Journal of Cancer Therapy最新文献

{"title":"CXCL12 Retargeting of an Oncolytic Adenovirus Vector to the Chemokine CXCR4 and CXCR7 Receptors in Breast Cancer.","authors":"Samia M O'Bryan,&nbsp;J Michael Mathis","doi":"10.4236/jct.2021.126029","DOIUrl":"https://doi.org/10.4236/jct.2021.126029","url":null,"abstract":"<p><p>Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant progress has been made in developing targeted therapies for breast cancer, advanced breast cancer continues to have high mortality, with poor 5-year survival rates. Thus, current therapies are insufficient in treating advanced stages of breast cancer; new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We showed that the modified virus targets and infects CXCR4- and CXCR7-overexpressing breast cancer cells more efficiently than a wild-type control vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the results of this study demonstrate the feasibility of retargeting adenovirus vectors to chemokine receptor-positive tumors.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"12 6","pages":"311-336"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225250/pdf/nihms-1705011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39113223","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":"Young Child-Rearing Latina Cancer Survivors Living in the US-Mexico Border Region: A Qualitative Study.","authors":"Clara L Reyes,&nbsp;Rebecca L Palacios,&nbsp;Karoline Sondgeroth,&nbsp;Ernesto A Moralez","doi":"10.4236/jct.2021.124018","DOIUrl":"https://doi.org/10.4236/jct.2021.124018","url":null,"abstract":"<p><strong>Background: </strong>Despite increasing cancer incidence among young Latinas (<50 yrs.) in the US, little is known about how young, child-rearing Latinas cope with cancer in the US-Mexico border region.</p><p><strong>Objective: </strong>The purpose of this study was to explore how young, child-rearing Latinas described their challenges, strengths, and social support sources for coping with cancer in the US-Mexico border region.</p><p><strong>Methods: </strong>Nine Latinas that had been diagnosed with cancer, had at least one child 5 to 13 years old, and lived in one of two targeted border counties participated in audio-recorded, semi-structured focus groups (n = 6) or interviews (n = 3) in their preferred language (<i>i.e.</i>, English or Spanish). Interview recordings were transcribed and inductively coded using methods based on grounded theory.</p><p><strong>Results: </strong>Three major themes emerged. First, in reporting their physical and emotional struggles with cancer as the most difficult time of their lives, participants described feeling alone as they navigated treatment side effects and continued fear of cancer. Second, they explained figuring out how to live day-by-day, reporting the negative impact of cancer on their families and on their ability to maintain their roles as mothers. Third, they highlighted factors that gave them the strength to fight and carry on, emphasizing their children and their inner strength.</p><p><strong>Conclusions: </strong>Even with a supportive family, young Latina mothers felt alone as they navigated cancer (<i>i.e.</i>, treatment, fear, and impact on their families) and as they worked to garner the strength to overcome the stress of cancer. Interventions for young Latina survivors should be designed to address their needs, build on their fighting spirit, incorporate the family, and connect them with other survivors for personalized support. Further research is warranted to better understand cancer survivorship among child-rearing Latina mothers experiencing a cancer diagnosis in under-resourced communities like the US-Mexico border region.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"12 4","pages":"174-185"},"PeriodicalIF":0.0,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39963619","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":"Characterization of Exosomes in Plasma of Patients with Breast, Ovarian, Prostate, Hepatic, Gastric, Colon, and Pancreatic Cancers.","authors":"Ming-Bo Huang,&nbsp;Meng Xia,&nbsp;Zhao Gao,&nbsp;Hu Zhou,&nbsp;Min Liu,&nbsp;Shan Huang,&nbsp;Rong Zhen,&nbsp;Jennifer Y Wu,&nbsp;William W Roth,&nbsp;Vincent C Bond,&nbsp;Jian Xiao,&nbsp;Jing Leng","doi":"10.4236/jct.2019.105032","DOIUrl":"https://doi.org/10.4236/jct.2019.105032","url":null,"abstract":"<p><p>Detection of circulating tumor-specific DNA, RNA or proteins can be difficult due to relative scarcity. Exosomes are extracellular vesicles, 30 - 150 nm in diameter derived from fusion of multivesicular bodies with the plasma membrane. They are composed of a lipid bilayer membrane and contain proteins, mRNA and miRNA. Exosomes are secreted by multiple cell types, including cancer cells. However, there is a relative lack of information concerning the contents of exosomes secreted by various tumor cell types. To examine exosomes in cancer, we collected blood plasma samples from patients with breast, ovarian, prostate, hepatic, gastric, colon, and pancreatic cancers. Exosomes were isolated from plasma and confirmed by AchE assay, transmission electron microscopy and expression of the CD63 exosomal marker. Expression of AFP, CA724, CA153, CEA, CA125, CA199 and PSA antigens were determined using an automated electro-chemiluminescence assay. Expression of the tumor-related chaperone protein, mortalin, was determined by Western blot analysis. Levels of exosome secretion were variable among the different tumor types. Both exosome levels and mortalin expression within tumor cell exosomes were higher than in healthy donors, except in pancreatic carcinoma, where exosomes were elevated but mortalin expression was not significantly different from healthy donors. Exosomes provide unique opportunities for the enrichment of tumor-specific materials and may be useful as biomarkers and possibly as tools of cancer therapies. Mortalin, which has been linked to cell proliferation and induction of epithelial-mesenchymal transition of cancer cells, may be useful as a prognostic bio-marker and as a possible therapeutic target.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"10 5","pages":"382-399"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10641315","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":"Confounders in Adenoma Detection at Initial Screening Colonoscopy: A Factor in the Assessment of Racial Disparities as a Risk for Colon Cancer.","authors":"Yakira David,&nbsp;Lorenzo Ottaviano,&nbsp;Jihye Park,&nbsp;Sadat Iqbal,&nbsp;Michelle Likhtshteyn,&nbsp;Samir Kumar,&nbsp;Helen Lyo,&nbsp;Ayanna E Lewis,&nbsp;Brandon E Lung,&nbsp;Jesse T Frye,&nbsp;Li Huang,&nbsp;Ellen Li,&nbsp;Jie Yang,&nbsp;Laura Martello,&nbsp;Shivakumar Vignesh,&nbsp;Joshua D Miller,&nbsp;Michele Follen,&nbsp;Evan B Grossman","doi":"10.4236/jct.2019.104022","DOIUrl":"https://doi.org/10.4236/jct.2019.104022","url":null,"abstract":"<p><strong>Background and aims: </strong>The incidence and mortality of colorectal cancer is persistently highest in Black/African-Americans in the United States. While access to care, barriers to screening, and poverty might explain these findings, there is increased interest in examining biological factors that impact the colonic environment. Our group is examining biologic factors that contribute to disparities in development of adenomas prospectively. In preparation for this and to characterize a potential patient population, we conducted a retrospective review of initial screening colonoscopies in a cohort of patients.</p><p><strong>Methods: </strong>A retrospective review was performed on initial average risk screening colonoscopies on patients (age 45-75 years) during 2012 at three institutions. Descriptive statistics and multivariable logistic regression models were used to examine the relationship between potential risk factors and the detection of adenomas.</p><p><strong>Results: </strong>Of the 2225 initial screening colonoscopies 1495 (67.2%) were performed on Black/African-Americans and 566 (25.4%) on Caucasians. Multivariable logistic regression revealed that older age, male sex, current smoking and teaching gastroenterologists were associated with higher detection of adenomas and these were less prevalent among Black/African-Americas except for age. Neither race, ethnicity, BMI, diabetes mellitus, HIV nor insurance were associated with adenoma detection.</p><p><strong>Conclusion: </strong>In this sample, there was no association between race and adenoma detection. While this may be due to a lower prevalence of risk factors for adenomas in this sample, our findings were confounded by a lower detection rate by consultant gastroenterologists at one institution. The study allowed us to rectify the problem and characterize patients for future trials.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"10 4","pages":"269-289"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482964/pdf/nihms-1023684.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37369115","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":"Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy.","authors":"Xiaonan Liu,&nbsp;Jing Li,&nbsp;Steven E Schild,&nbsp;Michael H Schild,&nbsp;William Wong,&nbsp;Sujay Vora,&nbsp;Michael G Herman,&nbsp;Mirek Fatyga","doi":"10.4236/jct.2017.82007","DOIUrl":"https://doi.org/10.4236/jct.2017.82007","url":null,"abstract":"<p><strong>Background: </strong>A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy.</p><p><strong>Methods: </strong>Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univa-riate and multivariate linear regression on log PSA values.</p><p><strong>Results: </strong>Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002).</p><p><strong>Conclusions: </strong>We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"8 2","pages":"73-85"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34766384","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":"Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine.","authors":"C P Coyne,&nbsp;Toni Jones,&nbsp;Ryan Bear","doi":"10.4236/jct.2015.61009","DOIUrl":"https://doi.org/10.4236/jct.2015.61009","url":null,"abstract":"<p><p>The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunochemotherapeutics that possess properties of selective \"targeted\" delivery. The simultaneous dual selective \"targeted\" delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition; prolong chemotherapeutic plasma half-life (reduces administration frequency); minimize innocent exposure of normal tissues and healthy organ systems; and ultimately enhance more rapid and thorough resolution of neoplastic cell populations.</p><p><strong>Materials and methods: </strong>A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/<i>neu</i> IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunochemotherapeutics, gemcitabine-(C₄-<i>amide</i>)-[anti-EGFR] and gemcitabine-(C₄-<i>amide</i>)-[anti-HER2/<i>neu</i>]. Cytotoxic anti-neoplastic potency of gemcitabine-(C₄-<i>amide</i>)-[anti-EGFR] and gemcitabine-(C₄-<i>amide</i>)-[anti-HER2/<i>neu</i>] between gemcitabine-equivalent concentrations of 10^-12 M and 10^-6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunochemotherapeutics.</p><p><strong>Results: </strong>Gemcitabine-(C₄-<i>amide</i>)-[anti-EGFR], gemcitabine-(C₄-<i>amide</i>)-[anti-HER2/<i>neu</i>] and the dual simultaneous combination of gemcitabine-(C₄-<i>amide</i>)-[anti-EGFR] with gemcitabine-(C₄-<i>amide</i>)-[anti-HER2/<i>neu</i>] all had anti-neoplastic cytotoxic potency against mammary adenocarcinoma. Gemcitabine-(C₄-<i>amide</i>)-[anti-EGFR] and gemcitabine-(C₄-<i>amide</i>)-[anti-HER2/<i>neu</i>] produced progressive increases in anti-neoplastic cytotoxicity that were greatest between gemcitabine-equivalent concentrations of 10^-9 M and 10^-6 M. Dual simultaneous combinations of gemcitabine-(C₄-<i>amide</i>)-[anti-EGFR] with gemcitabine-(C₄-<i>amide</i>)-[anti-HER2/<i>neu</i>] produced levels of anti-neoplastic cytotoxicity intermediate between each of the individual covalent gemcitabine immunochemotherapeutics. Total anti-neoplastic cytotoxici","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"6 1","pages":"62-89"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33172010","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":"Methylation Abnormalities in Mammary Carcinoma: The Methylation Suicide Hypothesis.","authors":"Anne H O'Donnell,&nbsp;John R Edwards,&nbsp;Robert A Rollins,&nbsp;Nathan D Vander Kraats,&nbsp;Tao Su,&nbsp;Hanina H Hibshoosh,&nbsp;Timothy H Bestor","doi":"10.4236/jct.2014.514131","DOIUrl":"https://doi.org/10.4236/jct.2014.514131","url":null,"abstract":"<p><p>Promoter silencing by ectopic <i>de novo</i> methylation of tumor suppressor genes has been proposed as comparable or equivalent to inactivating mutations as a factor in carcinogenesis. However, this hypotheses had not previously been tested by high resolution, high-coverage whole-genome methylation profiling in primary carcinomas. We have determined the genomic methylation status of a series of primary mammary carcinomas and matched control tissues by examination of more than 2.7 billion CpG dinucleotides. Most of the tumors showed variable losses of DNA methylation from all sequence compartments, but increases in promoter methylation were infrequent, very small in extent, and were observed largely at CpG-poor promoters. De novo methylation at the promoters of proto-oncogenes and tumor suppressor genes occurred at approximately the same frequency. The findings indicate that tumor suppressor silencing by <i>de novo</i> methylation is much less common than currently believed. We put forward a hypothesis under which the demethylation commonly observed in carcinomas is a manifestation of a defensive system that kills incipient cancer cells.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"5 14","pages":"1311-1324"},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33290930","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":"EWS Knockdown and Taxifolin Treatment Induced Differentiation and Removed DNA Methylation from p53 Promoter to Promote Expression of Puma and Noxa for Apoptosis in Ewing's Sarcoma.","authors":"Mohammad Motarab Hossain,&nbsp;Swapan Kumar Ray","doi":"10.4236/jct.2014.512114","DOIUrl":"https://doi.org/10.4236/jct.2014.512114","url":null,"abstract":"<p><p>Ewing's sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing's sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing's sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing's sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing's sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing's sarcoma in cell culture and animal models.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"5 12","pages":"1092-1113"},"PeriodicalIF":0.0,"publicationDate":"2014-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4236/jct.2014.512114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34382535","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":"Activation of various downstream signaling molecules by IGFBP-3.","authors":"Hanief Mohammad Shahjee, Nisan Bhattacharyya","doi":"10.4236/jct.2014.59091","DOIUrl":"10.4236/jct.2014.59091","url":null,"abstract":"<p><p>Insulin-like growth factor binding protein-3 (IGFBP-3), a secretory protein, is the most abundant IGF binding protein present in human serum among all IGF binding proteins. IGFBP-3 shows decreased level of expression in cancerous cells but has been known to be present in significant amounts in normal or non-cancerous cells. IGFBP-3 can induce apoptosis in prostate cancer cells either in an IGF-dependent manner or independently of IGF binding. Although putative cell death specific Insulin-like growth factor binding protein-3 (IGFBP-3R) receptor(s) has recently been identified by which IGFBP-3 may induce its anti-tumor effects, IGFBP-3 has also been known to activate various downstream intracellular signaling molecules via a different mechanistic pathway. Stat-1 has been known to be one of the candidate molecules activated by IGFBP-3. IGFBP-3 can also inhibit Akt/IGF-1 survival pathway in MCF- 7 breast cancer cells which ultimately leads to the induction of apoptosis in these cells. All these studies clearly demonstrate that IGFBP-3 regulates cell proliferation and promotes its pro-apoptotic effects in cancer cells in two different pathways,1) sequester IGF-I to bind to IGF-I receptor to inhibit cell proliferation and induce apoptosis, 2) independent of IGF-I pathway, IGFBP-3 binds to some putative receptor and activate various downstream pro-apoptotic molecules involved in cell death.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"5 9","pages":"830-835"},"PeriodicalIF":0.0,"publicationDate":"2014-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170070/pdf/nihms613619.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32695399","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":"Oncomorphic <i>TP</i>53 Mutations in Gynecologic Cancers Lose the Normal Protein:Protein Interactions with the microRNA Microprocessing Complex.","authors":"Pavla Brachova,&nbsp;Samuel R Mueting,&nbsp;Eric J Devor,&nbsp;Kimberly K Leslie","doi":"10.4236/jct.2014.56058","DOIUrl":"https://doi.org/10.4236/jct.2014.56058","url":null,"abstract":"<p><p>Mutations in the tumor suppressor <i>TP</i>53 occur in almost all advanced ovarian cancers and in many advanced serous endometrial cancers. Mutations in <i>TP</i>53 can alter the function of the p53 protein, and some mutations result in a mutated protein with oncogenic activity. Previously referred to as gain of function (GOF) p53 proteins, we now term these \"oncomorphic\" mutations to better describe their function as oncogenes. We reviewed the data from The Cancer Genome Atlas (TCGA) and demonstrate that of the patients diagnosed with endometrial cancer that harbor <i>TP</i>53 mutations, approximately 30% of these mutations are oncomorphic. In ovarian cancer, approximately 20% are oncomorphic. The wild type (WT) p53 protein transactivates genes and micro- RNAs (miRNAs) necessary in the response to cellular stress, which turn off growth and induce apoptosis. In addition to direct transcriptional activation, WT p53 also acts through protein:protein interactions with Drosha and the miRNA processing complex to mediate rapid, enhanced processing of a subset of anti-growth miRNAs. We validated the interaction of WT p53 with the Drosha complex in the cell line UCI-107. We observed that miRNAs that inhibit the expression of oncogenes were induced. Specifically, some miRNAs were induced very rapidly over minutes, consistent with enhanced processing, while others required hours, consistent with transcriptional activation. In contrast, the most common oncomorphic <i>TP</i>53 mutations failed to interact with the Drosha complex and lost the ability to rapidly induce the miRNAs which inhibit oncogene expression. These studies highlight one mechanism underlying the oncomorphic properties of specific <i>TP</i>53 mutations: loss of the enhanced processing of anti-proliferative miRNAs.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"5 6","pages":"506-516"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32766442","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}