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https://www.readbyqxmd.com/read/28445988/specific-up-regulation-of-p21-by-a-small-active-rna-sequence-suppresses-human-colorectal-cancer-growth
#1
Lu-Lu Wang, Hui-Hui Guo, Yun Zhan, Chen-Lin Feng, Shuai Huang, Yan-Xing Han, Wen-Sheng Zheng, Jian-Dong Jiang
The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53-/-) and HT-29 were transfected with the p21-saRNA-322...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445970/acid-ceramidase-is-a-novel-drug-target-for-pediatric-brain-tumors
#2
Ninh B Doan, Ha S Nguyen, Andrew Montoure, Mona M Al-Gizawiy, Wade M Mueller, Shekar Kurpad, Scott D Rand, Jennifer M Connelly, Christopher R Chitambar, Kathleen M Schmainda, Shama P Mirza
Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445956/rhbdd1-upregulates-egfr-via-the-ap-1-pathway-in-colorectal-cancer
#3
Fei Miao, Mengmeng Zhang, Yuechao Zhao, Xiaolu Li, Rongyan Yao, Fan Wu, Rong Huang, Kai Li, Shiying Miao, Changwu Ma, Hongge Ju, Wei Song, Linfang Wang
Our previous study showed that RHBDD1 can activate the EGFR signaling pathway to promote colorectal cancer growth. In the present study, EGFR was decreased when RHBDD1 was knocked down or inactivated. Further analysis found that c-Jun and EGFR protein expression was decreased in RHBDD1 knockdown and inactivated cells. c-Jun overexpression in RHBDD1-inactivated cells rescued EGFR expression in a dose-dependent manner. RHBDD1 overexpression in RHBDD1-inactivated cells restored EGFR expression, but this effect was counteracted by c-Jun knockdown...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445943/a-molecular-inversion-probe-based-next-generation-sequencing-panel-to-detect-germline-mutations-in-chinese-early-onset-colorectal-cancer-patients
#4
Junxiao Zhang, Xiaoyan Wang, Richarda M de Voer, Jayne Y Hehir-Kwa, Eveline J Kamping, Robbert D A Weren, Marcel Nelen, Alexander Hoischen, Marjolijn J L Ligtenberg, Nicoline Hoogerbrugge, Xiangling Yang, Zihuan Yang, Xinjuan Fan, Lei Wang, Huanliang Liu, Jianping Wang, Roland P Kuiper, Ad Geurts van Kessel
The currently known Mendelian colorectal cancer (CRC) predisposition syndromes account for ~5-10% of all CRC cases, and are caused by inherited germline mutations in single CRC predisposing genes. Using molecular inversion probes (MIPs), we designed a targeted next-generation sequencing panel to identify mutations in seven CRC predisposing genes: APC, MLH1, MSH2, MSH6, PMS2, MUTYH and NTHL1. From a consecutive series of 2,371 Chinese CRC patients, 140 familial and non-familial cases were selected that were diagnosed with CRC at or below the age of 35 years...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445743/egfr-targeted-micelles-containing-near-infrared-dye-for-enhanced-photothermal-therapy-in-colorectal-cancer
#5
Ying-Hsia Shih, Tsai-Yueh Luo, Ping-Fang Chiang, Cheng-Jung Yao, Wuu-Jyh Lin, Cheng-Liang Peng, Ming-Jium Shieh
The purpose of this research was to investigate the effectiveness of epidermal growth factor receptor (EGFR) targeted micelles loaded with IR-780 (Cetuximab/IR-780/micelles) for generating tumor targeting, multimodal images, and photothermal therapy (PTT). We initially studied the cellular uptake of these micelles using the HCT-116 and SW-620 cell lines. HCT-116 (high expression of EGFR) and SW-620 (low expression of EGFR) cell lines were used to examine biodistribution and antitumor effects of Cetuximab/IR-780/micelles...
April 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28445481/hypomethylating-agents-synergize-with-irinotecan-to-improve-response-to-chemotherapy-in-colorectal-cancer-cells
#6
Anup Sharma, Rajita Vatapalli, Eihab Abdelfatah, K Wyatt McMahon, Zachary Kerner, Angela A Guzzetta, Jasvinder Singh, Cynthia Zahnow, Stephen B Baylin, Sashidhar Yerram, Yue Hu, Nilofer Azad, Nita Ahuja
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA) in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28445257/do-inflammatory-markers-predict-prognosis-in-patients-with-synchronous-colorectal-cancer
#7
Wanbin He, Mingtian Wei, Xuyang Yang, Bingchen Chen, Qingbin Wu, Erliang Zheng, XiangBing Deng, Ziqiang Wang
Systematic inflammatory response markers are considered as the most informative prognostic factors in many types of cancer. However, in synchronous colorectal cancer (synCRC), the prognostic value of inflammatory markers, including prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), had rarely been evaluated. Thus, this present study reviewed our consecutive patients with synCRC to investigate the prognostic value of those factors...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#8
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445136/selective-eradication-of-cancer-cells-by-delivery-of-adenovirus-based-toxins
#9
Shiran Shapira, Assaf Shapira, Diana Kazanov, Gil Hevroni, Sarah Kraus, Nadir Arber
BACKGROUND AND OBJECTIVE: KRAS mutation is an early event in colorectal cancer carcinogenesis. We previously reported that a recombinant adenovirus, carrying a pro-apoptotic gene (PUMA) under the regulation of Ets/AP1 (RAS-responsive elements) suppressed the growth of cancer cells harboring hyperactive KRAS. We propose to exploit the hyperactive RAS pathway, rather than to inhibit it as was previously tried and failed repeatedly. We aim to improve efficacy by substituting PUMA with a more potent toxin, the bacterial MazF-MazE toxin-antitoxin system, under a very tight regulation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445124/a-novel-triazolonaphthalimide-induces-apoptosis-and-inhibits-tumor-growth-by-targeting-dna-and-dna-associated-processes
#10
Liyan Ji, Simin Yang, Shasha Li, Shan Liu, Shunan Tang, Zhongqiu Liu, Xiangbao Meng, Siwang Yu
DNA and DNA-associated processes have been classes of the most important targets of chemotherapeutic drugs. As classic DNA intercalators and topoisomerase inhibitors, naphthalimides have been extensively investigated as potential anti-cancer drugs. We recently synthesized a novel series of triazolonaphthalimides with excellent anti-cancer activities. In the present study, one of the most potent triazolonaphthalimides, LSS-11, was investigated. LSS-11 bound to DNA in vitro and in cell mainly by minor groove binding and significantly increased the stability of DNA, which could be fundamental for the biological activities of LSS-11...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444968/carcinoembryonic-antigen-directed-pet-cect-scanning-for-post-operative-surveillance-of-colorectal-cancer
#11
Karthik Chandra Vallam, Guruchannabasavaiah B, Archi Agrawal, Venkatesh Rangarajan, Vikas Ostwal, Reena Engineer, Avanish Saklani
AIM: During the follow-up of surgically resected colorectal cancer (CRC), positron emission tomography-contrast-enhanced computed tomography (PET-CECT) is indicated for asymptomatic elevation of carcinoembryonic antigen (CEA) > 5 ng/ml and no obvious site of recurrence on clinical examination and basic imaging. As an institutional policy, PET-CECT scan was performed at our institute whenever (1) CEA levels rose above 5 ng/ml and (2) CEA values were doubled (even if CEA level was <5 ng/ml)...
April 26, 2017: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/28444084/effects-of-zinc-supplementation-on-fatigue-and-quality-of-life-in-patients-with-colorectal-cancer
#12
Sofia Miranda de Figueiredo Ribeiro, Camila Bitu Moreno Braga, Fernanda Maris Peria, Edson Zangiacomi Martinez, José Joaquim Ribeiro da Rocha, Selma Freire Carvalho Cunha
Objective: To investigate the effects of oral zinc supplementation on fatigue intensity and quality of life of patients during chemotherapy for colorectal cancer. Methods: A prospective, randomized, double-blinded, placebo-controlled study was conducted with 24 patients on chemotherapy for colorectal adenocarcinoma in a tertiary care public hospital. The study patients received zinc capsules 35mg (Zinc Group, n=10) or placebo (Placebo Group, n=14) orally, twice daily (70mg/day), for 16 weeks, from the immediate postoperative period to the fourth chemotherapy cycle...
January 2017: Einstein
https://www.readbyqxmd.com/read/28443499/high-expression-of-partitioning-defective-3-like-protein-is-associated-with-malignancy-in-colorectal-cancer
#13
Taiyuan Li, Xiaoyang Liu, Qunguang Jiang, Xiong Lei, Dongning Liu
Partitioning defective 3-like protein is a novel cell polarity protein. Recently, partitioning defective 3-like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3-like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3-like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28443497/netrin-1-in-cancer-potential-biomarker-and-therapeutic-target
#14
Umut Kefeli, Aysegul Ucuncu Kefeli, Devrim Cabuk, Ulas Isik, Alper Sonkaya, Ozgur Acikgoz, Ercan Ozden, Kazim Uygun
Netrin-1, a laminin-related protein, is known to be involved in the nervous system development. Recently, Netrin-1's involvement in other processes such as cell adhesion, motility, proliferation, and differentiation that are important for the development of epithelial tissues has been described. In addition, Netrin-1 and its receptors, deleted in colorectal cancer and uncoordinated-5 homolog, have been linked to apoptosis and angiogenesis. Since these properties are essential for tumor development, Netrin-1 and its receptors have been reported to promote tumorigenesis in many types of cancers...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28443475/microrna-140-5p-inhibits-cell-proliferation-and-invasion-by-regulating-vegfa-mmp2-signaling-in-glioma
#15
Yuan Hu, Yanyan Li, Chun Wu, Liang Zhou, Xiaoxiao Han, Qingyue Wang, Xueshun Xie, Youxin Zhou, Ziwei Du
Glioma is the most common primary malignant tumor of the central nervous system, which results in both a poor prognosis and outcome because of the aggressive progression of disease, growth and resistance to surgery, chemotherapy, and radiotherapy. MiR-140-5p is a small, non-coding single-stranded RNA molecule, which was previously studied in the settings of human tongue cancer, hepatocellular carcinoma, and colorectal cancer. However, detailed data that formally demonstrate the contribution of miR-140-5p to glioma development are missing...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28443472/mir-26a-downregulates-retinoblastoma-in-colorectal-cancer
#16
Eduardo López-Urrutia, Jossimar Coronel-Hernández, Verónica García-Castillo, Carlos Contreras-Romero, Antonio Martínez-Gutierrez, Diana Estrada-Galicia, Luis Ignacio Terrazas, César López-Camarillo, Hector Maldonado-Martínez, Nadia Jacobo-Herrera, Carlos Pérez-Plasencia
MicroRNAs are non-coding short RNAs that target the 3' untranslated region of messenger RNAs (mRNAs) and lead to their degradation or to translational repression. Several microRNAs have been designated as oncomirs, owing to their regulating tumor suppressor genes. Interestingly, a few of them have been found to target multiple genes whose simultaneous suppression contributes to the development of a tumoral phenotype. Here, we have showed that miR-26a is overexpressed in colorectal cancer data obtained from TCGA Research Network and in human colon cancer pathological specimens; moreover, an orthotopic in vivo model of colon cancer showed overexpression of miR-26a, while Rb1 expression inversely correlated to miR-26a in TCGA Research Network data, pathological samples, and the in vivo model...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28442513/histopathological-significance-and-prognostic-impact-of-tumor-budding-in-colorectal-cancer
#17
Anurag Mehta, Malini Goswami, Rupal Sinha
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease with complex etiology. New prognostic factors for this group of disease need to be investigated. This study evaluated the histopathological significance and prognostic impact of tumor budding in CRC. DESIGN: A total of 60 treatment naive consecutive patients undergoing surgical resection for CRC during the period of January 2011 to December 2013 were included in the study. Details of each patient related to their demographic and tumor profile were recorded...
March 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28442448/phosphotyrosine-based-phosphoproteomics-scaled-down-to-biopsy-level-for-analysis-of-individual-tumor-biology-and-treatment-selection
#18
Mariette Labots, Johannes C van der Mijn, Robin Beekhof, Sander R Piersma, Richard R de Goeij-de Haas, Thang V Pham, Jaco C Knol, Henk Dekker, Nicole C T van Grieken, Henk M W Verheul, Connie R Jiménez
Mass spectrometry-based phosphoproteomics of cancer cell and tissue lysates provides insight in aberrantly activated signaling pathways and potential drug targets. For improved understanding of individual patient's tumor biology and to allow selection of tyrosine kinase inhibitors in individual patients, phosphoproteomics of small clinical samples should be feasible and reproducible. We aimed to scale down a pTyr-phosphopeptide enrichment protocol to biopsy-level protein input and assess reproducibility and applicability to tumor needle biopsies...
April 22, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28442322/in-vitro-and-in-vivo-antitumor-activities-of-t-3764518-a-novel-and-orally-available-small-molecule-stearoyl-coa-desaturase-1-inhibitor
#19
Satoru Nishizawa, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Satoshi Kitazawa, Kohei Honda, Hideo Araki, Kazuyo Kakoi, Keisuke Imamura, Masako Sasaki, Ikuo Miyahisa, Yoshinori Satomi, Ryuuichi Nishigaki, Megumi Hirayama, Kazunobu Aoyama, Hironobu Maezaki, Takahito Hara
Most cancer cells are characterized by elevated lipid biosynthesis. The rapid proliferation of cancer cells requires de novo synthesis of fatty acids. Stearoyl-CoA desaturase-1 (SCD1), a key enzyme for lipogenesis, is overexpressed in various types of cancer and plays an important role in cancer cell proliferation. Therefore, it has been studied as a candidate target for cancer therapy. In this study, we demonstrate the pharmacological properties of T-3764518, a novel and orally available small molecule inhibitor of SCD1...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28442242/dosimetric-analysis-of-liver-toxicity-after-liver-metastasis-stereotactic-body-radiation-therapy
#20
Aisling Barry, Andrew McPartlin, Patricia Lindsay, Lisa Wang, James Brierley, John Kim, Jolie Ringash, Rebecca Wong, Rob Dinniwell, Tim Craig, Laura A Dawson
PURPOSE: The aim of this study is to describe the incidence and type of liver toxicity seen following liver metastases stereotactic body radiation therapy (SBRT) and the corresponding clinical and dosimetric factors associated with toxicity. METHODS AND MATERIALS: Between 2002 and 2009, 81 evaluable patients with liver metastases were treated on 2 prospective studies assessing SBRT, with prescription doses based on the effective liver volume irradiated evaluated...
March 9, 2017: Practical Radiation Oncology
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