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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 three 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 ɣ-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
Rodrigo Esaki Tamura, Rafael Bento da Silva Soares, Eugenia Costanzi-Strauss, Bryan E Strauss
Alternative treatments for cancer using gene therapy approaches have shown promising results and some have even reached the marketplace. Even so, additional improvements are needed, such as employing a strategically chosen promoter to drive expression of the transgene in the target cell. Previously, we described viral vectors where high-level transgene expression was achieved using a p53-responsive promoter. Here we present an adenoviral vector (AdPGp53) where p53 is employed to regulate its own expression and which outperforms a traditional vector when tested in a model of gene therapy for prostate cancer...
September 19, 2016: Cancer Biology & Therapy
Jacklynn V Egger, Maria V Lane, Lisa A Antonucci, Brixhilda Dedi, Nancy A Krucher
The tumor suppressor Retinoblastoma (Rb) protein is highly phosphorylated in cancer cells largely due to the overexpression of cyclins or the loss of expression of cyclin dependent kinase inhibitors (cdki). Hyperphosphorylation of Rb promotes proliferation, and plays a role in the regulation of apoptosis. Recently, inhibition of cyclin dependent activity toward Rb has been identified as a strategy that has shown clinical efficacy. We utilized a method to induce phosphatase activity toward Rb in cells by shRNA silencing of PNUTS (Phosphatase Nuclear Targeting Subunit) that regulates PP1-mediated dephosphorylation of Rb...
September 19, 2016: Cancer Biology & Therapy
Jing Li, Changhua Zhou, Bin Dong, Hong Zhong, Siqi Chen, Qing Li, Zhong Wang
Bispecific antibodies have emerged as powerful therapeutic agents given their high specificity and ability to induce a potent immune response. Various bispecific antibody formats have been designed and studied regarding their applications in cancer therapy, though associated with issues of short half-life or manufacturing difficulties. Herein, a novel bispecific antibody, SS-Fc, was constructed by pairing two single-domain antibodies, anti-CD16 and anti-CEA, which were fused with CH3 "knobs into holes" mutations individually...
September 19, 2016: Cancer Biology & Therapy
Alexander Beck, Corinna Eberherr, Michaela Hagemann, Stefano Cairo, Beate Häberle, Christian Vokuhl, Dietrich von Schweinitz, Roland Kappler
Hepatoblastoma (HB) is the most common liver tumor of childhood, usually occurring in children under the age of 3 y. The prognosis of patients presenting with distant metastasis, vascular invasion and advanced tumor stages remains poor and children that do survive often face severe late effects from the aggressive chemotherapy regimen. To identify potential new therapeutics for high risk HB we used a 1,000-gene expression signature as input for a Connectivity Map (CMap) analysis, which predicted histone deacetylase (HDAC) inhibitors as a promising therapy option...
September 16, 2016: Cancer Biology & Therapy
Eiji Kashiwagi, Kazutoshi Fujita, Seiji Yamaguchi, Hiroaki Fushimi, Hiroki Ide, Satoshi Inoue, Taichi Mizushima, Leonardo O Reis, Rajni Sharma, George J Netto, Norio Nonomura, Hiroshi Miyamoto
To assess the expression status of steroid hormone receptors in upper urinary tract urothelial carcinoma (UUTUC), we immunohistochemically stained for androgen receptor (AR), estrogen receptor-α (ERα), ERβ, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired non-neoplastic urothelial tissues. AR/ERα/ERβ/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (P < 0.001)/40% (P = 0...
September 16, 2016: Cancer Biology & Therapy
Zhengbo Song, Xinmin Yu, Yiping Zhang
BACKGROUND: ALK, ROS1 and RET rearrangements represent three most frequent fusion genes in non-small cell lung cancer (NSCLC). Rearrangements of these three genes exist predominantly in lung adenocarcinoma while rarely in non-adenocarcinoma. Our objective was to explore the frequency, clinicopathological characteristics and survival of ALK, ROS1 and RET rearrangements in non-adenocarcinoma NSCLC patients. METHODS: ALK, ROS1 and RET rearrangements were screened by reverse transcriptase polymerase chain reaction (RT-PCR) in patients with completely resected non-adenocarcinoma NSCLC...
September 16, 2016: Cancer Biology & Therapy
Jacqueline E Reilly, Jeffrey D Neighbors, Raymond J Hohl
The isoprenoid biosynthetic pathway (IBP) plays a critical role in providing substrates and enzymes necessary for the post-translational modification and thus activation of a number of proteins involved in prostate cancer metastasis. Previous work by our lab found novel compound disodium [(6Z,11E,15E)-9-[bis(sodiooxy)phosphoryl]-17-hydroxy-2,6,12,16-tetramethyheptadeca-2,6,11,15-tetraen-9-yl]phosphonate (GGOHBP), which inhibits the IBP enzyme geranylgeranyl diphosphate synthase (GGDPS), reduced protein geranylgeranylation without altering protein farnesylation...
September 13, 2016: Cancer Biology & Therapy
Derek A Escalante, He Wang, Christopher E Fundakowski
Fusion proteins resulting from chromosomal rearrangements are known to drive the pathogenesis of a variety of hematological and solid neoplasms such as chronic myeloid leukemia and non-small-cell lung cancer. Efforts to elucidate the role they play in these malignancies have led to important diagnostic and therapeutic triumphs, including the famous development of the tyrosine kinase inhibitor dasatinib targeting the BCR-ABL fusion. Until recently, there has been a paucity of research investigating fusion proteins harbored by head and neck neoplasms...
August 15, 2016: Cancer Biology & Therapy
Aaron Baker, Fabian Camacho, Genevieve Andrews, Heath Mackley
Melanoma is a significant clinical problem, with rising rates of incidence. Surgery is the mainstay of treatment. The role of adjuvant radiotherapy in the control of locoregionally advanced cutaneous melanoma is controversial. A retrospective study of the Surveillance, Epidemiology, and End Results (SEER) database was performed. Patients with locoregionally confined cutaneous melanoma treated surgically between 2004 and 2009 were evaluated, with cancer-specific and all-cause mortality as primary end points...
August 15, 2016: Cancer Biology & Therapy
Emil Lou, Matthew Schomaker, Jon D Wilson, Mary Ahrens, Michelle Dolan, Andrew C Nelson
Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vismodegib, an SHH-pathway inhibitor FDA-approved in 2012 for treatment of basal cell carcinoma, has been used successfully in the setting of chemorefractory medulloblastoma, but not as a first-line therapy...
August 12, 2016: Cancer Biology & Therapy
Maria Cosenza, Monica Civallero, Stefania Fiorcari, Samantha Pozzi, Luigi Marcheselli, Alessia Bari, Paola Ferri, Stefano Sacchi
We investigated the cytotoxic interactions of romidepsin, a histone deacetylase inhibitor, and lenalidomide, an immunomodulatory agent, in a T-cell lymphoma preclinical model. Hut-78 and Karpas-299 cells were treated with romidepsin and lenalidomide alone and in combination. The interaction between romidepsin and lenalidomide was evaluated by the Chou-Talalay method, and cell viability and clonogenicity were also evaluated. Apoptosis, reactive oxygen species (ROS) levels, and cell cycle distribution were determined by flow cytometry...
August 12, 2016: Cancer Biology & Therapy
Yi-Fan Chen, Jonathan J Cho, Tsai-Hua Huang, Chao-Neng Tseng, Eng-Yen Huang, Chung-Lung Cho
ROGDI is a protein that contains a leucine zipper domain and may be involved in cell proliferation. In addition, ROGDI is associated with genome stability by regulating the activity of a DNA damage marker, γ-H2AX. The role of ROGDI in tumor radiosensitization has not been investigated. Previous studies have indicated that radiosensitivity is associated with DNA repair and the cell cycle. In general, the G2/M DNA damage checkpoint is more sensitive to radiation, whereas the G1/S phase transition is more resistant to radiation...
August 12, 2016: Cancer Biology & Therapy
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