tbuckley/cabot-search huggingface dataset:
Major complications and causes of death in patients treated for Hodgkin's disease.
Authors: R E van Rijswijk, J Verbeek, C Haanen, A W Dekker, W A van Daal, H A van Peperzeel
Journal: Journal of Clinical Oncology (1987)

A total of 340 patients with Hodgkin's disease were evaluated for the occurrence of intercurrent fatalities after treatment with radiotherapy, chemotherapy, combined modality therapy, and salvage chemotherapy. Mean follow-up time was 76.6 months. Causes of death were compared with the expected risk, calculated from mortality statistics of the Netherlands' population. Sixty-seven patients died of progressive Hodgkin's disease, whereas 37 patients died of causes unrelated to advanced disease. Patients showed an increased risk of dying of leukemia and solid tumors (P less than .001), whereas the risk of dying of cardiovascular complications was not increased. The 10-year actuarial risk of dying of leukemia varied between 0% for patients treated with radiotherapy only and 5.7% for those needing salvage chemotherapy. The 10-year risk of dying of solid tumors was 0% for patients treated with chemotherapy and 6.5% for those receiving radiotherapy. Treatment-related fatalities were highest after combined modality therapy (P less than .025); the corresponding 10-year risk was 6.1%. Compared with younger ones, patients greater than or equal to 40 years had an increased risk of dying of causes unrelated to progressive Hodgkin's diseases. The actuarial risk of developing intercurrent fatalities at 10 years was 4.9% in patients less than 40 years, and 34.7% in those greater than or equal to 40 years (P less than .001). Compared with population based statistics, patients successfully treated for Hodgkin's disease still showed an increased risk of dying (P less than .001). Treatment modality, stage, and histologic subtype were not predictors of intercurrent death.
Abstract 4466: New biomarkers to optimize preclinical development of the PDI inhibitor XCE853
Authors: Gregoire Pierre Prevost, Marine Garrido, Shili Xu, Celine Lefebvre, Anne Chauchereau, Denis Carniato, Jean François Briand, Mathieu Gutmann, Maria Serova, Annemilai Tijeras-Raballand, Armand De Grammont, Eric Raymond, Christian Gespach, Michèle Sabbah, Nouri Neamati, Marc-Henry Pitty, Paul Foster
Journal: Cancer Research (2015)

Abstract Protein disulfide isomerase (PDI) is a chaperone protein that regulates oxidative protein folding as well as cell viability. Increased PDI levels have been documented in a variety of human cancers, including ovarian, prostate, and lung cancers. Inhibition of PDI activity leads to apoptosis in cancer, suggesting that PDI is a promising druggable target. XCE853 was originally identified within a family of synthetic compounds displaying a preferential antiproliferative activity on drug-resistant human cancer cells (Gutmann et al, AACR annual meeting, 2013). XCE853 inhibits in vitro recombinant PDI activity and blocks in vitro proliferation of human tumor cells with IC50s in the nanomolar range through an irreversible cytolysis (Prevost et al, AACR annual meeting, 2014). By contrast, XCE853 has no or limited antiproliferative activity on several human non-tumoral immortalized cells (MCF10, RPE1 or RWPE1) even at high concentrations. The ex-vivo approach using fresh human hepatocellular carcinoma explants incubated 48h with XCE853 (100nM) has shown the decrease of the proliferation (KI-67 labeling) with an apoptosis induction (Caspase-3 labeling). In addition, XCE853 which displayed an excellent oral bioavailability in mouse blocks growth of human ovarian cancer using the in vivo OVCAR-3 xenograft model leading to complete tumor growth arrest even after the cessation of treatment. To optimize the preclinical and clinical development, we are now characterizing new biomarkers to 1) stratify the tumors which are sensitive and non-sensitive to XCE853 and to 2) identify the optimal dose regimen. Altogether, these data support further efforts on XCE853 preclinical studies to prepare the Phase-I clinical study entry. Citation Format: Gregoire Pierre Prevost, Marine Garrido, Shili Xu, Celine Lefebvre, Anne Chauchereau, Denis Carniato, Jean François Briand, Mathieu Gutmann, Maria Serova, Annemilai Tijeras-Raballand, Armand De Grammont, Eric Raymond, Christian Gespach, Michèle Sabbah, Nouri Neamati, Marc-Henry Pitty, Paul Foster. New biomarkers to optimize preclinical development of the PDI inhibitor XCE853. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4466. doi:10.1158/1538-7445.AM2015-4466
Truncation of Glycoprotein (GP) IIIa (▵ 616-762) Prevents Complex Formation With GPIIb: Novel Mutation in Exon 11 of GPIIIa Associated With Thrombasthenia
Authors: Milagros Ferrer, Jianming Tao, Gema Iruı́n, Matilde Sánchez-Ayuso, José González-Rodrı́guez, Roberto Parrilla, Consuelo González-Manchón
Journal: Blood (1998)
Is Hodgkin's Disease Infectious? Discussion of an Epidemiologic Method Used to Impute That It Is2
Authors: Nathan Mantel, William J. Blot
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Is Hodgkin's Disease Infectious? Discussion of an Epidemiologic Method Used to Impute That It Is Get access Nathan Mantel, Nathan Mantel 3Biostatistics Center, George Washington University, 7979 Old Georgetown Road, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar William J. Blot William J. Blot 4Epidemiology Branch, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 2, February 1976, Pages 413–414, https://doi.org/10.1093/jnci/56.2.413 Published: 01 February 1976 Article history Received: 23 May 1975 Accepted: 22 September 1975 Published: 01 February 1976
Prevalence of osteoporosis and osteopenia during androgen deprivation (ADT) for prostate cancer: Baseline data from a large randomized controlled trial
Authors: S. B. Malkowicz, F. Chu, J. Forrest, M. R. Smith, D. Price, P. Sieber, K. G. Barnette, D. Rodriguez, M. S. Steiner
Journal: Journal of Clinical Oncology (2007)

5116 Background: Androgen deprivation therapy (ADT) is the standard treatment for men with advanced prostate cancer. ADT decreases bone mineral density (BMD) and increases fracture risk although there is limited information about the prevalence of osteopenia and osteoporosis during ADT. We evaluated the baseline data from a large fracture prevention study to better characterize the prevalence of ostepenia and osteoporosis in men receiving ADT for prostate cancer. Methods: In an ongoing phase 3 fracture prevention study, 1,392 men = 50 years old with histologically documented prostate cancer and receiving ADT were randomized to placebo or toremifene 80 mg, a selective estrogen receptor modulator. The phase 3 study included men at increased risk of fracture based on age = 70 years or low baseline BMD of the hip or spine as assessed by dual energy x-ray absorptiometry. Subjects with metabolic bone disease or receiving treatment for osteoporosis were excluded. In the current analyses, we report the baseline BMD and prevalence of osteopenia (T score -1.0 to -2.5 total hip, femoral neck or spine) and osteoporosis (T score = -2.5 total hip, femoral neck or spine) for the 1,139 subjects older than 70 years. The analyses were restricted to subjects =70 years because these subjects were included in the study regardless of baseline BMD. Results: Mean (± standard deviation) age was 76 ± 7 years. Mean duration on ADT was 39 ± 36 months. For men 70 years of age or older, mean T scores for the total hip, femoral neck, and spine are -1.01 ± 1.14, -1.50 ± 1.06 and 0.37 ± 1.88 respectively. A total of 73% of subjects 70 years of age or older were classified with osteopenia (55%) or osteoporosis (18%). Conclusions: In this large cross- sectional analysis, the vast majority of older men receiving ADT for prostate cancer have either osteopenia or osteoporosis. These observations provide further evidence that close attention to skeletal health is warranted during ADT for prostate cancer. No significant financial relationships to disclose.
Genetic determination of height-mediated mate choice
Authors: Albert Tenesa, Konrad Rawlik, Pau Navarro, Oriol Canela-Xandri
Journal: Genome biology (2015)

Numerous studies have reported positive correlations among couples for height. This suggests that humans find individuals of similar height attractive. However, the answer to whether the choice of a mate with a similar phenotype is genetically or environmentally determined has been elusive.Here we provide an estimate of the genetic contribution to height choice in mates in 13,068 genotyped couples. Using a mixed linear model we show that 4.1% of the variation in the mate height choice is determined by a person's own genotype, as expected in a model where one's height determines the choice of mate height. Furthermore, the genotype of an individual predicts their partners' height in an independent dataset of 15,437 individuals with 13% accuracy, which is 64% of the theoretical maximum achievable with a heritability of 0.041. Theoretical predictions suggest that approximately 5% of the heritability of height is due to the positive covariance between allelic effects at different loci, which is caused by assortative mating. Hence, the coupling of alleles with similar effects could substantially contribute to the missing heritability of height.These estimates provide new insight into the mechanisms that govern mate choice in humans and warrant the search for the genetic causes of choice of mate height. They have important methodological implications and contribute to the missing heritability debate.
Survival of patients with HER2-positive gastric cancer with introduction of trastuzumab.
Authors: Kohei Shitara, Yasushi Yatabe, Masato Sugano, Keitaro Matsuo, Chihiro Kondo, Daisuke Takahari, Takashi Ura, Masahiro Tajika, Kei Muro
Journal: Journal of Clinical Oncology (2012)

128 Background: ToGA study showed that trastuzumab given in combination with first-line chemotherapy (fluoropyrimidine plus cisplatin) improved the overall survival of HER2-positive patients with advanced gastric cancer (AGC). Meanwhile, the prognostic value of HER2 or the efficacy of trastuzumab in second- or further-line chemotherapy remains controversial. Methods: We retrospectively analyzed 567 patients with AGC who initiated systemic chemotherapy before March 2011. Among them, 287 were evaluated for their HER2 status. HER2 positivity was defined as IHC 3+ or IHC 2+ with amplification by FISH. Treatment outcomes were compared between patients with HER2-positive and HER2-negative AGC. To evaluate the impact of exposure to trastuzumab in any line of chemotherapy, we applied time-varying covariates (TVC) analysis to avoid possible lead-time bias. Results: The median survival time (MST) of HER2-evaluated patients (n=287) tended to be better than that of HER2-non-evaluated patients (n=280, 14.5 vs. 13.2 months; P=0.03). Among the HER2-evaluated patients, 47 (16.3%) were HER2-positive and had longer survival than HER2-negative patients (24.1 vs. 13.4 months; P=0.05). Among the HER2-positive patients, 35 received trastuzumab; 15 patients received it as first-line therapy and 20 received it as second- or further-line therapy. The MST of HER2-positive patients with trastuzumab treatment was significantly longer than that of HER2-positive patients without trastuzumab (26.6 vs. 13.5 months; P=0.015). HER2-negative patients and HER2-positive patients without trastuzumab had similar survival durations. According to multivariate analysis with TVCs, exposure to trastuzumab was independently associated with better prognosis (HR 0.54, P=0.04). Conclusions: Although the retrospective nature and small sample size are major limitations of this study, recent HER2-positive AGC patients showed a better prognosis than HER2-negative patients, especially with the introduction of trastuzumab.
Blocking cell microtubule assembly inhibits the alloimmune response in vitro and prolongs renal allograft survival by inhibition of Th1 and sparing of Th2 cell function in vivo.
Authors: E Akalin, W W Hancock, N Perico, G Remuzzi, O Imberti, C B Carpenter, M H Sayegh
Journal: Journal of the American Society of Nephrology (1995)

Colchicine inhibits cell microtubule assembly by binding to and preventing the polymerization of tubulin monomers. Although there are data to indicate that colchicine inhibits a variety of cell-mediated immune responses, the effects and mechanisms of inhibiting cell microtubule assembly on the alloimmune response have not been thoroughly investigated. It has recently been shown that colchicine prevents acute rejection and promotes the long-term survival of rat renal allografts. In this study, the effects and mechanisms of inhibiting cell microtubule assembly by colchicine on the alloimmune response in vitro and in vivo were examined. First, the effects of colchicine on T lymphocyte response to alloantigen in vitro were tested. In the standard one-way mixed lymphocyte response (MLR), responder Lewis rat lymph node cells were cultured with irradiated Brown-Norway stimulators. Colchicine inhibited the MLR in a dose-dependent manner, with 100% inhibition at a concentration of 25 ng/mL (6.25 x 10(-8) M) and 50% inhibition at a concentration of approximately 5 to 10 ng/mL. Colchicine also inhibited the generation of cytotoxic T lymphocytes as well as cytotoxic T cell effector function in vitro in a dose-dependent fashion. Second, detailed immunohistologic studies of renal allografts harvested from unmodified control (acutely rejecting) and colchicine-treated rats (Day 15 or 30) were performed. These studies showed that grafts from colchicine-treated animals had significantly fewer mononuclear cell infiltrates and less edema, and moderately decreased deposition of immunoglobulin M, C3, and fibrin, as compared with acutely rejecting control grafts.(ABSTRACT TRUNCATED AT 250 WORDS)
Retrospective study of the efficacy and safety of fotemustine in 170 patients with metastatic melanoma.
Authors: J. L. Gonzalez-Larriba, A. Berrocal, P. Cerezuela, A. Galan, J. Jimenez, A. Moreno, J. M. Piulats, J. Fra, G. Crespo, J. Gonzalez
Journal: Journal of Clinical Oncology (2010)

e19011 Background: Fotemustine is a third-generation nitrosourea authorized in Europe for the treatment of metastatic melanoma. Fotemustine crosses the brain-blood barrier with a relevant activity on brain metastases (BM) and it is authorized in some European countries for primary brain tumors. Methods: We assessed the pattern of use, efficacy (tumor response, median progression-free survival [PFS], and median overall survival [OS]) and toxicity of fotemustine in Spain through a retrospective study on medical record data of 170 patients (pts) (56% male, 44% female). Median age: 61 years (range 20–87). ECOG PS: 0 in 28% of pts, 1 in 55%, ≥ 2 in 17%. High LDH values: 42 pts. Results: The most used scheme was induction at a 100 mg/m2 i.v. dose (days 1, 8, 15), 4-5 weeks of therapeutic rest and maintenance (100 mg/m2 i.v. every 3 weeks). 41% of pts were treated in first line, 38% in second, and 21% in third or higher. The median number of cycles was 3 (range 1-10). 160 pts were evaluable for efficacy. Tumor response: 3% complete response (CR), 14% partial response (PR), 31% stable disease (SD), 52% progression disease (PD). The clinical benefit in first line was 61% (CR=5%, PR=14%, SD=42%) and 39% (CR=3%, PR=14%, SD=22%) in second line. PFS was 84 days (95% CI 71-109), 100 days (95% CI 72-127) in first line and 77 days (95% CI 63-110) in second line. OS was 200 days (6.5 months) (95% CI 172–284). In 17 pts (10.3%) with BM the tumor response was CR=6% (1 pt), PR=18% (3 pts), SD=35% (6 pts), PD=41% (7 pts). 165 pts were evaluable for toxicity. The most common grade 3/4 toxicities were hematological and included neutropenia (40 pts, 24.2%), thrombocytopenia (39 pts, 23.6%), and anemia (14 pts, 8.5%). Conclusions: Fotemustine is an active and well-tolerated agent in metastatic melanoma, including brain metastases. Tumor response n % CR 5 3 PR 23 14 SD 49 31 Clinical benefit (CR+PR+SD) 77 48 PD 83 52 Total 160 100 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Italfarmaco, S.A.
Intratumoral DPD gene expression has a clinical significance in pancreatic adenocarcinoma (PAC) patients treated with S-1
Authors: K. Hayashi, T. Imaizumi, K. Uchida, T. Hatori, H. Kuramochi, K. Takasaki
Journal: Journal of Clinical Oncology (2004)

4113 Background: Although the prognosis in patients with pancreatic adenocarcinoma (PAC) has been poor, we recently reported unusually high response rate and survival benefit of S-1 treatment in patients with PAC (Proc ASCO, #1042 2003). The aim of this study was to reveal genetic background of this unique activity of S-1 against PAC. S-1 is a novel oral fluoropyrimidine derivative consisting of Tegafur (FT) and DPD inhibitor (5-chloro-2, 4-dihydroxypyridine; CDHP). Accordingly intratumoral DPD mRNA expression level was measured to reveal whether the level was differenct from other GI cancer and whether it was relevant to chemosensitivity in PAC. Patients & Methods: Among 28 recurrent PAC patients treated with S-1, we obtained 15 responders and 13 non-responders. The mRNA was extracted from paraffin-embedded surgical specimens using laser captured microdissection, and relative expression levels of each DPD/β-actin were measured using a quantitative reverse transcription polymerase chain reaction (RT-PCR) (Taqman“) system. 30 colorectal cancer (CRC) patients treated with S-1 were enrolled as a control group. Results: Intrarumoral DPD mRNA expression level was significantly higher in PAC than that in CRC (P<0.0001: median expression; 1.38 / 0.56). DPD expression among responded PAC was significantly lower than non-responded PAC. (P= 0.012, Mann-Whitney U test). Conclusions: Intratumoral DPD mRNA expression level in PAC was relatively high, and the unique and intense S-1 activity against PAC could be resulted from compounded DPD inhibitor. And DPD gene expression was supposed to be a reliable factor for chemosensitivity with S-1 in PAC. No significant financial relationships to disclose.
Cross-Study Comparison Reveals Common Genomic, Network, and Functional Signatures of Desiccation Resistance in<i>Drosophila melanogaster</i>
Authors: Marina Telonis-Scott, Carla M. Sgrò, Ary A. Hoffmann, Philippa C. Griffin
Journal: Molecular Biology and Evolution (2016)

Repeated attempts to map the genomic basis of complex traits often yield different outcomes because of the influence of genetic background, gene-by-environment interactions, and/or statistical limitations. However, where repeatability is low at the level of individual genes, overlap often occurs in gene ontology categories, genetic pathways, and interaction networks. Here we report on the genomic overlap for natural desiccation resistance from a Pool-genome-wide association study experiment and a selection experiment in flies collected from the same region in southeastern Australia in different years. We identified over 600 single nucleotide polymorphisms associated with desiccation resistance in flies derived from almost 1,000 wild-caught genotypes, a similar number of loci to that observed in our previous genomic study of selected lines, demonstrating the genetic complexity of this ecologically important trait. By harnessing the power of cross-study comparison, we narrowed the candidates from almost 400 genes in each study to a core set of 45 genes, enriched for stimulus, stress, and defense responses. In addition to gene-level overlap, there was higher order congruence at the network and functional levels, suggesting genetic redundancy in key stress sensing, stress response, immunity, signaling, and gene expression pathways. We also identified variants linked to different molecular aspects of desiccation physiology previously verified from functional experiments. Our approach provides insight into the genomic basis of a complex and ecologically important trait and predicts candidate genetic pathways to explore in multiple genetic backgrounds and related species within a functional framework.
Brentuximab Vedotin Improves HCT-CI, CR Status, and Peri-Transplant Toxicity In Patients With Relapsed/Refractory Hodgkin Lymphoma Heading To RIC Allo-HCT
Authors: Robert Chen, Joycelynne Palmer, Ni-Chun Tsai, Sandra H. Thomas, Tanya Paris, Leslie Popplewell, Chatchada Karanes, Tanya Siddiqi, Auayporn Nademanee, Ji-Lian Cai, Stephen J. Forman
Journal: Blood (2013)
Prolonged survival in objective responders to ipilimumab therapy
Authors: J. D. Powderly, S. J. O’Day, E. M. Hersh, S. Tchekmedyian, F. S. Hodi, G. Nichol, M. J. Yellin, W. J. Urba, W. E. Samlowski, J. S. Weber
Journal: Journal of Clinical Oncology (2008)

20004 Background: Ipilimumab is a fully human, anti-CTLA-4 monoclonal antibody that has been associated with complete and partial responses when administered as monotherapy or in combination with a vaccine or chemotherapy in patients with advanced metastatic melanoma. Responses have tended to be durable, many lasting months, but the effect of treatment on overall survival (OS) has not been previously characterized. This follow-up study was undertaken to determine OS for patients with advanced metastatic melanoma previously enrolled in 3 distinct ipilimumab phase I and II studies designed to assess varying ipilimumab dosing regimens performed between 2000 and 2005. Methods: Survival status for patients alive at completion of the core studies was determined. OS was determined by combining survival data from the core and follow-up studies and estimated using the Kaplan-Meier method. Median OS and 95% CI were determined according to Brookmeyer and Crowley. If survival status was unknown or missing then OS was censored at the date of last contact or last visit of the core studies. Results: As of November 29, 2007, follow-up data were available from 132 patients and 18 patients were alive. The median OS (95% CI) for patients in Medarex studies -02, -08, and -15 were 19.4 (5.9, 22.9), 12.9 (10.4, 18.0), and 10.0 (10.0, 11.9) months, respectively. There was a total of 13 responders in all 3 core studies. Survival data were unavailable for 2 responders. The median OS for responders has not been reached with a 25th percentile of 21.7 months. In contrast, the median OS for non- responders was 10.9 months (95% CI 8.4, 12.6), with 25th and 75th percentile OS of 5.7 and 19.4 months, respectively. Additional data will be presented. Conclusions: Median OS for patients with advanced metastatic melanoma administered ipilimumab in these studies appears to compare favorably to that reported in the literature. Overall survival was better in responders than in non-responders. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Medarex Bristol-Myers Squibb, Medarex Medarex Bristol-Myers Squibb, Medarex Bristol-Myers Squibb, Medarex