tbuckley/cabot-search huggingface dataset:
Abstract 2210: Multiple antigens stimulating cellular therapy increases immune responses in patients with hepatocellular carcinoma
Authors: Yanyan Han, Jing Huang, Ran Tao, Yabing Guo, Li Liu, Dongyun Wu, Jin Li, Xiangjun Zhou, Jinlin Hou
Journal: Cancer Research (2016)

Abstract Background &amp; Aims: Hepatocellular carcinoma (HCC) is one of the most common tumors in China, and frequently occurs in the patients with chronic hepatitis B virus (HBV) infection. To investigate whether adoptive cell therapy induces tumor specific immune responses in HCC patients and further brings clinical benefits, Multiple Antigens Stimulating Cellular Therapy (MASCT) was applied in addition to conventional therapies. Methods: Activated T cells that were prepared from the autologous peripheral blood mononuclear cells (PBMCs). Cells were stimulated and amplified with dendritic cells (DCs) pulsed by multiple tumor antigen peptides, including tumor associated antigen peptides and HBV antigen peptides. All patients received infusions of 5-10×107cells/kg of body weight of the resulting T cells every 1-3 months. The immune responses in the patients' PBMCs were examined before and after the treatment. Results: The resulting amplified cells were almost exclusively CD3+ (95% ± 1%), with a major percentage being CD3+CD8+ cells (70% ± 5%) and a minor proportion being CD3+CD4+(19% ± 3%) and CD3+CD56+ (14% ± 1%) cells, while there were insignificant amounts of CD4+CD25+Foxp3+ regulatory T cells (0.4% ± 0.1%). These T cells have restored immune functions and HLA-restricted specific cytotoxicity against HCC cells. After repeating treatment of MASCT, the frequency of regulatory T cells in the patients’ PBMCs was significantly decreased, and the proliferation and function of tumor antigen specific T cells were enhanced. The specific immune responses against each kind of tumor antigens were also detected in patients. And these immune responses were gradually increased during the treatment of MASCT. Moreover, in retrospective study, the disease control rate (DCR) in one year was found to be raised to 80% in stage B HCC patients receiving MASCT combined with conventional therapies. Conclusions: Our study has demonstrated that MASCT is a well tolerate immunotherapy in patients with HCC. Specific T cell responses against tumor antigens can be strongly induced in vivo. Our study also indicated that repeated MASCT treatment improves both the immunologic function and disease control of patients with HCC. Citation Format: Yanyan Han, Jing Huang, Ran Tao, Yabing Guo, Li Liu, Dongyun Wu, Jin Li, Xiangjun Zhou, Jinlin Hou. Multiple antigens stimulating cellular therapy increases immune responses in patients with hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2210.
Joint Bleeding Patterns in Patients Treated Prophylactically with an Extended Half-Life, Pegylated, Full-Length Recombinant Factor VIII (BAX 855)
Authors: Marilyn J. Manco-Johnson, Alice D. Ma, Robert Klamroth, Werner Engl, Lorena Griparic, Jacqueline A Dyck-Jones, Brigitt E. Abbuehl
Journal: Blood (2015)
Abstract 901: Transgenerational inheritance of increased mammary cancer risk in the offspring of high fat diet fed dams: Changes in oxidative stress pathways
Authors: Nguyen M. Nguyen, Fabia O. Andrade, Sonia DeAssis, Idalia Cruz, Carlos Benitez, Roger Godschalk, Leena Hilakivi-Clarke
Journal: Cancer Research (2016)

Abstract Maternal high fat diet has been shown to increase mammary cancer risk among female offspring. We investigated here if the increase is seen across multiple generations. For that purpose, pregnant C57BL/6NTac dams (F0) were fed either a control (CON, 6% corn oil) or an isocaloric high n-6 polyunsaturated fat (HF) diet (18% corn oil) between gestation days 8 and 21. Offspring in subsequent generations (F1-F3) were not exposed to any further dietary modifications, and kept on CON diet. Mammary tumors were initiated by priming the mammary glands with 15 mg medroxyprogesterone (MPA) at week 6, followed by a 1 mg dose of 7,12-dimethylbetz(a)anthracene (DMBA) given on weeks 7-9 for a total of 3 doses. Animals were monitored for 20 weeks after the final dose of DMBA for tumors. Both F1 and F3 generation female HF offspring exhibited a significantly higher mammary tumor incidence and tumor burden than the control offspring. In F3 generation, the increase was seen from week 12 of tumor monitoring until the end of the study. The increase in risk was preceded by a higher number of terminal end buds in the F1 and F3 generation mammary glands. Malondialdehyde (MDA) adduct levels were found to be significantly elevated in the HF group of F3 offspring, suggesting that the increased mammary cancer risk in this generation was attributed to oxidative stress. Western blot analysis of mammary glands identified significantly elevated Keap1 (a repressor of the antioxidant response) and PERK levels in HF F3 offspring; and elevated levels of Beclin-1 and p62 in both F1 and F3 generations compared with CON offspring, corroborating with the idea that oxidative stress was the culprit. miRNA analysis of F3 mammary glands showed decreased expression of mir-324-5p, mir-136 and mir-378 that target Keap1 and p62, potentially explaining the increase in Keap1 and p62 levels. Our results suggest that oxidative stress and antioxidant response plays a role in explaining transgenerational increase in mammary cancer risk among offspring exposed to high fat diet through F0 dams. Citation Format: Nguyen M. Nguyen, Fabia O. Andrade, Sonia DeAssis, Idalia Cruz, Carlos Benitez, Roger Godschalk, Leena Hilakivi-Clarke. Transgenerational inheritance of increased mammary cancer risk in the offspring of high fat diet fed dams: Changes in oxidative stress pathways. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 901.
Measuring implementation of early, concurrent palliative care in community settings.
Authors: Marie Bakitas, J Nicholas Dionne-Odom, Maria Pisu, Dilip Sankar Babu, Tasha Smith, Imatullah Akyar, Lisa Zubkoff
Journal: Journal of Clinical Oncology (2015)

145 Background: ASCO recommends “…combined standard oncology and palliative care…early in the course of illness for any patient with metastatic cancer and/or high symptom burden”. Few settings have implemented this recommendation and rural community cancer centers (CCC) are particularly disadvantaged due to scarce palliative care (PC) resources. The evidenced-based ENABLE (Educate, Nurture, Advise, Before Life Ends) early concurrent PC intervention has demonstrated efficacy and benefit for rural patients and caregivers and we are implementing ENABLE using a virtual learning collaborative funded by the American Cancer Society. Since no PC-specific implementation measures exist, one of our primary efforts has been instrument development. Methods: This Implementation Study includes 4 racially-diverse CCCs: Gibbs Cancer Center, Spartanburg, SC; Mitchell Cancer Institute, Mobile, AL; Birmingham VAMC; and Gyn Oncology/University of Alabama at Birmingham. The project aims are to: 1. Build an interactive research community to assess sites’ institutional structure and PC resources; and 2. Evaluate pre- and post-ENABLE implementation using RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. An expert panel assisted with implementation measure development specific to ENABLE’s essential elements. Instruments include: the General Organizational Index, the RE-AIM Assessment Tool, Oncology Providers Perceptions of Early Concurrent PC, and Implementation Costs. Results: All measures were found to have face and content validity. Feasibility and inter-rater reliability were determined during pilot-testing. Data, (housed in a REDCap database), have been collected using face-to-face interviews and web-based platforms over 2 cycles of pre- and post-implementation site visits. Measurement challenges include: 1. Inconsistent IRB interpretation of implementation science practices; 2. Limited implementation resources (space, staff, and time); and 3. Difficulties with centralized data collection. Conclusions: Valid measures are critical to determine implementation success. We will present implementation measures (Toolkit) and examples of outcome data.
Abstract 1290: Actinomycin D enhanced immunotoxin RG7787 killing of cancer cells
Authors: Xiu Fen Liu, Laiman Xiang, Marco Prunotto, Gerhard Niederfellner, Ira Pastan
Journal: Cancer Research (2016)

Abstract Immunotoxins are recombinant fusion proteins that contain an antibody fragment directed against a tumor selective surface antigen attached to a protein toxin. RG7787 is a newly developed, mesothelin-targeted immunotoxin designed to be less immunogenic and better tolerated than the previous clinical candidate SS1P. The targeting moiety of RG7787 consists of a humanized anti-mesothelin Fab, while its effector moiety is a truncated portion of Pseudomonas exotoxin A (PE) consisting essentially only of the catalytic domain III fused via a furin cleavable linker to the Fab fragment. The domain III variant used in RG7787 contains mutations that silence all known human B-cell and some T-cell epitopes. RG7787 targets and kills mesothelin-positive tumor cells, which are prevalent in mesothelioma, ovarian, lung, and pancreatic cancers. Safety and immunogenicity of RG7787 are being assessed in these tumor indications in an ongoing phase I trial. In order to further enhance the anti-tumoral activity of RG7787, we screened for clinically used drugs that can synergize with RG7787 in vitro and/or in vivo. Actinomycin D (Act D) is a potent transcription inhibitor and is used for treating a variety of cancers, including gestational trophoblastic neoplasia, Wilms tumor, rhabdomyosarcoma, and Ewing's sarcoma. In this study we found that the combination of Act D with RG7787 greatly stimulated cell killing of mesothelin positive cell lines, such as KB31, KLM1, and Hay. The combination also produced complete regressions of KLM1 pancreatic tumor xenografts in mice. To investigate the mechanism of killing we used an apoptosis RNA array and found that both Act D and RG7787 stimulate apoptotic stress responsive genes including TNFα, TRAILR2 (DR5), NFκB, GAD45A and TP53. The combination also increased cleavage and activation of the pro-apoptotic proteins caspase-3, -9, and PARP. Taken together our data indicate that combining RG7787 and Act D reduces the threshold for activation of apoptosis in cancer cells. Citation Format: Xiu Fen Liu, Laiman Xiang, Marco Prunotto, Gerhard Niederfellner, Ira Pastan. Actinomycin D enhanced immunotoxin RG7787 killing of cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1290.
Focal ST-Segment Elevation in a Young Man
Authors: Joshua R. Shak, Amanda K. Johnson, Nora Goldschlager
Journal: JAMA Internal Medicine (2016)

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Abstract 5145: To explore the tumorigenic regulation mechanism of SPZ1 in hepatocellular carcinoma
Authors: LI-TING WANG, SHIH-HSIEN HSU
Journal: Cancer Research (2016)

Abstract Cancer directly affects at least one-third of the human population. Despite this extensively, the genetic determinants of cancer risk remain unknown. Spermatogenic leucine zipper 1 (SPZ1), a basic helix loop helix leucine zipper (bHLH-Zip) transcription factor, acted as a proto-oncogene in mouse and human. It has been demonstrated that SPZ1 was involved in early embryonic development, cell growth and differentiation. In this study, we compared the expression of SPZ1 in 168 paired specimens of HCCs and adjacent normal tissues and also in paired specimens from 140 patients with non-HCCs. In pathologic analysis, SPZ1 exhibited a tumor-specific expression pattern and a high correlation to patient survival time, tumor size, tumor number, and progression stage. Enforced expression of SPZ1 accelerated cell proliferation and tumorigenic activity in hepatoma cells. In contrast, short hairpin RNA-mediated attenuation of SPZ1 in hepatoma cells decreased cell proliferation and malignant transformation in vitro and in vivo. Together, we speculated that SPZ1 as a potential therapeutic target of HCCs Citation Format: LI-TING WANG, SHIH-HSIEN HSU. To explore the tumorigenic regulation mechanism of SPZ1 in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5145.
Mothers after Gestational Diabetes in Australia (MAGDA): A Randomised Controlled Trial of a Postnatal Diabetes Prevention Program
Authors: Sharleen L. O’Reilly, James A. Dunbar, Vincent Versace, Edward Janus, James D. Best, Rob Carter, Jeremy J. N. Oats, Timothy Skinner, Michael Ackland, Paddy A. Phillips, Peter R. Ebeling, John Reynolds, Sophy T. F. Shih, Virginia Hagger, Michael Coates, Carol Wildey
Journal: PLoS Medicine (2016)

Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for type 2 diabetes. We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year.In this study, 573 women were randomised to either the intervention (n = 284) or usual care (n = 289). At baseline, 10% had impaired glucose tolerance and 2% impaired fasting glucose. The diabetes prevention intervention comprised one individual session, five group sessions, and two telephone sessions. Primary outcomes were changes in diabetes risk factors (weight, waist circumference, and fasting blood glucose), and secondary outcomes included achievement of lifestyle modification goals and changes in depression score and cardiovascular disease risk factors. The mean changes (intention-to-treat [ITT] analysis) over 12 mo were as follows: -0.23 kg body weight in intervention group (95% CI -0.89, 0.43) compared with +0.72 kg in usual care group (95% CI 0.09, 1.35) (change difference -0.95 kg, 95% CI -1.87, -0.04; group by treatment interaction p = 0.04); -2.24 cm waist measurement in intervention group (95% CI -3.01, -1.42) compared with -1.74 cm in usual care group (95% CI -2.52, -0.96) (change difference -0.50 cm, 95% CI -1.63, 0.63; group by treatment interaction p = 0.389); and +0.18 mmol/l fasting blood glucose in intervention group (95% CI 0.11, 0.24) compared with +0.22 mmol/l in usual care group (95% CI 0.16, 0.29) (change difference -0.05 mmol/l, 95% CI -0.14, 0.05; group by treatment interaction p = 0.331). Only 10% of women attended all sessions, 53% attended one individual and at least one group session, and 34% attended no sessions. Loss to follow-up was 27% and 21% for the intervention and control groups, respectively, primarily due to subsequent pregnancies. Study limitations include low exposure to the full intervention and glucose metabolism profiles being near normal at baseline.Although a 1-kg weight difference has the potential to be significant for reducing diabetes risk, the level of engagement during the first postnatal year was low. Further research is needed to improve engagement, including participant involvement in study design; it is potentially more effective to implement annual diabetes screening until women develop prediabetes before offering an intervention.Australian New Zealand Clinical Trials Registry ACTRN12610000338066.
Abstract 4623: Reevaluation of the role of Notch signaling in melanoma tumor development, melanoma cell survival and drug resistance
Authors: Dareen Mikheil, Carlos Rodriguez, Ashika Jayanthi, Prithvi Yarlagadda, Vijaysaradhi Setaluri
Journal: Cancer Research (2016)

Abstract Notch is one of the simplest signaling pathways that is required for almost every cell type in the body. It plays several roles such as cell fate decision, differentiation and stem cell maintenance. Notch signaling plays a role in the maintenance of melanoblasts and melanocyte stem cells of the epidermis by preventing their apoptosis. Notch signaling has also been implicated in different aspects of melanoma biology including tumor initiation, progression and metastasis. Accordingly, Notch has been targeted for melanoma therapy both in preclinical xenograft models as well as clinical trials. Notch inhibitors, mainly γ-secretase inhibitors, have been widely used for this purpose. However, clinical trials with these agents have not been proven to be highly effective for melanoma treatment. In previously published studies we showed that Notch signaling is involved in regulation of melanoma trans-differentiation, a prognostic feature in primary melanoma. In this study, we reevaluated the role of Notch in melanoma development, cell survival and sensitivity to BRAF and MEK inhibitors. First, our preliminary data using the BRAFV600E/Pten mouse model showed that topical application of γ-secretase inhibitor DAPT delays tumor formation and growth. In several early passage metastatic human melanoma cell lines, we found that Notch receptors (Notch 1-3) are highly upregulated compared to normal epidermal melanocytes. Interestingly, mRNA levels for Notch1-3 receptors in normal melanocytes were either higher or comparable to their levels in the cell lines. This suggested that Notch receptor levels are tightly regulated in normal melanocytes by post-transcriptional mechanisms. Presence of cleaved Notch intracellular domain (NICD), both cytoplasmic and nuclear, in melanoma cells, but not in melanocytes, indicated constitutive activation of Notch signaling in melanoma cells. However, inhibition of Notch activation by treatment with γ-secretase inhibitor had no significant effect on survival of melanoma cells in vitro. Thus, Notch signaling appears to be dispensable for melanoma cell survival. Additionally, inhibition of Notch activation did not alter the sensitivity of melanoma cells to BRAF(V600E) and MEK inhibitors. Our results highlight the need for re-examination of Notch-regulated melanoma trans-differentiation as a therapeutic outcome. Citation Format: Dareen Mikheil, Carlos Rodriguez, Ashika Jayanthi, Prithvi Yarlagadda, Vijaysaradhi Setaluri. Reevaluation of the role of Notch signaling in melanoma tumor development, melanoma cell survival and drug resistance. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4623.
Incidence and severity of prostate cancer in 360 hypogonadal men treated with testosterone undecanoate injections (TU) for up to 8 years and 296 untreated hypogonadal controls.
Authors: Ahmad Haider, Karim Sultan Haider
Journal: Journal of Clinical Oncology (2016)

50 Background: Testosterone therapy (TTh) in middle-aged and elderly men is still associated with concerns regarding prostate cancer (PCa). In this registry study, we investigated the incidence of PCa in hypogonadal patients on long-term treatment with TU in comparison to an untreated hypogonadal control group (CTRL). Methods: In a cumulative registry study, 360 men (mean age: 57.37±7.29 years, range: 33-70) with testosterone (T) ≤12.1 nmol/L received TU 1000 mg every 12 weeks following an initial interval of 6 weeks for up to 8 years. 296 hypogonadal men (mean age: 64.79±4.28 years, range: 57-74) decided against TTh, mainly due to financial reasons. Prostate volume (PV) and PSA were measured and digital rectal examination (DRE)/ transrectal ultrasound (TRUS) performed before treatment initiation and then regularly every 3-6 months. Biopsies were performed when indicated according to EAU guidelines. Results: From baseline to 8 years, PV increased from 29.24±10.38 to 31.13±11.45 ml in the T group and remained stable from 34.45±5.89 to 33.51±12 in CTRL. PSA increased slightly from 1.74 ± 0.93 to 1.83±0.93 ng/ml in the T group and remained stable from 2.25±1.34 to 2.19±1.17 in CTRL. In T-treated patients, 7 men (1.9%) were diagnosed with PCa. In the control group, 12 (4.1%) were diagnosed with PCa. The incidence per 10,000 years was 30.05 in the T group and 63.54 in CTRL. The mean age of PCa patients was 64 years in the T group and 65 years in CTRL. All patients underwent radical prostatectomy. The predominant Gleason score was 3 in all patients in the T group, lymph nodes and surgical margins were negative. In CTRL, three men had a predominant Gleason score of 3, 8 had 4, and 1 had 5. 7 patients had positive lymph nodes and no patient had a positive surgical margin. Conclusions: Long-term treatment with TU in hypogonadal men undergoing regular monitoring according to EAU guidelines does not increase the incidence of PCa in comparison to an untreated hypogonadal CTRL group. PCa was more severe in the CTRL group.
Safety and efficacy of thalidomide in patients with POEMS syndrome: a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Sonoko Misawa, Yasunori Sato, Kanako Katayama, Kengo Nagashima, Reiko Aoyagi, Yukari Sekiguchi, Gen Sobue, Haruki Koike, Ichiro Yabe, Hidenao Sasaki, Osamu Watanabe, Hiroshi Takashima, Masatoyo Nishizawa, Izumi Kawachi, Susumu Kusunoki, Yoshiyuki Mitsui, Seiji Kikuchi, Ichiro Nakashima, Shu-ichi Ikeda, Nobuo Kohara, Takashi Kanda, Jun-ichi Kira, Hideki Hanaoka, Satoshi Kuwabara
Journal: The Lancet Neurology (2016)