tbuckley/cabot-search huggingface dataset:
A 94,OOO-Dalton Glycoprotein Expressed by Human Melanoma and Carcinoma Cells&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: K Imai, B S Wilson, A Bigotti, P G Natali, S Ferrone
Journal: JNCI Journal of the National Cancer Institute (1982)

The IgG2a monoclonal antibody (MoAb) 376.96S, secreted by a hybridoma derived from a mouse immunized with cultured human melanoma cells COLO 38, reacts with a single 94,000-dalton glycoprotein that is peripherally associated with the plasma cell membrane of cultured melanoma cells. Indirect immunofluorescence analysis with cryostat thin sections of human tissues showed that this antigen is absent from a large variety of normal tissues but is readily detectable on melanomas, nevi, and several different carcinomas. The MoAb 376.96S binds with cultured melanoma and carcinoma cell lines to a similar extent and can mediate both complement-dependent and cell-dependent lysis of these cells. The 94,000-dalton glycoprotein detected by MoAb 376.96S is distinct in its tissue distribution, antigenicity, and molecular profile from several structures previously identified with monoclonal antibodies that have similar molecular weights.
Prevalence of Sugar-Sweetened Beverage Intake Among Adults — 23 States and the District of Columbia, 2013
Authors: Sohyun Park, Fang Xu, Machell Town, Heidi M. Blanck
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

The 2015-2020 Dietary Guidelines for Americans recommend that the daily intake of calories from added sugars not exceed 10% of total calories. Sugar-sweetened beverages (SSBs) are significant sources of added sugars in the diet of U.S. adults and account for approximately one third of added sugar consumption. Among adults, frequent (i.e., at least once a day) SSB intake is associated with adverse health consequences, including obesity, type 2 diabetes, and cardiovascular disease. According to the 2009-2010 National Health and Nutrition Examination Survey (NHANES), an in-person and phone follow-up survey, 50.6% of U.S. adults consumed at least one SSB on a given day. In addition, SSB intake varies by geographical regions: the prevalence of daily SSB intake was higher among U.S. adults living in the Northeast (68.4%) and South (66.7%) than among persons living in the Midwest (58.8%). In 2013, the Behavioral Risk Factor Surveillance System (BRFSS), a telephone survey, revised the SSB two-item optional module to retain the first question on regular soda and expand the second question to include more types of SSBs than just fruit drinks. Using 2013 BRFSS data, self-reported SSB (i.e., regular soda, fruit drinks, sweet tea, and sports or energy drinks) intake among adults (aged ≥18 years) was assessed in 23 states and the District of Columbia (DC). The overall age-adjusted prevalence of SSB intake ≥1 time per day was 30.1% and ranged from 18.0% in Vermont to 47.5% in Mississippi. Overall, at least once daily SSB intake was most prevalent among adults aged 18-24 years (43.3%), men (34.1%), non-Hispanic blacks (blacks) (39.9%), unemployed adults (34.4%), and persons with less than a high school education (42.4%). States can use the data for program evaluation and monitoring trends, and information on disparities in SSB consumption could be used to create targeted intervention efforts to reduce SSB consumption.
Phase I study of the specific endothelin A receptor antagonist zibotentan (ZD4054) combined with docetaxel in patients with metastatic castration-resistant prostate cancer: Assessment of efficacy, pain, and safety.
Authors: D. L. Trump, H. Payne, K. Miller, J. S. De Bono, J. Stephenson, H. A. Burris, F. E. Nathan, M. Taboada, T. Morris, A. Hübner
Journal: Journal of Clinical Oncology (2010)

4664 Background: The combination of docetaxel and prednisone is the current standard care for patients with advanced castration-resistant prostate cancer (CRPC), however, survival benefits are limited. This two-part, phase I study assessed the effect of combined treatment with the specific endothelin A receptor antagonist zibotentan (ZD4054) and docetaxel in patients with metastatic CRPC. Methods: An open-label, dose-finding phase (Part A) determined the maximum tolerated dose (MTD) of zibotentan in combination with docetaxel. Patients received docetaxel 75 mg/m2 every 21 days for ≤10 cycles in combination with oral zibotentan at a dose of 10 mg/day (initial cohort) or 15 mg/day determined by toxicity evaluation. Once the MTD of zibotentan had been identified, a double- blind phase (Part B) determined the safety and efficacy of zibotentan plus docetaxel. Patients were randomized in a 2:1 ratio to receive zibotentan (MTD) plus docetaxel or placebo plus docetaxel. Pain was assessed using the brief pain inventory. Results: Six patientswere enrolled in Part A, 3 received zibotentan 10 mg/day and 3 received zibotentan 15 mg/day. No dose-limiting toxicity was observed confirming 15 mg/day as the MTD of zibotentan in combination with docetaxel. In Part B, 31 patients were enrolled, 20 in the zibotentan plus docetaxel group and 11 in the placebo plus docetaxel group. Overall, the most commonly (>30%) reported adverse events were nausea, peripheral edema, anemia, and fatigue in the zibotentan plus docetaxel group, and fatigue and neutropenia in the placebo plus docetaxel group. Pain levels at baseline were low and remained low over the course of the study on both treatment arms. Objective response rates (RECIST) were 22% (2/9) and 17% (1/6) for patients receiving zibotentan and placebo, respectively. New bone lesions occurred in 30% and 45% of patients in the zibotentan and placebo groups, respectively. Conclusions: Treatment withzibotentan plus docetaxel was well tolerated in patients with metastatic CRPC and their co-administration is being further evaluated in an ongoing phase III program (NCT00314782). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, sanofi-aventis AstraZeneca AstraZeneca, sanofi-aventis AstraZeneca, Bristol-Myers Squibb, ImClone Systems AstraZeneca AstraZeneca, sanofi-aventis
Immunization of ovarian cancer patients with an NY-ESO-1 peptide of dual MHC class I and II specificities plus incomplete Freund adjuvant induces simultaneous humoral, CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses
Authors: K. Odunsi, F. Qian, S. Gnjatic, A. Jungbluth, E. Hoffman, G. Ritter, J. Kepner, J. Skipper, S. Lele, L. J. Old
Journal: Journal of Clinical Oncology (2005)

5040 Background: NY-ESO-1 is a highly immunogenic “cancer-testis” antigen expressed in epithelial ovarian cancer (EOC). The NY-ESO-1 peptide epitope, ESO:157–170, is recognized by HLA-DP4 restricted CD4+ T cells, and HLA-A2 and A24 restricted CD8+ T cells. To test whether providing cognate helper CD4+ T cells would enhance the anti-tumor immune response, we conducted a phase I clinical trial of immunization with ESO:157–170 plus incomplete Freund’s adjuvant (Montanide ISA51). Methods: Eighteen HLA-DP4-positive EOC patients who had no evidence of disease, or minimal residual disease, following chemotherapy for primary or recurrent disease were enrolled. Tumor expression of NY-ESO-1 was determined by RT-PCR and immunohistochemistry. Patients were immunized with 100 μg of ESO:157–170, mixed with Montanide, every 3 weeks for a minimum of 5 injections, or up to 15 injections, or until disease progression. Immune responses were measured by DTH, ELISA, tetramer, and IFN-γ ELISPOT assays. Results: There were no vaccine related adverse events. 16/18 patients were NY-ESO-1 serum antibody negative, and 2/18 patients were NY-ESO-1 serum antibody positive at the outset of the study. So far, 12 patients have been analyzed for immune responses. Primary peptide-specific CD4+ IFN-γ T-cell reactivity was generated in 8 out of 10 (80%) NY-ESO-1 antibody-negative patients. Three of the eight patients had DTH responses, and one had an antibody response. In one patient, induction of a specific CD4+ T-cell response was associated with complete regression of a single metastasis. One of the two NY-ESO-1 antibody-positive patients developed significant increase in specific CD4+T-cell reactivity. Two of nine (22%) HLA-A2 and/or HLA-A24 patients demonstrated simultaneous peptide specific CD8+ T cell reactivity. Conclusions: Our results indicate that primary NY-ESO-1-specific antibody, CD4+ and CD8+ T-cell responses can be induced by immunization with ESO:157–170. The peptide vaccine was found to be safe and well tolerated. A phase II study design utilizing this epitope, or the full length protein, is warranted in patients with EOC. No significant financial relationships to disclose.
Hepatitis B screening and positivity prior to chemotherapy.
Authors: J. Hwang, M. Fisch, H. Zhang, M. A. Kallen, M. Routbort, L. Lal, J. Vierling, M. Suarez-Almazor
Journal: Journal of Clinical Oncology (2010)

9008 Background: Hepatitis B virus (HBV) reactivation after chemotherapy occurs in patients positive for HBsAg or anti-HBc and causes delays in cancer care, liver failure, and death. Patterns of screening and positivity are not well described. Methods: In this retrospective, cross-sectional study, we reviewed M. D. Anderson databases to identify new adult cancer patients who received chemotherapy between 1/1/04 and 12/31/08. We defined chemotherapy as receipt of intravenous chemotherapy at least once in each of 2 consecutive months. We determined proportion of patients with HBV screening (HBsAg or anti-HBc) 2 months before or 1 month after first chemotherapy. We used chi-squared to examine differences in prevalence of HBV screening and positivity between solid and hematological cancer patients. Results: Of 70,737 patients in the study period, 12,340 (17.4%) received chemotherapy. 53% were women and 73% white. Overall, 13% had HBV screening; ∼1% of HBsAg and ∼8% of anti-HBc were positive. Although proportions of solid cancer patients who had HBV screening was significantly lower than hematologic cancer patients (p<0.01), the prevalence of positive HBV screening test was significantly higher among solid cancer patients (HBsAg, p = 0.04; anti-HBc, p<0.01). Conclusions: HBV screening prevalence is low but varies by cancer type. Positive HBV tests are more common in solid cancer patients despite lower screening prevalence compared to hematologic cancer patients. To improve care of cancer patients, studies are needed to develop new screening strategies. HBV screening among patients receiving chemotherapy Solid cancer Hematologic cancer Breast N = 2,327 Lung N = 1,100 Colon N = 601 Total N = 4,028 Hodgkin's or non-Hodgkin's lymphoma N = 1,245 Acute leukemia N = 547 Chronic leukemia N = 178 Total N = 1,970 p value* HBsAg screen (%) 81 (3) 18 (2) 34 (6) 133 (3) 655 (53) 297 (54) 56 (31) 1,008 (51) <0.01 Anti-HBc screen(%) 80 (3) 19 (2) 34 (6) 133 (3) 663 (53) 314 (57) 59 (33) 1,036 (53) <0.01 HBsAg+ (%) 0/81 (0) 4/18 (22) 1/34 (3) 5/133 (4) 9/655 (1) 3/297 (1) 0/56 (0) 12/1,008 (1) 0.04 Anti-HBc+ (%) 12/80 (15) 8/19 (42) 6/34 (18) 26/133 (20) 36/663 (5) 18/314 (6) 4/59 (7) 58/1,036 (6) <0.01 * For the difference between solid and hematologic cancer patients, p values ≤0.05 are considered significant. No significant financial relationships to disclose.
17-Allylamino-17-Demethoxygeldanamycin (17-AAG) abrogates the G<sub>2</sub>/M cell cycle checkpoint by down-regulating chk1 and selectively sensitizes tumor cells with defective p53 to topoisomerase I poison
Authors: A. N. Tse, D. Solit, N. Rosen, G. Schwartz
Journal: Journal of Clinical Oncology (2004)

3069 Background: AAG is an inhibitor of the molecular chaperone Hsp90 currently in clinical trials. Treatment with AAG causes a proteosome-dependent degradation of key oncogenic proteins e.g. Her2, raf1, Akt and cdk4 in tumors. Chk1 is a protein kinase critical for the G2/M cell cycle checkpoint and has recently been shown to be a target for AAG. We evaluated the activity of combining AAG with SN38 (SN), an active metabolite of irinotecan, in colon cancer cells. We hypothesized that tumors defective in the G2/M checkpoint by lacking p53 will be more sensitive to the combination. Methods: Parental (p53+/+) and p53-null (p53-/-) HCT116 colon cancer cells were treated with clinically achievable concentrations of SN (20 nM) and AAG (500 nM) in various sequences. Cells were analyzed for apoptosis and cell cycle progression; chk1 expression was measured in these cells and in the peripheral blood lymphocytes (PBLs) of patients treated with AAG and docetaxel in a separate ongoing phase I trial. Results: Single agent SN and AAG resulted in minimal apoptosis (<4%) in both cell lines. A significant enhancement of apoptosis was demonstrated in p53-/- cells exposed to either concurrent (SN+AAG) or sequential (SN◊AAG) treatment (12% and 27%, respectively); no enhancement was seen in p53+/+ cells. Treatment with SN alone resulted in a complete G2 arrest with <1% mitosis whereas concurrent or sequential treatment in p53-/- cells resulted in a marked increase in mitosis (31% and 78%, respectively), indicating that AAG abrogated the SN-induced G2 arrest. We also confirmed that AAG treatment resulted in a time- and dose-dependent depletion of chk1 but not chk2, another key G2/M checkpoint regulator. Chk1 protein was undetectable in pre-treatment PBLs. Conclusions: AAG inhibits the chk1-mediated G2/M checkpoint and potently enhances the cytotoxicity of SN selectively in p53-/- cells. Our results justify the initiation of a phase I study combining AAG and irinotecan, especially for patients with mutant p53. The lack of chk1 in PBL argues against its use as a pharmacodynamic surrogate. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Conforma
Long-Term Survival With Cybord Induction Therapy In Newly Diagnosed Multiple Myeloma
Authors: Donna E. Reece, Vishal Kukreti, Joseph Mikhael, Christine I. Chen, Suzanne Trudel, Kristina Laumann, Joseph Hentz, Giovani Piza, Rafael Fonseca, P. Leif Bergsagel, Jose F Leis, Rodger E. Tiedemann, Frcpa, Jacy Spong, Angela Mayo, Keith Stewart
Journal: Blood (2013)
Abstract 19085: Outcomes After Cardiopulmonary resuscitation With Chest Compressions Only versus Conventional CPR: A Meta-Analysis of 84,888 Patients
Authors: Ajay Vallakati, Madhu Y Reddy, Vivek Yarlagadda, Karthik Murugiah, Pramod Janga, Ryan Maybrook, Arun Raghav Mahankali Sridhar, Donita Atkins, Suddharani Bommana, Andrea Natale, Dhanunjaya Lakkireddy
Journal: Circulation (2013)

Objectives: Optimal method of by-stander cardiopulmonary resuscitation (CPR) is still controversial. Studies comparing “chest compressions only CPR” with “conventional CPR” have yielded mixed results. We intended to compare the effectiveness of the above two strategies on survival after cardiac arrest out of hospital by performing a meta-analysis of all available clinical studies till date. Methods: We searched Medline and Embase for randomized control trials (RCT) and prospective observational studies comparing “chest compressions only CPR” with “conventional CPR”. Only studies presenting survival outcomes were included. Random effects model with inverse variance weighting was used to calculate pooled risk ratio (RR). Subgroup analyses were also performed as deemed necessary. Results: We identified 15 studies (12 observational and 3 RCTs) including 84,888 patients, of whom 39,572 received chest compressions only and 45,316 received conventional CPR. There was no significant difference in the survival with either technique (RR: 1.08; 0.93 - 1.26, p = 0.33). Exclusion of one study which reported only neurologically favorable survival did not alter the composite analysis. There was a significant heterogeneity among the studies (I2 = 85%, p&lt;0.001). Begg’s and Egger’s regression test did not reveal any publication bias. Sub-group analyses of observational studies (RR: 0.97; 0.85-1.12, p=0.71) and RCTs (RR: 1.6; 0.88 - 3.1, p =0.12) did not demonstrate any difference in the survival outcome between the two techniques. Conclusion: By-stander “chest compressions-only CPR” is associated with similar survival rate when compared to “conventional CPR”.
Phase II trial of neoadjuvant capecitabine (C) with irinotecan (I) followed by capecitabine-based chemoradiotherapy (CRT) for patients (pts) with locally advanced rectal cancer (LARC): HOG GI03-53.
Authors: H. R. Cardenes, S. Sanghani, M. Burns, B. Robb, D. T. Hinkle, C. S. Johnson, M. Yu, C. R. Currie, P. J. Loehrer, E. G. Chiorean
Journal: Journal of Clinical Oncology (2010)

e14026 Background: Fluoropyrimidine-based neoadjuvant CRT is standard therapy for LARC, but high systemic failure rates suggest the addition of induction chemotherapy to this regimen. I and C are pro-drugs that require activation by carboxylesterase enzymes (CES). The purpose of this multi-institutional study was to determine the pathological response rate (complete pCR, and non-complete pNCR), the toxicity and progression-free survival (PFS) with this regimen, and to analyze the gene expression profile of enzymes involved in the metabolism of C and I. Methods: Pts with endoscopic ultrasound staged T3/T4 or ≥ N1 rectal cancer were treated with C 1,000 mg/m2 BID d1-14, and I 200 mg/m2 on d1 q21 days for 2 cycles, followed by C 825 mg/m2 BID d1-5/week with concurrent RT 50.4 Gy in 28 fractions. Surgical resection occured 4-6 wks after completion of therapy. Gene expression levels or sequencing were used to analyze CES1, CES2, thymidylate synthase, thymidine phosphorylase, topoisomerase1 and UGT1A in pre- and posttreatment tumor samples, and t-test was used to study the association with response and toxicity. Results: 22 pts were enrolled, median age 54 yrs (36-67), M/F 11/11, T3/T4 86%/9% and 91% ≥ N1. 18 pts completed all neoadjuvant therapy (3 pts discontinued for social reasons, and 1 pt due to metastatic disease). The most common toxicities were diarrhea (86%), fatigue (73%), nausea (73%), alopecia (59%) and rectal pain (36%). The only grade (gr) 3 toxicity occuring in > 1 pt was diarrhea (n = 4), and 1 pt had gr 4 febrile neutropenia. All 18 pts underwent R0 resection. Downstaging was noted in 16 pts (89%), and 6 (33%) obtained pCR. After a median follow-up of 43 mos (95% CI 20-49), 3 pts progressed, 1 pt died, and the median PFS has not yet been reached. We observed a trend for higher CES2 expression in the pNCR vs pCR groups (p = 0.07), and an increased incidence of gr ≥ 2 diarrhea associated with higher CES1 levels (p = 0.09). Conclusions: The combination of C+I followed by CRT has significant antitumor activity and tolerable toxicity. The effect of CES on toxicity and efficacy from C and I needs to be validated in larger studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche
EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome
Authors: L Andreoli, G K Bertsias, N Agmon-Levin, S Brown, R Cervera, N Costedoat-Chalumeau, A Doria, R Fischer-Betz, F Forger, M F Moraes-Fontes, M Khamashta, J King, A Lojacono, F Marchiori, P L Meroni, M Mosca, M Motta, M Ostensen, C Pamfil, L Raio, M Schneider, E Svenungsson, M Tektonidou, S Yavuz, D Boumpas, A Tincani
Journal: Annals of the Rheumatic Diseases (2016)

Objectives Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Methods Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. Results Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. Conclusions Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.
Optimizing Follow up Schedule for Non Hodgkin Lymphoma' Patients by Multi-Objective Analysis.
Authors: Matteo Pelosini, Flavio Baronti, Francesco Caracciolo, Sara Galimberti, Edoardo Benedetti, Federico Papineschi, Enrico Orciuolo, Gabriele Buda, Antonina Starita, Mario Petrini
Journal: Blood (2009)