Oncomedicine最新文献

{"title":"Telomere and Its Role in Diseases","authors":"Stephanie W. Wang, Chikezie O Madu, Yi Lu","doi":"10.7150/ONCM.28210","DOIUrl":"https://doi.org/10.7150/ONCM.28210","url":null,"abstract":"Telomeres are highly conservative repeated nucleotide sequences at the ends of linear chromosomes. Allowing effective DNA replication to keep the integrity of gene structure and the stability of chromosomes, telomeres protect the ends of the chromosome from deterioration or from fusion with neighboring chromosomes. Reduction in the telomere length leads to the cessation of cell division and thus cellular senescence. On the other hand, telomerase is a ribonucleoprotein complex with reverse transcriptase activity, protecting the telomere from being shortened. Thus, it is inactivated by synthesis and adds the repeated sequences onto the telomeres. Telomerase plays an important role in cell senescence and tumor formation. Telomere length and telomerase activity may be mediated by immune, endocrine, and metabolic pathways and accelerate cellular dysfunction, ageing, and even induce cancer over one’s lifespan. Significant attainment of telomerase to maintain telomere length could stop the cell senescence and aging related disease and also is required for the evolution of malignancy. This review discusses the role of telomeres and telomerase in humans during senescence and cancer. The evidence indicates that telomerase-induced telomere length manipulations could be targeted for anti-aging and anti-cancer therapy in the future.","PeriodicalId":91781,"journal":{"name":"Oncomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.7150/ONCM.28210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71121132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Duel” and “Duet”: The Paradox of Carcinogenic Viruses and Targeted Virotherapeutics","authors":"A. Challa, Chikezie O Madu, Yi Lu","doi":"10.7150/oncm.34897","DOIUrl":"https://doi.org/10.7150/oncm.34897","url":null,"abstract":"","PeriodicalId":91781,"journal":{"name":"Oncomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71121197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Functional Role of Bcl-2 Family of Proteins in the Immune System and Cancer","authors":"Aileen Chen, Chikezie O Madu, Yi Lu","doi":"10.7150/oncm.27020","DOIUrl":"https://doi.org/10.7150/oncm.27020","url":null,"abstract":"The Bcl-2 family of proteins plays a significant role in regulating the cell cycle. It plays a crucial role in regulating homeostasis by helping to maintain proper cell number and eliminating potentially malignant cells. The cell achieves the delicate balance through apoptosis or programmed cell death. The Bcl proteins are involved in the intrinsic apoptotic pathway, which is especially important in the development of the immune system. Apoptosis is involved in proper positive and negative selection during the development of Band T-cells. The detection of any gene of the Bcl-2 family often results in the abnormal development of lymphocytes. The balance of pro-apoptotic proteins versus anti-apoptotic proteins, which operate at the organelle level, determines if the lymphocyte proliferates normally or abnormally. A critical tumor suppressor is the ability of cells to self-disrupt and undergoes cell death through apoptosis. Cooperation between cells is essential; without the ability to respond to external stimuli, cells lose the ability to respond correctly to developmental cues. Cells that evade apoptosis have a greater potential to become malignant because they are unregulated and do not respond correctly to external signals. The overexpression of the pro-survival (anti-apoptotic) proteins of the Bcl-2 family induces the cell to not respond to an external signal, prolonging cell survival and increasing the chance of becoming malignant.","PeriodicalId":91781,"journal":{"name":"Oncomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.7150/oncm.27020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71121118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological profile of female breast cancer in reproductive age-group and its association with maternal characteristics: -A population-based observational study in India","authors":"P. Vanamail","doi":"10.7150/oncm.32297","DOIUrl":"https://doi.org/10.7150/oncm.32297","url":null,"abstract":"Purpose: Even though the cancer incidence rate in India is lower than in developed countries, the mortality rate among cancer patients stood at 50%. Further, India topped the list for mortality of breast and cervical cancers. In this scenario studying the epidemiological profile of women-based breast cancer among the reproductive age group (15-49 years) and determination of risk causes remains unknown. Methods: Breast cancer data from 27 centres of the National Cancer Registry Programme in India during 2012-2014, provided the age-standardised incidence rate per 100,000 population and comparative incidence ratio (CIR) for different regions. Using all possible risk causes got from National Family Health Survey-4 report as covariates, Poisson regression model on cases provided incidence risk ratio (IRR) with 95% confidence interval (CI). Results: Around 8.33 (14.2% of the population) crores females under surveillances formed into six regions based on the geographical location of each centre. Overall breast cancer incidence rate was 22.72 (CI: 22.41-23.04) and varied between 10.46 in the North-eastern region and 33.86 in North region. About 40% of breast cancers formed in the reproductive age group and incidence rate was 16.5 (CI: 16.116.8). For women using IUD or with blood sugar more than 160 mg/dl, IRR was 1.06 (CI: 1.04 -1.08) and 1.19 (CI: 1.11-1.28) respectively. Women with unmet need for spacing or with higher empowerment index were likely to be at lower risk. IRR for these two types of women was 0.97 (CI: 0.96 – 0.98) and 0.17 (CI: 0.10-0.28) respectively. Conclusion: Population-based observational study from India, which contributes about 18% of the total world population revealed that IUD usage and high blood sugar are significant risk factors. On the other hand, higher empowerment index emerged as a significant protective factor. Therefore, by approving the women for their health status and creating awareness using existing mobile-based social media such as WhatsApp, Facebook and Twitter on the importance of early detection followed by treatment, the chances of reducing maternal mortality associated with breast cancer will be possible.","PeriodicalId":91781,"journal":{"name":"Oncomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.7150/oncm.32297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71121181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Delivery of a Novel Conjugate Nef-M1 Peptide and Single-Walled Carbon Nanotubes promotes Growth Inhibition and Mortality for Breast and Colon Tumorspheres","authors":"H. Bumpers, J. Goud, U. Manne, V. Katkoori","doi":"10.7150/ONCM.30990","DOIUrl":"https://doi.org/10.7150/ONCM.30990","url":null,"abstract":"The Nef-M1 peptide (Nef-M1) has been shown to be an inhibitor of growth and metastasis of breast cancer (BC) and colorectal cancer (CRC) cells. Since a nano-construct for Nef-M1 could enhance its efficacy, we developed three-dimensional (3-D) cultures of tumorspheres of BC and CRC cells and treated them with functionalized, single-walled carbon nanotubes (SWNTs) conjugated with Nef-M1 (SWNTs-Nef-M1) to evaluate inhibition of cell growth. We hypothesized that cancer cells cultured as tumorspheres would be more sensitive to SWNTs-Nef-M1 than to Nef-M1 alone. 3-D cultures of human BC cells (MDA-MB-231 and MDA-MB-468) and CRC cells (SW480) were developed with 1% Sea Prep Hydrogel in supplemented RPMI-1640 medium. SWNTs-Nef-M1 was prepared by use of thionine, and its structure was confirmed by ultraviolet (UV) spectral analysis and gel electrophoresis. The tumorspheres were treated with Nef-M1 or SWNTs-Nef-M1 to compare their relative effects. Internalization of SWNTs-Nef-M1 was evaluated by transmission electron microscopy. The viability/apoptosis status of the tumorspheres was established by use of ethidium bromide and acridine orange staining using fluorescent microscopy. Gel electrophoresis and UV spectral analysis confirmed formation of the SWNTs-Nef-M1 conjugate. After 3 weeks, 3-D cultures of BC and CRC cells developed as tumorspheres, which, in the presence of Nef-M1, showed reduced growth and increased apoptosis. This effect was greater in the presence of SWNTs-Nef-M1, consistent with enhanced delivery of Nef-M1 to the cells via SWNTs. This sets the stage for more detailed evaluation to quantify apoptosis and elaboration of the mechanism of increased apoptotic activity. Delivery of an apoptotic peptide, Nef-M1, into 3-D cultures of BC and CRC cells was achieved via a nanoparticle construct with SWNTs. Furthermore, compared to Nef-M1, SWNTs-Nef-M1 suggests more extensive apoptosis.","PeriodicalId":91781,"journal":{"name":"Oncomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71121171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stressed Out - Therapeutic Implications of ER Stress Related Cancer Research.","authors":"Randal Riha,&nbsp;Pooja Gupta-Saraf,&nbsp;Payel Bhanja,&nbsp;Samyak Badkul,&nbsp;Subhrajit Saha","doi":"10.7150/oncm.22477","DOIUrl":"https://doi.org/10.7150/oncm.22477","url":null,"abstract":"<p><p>The unfolded protein response (UPR) is an established and well-studied cellular response to the stress and serves to relieve the stress and reinstate cellular homeostasis. It occurs in the endoplasmic reticulum (ER), responsible of properly folding and processing of secretory and transmembrane proteins. It is extremely sensitive to alteration in homeostasis caused by various internal or external stressors which leads to accumulation of misfolded or unfolded proteins in the ER lumen. The UPR works by restoring protein homeostasis in the ER, either through the boosting of protein-folding and degradation capability or by assuaging the demands for such effects, and can cause the activation of cell death if unable to do so. Cancer cells have adapted to gain advantage from the UPR and keeping the cell away from apoptosis and promoting survival, including survival of the cancer stem cells and evading the immune system. Several components of the UPR are overexpressed in a malignant cell and are responsible for resistance from various chemotherapy options and radiotherapy, which are also responsible for causing ER stress and activating the UPR. In this review, we discuss the various ways in which UPR can aid different cancers to survive and evade therapy and highlight recent research, which exploits the UPR to confer sensitivity to these cancer cells against various drugs and radiation.</p>","PeriodicalId":91781,"journal":{"name":"Oncomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.7150/oncm.22477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35832823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Remotely Triggered Liposomes to Target Triple Negative Breast Cancer","authors":"A. Sneider, Rahul Jadia, B. Piel, D. VanDyke, C. Tsiros, P. Rai","doi":"10.7150/oncm.17406","DOIUrl":"https://doi.org/10.7150/oncm.17406","url":null,"abstract":"Triple Negative Breast Cancer (TNBC) continues to present a challenge in the clinic, as there is still no approved targeted therapy. TNBC is the worst sub-type of breast cancer in terms of prognosis and exhibits a deficiency in estrogen, progesterone, and human epidermal growth factor 2 (HER2) receptors. One possible option for the treatment of TNBC is chemotherapy. The issue with many chemotherapy drugs is that their effectiveness is diminished due to poor water solubility, and the method of administration directly or with a co-solvent intravenously can lead to an increase in toxicity. The issues of drug solubility can be avoided by using liposomes as a drug delivery carrier. Liposomes are engineered, biological nanoconstructs that possess the ability to encapsulate both hydrophobic and hydrophilic drugs and have been clinically approved to treat cancer. Specific targeting of cancer cell receptors through the use of ligands conjugated to the surface of drug-loaded liposomes could lessen damage to normal, healthy tissue. This study focuses on polyethylene glycol (PEG)-coated, folate conjugated, benzoporphyrin derivative (BPD)-loaded liposomes for treatment via photodynamic therapy (PDT). The folate receptor is over expressed on TNBC cells so these liposomes are targeted for greater uptake into cancer cells. PDT involves remotely irradiating light at 690 nm to trigger BPD, a hydrophobic photosensitive drug, to form reactive oxygen species that cause tumor cell death. BPD also displays a fluorescence signal when excited by light making it possible to image the fluorescence prior to PDT and for theranostics. In this study, free BPD, non-targeted and folate-targeted PEGylated BPD-loaded liposomes were introduced to a metastatic breast cancer cell line (MDA-MB-231) in vitro. The liposomes were reproducibly synthesized and characterized for size, polydispersity index (PDI), zeta potential, stability, and BPD release kinetics. Folate competition tests, fluorescence confocal imaging, and MTT assay were used to observe and quantify targeting effectiveness. The toxicity of BPD before and after PDT in monolayer and 3D in vitro cultures with TNBC cells was observed. This study may contribute to a novel nanoparticle-mediated approach to target TNBC using PDT.","PeriodicalId":91781,"journal":{"name":"Oncomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.7150/oncm.17406","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48550312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}