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Targeted cancer therapy molecular level

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https://www.readbyqxmd.com/read/29348846/st6galnac1-plays-important-roles-in-enhancing-cancer-stem-phenotypes-of-colorectal-cancer-via-the-akt-pathway
#1
Tadashi Ogawa, Yoshihiko Hirohashi, Aiko Murai, Toshihiko Nishidate, Kenji Okita, Liming Wang, Yuzuru Ikehara, Tetsuta Satoyoshi, Akihiro Usui, Terufumi Kubo, Munehide Nakastugawa, Takayuki Kanaseki, Tomohide Tsukahara, Goro Kutomi, Tomohisa Furuhata, Koichi Hirata, Noriyuki Sato, Toru Mizuguchi, Ichiro Takemasa, Toshihiko Torigoe
Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348271/intratumoral-payload-concentration-correlates-with-the-activity-of-antibody-drug-conjugates
#2
Donglu Zhang, Shang-Fan Yu, S Cyrus Khojasteh, Yong Ma, Thomas H Pillow, Jack D Sadowsky, Dian Su, Katherine R Kozak, Keyang Xu, Andrew G Polson, Peter Dragovich, Cornelis Eca Hop
Antibody-drug conjugates (ADCs) have become important scaffolds for targeted cancer therapies. However, ADC exposure - response correlation is not well characterized. We demonstrated that intratumor payload exposures correlated well with the corresponding efficacies of several disulfide-linked ADCs bearing an DNA alkylating agent, pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD), in HER2-expressing xenograft models. The correlation suggests that a threshold concentration of intratumor payload is required to support sustained efficacy and an ADC can deliver an excessive level of payload to tumors that does not enhance efficacy ('Plateau' effect)...
January 18, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29345394/viruses-as-key-modulators-of-the-tgf-%C3%AE-pathway-a-double-edged-sword-involved-in-cancer
#3
REVIEW
Habibollah Mirzaei, Ebrahim Faghihloo
Transforming growth factor-β (TGF-β) signaling pathway is a key network in cell signaling that controls vital processes such as proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and migration, thus acting as a double-edged sword in normal development and diseases, in particular organ fibrosis, vascular disorders, and cancer. Early in tumorigenesis, the pathway exerts anti-tumor effects through suppressing cell cycle and inducing apoptosis, while during late stages, it functions as a tumor promoter by enhancing tumor invasiveness and metastasis...
January 18, 2018: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29344654/tunicamycin-inhibits-colon-carcinoma-growth-and-aggressiveness-via-modulation-of-the-erk-jnk-mediated-akt-mtor-signaling-pathway
#4
Shuping You, Weihong Li, Yun Guan
Epidemiology and evidence have demonstrated that colon carcinoma is one of the most common gastrointestinal tumors in the clinic. Reports have suggested that Tunicamycin significantly inhibits aggressiveness of colon carcinoma cells by promotion of apoptosis. In the present study, the inhibitory effect of tunicamycin on colon cancer cells and the potential underlying molecular mechanism was investigated. Western blotting, immunohistochemistry, apoptotic assays and immunofluorescence were used to analyze the therapeutic effects of tunicamycin on apoptosis, growth, aggressiveness and cell cycle of colon tumor cells, by downregulation of fibronectin, vimentin and E‑cadherin expression levels...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344236/alterations-in-expression-levels-of-genes-in-p53-related-pathways-determined-using-rna-seq-analysis-in-patients-with-breast-cancer-following-cik-therapy
#5
Zuowei Hu, Xiaoye Zhang, Hang Yang, Shuanglai Qin, Yaqi Liu, Wei Xiong, Bing Yuan, Liping Li, Weiqi Yao, Dongcheng Wu
The present study aimed at investigating the underlying molecular mechanisms for patients following cytokine-induced killer (CIK) therapy, particularly involving the alterations in p53-associated signaling pathways, to elucidate whether CIK therapy serves a function in cancer treatment. Samples of blood were collected from patients with breast cancer prior to and following CIK therapy. Two group samples were used for RNA sequencing (RNA-Seq) to determine the alterations in gene expression levels following CIK therapy and one for the quantitative polymerase chain reaction (qPCR), to analyze the reliability of RNA-Seq results...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29337987/identification-of-a-noncanonical-function-for-ribose-5-phosphate-isomerase-a-promotes-colorectal-cancer-formation-by-stabilizing-and-activating-%C3%AE-catenin-via-a-novel-c-terminal-domain
#6
Yu-Ting Chou, Jeng-Kai Jiang, Muh-Hwa Yang, Jeng-Wei Lu, Hua-Kuo Lin, Horng-Dar Wang, Chiou-Hwa Yuh
Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5-phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80 patients' CRC tissues and paired nontumor tissues and protein levels, as well as a CRC tissue array, indicate RPIA is significantly elevated in CRC...
January 16, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29336624/potential-molecular-targets-in-the-treatment-of-lung-cancer-using-sirna-technology
#7
Habib Zarredar, Khalil Ansarin, Behzad Baradaran, Shiva Ahdi Khosroshahi, Safar Farajnia
Lung cancer is the leading cause of cancer-related mortality with about 1.6 million deaths every year worldwide. Gene mutations and overexpression of oncogenes play a central role in malignant transformation in NSCLC. Conventional approaches for treatments of NSCLC have shown low levels of success while showing severe side effects. Target therapy using siRNA has recently emerged as a new strategy for cancer treatment by specific targeting of genes involved in the development and metastasis of cancer. This article dedicated to an update review of molecular targets could potentially be used for target therapy of lung cancer using SiRNA technology...
January 16, 2018: Cancer Investigation
https://www.readbyqxmd.com/read/29330298/stemness-is-enhanced-in-gastric-cancer-by-a-set-pp2a-e2f1-axis
#8
Shuhei Enjoji, Ryotaro Yabe, Shunya Tsuji, Kazuhiro Yoshimura, Hideyoshi Kawasaki, Masashi Sakurai, Yusuke Sakai, Hiroko Takenouchi, Shigefumi Yoshino, Shoichi Hazama, Hiroaki Nagano, Hiroko Oshima, Masanobu Oshima, Michael P Vitek, Tetsuya Matsuura, Yoshitaka Hippo, Tatsuya Usui, Takashi Ohama, Koichi Sato
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possess the ability to self-renew and de-differentiate. These cancer stem cells are critical for initiation, maintenance, metastasis, and relapse of cancers; however, the molecular mechanisms supporting cancer stemness remain largely unknown...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29329585/involvement-of-hedgehog-pathway-in-early-onset-aggressive-molecular-subtypes-and-metastatic-potential-of-breast-cancer
#9
Syeda Kiran Riaz, Jahangir Sarwar Khan, Syed Tahir Abbas Shah, Fen Wang, Lin Ye, Wen G Jiang, Muhammad Faraz Arshad Malik
BACKGROUND: Dysregulation of hedgehog pathway is observed in numerous cancers. Relevance of hedgehog pathway genes in cancer cohort and inhibition of its downstream effector (GLI1) towards metastasis in cell lines are explored in the study. METHOD: One hundred fifty fresh tumours of breast cancer patients were collected for the study. Based on differential expression, panel of 6 key regulators of the pathway (SHH, DHH, IHH, PTCH1, SMO and GLI1) in microarray datasets were identified...
January 8, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29328475/heat-shock-protein-27-knockdown-using-nucleotide%C3%A2-based-therapies-enhances-sensitivity-to-5-fu-chemotherapy-in-sw480-human-colon-cancer-cells
#10
Takehiro Shimada, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Kohei Shigeta, Takashi Ishida, Yusuke Asada, Hirofumi Suzumura, Kaoru Koishikawa, Shingo Akimoto, Yuko Kitagawa
Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328417/microrna-129-5p-suppresses-cell-proliferation-migration-and-invasion-via-targeting-rock1-in-osteosarcoma
#11
Chaofan Han, Wenbo Wang
Osteosarcoma (OS) is the most common primary malignancy of the bone in teenagers and accounts for 20‑35% of all malignant primary bone tumors. Increasing evidence shows that microRNAs (miRNAs) are abnormally expressed in several types of human cancer. miRNAs are necessary to maintain the malignant phenotype of cancer cells and can function as either tumor suppressors or oncogenes. The present study aimed to measure the expression of miRNA‑129‑5p (miR‑129‑5p) in OS, determine the effects of miR‑129‑5p on the malignant behaviors of OS cells, and elucidate the molecular mechanism underlying the oncogenesis and progression of OS...
January 4, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29324317/tincr-suppresses-proliferation-and-invasion-through-regulating-mir-544a-fbxw7-axis-in-lung-cancer
#12
Xiaochun Liu, Jing Ma, Feng Xu, Li Li
BACKGROUND: Long noncoding RNAs (LncRNAs) play critical roles in multiple biological processes implicated in the development and progression of cancers. Terminal differentiation-induced lncRNA (TINCR) has been demonstrated to be associated with the carcinogenesis of several cancers. However, little is known about the function and mechanism of TINCR in lung cancer. METHODS: qRT-PCR was performed to measure the expression of TINCR, miR-544a or FBXW7 mRNA in lung cancer tissues or cells...
January 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29324312/the-hypoxia-responsive-long-non-coding-rnas-may-impact-on-the-tumor-biology-and-subsequent-management-of-breast-cancer
#13
REVIEW
Andrea Kapinova, Peter Kubatka, Pavol Zubor, Olga Golubnitschaja, Zuzana Dankova, Sona Uramova, Ivana Pilchova, Martin Caprnda, Radka Opatrilova, Jan Richnavsky, Peter Kruzliak, Jan Danko
Long non-coding RNAs (lncRNAs) are DNA transcripts longer than 200 nucleotides without protein-coding potential. As they are key regulators of gene expression at chromatic, transcriptional and posttranscriptional level, they play important role in various biological and pathological processes. Dysregulation of lncRNAs has been observed in several diseases including cancer. Breast cancer is heterogeneous disease with many molecular subtypes specific in different prognosis and treatment responses. Hypoxia, a common micro-environmental feature of rapidly growing tumour is associated with metastases, recurrences and resistance to therapy...
January 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29322783/micrornas-in-triple-negative-breast-cancer
#14
M Koleckova, M Janikova, Z Kolar
Triple-negative breast cancer (TNBC) is a molecular subtype of breast cancer with one of the worst prognoses. Current treatment is based on chemo- and/or radiotherapy and surgery. New targets, however, offering other therapeutic approaches, have been identified. These involve poly (ADP-ribose) polymerase (PARP), vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), androgen receptor (AR), long non-coding RNAs (lncRNAs) and microRNAs (miRs). The latter are non-coding RNAs which control the expression of more than 50% of human genes via regulation of basic cellular processes at post-transcriptional level and dysregulation of miRs is found in many types of tumors...
2018: Neoplasma
https://www.readbyqxmd.com/read/29321190/genomic-landscape-of-pancreatic-neuroendocrine-tumours-the-international-cancer-genome-consortium
#15
Andrea Mafficini, Aldo Scarpa
Neuroendocrine tumours (NETs) may arise throughout the body and are a highly heterogeneous, relatively rare class of neoplasms difficult to study also for the lack of disease models. Despite this, knowledge on their molecular alterations has expanded in the latest years, also building from genetic syndromes causing their onset. Pancreatic NETs (PanNETs) have been among the most studied, and research so far has outlined a series of recurring features, as inactivation of MEN1, VHL, TSC1/2 genes, and hyperactivation of the PI3K/mTOR pathway...
January 10, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29315726/single-cell-analysis-reveals-cancer-stem-cell-heterogeneity-in-hepatocellular-carcinoma
#16
Hongping Zheng, Yotsawat Pomyen, Maria Olga Hernandez, Caiyi Li, Ferenc Livak, Wei Tang, Hien Dang, Tim F Greten, Jeremy L Davis, Yongmei Zhao, Monika Mehta, Yelena Levin, Jyoti Shetty, Bao Tran, Anuradha Budhu, Xin Wei Wang
Intratumor molecular heterogeneity of hepatocellular carcinoma (HCC) is partly attributed to the presence of hepatic cancer stem cells (CSCs). Different CSC populations defined by various cell surface markers may contain different oncogenic drivers, posing a challenge in defining molecular-targeted therapeutics. We combined transcriptomic and functional analyses of HCC cells at the single cell level to assess the degree of CSC heterogeneity. We provide evidence that hepatic CSCs at the single-cell level are phenotypically, functionally and transcriptionally heterogeneous...
January 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29312563/trkb-promotes-laryngeal-cancer-metastasis-via-activation-pi3k-akt-pathway
#17
Liang Jiang, Zhihai Wang, Chuan Liu, Zhitao Gong, Yucheng Yang, Houyong Kang, Yanshi Li, Guohua Hu
Objectives: The aim of our study was to investigate the role of TrkB pathway in tumor occurrence and development for in order to provide theoretical basis to laryngeal cancer therapy. Materials and methods: Biological characteristics of the cells were studied by migration tests and colony forming assay. Gene and protein expression analysis was performed by RT-PCR or western blot. in vivo experiments were conducted in syngeneic BALB/c mice. Results: Significant changes in protein and gene expression, including higher expression level of TrkB, were found in cells and laryngeal cancer specimens...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29308745/polyphyllin-i-induces-cell-cycle-arrest-and-cell-apoptosis-in-human-retinoblastoma-y-79-cells-through-targeting-p53
#18
Xue Zhu, Ke Wang, Kai Zhang, Yi Pan, Fanfan Zhou, Ling Zhu
Retinoblastoma is the most common intraocular malignant tumor in childhood. Although external beam radiation and enucleation are effective to control retinoblastoma, eye salvage and vision preservation are still significant challenges. Polyphyllin I (PPI), a natural compound extracted from Paris polyphylla rhizomes, has a wide range of activities against many types of cancers. However, the potential effect of this herbal compound on retinoblastoma has not yet been investigated. In the present study, we evaluated the cytotoxic effect of PPI on human retinoblastoma Y-79 cells as well as its underlying molecular mechanism...
January 7, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29305191/decreased-cytoplasmic-x-box-binding-protein-1-expression-is-associated-with-poor-prognosis-and-overall-survival-in-patients-with-oral-squamous-cell-carcinoma
#19
Hui-Ting Hsu, Ming-Tai Hsing, Chung-Min Yeh, Chih-Jung Chen, Jia-Sin Yang, Kun-Tu Yeh
INTRODUCTION: Squamous cell carcinoma is the most common cancer of the oral cavity. In spite of advancements in surgical, chemoradiological and targeted therapies, these therapeutic strategies still have had little impact on survival rates. X-box binding protein-1 (XBP-1) is a potent transcription factor that is involved in the unfolded protein response (UPR) pathway, which itself is activated in response to endoplasmic reticulum stress as a method to restore cellular homeostasis. The role XBP-1 plays in oral squamous cell carcinoma (OSCC) has yet to be determined...
January 2, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29296874/crosstalk-between-ror1-and-bcr-pathways-defines-novel-treatment-strategies-in-mantle-cell-lymphoma
#20
Hanna Karvonen, David Chiron, Wilhelmiina Niininen, Sara Ek, Mats Jerkeman, Elaheh Moradi, Matti Nykter, Caroline A Heckman, Olli Kallioniemi, Astrid Murumägi, Daniela Ungureanu
Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin B-cell lymphoma with poor prognosis due to drug resistance. Introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib has markedly improved MCL therapy outcome, but drug resistance remains a challenge. The selective cell-surface expression of oncogenic receptor tyrosine kinase-like orphan receptor 1 (ROR1) pseudokinase in hematological malignancies has made this receptor a promising candidate for targeted therapy. We sought to identify the molecular mechanism underlying divergent ROR1-mediated apoptotic responses in MCL cell lines and primary samples...
November 14, 2017: Blood Advances
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