{"title":"Improving Detection of Somatic Mutations","authors":"T. Moorthy","doi":"10.17303/jcrto.2019.7.101","DOIUrl":"https://doi.org/10.17303/jcrto.2019.7.101","url":null,"abstract":"J Cancer Res Therap Oncol 2019 | Vol 7: 101 Interest in this topic originated from studies on the detection of Braf p. V600E/K mutations using Allele Specific Multiplex Sequencing (ASMS) technology, which was compared to detection of Braf p. V600E by either SNapShot or Ion Torrent. Although there was no discordance among the positives, there was significant discordance among the negatives, indicative of potential false negatives by the latter two methods [1]. A similar pattern was observed when ASMS Braf p. V600E/K mutations was compared to an FDA approved Braf Test (ThxID) (unpublished data). Is there any clinical significance to such discordant results? If so, can testing protocols of somatic mutations be improved to accommodate for potential discrepancies among the test methods so that the results generated could be graded for meaningful clinical interpretation? There are at least four areas that could be affected by such discordant results;","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85182802","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":"Pilot Study of the Antitumor Efficacy and Tolerability of Orally Administered Rrx-001 in Normal and Tumor-Bearing Mice","authors":"S. Knox","doi":"10.17303/jcrto.2018.6.102","DOIUrl":"https://doi.org/10.17303/jcrto.2018.6.102","url":null,"abstract":"Purpose RRx-001 is a novel anticancer drug that will be entering Phase III clinical trials as a pre-sensitizer or resensitizer to chemotherapy and radiotherapy. To date, it has been very well tolerated, with the main adverse event being infusion-related reactions, consisting primarily of discomfort, itching and tingling at the site of infusion. The purpose of this preclinical pilot study was to study the antitumor efficacy and tolerability of oral administration of RRx-001 in a preclinical mouse model. Methods The maximum tolerated dose (MTD) of oral administration of RRx-001 was studied in normal C3H mice. For antitumor efficacy study, mice bearing SCC VII tumors were administered by oral gavage with RRx-001 either alone or in combination with external beam radiation therapy. Tumor growth delay time and body weight were used as the endpoints for antitumor efficacy and systemic toxicity. Results The estimated MTD for oral RRx-001 in 10% dimethyl sulfoxide (DMSO) daily for 5 days was 10-20 mg/kg. In tumor-bearing mice, oral dosing of RRx-001 at a total equivalent dose of 60 mg/kg, given either daily, or every other day, or as a single dose, significantly inhibited tumor growth (p < 0.01 vs. vehicle control). There were no statistically significant differences in tumor growth delay time among three treatment regimens (P > 0.05). However, a single dose of 60 mg/kg caused a 28% modality (2 death among 7 treated mice). When combined with local tumor radiation therapy, oral RRx-001 significantly increased the antitumor efficacy of radiation therapy (p = 0.02, combination vs. radiation alone). There were no obvious systemic or additional toxicities for combination of oral RRx-001 (10-20 mg/kg) and radiation therapy. Conclusion Oral administration of RRx-001 was safe and effective in the SCC VII tumor model in mice, and merits further study.","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80889088","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":"Retrospective Analysis of 5-Year Survival Rate of Nasopharyngeal Carcinoma: Correlation with Clinical Features and Prognosis","authors":"Zhonglin Mu","doi":"10.17303/jcrto.2019.7.102","DOIUrl":"https://doi.org/10.17303/jcrto.2019.7.102","url":null,"abstract":"","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89448726","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":"Treatment of Metastatic Sweat Gland Carcinomas: Response in Two Cases","authors":"L. Liqiong","doi":"10.17303/jcrto.2019.7.104","DOIUrl":"https://doi.org/10.17303/jcrto.2019.7.104","url":null,"abstract":"Sweat gland carcinomas are a rare group of tumors with the potential of destructing local tissue infiltration as well as regional and distant metastasis. Due to the limited availability of reference from the literature, the management of sweat gland carcinomas is both complex and cumbersome. Sweat gland carcinomas can be divided into eccrine and apocrine categories and occur primarily in adult patients, with a peak incidence during the fifth and sixth decades [1-2]. The majority of sweat gland carcinomas occur in the genital skin and perineum, followed by the trunk, head, neck and lower extremities. Regional and distant lymph node metastases frequently occur in a certain number of patients, but visceral metastases are seldom found. The metastasis sites mainly include lymph nodes, lungs and bone [3-5]. According to the available literature, radical surgical excision is the prior and standard treatment with the clearance of draining lymph nodes [6]. Some chemotherapeutic drugs, such as fluoropyrimidines, taxanes and cisplatin, have been reported to be active agents for metastatic sweat gland carcinomas [2,7-8]. However, the effect of adjuvant chemotherapy and radiotherapy remain elusive, and classical standards of diagnosis and therapy are still not clarified. Here, we report two cases of metastatic sweat gland carcinomas. In one case, the remission of nearly 6 months was achieved through chemotherapy of GP regimen; while in another case, the size of draining axillary lymph nodes was effectively controlled by oral administration of tamoxifen.","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88826874","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":"Cancer as an Emergent Phenomenon?","authors":"Anderson Km","doi":"10.17303/JCRTO.2018.6.103","DOIUrl":"https://doi.org/10.17303/JCRTO.2018.6.103","url":null,"abstract":"Many biological events exhibit major features of emergent phenomena in which the detailed behavior of a collective ensemble of entities or agents is not predictable from summing their individual behaviors. The relationship between the emergent phenomena of evolution, including the development of cancer cells expressing apparently “random” genetic / epigenetic events and the influence of “scale” are also not yet widely understood or well defined. Presumably this uncertainty is also subject to further influence from non-oncologic random genetic and epigenetic events. A forward or a retrogressive evolution of individual cancer cells could be viewed as subsets of emergent phenomena in which random genetic / epigenetic events can also meld with other ongoing, underlying emergent processes, contributing to unpredictable outcomes. The extent to which such an interplay may subvert attempts at cancer therapy is not presently well identified nor are conditions that might promote or retard the incidence of random responses during the process. The rare reports of what may have included occasional random reversals of established cancers is another subject of interest. Some discussion of these questions seems merited.","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"2017 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85481226","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":"Primary Cultures Derived From Bovine Papillomavirus-Infected Lesions As Model To Study Metabolic Deregulation","authors":"R. C. Stocco","doi":"10.17303/JCRTO.2016.4.103","DOIUrl":"https://doi.org/10.17303/JCRTO.2016.4.103","url":null,"abstract":"Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, disease characterized by the presence of multiple papillomas that can regress or to progress to malignances. Due to the pathological similarities with the human papillomavirus (HPV), BPV is considered a prototype to study the papillomavirus-associated oncogenic process. Although it is clear that both BPV and HPV can interact with host chromatin, the interaction of these viruses with cell metabolism remains understudied due to the little attention given to primary cultures derived from papillomavirus-infected lesions. Thus, this study analyzed the energy metabolism, including the mitochondrial membrane potential (ΔΨm) and Reactive Oxygen Species (ROS) of cells derived from cutaneous papilloma, fibropapilloma and Esophageal Carcinoma (EC) as model to evaluate the cell metabolism. These cells were cultivated until sixth passage and subjected to BPV DNA sequences identification by PCR using specific primers to BPV-1, 2 and 4. PCR results showed the presence and maintenance of at least one BPV type along the six passages analyzed. Cells derived from normal skin, without BPV DNA sequences were used as control. Results of energy metabolism showed the loss of ΔΨm in fibropapilloma and EC cells, suggesting a metabolic switch compatible to the activation of aerobic glycolysis. Cutaneous papilloma and normal skin cells showed the maintenance of ΔΨm. Paradoxically, cutaneous papilloma and fibropapilloma presented high levels of ROS production, while the EC cells reduced the ROS levels, reinforcing the activation of glycolytic metabolism. Our results suggest that the metabolic switch is mediated by BPV E6 oncoprotein, since the addition of this oncoprotein in normal cells promoted the oxidative stress. The oxidative stress showed able to activate the STAT3 nuclear factor in papilloma and fibropapilloma cells, contributing to metabolic deregulation. These data suggest that primary cultures are useful model to study the interaction between BPV and cell metabolism.","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85684416","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}
Miguel Otero, Beatriz Zayas, Eric Miranda, Christian Velez, Wigberto J Hernandez, Luis A Rivera, Osvaldo Cox
{"title":"Immunomodulatory Response Triggered by the Alkaloids, 3-Amino-7-Benzylbenzimidazo[3,2-<i>a</i>] Quinolinium Chloride (ABQ-48) and 3-Nitro-7-Benzylbenzimidazo [3,2-<i>a</i>] Quinolinium Chloride (NBQ-48).","authors":"Miguel Otero, Beatriz Zayas, Eric Miranda, Christian Velez, Wigberto J Hernandez, Luis A Rivera, Osvaldo Cox","doi":"10.17303/jcrto.2015.103","DOIUrl":"https://doi.org/10.17303/jcrto.2015.103","url":null,"abstract":"<p><p>ABQ-48 (3-amino-7-benzylbenzimidazo[3,2-<i>a</i>]quinolinium chloride) and NBQ-48 (3-nitro-7-benzylbenzimidaw[3,2-<i>a</i>] quinolinium chloride) are un-natural alkaloids containing a planar heteroaromatic systems characterized by quaternized nitrogen fused to benzothiazole nucleus. Both compounds are structurally related to naturally occurring substances such as elliptine (from Ochrosia), and berberine (from Berberis). Previous in vitro studies have shown these agents to control tumor-cell proliferation indicating that both BQS are active but especially ABQ-48 at a 1 OuM dose with over 80% control of the proliferation of multiple cancer cell lines from various etiologies including colon, melanoma, CNS and ovarian cells. Mechanism of action studies have also been conducted however this is the first approach to evaluate immune modulatory activity of these novel BQS. Immune-based therapy is an increasing field in which scientists identify how the immunomodulatory activity of known and newly discovered compounds elicits an immune response that could be used against diseases. In this study, our main objective was to apply an in vitro model to show the immunomodulatory effects of ABQ-48 and NBQ-48 by analyzing the cytokine profile resulting after extracted murine spleen cells were treated with both BQS using a fluorescence-based multiplex ELISA approach. Screened cytokines included: G-CSF, GM-CSF, IL-1a, IL-2, IL-3, IL-5, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-21, IL-23, IFN-γ, and TNF-α. Our study results show ABQ 48 and NBQ-48 to stimulate the release of G-CSF, IL-2, IL-6, and, IFN-γ when mouse splenocytes are incubated with serial dilutions of these agents. Our finding opens new possibilities of potentially using ABQ-48 and NBQ-48 as immunomodulatory agents; with intend to activate the immune system such as the production of neutrophils against cancer or reducing chemotherapy side effects.</p>","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33398394","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":"Post-mastectomy Hypofractionation Radiotherapy in Breast Cancer Patients","authors":"Elsayed M Ali, Magdy Khalil Abd AlMageed","doi":"10.13189/cor.2014.020701","DOIUrl":"https://doi.org/10.13189/cor.2014.020701","url":null,"abstract":"","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90061287","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":"Lymphoma Caused by Intestinal Microbiota","authors":"Mitsuko L. Yamamoto, Robert H. Schiestl","doi":"10.13189/cor.2014.020601","DOIUrl":"https://doi.org/10.13189/cor.2014.020601","url":null,"abstract":"","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89192295","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}
Leena Rivina, Michael J Davoren, R. Schiestl, C. Young
{"title":"Mouse Models for Radiation-Induced Breast Cancer","authors":"Leena Rivina, Michael J Davoren, R. Schiestl, C. Young","doi":"10.13189/COR.2014.020602","DOIUrl":"https://doi.org/10.13189/COR.2014.020602","url":null,"abstract":"Radiation is a widely known, and prototypical, inducer of genotoxic damage. With every moment of exposure to ionizing radiation, lesions and breaks are induced in the DNA, increasing an individual's lifetime risk of developing cancer. At the same time, radiation therapy is a key part of the effective treatment of the very same disease. Radiation therapy is effective, capable of shrinking and even eliminating tumors. In conjunction with surgery, its use is extremely common for the treatment of breast cancer. Even when radiation is our ally, however, the risks remain. Therapeutic use to treat existing cancers paradoxically leads to the incidence of secondary, radiation-induced neoplasias. One strategy to reduce this secondary risk while still encouraging the use of radiotherapy to its full potential would be the development co-administered therapeutic compounds or strategies designed to preferentially protect healthy cells while leaving cancer cells vulnerable. The development and efficacy testing such agents would require not only extensive in vitro testing, but also a well investigated set of in vivo models to actively recapitulate the complex nature of radiation-induced carcinogenesis. The laboratory mouse Mus musculus is probably the best choice for this endeavor. As a cancer model it possesses a combination of favorable attributes: a well annotated genome, molecular and physiological similarities with man and other mammals, and a small size and high breeding rate for ease of use. This work will focus on the description of m. musculus inbred and F1 hybrid animal models of radiation-induced breast cancers and their associated molecular pathologies.","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85182387","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}