bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4677: Non-prostate cancer death within 5 years after radical therapy in men with localized prostate cancer.
Authors: Kobayashi Takashi , Kamba Tomomi , Terada Naoki , Yamasaki Toshinari , Ikeda Itaru , Inokuchi Haruo , Norihisa Yoshiki , Mizowaki Takashi , Inoue Takahiro , Okubo Kazutoshi , Yoshimura Koji , Hiraoka Masahiro , Ogawa Osamu 
Published: August 2014

Abstract
Background: As AUA guideline for the Management of Clinically Localized Prostate Cancer: 2007 Update states “An assessment of the patient's life expectancy, overall health status, and tumor characteristics should be undertaken before any treatment decisions can be made," definitive therapy for localized prostate cancer is usually recommended for patients with 5-year life expectancy or more. In some cases, however, unexpected lethal disease is diagnosed and causes death within 5 years after prostate cancer treatment. It seems important to elucidate the characteristics of other causes of death during follow up period after definitive therapy for localized prostate cancer (PCa). Patients and Methods: We reviewed 664 consecutive patients who had received radical prostatectomy (RP, n = 107) or external beam radiotherapy (EBRT, n = 557) and been followed up over 5 years at our institute. Survival status was evaluated and cause of death was identified in dead cases. All cases underwent chest and abdominal computed tomography (CT) and bone scan that were negative for metastasis. Results: At latest follow up, 103 (15.5%) patients were dead of PCa (n = 48) and other causes (n = 55), respectively. Of the 55 patients who died of other causes, 26 did not survive 5 years after radical treatment for PCa. 54% of them died of other malignancies including lung (n = 7) and gastrointestinal (GI) tract (n = 3), lymphoma (n = 2), liver (n = 1), and pancreatic (n = 1) cancers. Non-cancer causes included cerebrovascular disease (n = 3), pulmonary disease (n = 3), ischemic heart disease (n = 2), and unknown (n = 3). Conclusions: Since all patients had negative chest CT for primary lung cancer, some patients with localized PCa seemed to have developed more lethal and rapid malignancy after treatment for PCa. Urologists may need to pay their attention that their patients undergo regular mass screening for common diseases even if they were under urological follow up. Pretreatment test for fecal occult blood may be useful to screen GI tract cancer before treatment initiation.
Citation Format: Takashi Kobayashi, Tomomi Kamba, Naoki Terada, Toshinari Yamasaki, Itaru Ikeda, Haruo Inokuchi, Yoshiki Norihisa, Takashi Mizowaki, Takahiro Inoue, Kazutoshi Okubo, Koji Yoshimura, Masahiro Hiraoka, Osamu Ogawa. Non-prostate cancer death within 5 years after radical therapy in men with localized prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4677. doi:10.1158/1538-7445.AM2013-4677
Abstract 4682: Phase II study of first line chemotherapy with tegafur/uracil and oral leucovorin in elderly patients with advanced or metastatic colorectal cancer.
Authors: Murata Kohei , Yamamoto Hirofumi , Fukunaga Mutsumi , Kato Takeshi , Ohnishi Tadashi , Uemura Yoshio , Ohta Hirofumi , Kimura Fumihiko , Ohue Masayuki , Nezu Riichiro , Sekimoto Mitsugu , Ikeda Masataka , Mizushima Tsunekazu , Doki Yuichiro , Mori Masaki ,   Clinical Study Group of Osaka University (CSGO), Colorectal Group
Published: August 2014

Abstract
Objective: This phase II trial was performed to evaluate the efficacy and tolerability of tegafur/uracil (UFT) and oral leucovorin (LV) in elderly patients with advanced or metastatic colorectal cancer who had not received prior chemotherapy. Methods: Patients aged ≥70 years were eligible. UFT and LV were taken orally on days 1-28 of the cycle at doses of 300 mg/m2/day and 75 mg/body/day, respectively. Treatment was administered on an outpatient basis every 35 days and consisted of at least two cycles until disease progression.
Results: A total of 30 patients were enrolled in this study. The median age of the patients was 81.5 years (range: 74-88 years). The observed overall response rate was 17.9%. The estimated median overall survival time was 23.5 months. Two patients (7%) experienced toxicities with a worst grade of 3, and one patient (4%) experienced toxicities with a worst grade of 4. There were no treatment-related deaths. No patients experienced grade 3 or 4 hematological adverse events.
Conclusions: Although the response rate to UFT/LV was moderate, a favorable survival time and good tolerability were observed. UFT/LV can be one of the optional treatments for elderly colorectal cancer patients.
Citation Format: Kohei Murata, Hirofumi Yamamoto, Mutsumi Fukunaga, Takeshi Kato, Tadashi Ohnishi, Yoshio Uemura, Hirofumi Ohta, Fumihiko Kimura, Masayuki Ohue, Riichiro Nezu, Mitsugu Sekimoto, Masataka Ikeda, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Clinical Study Group of Osaka University (CSGO), Colorectal Group. Phase II study of first line chemotherapy with tegafur/uracil and oral leucovorin in elderly patients with advanced or metastatic colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4682. doi:10.1158/1538-7445.AM2013-4682
Abstract 4711: Targeted inhibition of STAT3 dimerization by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo.
Authors: Shanmugam Muthu K. , Chatterjee Snehajyoti , Peramaiyan Rajendran , Li Feng , Senapati Parijat , Wong Kwong Fai , Wong Kwong Fai , Kumar Alan Prem , Kumar Alan Prem , Kumar Alan Prem , Luk John M. , Luk John M. , Luk John M. , Hui Kam M. , Hui Kam M. , Sethi Gautam , Sethi Gautam , Kundu Tapas K. 
Published: August 2014

Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third cause of global cancer mortality. Activation of signal transducer and activator of transcription 3 (STAT3) is commonly encountered in tumor cells and is a critical mediator of oncogenic signaling in HCC and controls the expression of several genes involved in proliferation, survival, metastasis and angiogenesis. Current drug-targeted therapies, besides being expensive, are associated with serious side effects and morbidity. Thus, novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC. In the present report, we investigated whether the potent HAT/KAT inhibitor, garcinol, (a polyisoprenylated benzophenone), could suppress STAT3 activation in HCC cells and nude mice model. We found that garcinol could inhibit constitutive STAT3 activation in a dose- and time-dependent manner both by inhibiting STAT3 phosphorylation and acetylation in HCC cells. When investigated for molecular mechanism(s), we found that garcinol interferes with the dimer formation of STAT3 thereby inhibits its nuclear localization. Computational modeling showed that garcinol could bind to the SH2 domain of STAT3 and suppresses its dimerization in vitro. To understand the cellular mechanism(s) of inhibition of STAT3 function by garcinol, we observed that upon inhibition of STAT3 dimerization by garcinol, STAT3 DNA binding ability gets repressed. The inhibition of STAT3 activation by garcinol led to the suppression of various gene products involved in proliferation, survival, and angiogenesis. Finally, when administered i.p., garcinol inhibited the growth of human HCC xenograft tumors in male athymic nu/nu mice. In conclusion, results from in vitro and in vivo studies suggest that garcinol exerts its anti-proliferative and pro-apoptotic effects through suppression of STAT3 signaling cascade in HCC by inhibiting its phosphorylation, acetylation and ultimately dimerization.
Citation Format: Muthu K. Shanmugam, Snehajyoti Chatterjee, Rajendran Peramaiyan, Feng Li, Parijat Senapati, Kwong Fai Wong, Kwong Fai Wong, Alan Prem Kumar, Alan Prem Kumar, Alan Prem Kumar, John M. Luk, John M. Luk, John M. Luk, Kam M. Hui, Kam M. Hui, Gautam Sethi, Gautam Sethi, Tapas K. Kundu. Targeted inhibition of STAT3 dimerization by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4711. doi:10.1158/1538-7445.AM2013-4711
Abstract 4718: Withaferin A, a potent and abundant component of Withania somnifera root extract, reduces myeloid-derived suppressor cell function.
Authors: Sinha Pratima , Ostrand-Rosenberg Suzanne 
Published: August 2014

Abstract
Myeloid cells play a crucial role in growth and metastasis of malignant tumors. Tumor infiltrating myeloid cells includes myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAMS) and dendritic cells (DC). These cells infiltrate into tumor and suppress tumor immunity by their inherent immune suppressive activity which is enhanced by interactions with each other (cross-talk). Therapeutic strategies targeting manipulation of these cells are being developed. The root extract of the plant Withania somnifera (Ashwagandha) (WRE) has been reported to reduce tumor cell proliferation and angiogenesis. Whether the anti-tumor effects of WRE are due to direct effects on malignant cells, or whether WRE also impacts immune suppressive myeloid cells is unknown. We hypothesize that WRE or its constituents impact tumor infiltrating myeloid cells and thereby boost anti-tumor immunity. HPLC and mass spectrometry analysis revealed that Withaferin A (WA) is the most abundant constituent of Withania somnifera root powder (ChromaDex, Inc. Irvine, CA). In comparison with the other constituents, WA has the most potent effect on reducing suppressive functions of myeloid cells. A prominent effect of MDSC is their production of IL-10 which increases upon cross-talk with macrophages, thus polarizing immunity to a tumor promoting type-2 phenotype. WA reduces inherent and cross-talk induced IL-10 secretion from MDSC in a dose dependent manner. Macrophage secretion of IL-6 and TNFα cytokines that are characteristic of M1-type macrophages and that also increase MDSC accumulation and function, are also reduced by WA. Much of the T cell suppressive activity of MDSC is due to MDSC production of reactive oxygen species (ROS), and WA significantly reduces MDSC production of ROS. Thus adjunctive treatment with WA has the potential to concomitantly reduce myeloid cell mediated immune suppression, to polarize immunity towards a tumor-rejecting type I phenotype, and to facilitate the development of anti-tumor immunity.
Supported by NIH RO1CA115880, RO1CA84232, and American Cancer Society IRG-97-153-07
Citation Format: Pratima Sinha, Suzanne Ostrand-Rosenberg. Withaferin A, a potent and abundant component of Withania somnifera root extract, reduces myeloid-derived suppressor cell function. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4718. doi:10.1158/1538-7445.AM2013-4718
Abstract 4732: Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb.
Authors: Kurose Koji , Eikawa Shingo , Mizote Yu , Ohue Yoshihiro , Isobe Midori , Uenaka Akiko , Oka Mikio , Nakayama Eiichi 
Published: August 2014

Abstract
Objectives: Tregs down-regulate immune responses against various antigens including tumor cells. Impairment of Tregs cause autoimmune responses. CC chemokine receptor 4 (CCR4) is expressed selectively on Foxp3+CD4 T-cells, so that the treatment of PBMCs with KM2760, anti-human CCR4 mAb with a defucosylated Fc region, could deplete CCR4+Tregs by ADCC. In this study, we analyzed depletion of Tregs phenotypically and functionally after treatment of PBMCs with KM2760.
Methods and main results: CCR4 expression was analyzed on CD4 T-cells purified from healthy donor PBMCs by FACS. CCR4 positivecells were 21% in CD4 T-cells, and 71% in Foxp3+cells. Depletion of CCR4 positive cells by treatment with KM2760 was examined. PBMCs were incubated with KM2760 (0, 0.01, 0.1, 1, 10 μg/ml) for 4 or 20 hours, and analyzed by FACS. Efficient depletion was observed with higher antibody concentration and longer incubation time. Then we examined inhibition of CFSE dilution of labeled CD4 or CD8 T cells stimulated with anti-CD3 mAb after culture with an equal number of CD4+25+127low Tregs and CD4-8- cells pretreated with or without KM2760. Proliferating responder cells were 68% in culture with CD4+25+127low Tregs pretreated with KM2760, whereas those cells with CD4+25+127low Tregs without pretreatment was 38% in CD4 T-cells, 77%and 40% in CD8 T-cells,respectively.
Conclusions: Efficient Treg depletion was observed in vitro by treatment of PBMCs with KM2760. In vivo treatment with the same mAb may induce tumor immune responses by Treg depletion.
Citation Format: Koji Kurose, Shingo Eikawa, Yu Mizote, Yoshihiro Ohue, Midori Isobe, Akiko Uenaka, Mikio Oka, Eiichi Nakayama. Depletion of Tregs from PBMCs by treatment with defucosylated anti-CCR4 mAb. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4732. doi:10.1158/1538-7445.AM2013-4732
Abstract 4745: Quantitative single-cell functional characterization of CD19-specific CAR+ T Cells for immunotherapy.
Authors: Varadarajan Navin , Liadi Ivan , Romain Gabrielle , Singh Harjeet , Cooper Laurence J.N. 
Published: August 2014

Abstract
Adoptive cell therapy (ACT) utilizing chimeric antigen receptor (CAR) T cells rendered specific for CD19 have demonstrated significant anti-tumor effects in patients with CD19+ chronic lymphocytic leukemia (CLL) that were considered untreatable, including the use of stem-cell transplantation. In spite of the clinical promise of ACT in achieving complete responses, their efficacy remains unpredictable and new approaches are needed to address a priori define the therapeutic potential of T-cell based therapies. In our current work, we characterize the in vitro functionality of CD19-specific (CD19RCD28) CAR+ T cells propagated using artificial antigen presenting cells expressing membrane bound IL-21, by employing a novel methodology single-cell nanowell screening that determines their cytotoxic ability and cytokine secretion capability at single-cell resolution.
We show that CAR+ T cells exert specific cytotoxicity against NALM6 cells (31 ± 8 %) when co-incubated at a 1:1 ratio in nanowell containers. Furthermore, single CAR+ T cells were capable of engaging and killing multiple targets; 17 ± 8% of T cells killed two target cells and 9 ± 3% killed three target cells within the 6 hour window of observation. In parallel, microengraving was used to determine the cytokine secretion profile of these same cells. Hierarchical clustering of the two functions indicated that interferon-gamma (IFNγ) secretion is not correlated to cytotoxicity or the ability of T cells to kill multiple target cells. Simultaneously, monitoring apoptosis on CAR+ T cells allowed us to quantify their activation-induced cell death (AICD). CAR+ T cells that secreted IFNγ upon target ligation did not undergo AICD whereas T cells that engaged in repeated killing showed an increased propensity to undergo AICD (p = 0.04).
Finally, automated time-lapse microscopy of hundreds of these effector target interactions allowed us to quantify the kinetics of effector mediated lysis and effector cell velocity profiles before and after lysis. These analyses demonstrate that individual CAR+ T cells demonstrate vastly different individual killing profiles, at least in vitro.
In summary, our SNS based methodology allows the deep functional characterization of clinical grade CAR+ T cells and can be used to determine in vitro functions of CAR+ T cells that correlate with clinical efficacy.
Citation Format: Navin Varadarajan, Ivan Liadi, Gabrielle Romain, Harjeet Singh, Laurence J.N. Cooper. Quantitative single-cell functional characterization of CD19-specific CAR+ T Cells for immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4745. doi:10.1158/1538-7445.AM2013-4745
Abstract 4771: Regulatory role of an orphan nuclear receptor LRH-1 in castration-resistant growth of prostate cancer cells.
Authors: Xiao Lijia , Yu Shan , Hsiao Wendy W.L. , Chan Franky Leung 
Published: August 2014

Abstract
The advanced development of castration-resistant prostate cancer (CRPC) in patients upon androgen-deprivation therapy is generally believed to be mostly mediated by reactivation of androgen receptor (AR) signaling or its bypass with mechanisms involved, including clonal selection of androgen-independent or stem cell-like cell populations, AR hypersensitivity due to AR overexpression, and ligand promiscuity or independence by AR mutations, intratumoral conversion of adrenal androgens to high affinity AR ligands. Besides, the de novo steroid synthesis from cholesterol in CRPC has also been proposed. In this study, we found that the nuclear receptor liver receptor homolog-1 (LRH-1) might contribute to the CRPC growth or de novo steroid synthesis in prostate cancer cells through its positive regulation on expression of several critical enzymes in steroidogenesis, including CYP17A1, HSD3B1, HSD3B2 and StAR. Functional analyses showed that overexpression of LRH-1 could induce higher resistance to antiandrogen bicalutamide and steroid-depleted culture condition in AR-positive androgen-sensitive (LNCaP) but not in AR-negative androgen-insensitive (DU145) prostate cancer cells. In vivo tumorigenicity study showed that LNCaP-LRH-1 cells grew more aggressively in castrated or intact SCID mice, contrary to LNCaP-vector control cells that did not grow in castrated mice. Importantly, liquid chromatography-tandem mass spectrometry showed that intratumoral androgen concentrations (testosterone and DHT) were significantly higher in tumors formed by LNCaP-LRH-1 cells than those by LNCaP-vector control cells. Treatment of LNCaP-LRH-1 cells with a CYP17A1 inhibitor abiraterone could restore their sensitivity to bicalutamide and steroid-depleted culture condition. Gene knockdown of endogenous LRH-1 in AR-positive VCaP prostate cancer cells could not only suppress the mRNA expression of steroidogenic enzymes but also enhance their sensitivity to antiandrogen. Together, our results indicated that LRH-1 might play a regulatory role in advanced castration-resistant growth of prostate cancer via positive control on de novo steroid synthesis in prostate cancer cells.
(This work was supported by a Direct Grant for Research 2011/2012 and a RGC-GRF grant 2009/2010)
Citation Format: Lijia Xiao, Shan Yu, Wendy W.L. Hsiao, Franky Leung Chan. Regulatory role of an orphan nuclear receptor LRH-1 in castration-resistant growth of prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4771. doi:10.1158/1538-7445.AM2013-4771
Abstract 4915: Estrogen receptor β is expressed within breast cancer cells with stem cell like capacity and confers endocrine sensitivity.
Authors: Ma Ran , Govindasamy Karthik Muralidharan , Rosin Gustaf , Gustafsson John , Katchy Anne , Lindström Linda , Hilliges Camilla , Viberg Lisa , Blomqvist Lennart , Frisell Jan , Williams Cecilia , Fredriksson Irma , Bergh Jonas , Hartman Johan 
Published: August 2014

Abstract
Breast cancer stem-cells (BCSCs) are tumor-initiating cells expressing classical embryonal genes such as NANOG, SOX2 and NOTCH1, with a capacity to differentiate and form the heterogenous tumor mass in breast cancer. BCSCs are defined by their potential to grow as mammospheres in vitro together with their distinct cell-surface antigenic profile CD44+/CD24-/EpCAMlow as well as ALDH1-expression. It has been suggested that BCSCs are responsible for therapeutical resistance and metastasis.
About 70-80% of diagnosed breast cancers express ERα, which is demonstrated to have a central role in breast cancer progression and considered as a marker for endocrine sensitivity. However, in our research, BCSCs are confirmed to be ERα negative and supposed to be responding to estrogens only through paracrine signaling via stromal cells. We show that BCSCs purified from fresh surgically resected breast cancers express the second estrogen receptor; ERβ. It is also present in normal mammary stem cells (MSCs) isolated from breast reduction specimens. Surprisingly, stimulation of ERβ with a specific agonist expands the population of BCSCs but not MSCs . Knockdown of ERβ causes reduction in the number of mammospheres significantly along with decreased ALDH1 expression. We also find that treatment with tamoxifen is not sufficient to inhibit BCSCs proliferation although a specific ERβ antagonist reduces tumor growth in xenograft experiments as well as inhibits proliferation of primary cancer stem cells. In conclusion, we suggest endogenous ERβ is proliferative in cancer stem cells in vivo and in vitro, thus can be targeted by specific ligands, in turn opening up for a new direction in endocrine stem-cell specific therapy for breast cancer.
Citation Format: Ran Ma, Karthik Muralidharan Govindasamy, Gustaf Rosin, John Gustafsson, Anne Katchy, Linda Lindström, Camilla Hilliges, Lisa Viberg, Lennart Blomqvist, Jan Frisell, Cecilia Williams, Irma Fredriksson, Jonas Bergh, Johan Hartman. Estrogen receptor β is expressed within breast cancer cells with stem cell like capacity and confers endocrine sensitivity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4915. doi:10.1158/1538-7445.AM2013-4915