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Anti tumor

Wohn-Jenn Leu, Sharada Prasanna Swain, She-Hung Chan, Jui-Ling Hsu, Shih-Ping Liu, Mei-Ling Chan, Chia-Chun Yu, Lih-Ching Hsu, Yen-Lin Chou, Wei-Ling Chang, Duen-Ren Hou, Jih-Hwa Guh
A series of triazole-based small molecules that mimic FTY720-mediated anticancer activity but minimize its immunosuppressive effect have been produced. SPS-7 is the most effective derivative displaying higher activity than FTY720 in anti-proliferation against human hormone-refractory prostate cancer (HRPC). It induced G1 arrest of cell cycle and subsequent apoptosis in thymidine block-mediated synchronization model. The data were supported by a decrease of cyclin D1 expression, a dramatic increase of p21 expression and an associated decrease in RB phosphorylation...
October 19, 2016: Oncotarget
Amber A Bokhari, Laura R Lee, Dewayne Raboteau, Jane Turbov, Isabel V Rodriguez, J Wesley Pike, Chad A Hamilton, G Larry Maxwell, Gustavo C Rodriguez, Viqar Syed
Here, we evaluated the expression of CYP24A1, a protein that inactivates vitamin D in tissues. CYP24A1 expression was increased in advanced-stage endometrial tumors compared to normal tissues. Similarly, endometrial cancer cells expressed higher levels of CYP24A1 than immortalized endometrial epithelial cells. RT-PCR and Western blotting were used to examine CYP24A1 mRNA and protein levels in endometrial cancer cells after 8, 24, 72, and 120 h of exposure to progesterone, progestin derivatives and calcitriol, either alone or in combination...
October 18, 2016: Oncotarget
Massimo Nabissi, Maria Beatrice Morelli, Massimo Offidani, Consuelo Amantini, Silvia Gentili, Alessandra Soriani, Claudio Cardinali, Pietro Leoni, Giorgio Santoni
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy...
October 18, 2016: Oncotarget
Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
October 17, 2016: Oncotarget
Rania R Abdelaziz, Wagdi F Elkashef, Eman Said
Silicosis is a crippling respiratory disorder characterized by massive lung inflammation and fibrosis. The current study provides evidence on the protective potential of tadalafil; a specific phosphodiesterase-5 (PDE-5) inhibitor against experimentally-induced pulmonary silicosis in rats. Silicosis was induced by intranasal instillation of crystalline silica (50mg/rat). Halofuginone hydrobromide; a standard collagen-1 synthesis inhibitor was selected as a reference anti-fibrotic. Daily oral administration of tadalafil (1mg/kg) for 8weeks significantly ameliorated silica-induced pulmonary damage...
October 18, 2016: International Immunopharmacology
Xu Chu, Xiao-Ju Liu, Jing-Man Qiu, Xiao-Li Zeng, Hai-Rong Bao, Juan Shu
Astragalus and Codonopsis pilosula are used for their immunomodulatory and anti-inflammatory effects. Here, we investigated the effects of Astragalus polysaccharides (APS) and Codonopsis pilosula polysaccharides (CPP) on alveolar macrophage (AM) phagocytosis and inflammation in chronic obstructive pulmonary disease (COPD) associated with exposure to particulate matter with a mean aerodynamic diameter ≤2.5μm (PM2.5). A mouse model of COPD was established by cigarette smoke exposure. PM2.5 exposure was performed by inhalation of a PM2...
October 14, 2016: Environmental Toxicology and Pharmacology
Guosheng Song, Chenghong Ji, Chao Liang, Xuejiao Song, Xuan Yi, Ziliang Dong, Kai Yang, Zhuang Liu
Cancer radiotherapy (RT) is a clinically used tumor treatment strategy applicable for a wide range of solid tumors. However, during RT treatment of tumors, only a small portion of applied ionizing irradiation energy is absorbed by the tumor, in which the largely hypoxic microenvironment also limits the anti-tumor efficacy of RT. In this work, we rationally fabricate polyethylene glycol (PEG) stabilized perfluorocarbon (PFC) nano-droplets decorated with TaOx nanoparticles (TaOx@PFC-PEG) as a multifunctional RT sensitizer...
October 11, 2016: Biomaterials
George A Alexiou, Paraskevi Gerogianni, Evrysthenis Vartholomatos, Athanasios P Kyritsis
Glioblastoma is the most malignant primary brain tumor with a median survival of 15 months. Temozolomide (TMZ) is the standard of care for these patients. Iron chelators have been shown to have anti-tumor activity; however, deferiprone (DFP), an orally administered iron chelator, has not been previously evaluated in gliomas. In the present study, we found that combination treatment in glioma cells with TMZ and DFP significantly reduced cell viability, produced cell cycle arrest at G2/M phase, and enhanced apoptosis...
October 21, 2016: Cancer Investigation
Stacey Bagby, Wells A Messersmith, Todd M Pitts, Anna Capasso, Marileila Varella-Garcia, Peter J Klauck, Jihye Kim, Aik-Choon Tan, S Gail Eckhardt, John J Tentler, John Arcaroli
Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor pieces are injected subcutaneously into athymic nude mice (immunocompromised, T cell deficient) to create a bank of tumors and subsequently are passaged into different generations of mice in order to maintain these tumors from patients. Importantly, cellular heterogeneity of the original tumor is closely emulated in this model, which provides a more clinically relevant model for evaluation of drug efficacy studies (single agent and combination), biomarker analysis, resistant pathways and cancer stem cell biology...
September 30, 2016: Journal of Visualized Experiments: JoVE
Katie M Parkins, Amanda M Hamilton, Ashley V Makela, Yuanxin Chen, Paula J Foster, John A Ronald
Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i...
October 21, 2016: Scientific Reports
E Faghihloo, Y Araei, M Mohammadi, H Mirzaei, H R Mohammadi, T Mokhtari-Azad
Gastric cancer is among the leading causes of cancer-related death, and the symptoms are commonly characterized in advanced stages. Histone acetylation is among the most important epigenetic alterations occurring during cancer development. In addition, reduced E-cadherin expression is a major contributor in the process of tumor cell invasion and metastasis. Oxamflatin is a histone deacetylase inhibitor that has been suggested as a promising anti-tumor agent; yet its effect on the viability and invasion of gastric tumor cells is unclear...
October 21, 2016: Cancer Gene Therapy
Vidya Ramachandraiah, Wilbert Aronow, Dipak Chandy
Sarcoidosis is a multisystem disease characterized by the presence of noncaseating granulomas, the exact etiology of which is yet to be determined. Pulmonary involvement occurs in the majority of patients and its severity ranges from asymptomatic involvement of mediastinal lymph nodes to progressive pulmonary fibrosis and chronic respiratory failure that is insensitive to treatment. Diagnosis of pulmonary sarcoidosis requires a compatible clinical picture supported by radiologic and pathologic data. A recent development in establishing the diagnosis of pulmonary sarcoidosis is endobronchial ultrasound that increases the yield of transbronchial needle aspiration of hilar and/or mediastinal lymph nodes...
October 21, 2016: Postgraduate Medicine
Athanasios Tragiannidis, Ioannis Kyriakidis, Ilse Zündorf, Andreas H Groll
Macromolecular immunosuppressive monoclonal antibodies and fusion proteins directed against molecules or cells involved in inflammation and immunity represent a recent and important addition to our therapeutic armamentarium. Tumor necrosis alpha (TNFα) is a cytokine involved in systemic inflammation and clinical utilization of its antagonists has revolutionized treatment of juvenile rheumatoid and psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, and plaque psoriasis. Clinical utility has also been demonstrated for use against steroid-refractory graft-vs-host disease and other immune-mediated conditions...
October 21, 2016: Mycoses
Farhad Jahanfar, Akbar Hasani, Dariush Shanebandi, Mohammad Rahmati, Hamed Hamishehkar
Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied...
September 2016: Advanced Pharmaceutical Bulletin
Nadia F Nocera, M Catherine Lee, Lucy M De La Cruz, Cinthia Rosemblit, Brian J Czerniecki
The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy...
2016: Frontiers in Pharmacology
Tur-Fu Huang, Chun-Chieh Hsu, Yu-Ju Kuo
Snake venoms affect blood coagulation and platelet function in a complex manner. However, two classes of venom proteins, snaclecs and disintegrins have been shown to specifically target receptors including GPIb, α2β1, GPVI, CLEC-2 and integrins αIIbβ3, αvβ3, α5β1 expressed on platelets, endothelial cells, phagocytes, tumor cells, thus affecting cell-matrices and cell-cell interactions. Here, we focus on disintegrins, a class of low molecular mass Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing, cysteine-rich polypeptide derived from various viper snake venoms...
2016: Thrombosis Journal
Yukihiko Hiroshima, Ali Maawy, Yong Zhang, Nan Zhang, Takashi Murakami, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Robert M Hoffman
Patient-derived xenograft (PDX) mouse models of cancer are emerging as an important component of personalized precision cancer therapy. However, most models currently offered to patients contain their tumors subcutaneously-transplanted in immunodeficient mice, which rarely metastasize. In contrast, orthotopic-transplant patient-derived models, termed patient-derived orthotopic xenografts (PDOX), usually metastasize as in the patient. We have demonstrated in the present report why orthotopic models are so important for the patient, since primary and metastatic tumors developed in an orthotopic model can have differential chemosensitivity, not detectable in standard subcutaneous tumor models...
September 28, 2016: Oncotarget
Ming Yang, Haiyong Wang, Mo Zhou, Weilin Liu, Pengqun Kuang, Hao Liang, Qipeng Yuan
Lung cancer is one of the leading causes of cancer death worldwide. Isothiocyanates from cruciferous vegetables been shown to possess anticarcinogenic activities in lung malignances. We previously found sulforaphene (4-methylsufinyl-3-butenyl isothiocyanate, SFE), one new kind of isothiocyanates, existing in a relative high abundance in radish seeds. An efficient methodology based on macroporous resin and preparative high-performance liquid chromatography was developed to isolate SFE in reasonably large quantities, high purity and low cost...
September 28, 2016: Oncotarget
Hiroko Mataki, Naohiko Seki, Keiko Mizuno, Nijiro Nohata, Kazuto Kamikawaji, Tomohiro Kumamoto, Keiichi Koshizuka, Yusuke Goto, Hiromasa Inoue
Patients with lung adenocarcinoma may benefit from recently developed molecular targeted therapies. However, analogous advanced treatments are not available for patients with lung squamous cell carcinoma (lung SCC). The survival rate of patients with the advanced stage of lung SCC remains poor. Exploration of novel lung SCC oncogenic pathways might lead to new treatment protocols for the disease. Based on this concept, we have identified microRNA- (miRNA) mediated oncogenic pathways in lung SCC. It is well known that miR-145-5p (the guide strand) functions as a tumor suppressor in several types of cancer...
September 27, 2016: Oncotarget
Yu Jin Lee, Kyeong Jin Shin, Soo-Ah Park, Kyeong Su Park, Seorim Park, Kyun Heo, Young-Kyo Seo, Dong-Young Noh, Sung Ho Ryu, Pann-Ghill Suh
G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo...
September 27, 2016: Oncotarget
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