of IGF-1R such as antibodies or small tyrosine-kinase inhibitors. In this study we analyzed the mechanism of action and the antiproliferative activity of an specific IGF-1R tyrosine-kinase inhibitor termed NVP-AEW541 alone and in combination with Herceptin. Methods: MCF7, SKBR3, BT474, and MDA-MB-231 breast cancer cells were used for this study. Proliferation and apoptosis were analyzed by MTT uptake assays or Annexin-V-FITC, respectively. The levels of different signalling proteins were analyzed by Western blotting. Microarray studies were performed using the HU-133A oligonucleotide arrays (Affymetrix, Santa Clara, CA). Real time quantitative PCR was used to confirm the differentially regulated genes. Results: The IGF-1R was expressed in all the cell lines studied. Exogenous addition of IGF-1 increased the tyrosine phosphorylation of IGF-1R, and this was prevented by preincubation with NVP- AEW541. The latter also decreased MTT uptake, and provoked a slight increase in apoptosis of BT474 cells. Combination of NVP-AEW541 and Herceptin had a synergistic effect on the inhibition of BT474 proliferation. Cell cycle analyses indicated that the combined addition of NVP- AEW541 and Herceptin increased the number of cells in the G0/G1 phases. These data were complemented with an increase in p27 levels upon treatment with both compounds. Microarray analyses identified several genes whose expression was modified by each agent alone and by the combination. Conclusions: Our results indicate that the combined targeting of two receptor tyrosine kinases known to play important roles in tumor cell proliferation may be more efficient than individual targeting of these receptors. No significant financial relationships to disclose.