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   2017| May-June  | Volume 3 | Issue 3  
    Online since June 8, 2017

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Fish oil and prostate cancer: Effects and clinical relevance
Pei Liang, Michael Gao
May-June 2017, 3(3):80-86
Men who intake high ratios of fish oil or omega-3 fatty acids (FAs), especially docosahexaenoic acid and eicosapentaenoic acid, relative to omega-6 arachidonic acid have been found to have a decreased risk of prostate cancer compared to those with low ratios in some but not all case-control and cohort studies. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints regarding the association between omega-3 FA consumption and risk of prostate cancer are studded with controversial results. However, many clinical trials have shown that fish oil could decrease the risk of developing prostate cancer. The anticancer properties of anticancer drugs could be greatly improved when combined with fish oil. We briefly reviewed fish oil and relevant omega-3 FAs as well as early investigations in prostate cancer prevention and treatment.
  3,961 308 1
Stemness-related markers in cancer
Wenxiu Zhao, Yvonne Li, Xun Zhang
May-June 2017, 3(3):87-95
Cancer stem cells (CSCs), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute toward a “stemness” phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers, and signaling pathways.
  2,368 450 5
Autophagy regulated by miRNAs in colorectal cancer progression and resistance
Andrew Fesler, Hua Liu, Ning Wu, Fei Liu, Peixue Ling, Jingfang Ju
May-June 2017, 3(3):96-100
The catabolic process of autophagy is an essential cellular function that allows for the breakdown and recycling of cellular macromolecules. In recent years, the impact of epigenetic regulation of autophagy by noncoding miRNAs has been recognized in human cancer. In colorectal cancer, autophagy plays critical roles in cancer progression as well as resistance to chemotherapy, and recent evidence demonstrates that miRNAs are directly involved in mediating these functions. In this review, we focus on the recent advancements in the field of miRNA regulation of autophagy in colorectal cancer.
  2,168 256 6
Gastric metastases mimicking primary gastric cancer: A brief literature review
Simona Gurzu, Marius Alexandru Beleaua, Laura Banias, Ioan Jung
May-June 2017, 3(3):101-105
Gastric cancer is the fifth most common cancer worldwide, with most cases presenting in the form of primary tumors. In this paper, we performed a literature review on the incidence and particularities of extragastric metastases. These lesions are rare in clinical practice and can be misdiagnosed as primary undifferentiated gastric carcinomas as the differential diagnosis between primary and secondary malignancy is difficult to make. As per the literature, the most common malignancies which can present gastric metastases are lung cancer, followed by carcinoma of the breast, esophagus, kidney, and head and neck carcinomas. Malignant melanoma, ovarian cancer, prostate cancer, and adrenal gland carcinomas are rarely described as presenting metastases in the stomach. In most cases, the literature addressed poorly differentiated tumors with high-grade malignancy. The most common feature was the ulcerated tumor with depressed area, associated with identifiable extragastric tumor cells in the gastric submucosa. The linitis plastica-like feature is unusual and is more characteristic of breast lobular carcinoma. The accurate diagnosis of such rare extragastric metastatic cases depends on the appropriate clinical history and precise pathological diagnosis, which is mandatory for initiating the best therapeutic options.
  2,059 176 1
Novel molecular multilevel targeted antitumor agents
Poonam Sonawane, Young A Choi, Hetal Pandya, Denise M Herpai, Izabela Fokt, Waldemar Priebe, Waldemar Debinski
May-June 2017, 3(3):69-79
Aim: A multifunctional fusion protein, IL-13.E13K-D2-NLS, effectively recognizes glioblastoma (GBM) cells and delivers its portion to the cell nucleus. IL-13.E13K-D2-NLS is composed of a cancer cell targeting ligand (IL-13.E13K), specialized cytosol translocation bacterial toxin domain 2 of Pseudomonas exotoxin A (D2) and SV40 Tantigen nuclear localization signal (NLS). We have now tested whether we can produce proteins that would serve as a delivery vehicle to lysosomes and mitochondria as well. Moreover, we examined whether IL-13.E13K-D2-NLS can deliver anticancer drugs like doxorubicin to their nuclear site of action in cancer cells. Methods: We have thus constructed two novel proteins: IL-13.E13K-D2-LLS which incorporates lysosomal localization signal (LLS) of a human lysosomal-associated membrane protein 1 (LAMP-1) for targeting to lysosomes and IL-13-D2-KK2, which incorporates a pro-apoptotic peptide (KLAKLAK)2 (KK2) exerting its action in mitochondria. Furthermore, we have produced IL-13.E13K-D2-NLS and IL-13.E13K-D2-LLS versions containing a cysteine for site-specific conjugation with a modified doxorubicin, WP936. Results: We found that single-chain recombinant proteins IL-13.E13K-D2-LLS and IL-13-D2-KK2 are internalized and localized mostly to the lysosomal and mitochondrial compartments, respectively, without major trafficking to cells' nuclei. We also determined that IL-13.E13K-D2-NLS-cys[WP936], IL-13.E13K-D2-LAMP-cys[WP936], and IL-13-D2-KK2 were cytotoxic to GBM cells overexpressing interleukin 13 receptor alpha 2, while much less cytotoxic to GBM cell lines expressing low levels of the receptor. IL-13.E13K-D2-NLS-cys[WP936] was the most potent of the tested antitumor agents including free WP936. Conclusion: We believe that our receptor-directed intracellular organelle-targeted proteins can be employed for numerous specific and safer treatment applications when drugs have specific intracellular sites of their action.
  1,818 276 5
Possibility of specific expression of the protein toxins at the tumor site with tumor-specialized promoter
Liyuan Zhou, Yujun Li, Changchen Hu, Binquan Wang
May-June 2017, 3(3):106-108
The ultimate goal of cancer therapy is to establish a treatment regimen that will ensure complete eradication of cancers with minimal toxicity to the surrounding normal tissues. Protein toxins are highly efficient when they are used as treatment reagents of cancer but are associated with toxicity in normal tissues. Given that specialized promoters have been widely investigated for specific expressions, we speculated that tumor-specialized promoters would play an important role in protein toxin tumor therapy. Therefore, we hypothesize that a tumor-specialized promoter can be inserted into a truncated protein toxin expression vector. Then, the vector can be introduced into the human body by either a viral or nonviral vector. These protein toxin genes would be specifically expressed in tumor cells, but not in normal tissue cells. The proposition may provide a new strategy with the development of protein toxins for specific targeting to neoplastic tumors.
  1,323 104 -