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Cancer Biology & Therapy

Chengming Fan, Demiao Kong, Changming Tan, Jinfu Yang
BACKGROUND: Peripheral primitive neuroectodermal tumor isolated in the heart, presenting as a primary cardiac tumor is considered as extremely rare. METHODS: We present a 53-year-old Chinese female with a cardiac tumour which was discovered by computed tomography. RESULTS: A hypo-intense tumorous mass was shown extending from the left ventricle by Cardiac CT, and fused FDG positron emission tomography demonstrated no other abnormal FDG active lesions in the body...
December 1, 2016: Cancer Biology & Therapy
Kristian M Koller, Heath B Mackley, Jason Liu, Henry Wagner, Giampaolo Talamo, Todd D Schell, Colette Pameijer, Rogerio I Neves, Bryan Anderson, Kathleen M Kokolus, Carol A Mallon, Joseph J Drabick
There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not...
December 1, 2016: Cancer Biology & Therapy
Kristen Haberthur, Kathryn Brennan, Virginia Hoglund, Stephanie Balcaitis, Harrison Chinn, Amira Davis, Shannon Kreuser, Conrad Winter, Sarah E S Leary, Gail H Deutsch, Richard G Ellenbogen, Courtney A Crane
Adult brain tumors establish an immunosuppressive tumor microenvironment as a modality of immune escape, with several immunotherapies designed to overcome this barrier. However, the relationship between tumor cells and immune cells in pediatric brain tumor patients is not as well-defined. In this study, we sought to determine whether the model of immune escape observed in adult brain tumors is reflected in patients with pediatric brain tumors by evaluating NKG2D ligand expression on tissue microarrays created from patients with a variety of childhood brain tumor diagnoses, and infiltration of Natural Killer and myeloid cells...
November 11, 2016: Cancer Biology & Therapy
Jeffrey Q Nguyen, Rosalyn B Irby
The prostate apoptosis response protein 4 (Par-4) is a tumor-suppressor that has been shown to induce cancer-cell selective apoptosis in a variety of cancers. The regulation of Par-4 expression and activity is a relatively understudied area, and identifying novel regulators of Par-4 may serve as novel therapeutic targets. To identify novel regulators of Par-4, a co-immunoprecipitation was performed in colon cancer cells, and co-precipitated proteins were identified by mass-spectometry. TRIM21 was identified as a novel interacting partner of Par-4, and further shown to interact with Par-4 endogenously and through its PRY-SPRY domain...
November 10, 2016: Cancer Biology & Therapy
Shi Yin, Wenzhong Du, Feng Wang, Bo Han, Yuqiong Cui, Dongbo Yang, Hui Chen, Daming Liu, Xing Liu, Chuanlu Jiang
Glioblastoma multiforme is the most malignant and common brain tumor in adults and is characterized by poor survival and high resistance to chemotherapy and radiotherapy. Among the new chemotherapy drugs, curcumin, a popular dietary supplement, has proven to have a potent anticancer effect on a variety of cancer cell types; however, it remains difficult to achieve a satisfactory therapeutic effect with curcumin using the traditional single-drug treatment. In this study, we found that expression of miR-326, a tumor suppressor microRNA in various tumor types, resulted in a marked increase of curcumin-induced cytotoxicity and apoptosis and a decrease of proliferation and migration in glioma cells...
November 7, 2016: Cancer Biology & Therapy
Wenchu Lin, Joshua M Francis, Hong Li, Xiaoping Gao, Chandra Sekhar Pedamallu, Patricia Ernst, Matthew Meyerson
The reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlying this disease. The Men1 knockout mouse model recapitulates the early stage of human PanNET development and can serve as a foundation for the development of advanced mouse models that are necessary for preclinical testing...
November 1, 2016: Cancer Biology & Therapy
Aaron P Havas, Kameron B Rodrigues, Anvi Bhakta, Joseph A Demirjian, Seongmin Hahn, Jack Tran, Margarethakay Scavello, Ana A Tula-Sanchez, Yi Zeng, Monika Schmelz, Catharine L Smith
Diffuse Large B-cell lymphoma (DLBCL) is an aggressive malignancy that has a 60 percent 5-year survival rate, highlighting a need for new therapeutic approaches. Histone deacetylase inhibitors (HDACi) are novel therapeutics being clinically-evaluated in combination with a variety of other drugs. However, rational selection of companion therapeutics for HDACi is difficult due to their poorly-understood, cell-type specific mechanisms of action. To address this, we developed a pre-clinical model system of sensitivity and resistance to the HDACi belinostat using DLBCL cell lines...
October 28, 2016: Cancer Biology & Therapy
Chao Shang, Bin Lang, Li-Rong Meng
ABSTACT Although the molecular therapeutics targeting key biomarkers such as epithelial growth factor receptor (EGFR), PI3K/AKT/mTOR, and vascular endothelial growth factor (VEGF) shows some success in clinical trials, some internally existing challenges in endothelial cancer biology hinder the drug effects. One of the major challenges stems from cancer stem cell-derived drug resistance. CD133 positive cells are well believed as cancer stem cells (CSC) in endometrial cancers and NOTCH pathway plays a critical role in retaining CD133+ cells by promoting CSC self-renewal and chemoresistance...
October 28, 2016: Cancer Biology & Therapy
Valerio Nardone, Cirino Botta, Michele Caraglia, Elodia Claudia Martino, Maria Raffaella Ambrosio, Tommaso Carfagno, Paolo Tini, Leonardo Semeraro, Gabriella Misso, Anna Grimaldi, Mariarosaria Boccellino, Gaetano Facchini, Massimiliano Berretta, Gianluca Vischi, Bruno Jim Rocca, Aurora Barone, Pierfrancesco Tassone, Pierosandro Tagliaferri, Maria Teresa Del Vecchio, Luigi Pirtoli, Pierpaolo Correale
Tumor immunologic microenvironment is strongly involved in tumor progression and the presence of tumor infiltrating lymphocytes (TIL) with different phenotypes has been demonstrated to be of prognostic relevance in different malignancies. We investigated whether TIL infiltration of tumor tissues could also predict the outcome of prostate cancer patients. To this end, we carried out a retrospective analysis correlating the outcome of locally advanced prostate cancer patients undergone salvage radiotherapy upon relapse after radical surgery with the infiltration by different TIL populations...
October 28, 2016: Cancer Biology & Therapy
Qinghai Zeng, Ke Cao, Rui Liu, Jinhua Huang, Kun Xia, Jintian Tang, Xiang Chen, Ming Zhou, Huiqing Xie, Jianda Zhou
BACKGROUND: Although recent studies have revealed TAR (trans-activating response region) DNA binding protein (TDP-43) as a potential therapeutic target for cancers, its role and clinical association with melanoma have not been explored. OBJECTIVE: To identify the role and function of TDP-43 during melanoma pathogenesis. METHODS: Firstly, the relationship between TDP-43 expression and patient survival was explored. Then TDP-43 expression level in melanoma tissue and different melanoma cell lines was measured...
October 27, 2016: Cancer Biology & Therapy
Quhuan Li, Qun Lin, Zhong Yun
Solid tumors contain numerous regions with insufficient oxygen concentrations, a condition termed hypoxia. Tumor hypoxia is significantly associated with metastasis, refractory to conventional cancer therapies, and poor patient survival. Therefore, eradication of hypoxic tumor cells will likely have significant impact on the overall progression-free patient survival. This article reports a new discovery that Benznidazole, a bioreductive drug currently used to treat Chagas disease caused by the parasitic protozoan Trypanosoma cruzi, is activated by hypoxia and can kill clonogenic tumor cells especially those under severe hypoxic conditions (≤0...
October 27, 2016: Cancer Biology & Therapy
Seung-Keun Hong, Dmytro Starenki, Pui-Kei Wu, Jong-In Park
Most BRAF-mutated melanomas initially responsive to the FDA-approved inhibitors preferentially targeting B-Raf mutated in Val600 residue eventually relapse, requiring additional therapeutic modalities. Recent studies report the significance of metabolic reprograming in mitochondria for maintenance of BRAF-mutated melanomas and for development of their drug resistance to B-Raf inhibitors, providing a rationale for targeting mitochondria as a potential therapeutic strategy for melanoma. We therefore determined whether mitochondria-targeted metabolism-interfering agents can effectively suppress human B-Raf(V600E) melanoma cell lines and their dabrafenib/PLX4032-resistant progenies using mitochondria-targeted carboxy-proxyl (Mito-CP) and ubiquinone (Mito-Q)...
October 27, 2016: Cancer Biology & Therapy
Fei Wang, Jiayao Zhao, Da Liu, Tong Zhao, Zeming Lu, Lin Zhu, Lingling Cao, Jiaxing Yang, Jingji Jin, Yong Cai
Capsaicin (CAP) is the major pungent component of chili pepper and is being evaluated for use against numerous types of tumors. Although CAP is indicated to target multiple signaling pathways, exact mechanisms of how it disturb cancer cell metablism remain obscure. Recent studies revealed Sirtuin 1 (SIRT1) serves as a potential target of CAP in cancer cells, indicating a direct regulation of cancer cell histone acetylation by capsaicin. The present study evaluated the effect of CAP on gastric cancer (GC) cell lines to understand the mechanism of cell growth inhibition...
October 7, 2016: Cancer Biology & Therapy
Kristine C Olson, Paige M Kulling, Thomas L Olson, Su-Fern Tan, Rebecca J Rainbow, David J Feith, Thomas P Loughran
Large granular lymphocyte leukemia (LGLL) is a rare incurable chronic disease typically characterized by clonal expansion of CD3+ cytotoxic T-cells. Two signal transducer and activator of transcription factors, STAT1 and STAT3, are constitutively active in T-LGLL. Disruption of this activation induces apoptosis in T-LGLL cells. Therefore, considerable efforts are focused on developing treatments that inhibit STAT activation. Calcitriol, the active form of vitamin D, has been shown to decrease STAT1 and STAT3 phosphorylation in cancer cell lines and autoimmune disease mouse models...
October 7, 2016: Cancer Biology & Therapy
Omar Nasser Rahal, Maamoun Fatfat, Carla Hankache, Bassam Osman, Hala Khalife, Khaled Machaca, Hala-Gali Muhtasib
Recently, we showed that the metal chelator TPEN targets colon cancer cells through redox cycling of copper. Here, we studied the DNA damage potential of TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in 3 human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the role of reactive oxygen species (ROS) in TPEN-induced DNA damage. TPEN reduced cell viability in a dose- and time-dependent manner. Cytotoxicity was associated with significant DNA damage and higher expression of γ-H2AX protein and activation of ATM/ATR signaling pathway...
October 3, 2016: Cancer Biology & Therapy
Sohei Matsumura, Tsuyoshi Ohta, Keiko Yamanouchi, Zhiyang Liu, Takeshi Sudo, Takanobu Kojimahara, Manabu Seino, Megumi Narumi, Seiji Tsutsumi, Toshifumi Takahashi, Kazuhiro Takahashi, Hirohisa Kurachi, Satoru Nagase
Activation of Estrogen receptor (ER) alpha (α) promotes cell growth and influences the response of cancer cell to chemotherapeutic agents. However, the mechanism by which ERα activation antagonizes cells to chemotherapy-induced cytotoxicity remains unclear. Here, we investigated the effect of cisplatin on ERα activation. In addition, we examined whether down-regulation of ERα modulate cisplatin-mediated cytotoxicity using two human ovarian cancer cells (Caov-3 and Ovcar-3) transduced with ERα short hairpin RNA (shRNA)...
September 30, 2016: Cancer Biology & Therapy
Feng Yan Yu, Yun Tu, Ying Deng, Cancan Guo, Jue Ning, Yuzhen Zhu, Xiaohua Lv, Hua Ye
This study aimed to understand the exact function and potential mechanism of miR-4500 in colorectal cancer (CRC). In this study, the expression of miR-4500 was decreased in both CRC cells and tissues, and downregulated miR-4500 indicated advanced tumor stage and poor survival. By bisulfite sequencing analysis, we found that the CpG island in the promoter region of miR-4500 was hypermethylated in CRC cells and tissues compared with normal control cells and non-tumor tissues, respectively. Functionally, gain- and loss-of-function analyses indicated the tumor suppressor role of miR-4500: it suppressed cell proliferation, cell cycle progression, migration, and invasion...
September 29, 2016: Cancer Biology & Therapy
Ali Afgar, Pezhman Fard-Esfahani, Amirhosein Mehrtash, Kayhan Azadmanesh, Farnaz Khodarahmi, Mahdis Ghadir, Ladan Teimoori-Toolabi
It is observed that upregulation of DNMT3B enzyme in some cancers, including colon cancer, could lead to silencing of tumor suppressor genes. MiR-339 and miR-766 have been predicted to target 3'UTR of DNMT3B gene. Luciferase reporter assay validated that individual and co-transfection of miR-766 and miR-339 into the HEK293T cell reduced luciferase activity to 26% ± 0.41%, 43% ± 0.42 and 64% ± 0.52%, respectively, compared to the control (P < 0.05). Furthermore, transduction of miR-339 and miR-766 expressing viruses into colon cancer cell lines (SW480 and HCT116) decreased DNMT3B expression (1...
September 26, 2016: Cancer Biology & Therapy
Yu Zhang, Xiaofeng Zhang, Jinling Zhang, Bin Sun, Lulu Zheng, Jun Li, Sixiu Liu, Guodong Sui, Zhengfeng Yin
Circulating tumor cells (CTCs) have been proposed to be an active source of metastasis or recurrence of hepatocellular carcinoma (HCC). The enumeration and characterization of CTCs has important clinical significance in recurrence prediction and treatment monitoring in HCC patients. We previously developed a unique method to separate HCC CTCs based on the interaction of the asialoglycoprotein receptor (ASGPR) expressed on their membranes with its ligand. The current study applied the ligand-receptor binding assay to a CTC-chip in a microfluidic device...
September 23, 2016: Cancer Biology & Therapy
Jun Hasegawa, Mayumi Sue, Michiko Yamato, Junya Ichikawa, Saori Ishida, Tomoko Shibutani, Michiko Kitamura, Teiji Wada, Toshinori Agatsuma
Overexpression of EPHA2 has been observed in multiple cancers and reported to be associated with poor prognosis. Here, we produced an afucosylated humanized anti-EPHA2 monoclonal antibody (mAb), DS-8895a for cancer treatment. The antibody recognizes the extracellular juxtamembrane region of EPHA2 and therefore can bind to both full-length and truncated forms of EPHA2, which are anchored to cell membranes and recently reported to be produced by post-translational cleavage in tumors. DS-8895a exhibited markedly increased antibody dependent cellular cytotoxicity (ADCC) in vitro and also inhibited tumor growth in EPHA2-positive human breast cancer MDA-MB-231 and human gastric cancer SNU-16 xenograft mouse models...
September 21, 2016: Cancer Biology & Therapy
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