tbuckley/cabot-search huggingface dataset:
Association of germ-line SNPs with overall survival (OS) in pazopanib-treated patients (Pts) with advanced renal cell carcinoma (RCC).
Authors: C. Xu, N. Bing, H. A. Ball, C. N. Sternberg, I. D. Davis, Z. Xue, L. McCann, K. King, J. C. Whittaker, C. F. Spraggs, V. E. Mooser, L. N. Pandite
Journal: Journal of Clinical Oncology (2011)

4558 Background: Pazopanib, an oral tyrosine kinase inhibitor of VEGFR, PDGFR and c-Kit, has been approved for the treatment of advanced RCC. Variability in response, progression free survival (PFS), and OS is observed among pazopanib treated RCC pts. Our previous analyses showed that SNPs in IL8, HIF1A, VEGFA and NR1I2 genes may predict PFS and response to pazopanib (ASCO 2010 abstract 4520). We now test the hypothesis that differences in OS can be explained, at least in part, by germline genetic variants in angiogenesis and exposure related genes. Methods: Baseline factors and 27 functional polymorphisms within 13 genes were evaluated in 241 pazopanib treated pts with advanced RCC from a phase III study and its extension study (GU ASCO 2011 abstract 303). Association with OS was analyzed using the Cox proportional hazards model. Results: High neutrophil count (>ULN) and low BMI were independent predictors of poor OS (P≤0.05). Despite including these covariates in the PGx analyses,five SNPs in IL8, FGFR2, NR1I2and ABCB1showed nominally significant association with OS (P≤0.05). A median OS of 30 months was observed in pts carrying wild-type IL82767 AA genotype, compared to 15 months in those with the TT variant genotype [HR (95%CI) = 2.2 (1.3, 3.6) for TT vs. AA, P=0.003]. The median OS for pts who were heterozygous for this IL8 polymorphism was 24 months. The FGFR2IVS2 + 906C>T variant TT genotype associated with inferior OS compared with the wild-type CC genotype [median OS, 21.4 vs. 28.0 months, HR (95%CI) = 1.7 (1.1, 2.8), P=0.02]. Similarly, the variant NR1I2 -25385TT genotype (23 months) and variant ABCB11236TT genotypes (20 months) associated with reduced median OS compared with the respective wild-type CC genotypes (29 months, P=0.02; 28 months, P=0.009). A multivariate analysis including baseline factors and SNPs from the four genes showed that these SNPs are independent predictors for OS. Conclusions: Germline variants in angiogenesis and exposure related genes may be associated with survival outcome for pazopanib monotherapy in pts with advanced RCC. These associations are considered exploratory and require confirmation in an independent dataset.
Ultrastructure of Blood Lymphocytes From Chronic Lymphocytic and Lymphosarcoma Cell Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Schrek
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Ultrastructure of Blood Lymphocytes From Chronic Lymphocytic and Lymphosarcoma Cell Leukemia Get access Robert Schrek Robert Schrek Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 1, January 1972, Pages 51–64, https://doi.org/10.1093/jnci/48.1.51 Published: 01 January 1972 Article history Received: 08 July 1971 Accepted: 13 September 1971 Published: 01 January 1972
Unbiased targeted next-generation sequencing molecular approach for primary immunodeficiency diseases
Authors: Hamoud Al-Mousa, Mohamed Abouelhoda, Dorota M. Monies, Nada Al-Tassan, Abdulaziz Al-Ghonaium, Bandar Al-Saud, Hasan Al-Dhekri, Rand Arnaout, Saleh Al-Muhsen, Nazema Ades, Sahar Elshorbagi, Sulaiman Al Gazlan, Farrukh Sheikh, Majed Dasouki, Lina El-Baik, Tanzeil Elamin, Amal Jaber, Omnia Kheir, Mohamed El-Kalioby, Shazia Subhani, Eman Al Idrissi, Mofareh Al-Zahrani, Maryam Alhelale, Noukha Alnader, Afaf Al-Otaibi, Rana Kattan, Khalid Al Abdelrahman, Muna M. Al Breacan, Faisal S. Bin Humaid, Salma Majid Wakil, Fadi Alzayer, Haya Al-Dusery, Tariq Faquih, Safa Al-Hissi, Brian F. Meyer, Abbas Hawwari
Journal: Journal of Allergy and Clinical Immunology (2016)
Crime and violence among mental patients
Authors: A Zitrin, A S Hardesty, E I Burdock, A K Drossman
Journal: American Journal of Psychiatry (1976)

The authors studied the arrest rates of 867 patients from the Bellevue catchment area who were discharged from the psychiatric division of Bellevue Hospital. They found that the arrest rates of these patients for two years preceding and two years following their admissions to the study were higher than the arrest rates for the general population of the Bellevue catchment area as well as those for 4,601 cities in the United States. They discuss the implications of this finding for the post discharge care of mental patients, particularly in the light of current discharge policies.
Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(β-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma
Authors: Cong Zhang, Tong An, Dan Wang, Guoyun Wan, Mingming Zhang, Hemei Wang, Sipei Zhang, Rongshan Li, Xiaoying Yang, Yinsong Wang
Journal: Journal of Controlled Release (2016)
Patient-reported outcomes for determining prognostic groups in veterans with stage IV solid tumors starting systemic therapy.
Authors: Victor T Chang, Charles B. Scott, Jan Einhorn, Houling Yan, Melanie L. Gonzalez, Maryann Sullivan, Shanthi Srinivas, Fengming Zhong, Emma R Paz-Querubin, Monica McPherson, Barbara Crump, Lourdes Duque, Basil Kasimis
Journal: Journal of Clinical Oncology (2013)

9567 Background: A Recursive Partitioning Analysis (RPA) algorithm predicted four groups with distinct median survivals in patients with advanced cancer entering palliative care (ASCO 2010, Abst 9040). We investigated whether this algorithm could apply to cancer patients starting systemic therapy. Methods: The RPA algorithm is based upon Karnofsky performance status (KPS), Functional Assessment of Cancer Therapy (FACT) physical well-being (PWB) subscale, and Memorial Symptom Assessment Scale Short Form (MSAS-SF) physical symptom distress (PHYS) subscale. Starting in 2007, a convenience sample of Veterans who were prescribed systemic treatment for their cancer was enrolled in an IRB approved protocol, and completed quality of life (FACT- G) and symptom (MSAS SF) questionnaires prior to starting the first cycle of treatment. We analyzed records of patients with stage IV metastatic solid tumors enrolled through August 2011, and determined survival as of December 1, 2012. Analyses were performed with STATA 11.0. Results: There were 72 patients (pts). The median age was 63 yrs, (range 46-86). Men comprised 71 (98%) pts. First line systemic therapy was given to 59 (82%) pts. The most common primary sites were lung cancer (25 pts, 35%), prostate 9 pts(12%) and colon 7 pts (10%). Median KPS was 90% (range 40-100%), PWB median 23 (range 6-28), and MSAS SF median PHYS 0.73 (range 0-2.93). Overall median survival was 269 days (range 6-1762) and 57 pts (79%) had died. There was 1 pt in group 1, 45 pts in group 2, 8 pts in group 3, and 18 pts in group 4. Median survival (days) by RPA group was 155 for group 1, 177 for group 2, 292 for group 3, and 610 for group 4 (p=.011). Conclusions: These preliminary findings suggest that this algorithm is capable of dividing patients with metastatic solid tumor who are starting chemotherapy into prognostic groups. It may have applications in clinical trials. Further development is indicated. [Table: see text]
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Lack of Correlation Between Malignancy and Sensitivity to Killing by Concanavalin A&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: F T Kao, H Harris
Journal: JNCI Journal of the National Cancer Institute (1975)

Eight mouse cell lines and seven hybrid clones, both malignant and nonmalignant, were tested for possible correlations between malignancy and sensitivity to killing by concanavalin A (Con A). These cells included six highly malignant and two less malignant cell lines, two malignant and three nonmalignant hybrid clones derived from five different crosses, and two malignant hybrid clones segregated from a cross between malignant and nonmalignant cells. The malignancy of the cells was determined by their ability to grow progressively in irradiated, syngeneic newborn mice and to kill the host. All these cells, except one, showed similar sensitivities to killing by Con A. No correlation could be established between the malignancy of a cell line or of a hybrid clone and its sensitivity to the lectin.
Acute hepatitis E virus infection in human immunodeficiency virus–positive men and women in Nepal: Not quite a rare entity
Authors: Birendra Prasad Gupta, Ananta Shrestha, Anurag Adhikari, Thupten Kelsang Lama, Binaya Sapkota
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with great interest the article published in Hepatology by Kuniholm et al., which showed that hepatitis E virus (HEV) genotype 3 infection is rare, but has potential to cause chronic HEV infection in human immunodeficiency virus (HIV)‐infected women in the United States.1 In Asian countries, contaminated water supply is the predominant route of HEV infection.2 Nepal is highly endemic for hepatitis E infection, and five epidemics have occurred over the last 30 years.5 All the reported sporadic and epidemic acute hepatitis E infections in Nepal have so far been caused by HEV genotype 1.2 We had this opportunity to study acute hepatitis E among a cohort of HIV‐positive men and women enrolled currently under national antiretroviral program treatment (ART) of Nepal. During the period of January to March 2015, 459 HIV‐infected individuals (274 male, 185 female) visited the ART center as a part of their regular follow‐up. Blood was collected in ethylenediaminetetraacetic acid and subjected for CD4 count within 3 hours. Plasma was separated and samples were used for HIV viral load, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody (anti‐HCV), and HEV antibody immunoglobulin M (anti‐HEV IgM; Wantai Biological Enterprise, Beijing, China) and liver enzyme estimation. Demographic variables along with duration of HIV infection were also recorded. During the same period, sera of 587 healthy blood donors were collected from Kathmandu Valley as a control group and assayed for anti‐HEV IgM. Collection of follow‐up sera and nucleic acid testing for HEV RNA was not performed in the current study. Of 459 HIV‐positive subjects, anti‐HEV IgM was detected in 70 (15.25%) subjects (40 male, 30 female), as compared to (4.42%) of blood donors (P < 0.001; odds ratio [OR]: 3.7 [2.35‐5.92]). HBsAg and anti‐HCV were detected in 24 (5.22%) and 342 (74.50%), respectively. In multivariate analysis, anti‐HEV IgM positivity was associated with CD4+ count >200 cells/µL (P < 0.005; OR, 3.257 [1.36‐7.76]), whereas HCV coinfected subjects were spared (P < 0.001; OR, 0.15 [0.08‐0.27]). We show that in a highly endemic region for HEV, HIV‐infected subjects are more prone to acquire acute HEV infection, as compared to a control population, particularly those with higher CD4+ count and those without HCV coinfection.
Capecitabine plus docetaxel (XT): A first line, phase II clinical trial in metastatic breast cancer
Authors: C. L. Vogel, E. Tan-Chiu, F. Gokce
Journal: Journal of Clinical Oncology (2006)

10624 Background: The XT combination originally published at (X) dosed at 1250 mg/m 2 bid po x 14 days and (T) at 75 mg/m 2 q3 weeks I.V. respectively yielded good response rates and an overall survival advantage compared with single agent docetaxel at 100 mg/m 2 . However, the toxicity profile of this regimen has led to major dose and schedule modifications by most oncologists. Methods/Results: We initiated a Phase II trial at doses of X at 900 mg/m 2 bid po x 14 days and T at 36 mg/m 2 d 1 and 8. Three responded and the mean no. of cycles for these patients was 3.8. Since four of 6 went off study because of toxicity two additional dose levels were studied in 6 patients each. A second cohort received X at 650 mg/m 2 bid and T at 30 mg/m 2 . With 6 evaluable patients, four of 6 responded but all 4 required further dose reductions. Mean no. of cycles received was 4.2. A third cohort of 6 patients received X at 825 mg/m 2 plus the lower T at 30mg/m 2 who received a mean no. of cycles of 6. While only 1/6 responded 3 additional patients had stable disease with marked decreases in CEA or CA 15–3 suggestive of anti-tumor response. Only 1/6 required a dose reduction. Among the 18 patients, epiphora was described by 5 (28%). Only 3 patients developed significant leukopenia, and thrombocytopenia was not seen. T-induced nail changes were uncommon but were severe in one patient. Two patients at the first dose level, but only one at lower levels developed mucositis. Grade 1 anemia was common but managed easily with growth factor support. Conclusions: The response rate of 44% is encouraging with these lower doses of XT. We recommend further studies using X at 825 mg/m 2 and T at 30mg/m 2 since these doses were associated with encouraging response rate and a better toxicity profile than higher doses. Even at this higher dose of X dose reductions may well be needed. (Supported by a grant from Roche Laboratories, Inc.) No significant financial relationships to disclose.
Increased detection and contrast enhancement of small malignant lung nodules in mice by a tumor-targeting nanoimmunocomplexed contrast agent
Authors: M. T. Freedman, K. F. Pirollo, E. H. Chang
Journal: Journal of Clinical Oncology (2007)

14131 Background: Lung cancer screening with CT results in the detection of many small lung nodules, few of which are cancerous. As a result many patients are followed to assess nodule growth. Contrast enhanced MRI and CT are used to determine whether small nodules are hypervascular or hypovascular, differentiating between nodules that are more/less likely to be malignant. For nodules 7 mm and larger, contrast enhancement has few false negatives, but a moderate number of false positives leading to unnecessary biopsies. Reported here is a new method of delivering contrast agent that transfers it directly into the cancer cells. This delivery system is a nano size immunoliposome complex containing gadopentetate dimeglumine which is targeted to the transferrin receptor on the cell. Methods: Syngeneic mouse model of lung metastases is used. Mouse renal carcinoma cells are tail vein injected into female BALB/c mice. For small lung nodules (1–4 pixels), the animals are imaged 7–9 days post inoculation. Images are obtained with a 7T MRI using RARE sequences. Results: Comparisons of pixel intensity were made between the pre- and post contrast images and between the novel and standard contrast agents. Using the complex, nodules as small as 2 pixels (200 μm) in size can be visualized and have greater pixel intensity. Conclusions: A novel carcinoma specific nanocomplexed MR contrast agent shows improved enhancement when compared to standard MR contrast. This agent is on the path towards clinical testing. It could help determine which small nodules identified on screening CT have a high or low probability of malignancy. Specific targeting to carcinoma cells should result in fewer false positives. This novel imaging contrast agent should enable detection, and earlier confirmation of malignancy, in nodules substantially smaller than currently possible. No significant financial relationships to disclose.
FGFR1 Induces Glioblastoma Radioresistance through the PLCγ/Hif1α Pathway
Authors: Valérie Gouazé-Andersson, Caroline Delmas, Marion Taurand, Judith Martinez-Gala, Solène Evrard, Sandrine Mazoyer, Christine Toulas, Elizabeth Cohen-Jonathan-Moyal
Journal: Cancer Research (2016)

Abstract FGF2 signaling in glioblastoma induces resistance to radiotherapy, so targeting FGF2/FGFR pathways might offer a rational strategy for tumor radiosensitization. To investigate this possibility, we evaluated a specific role for FGFR1 in glioblastoma radioresistance as modeled by U87 and LN18 glioblastomas in mouse xenograft models. Silencing FGFR1 decreased radioresistance in a manner associated with radiation-induced centrosome overduplication and mitotic cell death. Inhibiting PLCγ (PLCG1), a downstream effector signaling molecule for FGFR1, was sufficient to produce similar effects, arguing that PLCγ is an essential mediator of FGFR1-induced radioresistance. FGFR1 silencing also reduced expression of HIF1α, which in addition to its roles in hypoxic responses exerts an independent effect on radioresistance. Finally, FGFR1 silencing delayed the growth of irradiated tumor xenografts, in a manner that was associated with reduced HIF1α levels but not blood vessel alterations. Taken together, our results offer a preclinical proof of concept that FGFR1 targeting can degrade radioresistance in glioblastoma, a widespread problem in this tumor, prompting clinical investigations of the use of FGFR1 inhibitors for radiosensitization. Cancer Res; 76(10); 3036–44. ©2016 AACR.
Biomarkers of treatment benefit in a randomized phase II study of bevacizumab in combination with carboplatin and paclitaxel in metastatic melanoma patients (BEAM).
Authors: P. Hegde, B. Xing, S. O'Day, K. B. Kim, M. Schmidt, S. J. Scherer, H. Nguyen, A. C. Peterson, P. Cheverton, D. S. Chen
Journal: Journal of Clinical Oncology (2010)

10563 Background: Bevacizumab, a monoclonal antibody targeted against vascular endothelial growth factor A (VEGF), showed a clinically significant benefit in the analysis of a large (n=214) randomized placebo-controlled Phase II study (BEAM) when added to carboplatin and paclitaxel chemotherapy for the treatment of Stage IV metastatic melanoma. Approximately one third of patients in both bevacizumab-(CPB) and placebo-(CPP) containing study arms progressed within 12 weeks of starting treatment, with the benefit of bevacizumab being observed in the remaining two-thirds of patients. A set of baseline plasma samples was collected from patients representative of both groups and analyzed for potential biomarkers associated with early progression status. Methods: A total of 36 (17%) baseline patient plasma samples were collected, 29 from the bevacizumab-containing arm and 7 from the placebo-containing arm. The baseline samples were assessed by ELISA-based assays for VEGF and 89 other plasma proteins. Results: Baseline characteristics of patients from whom plasma was collected appear to be representative of the overall population. In a pooled analysis of samples from both study arms, 75% of patients who progressed at or prior to 12 weeks on study had high baseline VEGF levels. Additionally, unsupervised clustering of the analyzed plasma proteins revealed a signature of plasma protein expression (including VEGF, TIMP-1, vwf, and IL-8) that correlated with a poor overall prognosis. This poor prognostic signature identified 66% of the patients who progressed at or prior to 12 weeks on study. Conclusions: Baseline VEGF levels and a biomarker signature for poor outcome both appear to be prognostic of poor PFS, OS, and 12 week progression-free survival for patients with Stage IV malignant melanoma. Further evaluation for predictive value of baseline VEGF and the biomarker signature should be performed in the Phase III setting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Roche Roche Roche Roche Roche
Abstract 126: Public Knowledge and Attitude Toward Cardiopulmonary Resuscitation in Taiwan: A National Telephone Survey
Authors: Nai-Chuan Chen, Yu-Sheng Huang, Edward P Huang, Yen-Pin Chen, Chen, Matt, Weiting, Ko, Patrick, Chow-In, Wen-Chu Chiang, Chih-Wei Yang, Yu-Chuan Liu, Wui-Chiang Lee, Ming-Neng Shiu, Ming-Chin Yang, Ma, Matthew, Huei-Ming
Journal: Circulation (2013)

Background: Cardiovascular diseases are the leading cause of death worldwide, and the integrity and public awareness of the community chain-of-survival are pivotal to survival. Taiwan is now implem...
CK-19 expression by RT-PCR in the peripheral blood of prostate cancer patients
Authors: M. T. Machado, F. Fonseca, A. P. Fantinato, M. L. Wroclawski, E. Wroclawski, A. Del Giglio
Journal: Journal of Clinical Oncology (2005)

4636 Background: Presence of epithelial cells in the peripheral blood of prostate cancer patients correlates with adverse prognostic factors and seems to impart a poorer prognosis in terms of disease free and overall survival in several series in the literature. Sensitive RT-PCR-based techniques for detection of epithelial antigen expression, such as CK-19, in the in the peripheral blood mononuclear fraction (PBMN) of prostate cancer (PC) patients may allow the detection of tumor progression at molecular level. Methods: We studied CK-19 expression by RT-PCR (as described in Datta YH et al. J Clin Oncol 1994,12:475–482) in PBMN samples of 10 control men and serially in 44 patients with PC every three months for 18 months. PSA progression was defined as any elevation in PSA values that was confirmed by two other sequential measurements. We considered time to PSA progression as the time interval in months from study entry to the first of the three aforementioned progressively elevated PSA levels. Chi-square and Fisher exact tests were used to evaluate correlations between categorical variables. Overall survival was computed from the collection of the first sample for CK-19 determination. Overall survival comparisons between groups with CK-19 positive and negative results were conducted by the Peto-Wilcoxon test. Results: None of the 10 normal control men expressed CK-19 in their PBMN. In the patients, CK-19 positivity at entry was not associated with age, Gleason score, clinical stage, PSA or Alkaline Phosphatase. Interestingly, having at least one positive CK-19 result during follow up correlated significantly with time to PSA progression (p = 0.049), specially in the subgroup of metastatic patients (p = 0.032). Conclusions: We conclude that CK-19 expression by RT-PCR in the PBMN of PC patients correlates with time to PSA progression. Further studies are needed to confirm these findings. No significant financial relationships to disclose.
Short-term civil commitment and the violent patient
Authors: J A Yesavage, P D Werner, J M Becker, M J Mills
Journal: American Journal of Psychiatry (1982)

To explore the specificity of criteria for civil commitment for dangerousness, the authors examined the relationship between civil commitment for dangerousness to others under the California Civil Commitment Statute (the Lanterman-Petris-Short Act) and violent acts and behavioral ratings made immediately after commitment. Using a prospective design they evaluated 84 subjects. The ratings of violent acts for subjects considered dangerous to others were no different than those of a nondangerous control group. The subjects considered dangerous to others, however, differed on several subscales of the Brief Psychiatric Rating Scale. The authors discuss the implications of these results for civil commitment proceedings.