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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Downregulation of survivin by adenovirus-mediated shRNA promotes apoptosis in skin cancer cells

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          Abstract

          Background

          Survivin, a member of the inhibitor of apoptosis protein family, is highly expressed in many cancers and has important roles in inhibiting apoptosis by blocking caspase activation. However, its antitumor effects remain largely unknown. Here we explore the function of survivin in skin cancer.

          Methods

          We used qPCR and Western blot to examine survivin expression in skin cancer patients and cell line. We generated several survivin shRNA constructs and tested the effects of survivin shRNA on cancer cell viability using MTT assay, flow cytometry, and TUNEL assay.

          Results

          We found that survivin was upregulated in both skin cancer patients and skin cancer cell line A431. Knockdown survivin via shRNA inhibited cancer cell proliferation and promoted apoptosis in both A431 cell and in vivo xenograft tumor mouse model. The antitumor effect is comparable to resveratrol, a drug known to inhibit cancer progression. Moreover, we showed that inhibition of survivin was able to increase the expression of cleaved caspase 7/caspase 9 and activate the ataxia-telangiectasia mutated-NF-κB pathway in A431 cells.

          Conclusion

          Survivin-shRNA possesses antitumor abilities in vitro and in vivo by inhibiting the proliferation and promoting apoptosis of A431 cells. It may serve as a potential anticancer target for skin cancer therapy in the future.

          Most cited references22

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          A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma.

          Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy. Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma.
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            Resveratrol and cancer: focus on in vivo evidence

            Resveratrol is a naturally occurring polyphenol that provides a number of anti-aging health benefits including improved metabolism, cardioprotection, and cancer prevention. Much of the work on resveratrol and cancer comes from in vitro studies looking at resveratrol actions on cancer cells and pathways. There are, however, comparatively fewer studies that have investigated resveratrol treatment and cancer outcomes in vivo, perhaps limited by its poor bioavailability when taken orally. Although research in cell culture has shown promising and positive effects of resveratrol, evidence from rodents and humans is inconsistent. This review highlights the in vivo effects of resveratrol treatment on breast, colorectal, liver, pancreatic, and prostate cancers. Resveratrol supplementation in animal models of cancer has shown positive, neutral as well as negative outcomes depending on resveratrol route of administration, dose, tumor model, species, and other factors. Within a specific cancer type, there is variability between studies with respect to strain, age, and sex of animal used, timing and method of resveratrol supplementation, and dose of resveratrol used to study cancer endpoints. Together, the data suggest that many factors need to be considered before resveratrol can be used for human cancer prevention or therapy.
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              Cutaneous Squamous Cell Carcinoma: A Review of High-Risk and Metastatic Disease.

              Non-melanoma skin cancer represents one-third of all malignancies and its incidence is expected to rise until the year 2040. Cutaneous squamous cell carcinoma (cSCC) represents 20 % of all non-melanoma skin cancer and is a deadly threat owing to its ability to metastasize to any organ in the body. Therefore, a better understanding of cSCC is essential to strengthen preventative measures and curable treatment options. Currently, research demonstrates that cSCC is diagnosed at a rate of 15-35 per 100,000 people and is expected to increase 2-4 % per year. With respect to metastatic cSCC, this disease is more common in men; people over the age of 75 years; and inhabitants of the south and mid-west USA. In 2010, the American Joint Committee on Cancer updated the Cancer Staging Manual's primary tumor designation to now include high-risk factors; however, factors such as immunosuppression and tumor recurrence were not included. Other staging systems such as Brigham and Women's Hospital have allowed for increased stratification of cSCC. High-risk cSCC is defined as a cSCC that is staged as N0, extends beyond basement membrane, and has high-risk features associated with sub-clinical metastasis. High-risk features are depth of invasion (>2 mm), poor histological differentiation, high-risk anatomic location (face, ear, pre/post auricular, genitalia, hands, and feet), perineural involvement, recurrence, multiple cSCC tumors, and immunosuppression. Epidermal growth factor receptor and nuclear active IκB kinase (IKK) expression are also predictive of metastatic capabilities. Clinically, the initial lesions of a cSCC tumor can present as a painless plaque-like or verrucous tumor that can ultimately progress to being large, necrotic, and infected. Tumors can also present with paresthesias or lymphadenopathy depending on the location involved. With respect to prognosis, metastatic cSCC is lethal, with several large studies demonstrating a mortality rate of >70 %. Therefore, treatment of metastatic cSCC is difficult and depends on the location involved and extent of metastasis. Treatment options include surgery, radiation therapy, chemotherapy, and any combination of the above. Surgery alone can be used for metastatic cSCC treatment, but is not as effective as surgery in conjunction with radiation therapy. Radiation therapy has some success as a monotherapy in low-risk or cosmetically sensitive areas such as the external ear, eyelid or nose. According to the 2013 National Comprehensive Cancer Network Guidelines, cisplatin as a single agent or combined with 5-fluorouracil hold the strongest support for the treatment of metastatic cSCC; however, the supporting evidence is inconsistent and a curative chemotherapeutic approach is still lacking. Epidermal growth factor receptor inhibitors are a newer class of agents being used in metastatic cSCC and hold some promise as a therapy for this disease. Other areas of interest in finding curative treatments for metastatic cSCC include p53, hypermethylation of specific genes, chromatin remodeling genes, and the RAS/RTK/PI3K pathway. This review addresses the epidemiology, staging, risk factors, clinical presentation, management, and new trends in the treatment of high-risk and metastatic cSCC.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2019
                17 April 2019
                : 12
                : 2921-2930
                Affiliations
                [1 ]Department of Dermatology, Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, 014010, People’s Republic of China
                [2 ]Department of Pathology, Baotou Cancer Hospital, Baotou, 014030, People’s Republic of China
                [3 ]Inner Mongolia Medical University, Hohhot, 010000, People’s Republic of China, lizhehai8870@ 123456126.com
                [4 ]Hunan Youcheng Biotechnology Co. Ltd, Changsha, 410000, People’s Republic of China
                [5 ]Department of Orthopedics, Beijing Northern Hospital, China North Industries, Beijing, 100089, People’s Republic of China, lizhehai8870@ 123456126.com
                Author notes
                Correspondence: Zhehai Li, Department of Orthopedics, Beijing Northern Hospital, China North Industries, Beijing, 100089, People’s Republic of China, Tel +86 186 4721 7599, Email lizhehai8870@ 123456126.com
                Article
                ott-12-2921
                10.2147/OTT.S162150
                6475095
                52a383df-8a8e-4108-9c55-19b7106a7947
                © 2019 Hao et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                survivin,skin cancer,apoptosis,nf-κb,caspases 7/9
                Oncology & Radiotherapy
                survivin, skin cancer, apoptosis, nf-κb, caspases 7/9

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