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  • ISSN: 2373-9436
    Volume 3, Issue 1
    Short Communication
    Richard A. Bennett1*, Elizabeth Behrens1 andThomas J. Lamkin2
    Abstract: Mustard gas has been used as a chemical weapon since 1917 during World War I. Since then, many reports have shown that survivors of attacks and those who make mustard gas exhibit a higher incidence of cancer than the normal population. We have recently shown that centrosomes may play a role in mustard gas-induced cancers since the mustard gas surrogate 2-chloroethyl ethylsulfide (2-CEES) increases centrosome amplification (more than two centrosomes per cell) in the Saos2 cell line (human osteosarcoma). To begin to delineate some of the mechanisms that might regulate 2-CEES-induced centrosome amplification, we exposed Saos2 cells to the antioxidants Trolox and glutathione (GSH) and 2-CEES in various combinations for 24 hours. We show that Trolox has a minimal effect on inhibiting centrosome amplification, whereas glutathione prevented 2-CEES-induced centrosome amplification below control levels. These data provide insight as to how 2-CEES can induce centrosome amplification, but whether or not that is more related to protein, lipid, or DNA damage is yet to be determined and should be investigated.
    Sherman Silber* and Christina Usher
    Abstract: Freezing of eggs or ovarian tissue to preserve fertility for cancer patients has been studied since 1994 with Gosden's original paper in sheep, and before that in smaller mammals for decades prior. Clinically, this tactic has enjoyed great success. Despite the rising popularity of vitrification for egg freezing, it is often done incorrectly, forgetting the original principles Kuwayama established in 2005. So there will be many disappointed patients around the world whose egg freezing was not done well. Greater care to very gradual osmotic shifts and "open" super rapid freeze and thaw will be required to make egg freezing with vitrification more reliable. Many healthy children have been born from the Kuwayama egg vitrification technique for social indications, but until now very few cancer patients have yet to get pregnant from frozen eggs for several reasons. Often, oncologists do not wish to delay cancer treatment while the patient goes through multiple stimulation cycles to retrieve eggs, and the patient can only start using the oocytes after full recovery. Furthermore, egg vitrification is much more sensitive to error than ovary tissue freezing. However, over 40 healthy babies so far have been born from ovary tissue freezing for cancer patients and have had complete return of hormonal function, as well as fertility. Therefore both egg freezing and ovarian tissue freezing seem now to be ready to be applied to preserving fertility for cancer as well as for reasons other than cancer. But you must get the technique right.
    Review Article
    Malgorzata Klauzinska, Nadia P. Castro, M. Cristina Rangel, Daniel C. Bertolette and David Salomon*
    Abstract: Cripto-1 (TDGF-1) is a cell surface glycosylphosphatidylinositol-linked glycoprotein which functions as an obligatory co-receptor for transforming growth factor-β (TGF-β) family members. Cripto-1 is essential for early embryonic development and maintenance of embryonic stem cells. Cripto-1 has been shown to be activated in numerous human tumors. Notably, it is expressed in a population of cancer stem cells (CSCs) and facilitates the epithelial to mesenchymal transition (EMT) program. Furthermore, Cripto-1 can significantly enhance tumor cell migration, invasion and angiogenesis. Collectively, these facts suggest that Cripto-1 may be an attractive target in the diagnosis, prognosis and therapy aiming at cancer cell subpopulations with stem-like properties within aggressive tumors.
    Ernst Fredericks*, Gill Dealtry and Saartjie Roux
    Abstract: Colon cancer is a common malignancy associated with significant mortality. Colon carcinogenesis generally occurs in a slow and stepwise process of accumulating mutations under the influence of genetic and environmental factors, the so-called adenoma-carcinoma sequence. The cellular origin of human cancer remains controversial and the mechanisms responsible for the complexity and heterogeneity of this condition remains undefined. Despite identification of genetic mutations and aberrant signaling pathways, little clinical benefit in terms of early diagnosis or treatment of advanced disease have been attained. Many reviews have analyzed genetic mutations and molecular signaling abnormalities, but the process of carcinogenesis is incompletely understood. Adenomatous polyposis coli (APC), a tumor suppressor gene, play a central role in colorectal carcinogenesis through the wnt/β-catenin signaling pathway. Recent data suggests that peroxisome proliferator-activated receptor (PPAR) γ, a nuclear receptor, is important in cell differentiation protecting against carcinogenesis. COX-2 mRNA and protein are up-regulated in colorectal cancer, suggesting a possible role in the carcinogenic process. These three are the main known molecules involved in early colorectal carcinogenesis, although their respective interactions in this role have been poorly documented. In this review, we analyze the roles and relationships of these molecules and their interactions. We also evaluate the roles of genetic and epigenetic modifications on colorectal carcinogenesis, as well as the role of micro RNAs. Finally, we assess the impact of the gut microbiome and diet on this complex process.
    Madhu Kalia*
    Abstract: Colorectal cancer (CRC) which affects over one million individuals annually [1] has recently seen an increased interest in identifying biomarkers and new treatment strategies. This has resulted in a significant rise in the median overall survival of CRC from 6 to 24 months [2]. Standard treatment for CRC has progressed from 5-fluroruracil monotherapy to combination chemotherapy (5-flurouracil and irinotecan and/or oxaliplatin) and more recently to biological agents targeted at angiogenesis and the epidermal growth factor receptor (EGFR). The monoclonal EGFR antibodies, cetuximab and panitumumab have been shown to be effective in 10-15% of metastatic CRC patients. Patients who do not benefit from cetuximab or panitumumab have a K-RAS mutation at codon12. However patients with a K-RAS mutation at codon 13 (i.e. G13D) do respond positively to EGFR antibody therapy. Therefore it is recommended that the mutational status of K-RAS should be assessed in every CRC patient prior to initiating treatment with EGFR antibodies [2]. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation technologies make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of CRC oncotherapy and are successfully being used to evaluate benefits that can be achieved through molecularly targeted biomarker therapies (tyrosine kinase inhibitors). Prognostic biomarkers are useful in identifying somatic germ line mutations in CRC. This review discusses the current status of research on biomarkers for CRC and summarizes data on emerging therapeutic targets and emerging validated predictive biomarkers for CRC [3-5].
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