M. Matsuura, Akimasa Takahashi, H. Nomura, M. Matoda, S. Okamoto, H. Kanao, K. Omatsu, Kazuyoshi Kato, K. Utsugi, N. Takeshima
{"title":"Analysis of A Single Para-Aortic Lymph Node Metastasis in Endometrial Cancer","authors":"M. Matsuura, Akimasa Takahashi, H. Nomura, M. Matoda, S. Okamoto, H. Kanao, K. Omatsu, Kazuyoshi Kato, K. Utsugi, N. Takeshima","doi":"10.4172/1948-5956.1000510","DOIUrl":"https://doi.org/10.4172/1948-5956.1000510","url":null,"abstract":"Objective: To determine the indication for lymph node dissection in patients with endometrial cancer, we investigated the incidence and distribution of single metastatic lymph nodes in patients who underwent systematic pelvic and para-aortic lymph node dissection.Methods: This study involved 910 patients with endometrial cancer who were treated at the Cancer Institute Hospital, Japan, between January 1994 and December 2015. All patients underwent an open hysterectomy with bilateral salpingo-oophorectomy and pelvic and para-aortic lymph nodes dissection.Results: Lymph node metastasis was observed in 199 patients (21.9%), 45 (5%) of whom had single lymph node metastasis. Single lymph node metastasis accounted for 22.6% of all metastatic cases. Myometrial invasion >50% was observed in 30 patients, whereas 15 patients had <50% myometrial invasion. When mapping single lymph node metastatic sites, the para-aortic area had a frequency of 31.1% (14 cases). The distribution of single metastatic lymph nodes spanned a wide area between the pelvic and para-aortic regions. Considering single metastatic nodes and myometrial invasion, 8 patients (53.3%) who had myometrial invasion <50% had a single metastatic node in the para-aortic region. Four of 9 patients (45%) considered low-risk (endometrioid Grade 1-2, invasion depth <50%, no lymphovascular space invasion) showed metastasis to the para-aortic areas.Conclusion: Single metastatic lymph nodes were widely distributed between the pelvic and para-aortic regions, suggesting that detection of a sentinel lymph node in patients with endometrial cancer could be problematic.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"147 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2018-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91381539","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}
Natalia Filippova, Xiuhua Yang, Zixiao An, Louis B Nabors, Larisa Pereboeva
{"title":"Blocking PD1/PDL1 Interactions Together with MLN4924 Therapy is a Potential Strategy for Glioma Treatment.","authors":"Natalia Filippova, Xiuhua Yang, Zixiao An, Louis B Nabors, Larisa Pereboeva","doi":"10.4172/1948-5956.1000543","DOIUrl":"https://doi.org/10.4172/1948-5956.1000543","url":null,"abstract":"<p><strong>Objective: </strong>MLN4924, a pharmacological inhibitor of cullin neddylation, resulted in glioma cell apoptosis, deregulation of the S-phase of DNA synthesis and thus, offers great potential for the treatment of brain tumours. However, targeting the neddylation pathway with an MLN4924 treatment stabilized the hypoxia-inducible factor 1A (HIF1A), which is one of the main transcriptional enhancers of the immune checkpoint molecule PDL1 (programmid death ligand-1) in cancer cells. The influence of immune checkpoint molecules on glioma progression has recently been discovered; PDL1 overexpression in gliomas corresponds to a significant shortening of patient survival and a decrease of the anti-tumour immune response. We hypothesize that i) PDL1 is up-regulated in gliomas after treatment with MLN4924 and induces T-cell energy; ii) co-utilization of the PD1/PDL1 blockage with MLN4924 therapy may reduce T-cell energy and may engage MLN4924-induced tumour disruption with the immune response.</p><p><strong>Methods: </strong>PDL1 expression and its immunosuppressive role in gliomas, glioma microenvironments, and after treatments with MLN4924 were assessed by utilizing methods of immunohistochemistry, molecular biology, and biochemistry.</p><p><strong>Results: </strong>We confirmed PDL1 overexpression in clinical brain tumour samples, PDGx and established glioma cell lines, extracellular media from glioma cells, and CSF (cerebrospinal fluid) samples from tumour-bearing mice. Our primary T-cell based assays verified that the up-regulation of PDL1 in tumour cells protects gliomas from T-cell treatment and reduces T-cell activation. We found that a pharmacological inhibitor of cullin neddylation, MLN4924, exhibited strong cytotoxicity towards PDGx and established glioma cell lines, <i>in vitro</i>, with an IC50's range from 0.2 to 3 uM. However, we observed a significant increase of HIF1A and PDL1 in mRNA and protein levels in all glioma cell lines after treatment with MLN4924. The MLN4924-dependent induction of PDL1 in gliomas resulted in T-cell energy, which was blocked by a blockage of the PD1/PDL1 interaction.</p><p><strong>Conclusion: </strong>We conclude that i) PDL1 up-regulation in gliomas and the glioma microenvironment is an important chemotherapeutic target; ii) MLN4924 therapy, combined with a blockage of the PD1/PDL1 pathway, should be considered as a potential strategy for glioma treatment.</p>","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"10 8","pages":"190-197"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4172/1948-5956.1000543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36694216","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":"The Pretreatment Tumor Infiltrating T Lymphocytes (CD8 + , CD4 + , FOXP3 + ) and Systemic Neutrophil-Lymphocytes Ratio in Definitively Treated Cervical Cancer Patients: The Correlation to Clinicopathological Factors and Survival","authors":"Hala A El-Lathy, Ahlam A Dohal, M. Mashhour","doi":"10.4172/1948-5956.1000528","DOIUrl":"https://doi.org/10.4172/1948-5956.1000528","url":null,"abstract":"Purpose: To evaluate the prognostic potential of pre-treatment tumour infiltrating T lymphocytes (TILs) (CD8+, CD4+, FOXP3+) and systemic neutrophil to lymphocyte ratio (NLR) in predicting the outcome of definitively treated cervical cancer patients.Methods: Both densities of pre-treatment TILs (CD8+, CD4+, FOXP3+) in cervical biopsies and NLR were correlated with clinicopathological parameters. The prognostic value of pre-treatment TILs and NLR for disease free survival (DFS) and overall survival (OS) were assessed using Log rank and Cox regression.Results: The final analysis included 28 had who radical hysterectomy while 20 had definitive concurrent chemoradiation. Elevated CD8+, CD8+/CD4+ and low FOXP3+ were associated with node negative, early stage disease and radical hysterectomies. Conversely, elevated NLR was associated with advanced stages, nodal involvement and definitive chemoradiation. Cox regression multivariate revealed that elevated NLR along with nodal involvement were independently correlated with poor prognosis with hazard ratio (HR 3.06 (95% confidence interval [CI], 3.45-9.24),5.63 (95% CI, 2.61-9.32) for OS and (HR 8.21 (95% CI, 4.21-16.53) and 5.32 (95% CI, 2.37-10.24) for DFS respectively. Additionally, FOXP3+ ≥ 19 and CD8+/CD4+ < 2 were significantly associated with decreased OS (HR 4.37 (95% CI, 2.48-12.37), 2.31 (95% CI, 2.34-9.32) and poorer DFS (HR 3.61 (95% CI, 1.38- 9.32), 4.32 (95% CI,3.12-8.34) respectively.Conclusion: The Pre-treatment NLR, CD8+, FOXP3+ and C8/CD4+ showed a significant association with different clinicopathological prognostic factors in definitively treated cervical cancer patients. Additionally, they may be considered as potential independent prognostic indicators of clinical outcomes.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"1 1","pages":"1-113"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75232795","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}
Yoshikazu Kuwaharaa, K. Tomita, Shintaro Takahashi, Yusuke Urushihara, Yohei Saito, Mehryar Habibi Roudkenar, A. Roushandeh, Tomoaki Sato, A. Kurimasa, M. Fukumoto
{"title":"Mitochondrial Dysfunction in Cross-resistance of Clinically Relevant Radioresistant Cells to X-rays and Docetaxe","authors":"Yoshikazu Kuwaharaa, K. Tomita, Shintaro Takahashi, Yusuke Urushihara, Yohei Saito, Mehryar Habibi Roudkenar, A. Roushandeh, Tomoaki Sato, A. Kurimasa, M. Fukumoto","doi":"10.4172/1948-5956.1000571","DOIUrl":"https://doi.org/10.4172/1948-5956.1000571","url":null,"abstract":"","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73956460","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}
C. Pellegrini, B. Casadei, C. Cellini, L. Argnani, M. Cavo, P. Zinzani
{"title":"Sequential Double Bridging to Transplant with Diversified Anti- PD1 Monoclonal Antibodies Retreatment in Relapsed Hodgkin Lymphoma: A Case Report","authors":"C. Pellegrini, B. Casadei, C. Cellini, L. Argnani, M. Cavo, P. Zinzani","doi":"10.4172/1948-5956.1000534","DOIUrl":"https://doi.org/10.4172/1948-5956.1000534","url":null,"abstract":"Background: Nivolumab and pembrolizumab are the first two US FDA-approved monoclonal antibodies targeting PD-1 for Hodgkin lymphoma (HL) and provide promising results in the relapsed/refractory setting (HL patients relapsing after autologous stem cell transplantation [ASCT], or with chemorefractory disease and/ or ineligible for ASCT). An interesting area of ongoing research is the possibility of combining different immune checkpoint inhibitors given concomitantly or sequentially in the attempt to maximize the patient responsiveness. Case report: A heavily pre-treated young woman affected by HL, after several attempts, obtained a complete response after ASCT thanks to the bridge with pembrolizumab. After relapse, the patient achieved again a complete response with nivolumab, bridging her to allotransplant. The patient is still in response to a year since the transplant. Discussion and Conclusion: This is the first report which witnesses the safety and the antitumor activity of interchangeable anti-PD1 monoclonal antibodies administered as a retreatment option and as a bridge to allotransplant in a patient who previously got an objective response to another anti-PD1 which brought her to autologous transplant. Retreatment with anti-PD1 monoclonal antibodies could be considered in therapeutic algorithm of relapsed/refractory HL.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"40 1","pages":"149-151"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85879217","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}
N. Yu, Y. Jia, Yong Yu, L. Deng, Cong Shen, You-min Guo, H. Duan
{"title":"The Role of Estrogen Receptors in Proliferation of Non-Small Cell Lung Cancer","authors":"N. Yu, Y. Jia, Yong Yu, L. Deng, Cong Shen, You-min Guo, H. Duan","doi":"10.4172/1948-5956.1000516","DOIUrl":"https://doi.org/10.4172/1948-5956.1000516","url":null,"abstract":"To explore the expression pattern of ERs in NSCLC tissues and assess their relationship with tumor histopathological variable. In our study, Ers expression was examined using Real-time PCR with specimens of 28 NSCLC patients. It was shown that both ERɑ and Erβ were over expression in NSCLC tissues, and also the Mrna concentration of both ERɑ and Erβ were significantly higher in primary tumor T2 stage than in T1 stage and higher in squamous carcinoma than in adenocarcinoma. However, the activation of ERɑ and Erβ were completely different. To further explore the role of Ers in development and progression of NSCLC, we used Ers selective siRNA or antagonist in vitro experiments. The results showed that Erβ but not ERɑ can mediate E2 induced cell growth, since siRNA targeting Erβ but not ERɑ gene can induce cell cycle arrest at G1 phase by down regulation of cyclinD1 expression, and also cell cycle regulators p21Waf1/Cip1 and p53 were involved in this signaling pathway.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"31 1","pages":"45-51"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81646108","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":"Clinical Utility of Poly (ADP-Ribose) Polymerase Inhibitors in Ovarian Cancer","authors":"Dimple R. Bhatia, Sudeep Gupta","doi":"10.4172/1948-5956.1000551","DOIUrl":"https://doi.org/10.4172/1948-5956.1000551","url":null,"abstract":"Inhibitors of the enzyme poly (ADP-ribose) polymerase (PARP) are the most promising class of targeted therapies in ovarian cancers in recent times. Approximately 30% to 50% of these cancers are characterized by aberrant DNA repair pathways due to mutations in tumor suppressor genes: BRCA1 or BRCA2. Therapeutic approach with PARP inhibitors in BRCA deficient tumors exploits a synthetic lethal strategy targeting the deficiency in homologous recombination DNA repair pathway. This short review provides an overview of BRCAness in maintaining genomic integrity, the role of PARP in DNA repair, utility of PARP inhibitors as monotherapy or in combination with other therapies, mechanisms of resistance to PARP inhibitors and biomarkers for clinical utility of PARP inhibitors in management of ovarian cancer.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81179724","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":"High Rate of Glycolysis and Cancer","authors":"K-J Tian","doi":"10.4172/1948-5956.1000531","DOIUrl":"https://doi.org/10.4172/1948-5956.1000531","url":null,"abstract":"One hundred years ago, abnormal metabolism of cancer cell was regarded as one of the most important pathological features of malignancy. Recently, with the development of system biology, researchers regained the interest in regulating cancer metabolism. In 1920s’, Dr. Otto Warburg discovered that, even when oxygen is ample, malignant cells still prefer the anaerobic glycolysis, and the rate of glucose uptake is high while the overall glycolysis increases. Cancer cells divide faster than normal cells, hence they need more bioenergy, and they need to change their metabolism to produce the extra energy. In recent 20 years, the link between high rate of glycolysis and cancer was re-evaluated and has inspired enthusiasm upon research into the metabolism of cancer cells. Novel diagnostic methods and new drugs were created by the understanding of the features of cancer metabolism. Glycolysis in cancer cells has clinical implications in cancer diagnosis, treatment and prognosis. The purpose of this review is to focus on the mechanism of high rate of glycolysis in cancer and its significance in cancer diagnosis and therapies. The regulatory network of cancer is complex, system biology might help us to find the clue. There are evidences showing that mixture of drugs has therapeutic advantages in clinical practice. Combinations of anti-neoplasm drugs have already been administered with encouraging results. Therefore, the multi-targeted MCA advised therapy might be the most promising strategy for cancer. The study for novel inhibitors from medicinal herbs are now ongoing. We believe, there will be more and more therapeutic strategies coming in the near future to help human beings fighting with cancer.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"31 1","pages":"140-142"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91018945","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":"Comparative Analysis of Cilengitide with a Novel Integrin Antagonist AV-38/398 in 2D/3D Melanoma Cultures","authors":"E. Selzer","doi":"10.4172/1948-5956.1000561","DOIUrl":"https://doi.org/10.4172/1948-5956.1000561","url":null,"abstract":"","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90209208","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":"Prophetic Chemo Is the Safest, Cheapest and Most Effective Alternative to Modern Chemotherapy for the Cure of all Forms of Cancers – A Review","authors":"H. Deena, M. Hussain","doi":"10.4172/1948-5956.1000525","DOIUrl":"https://doi.org/10.4172/1948-5956.1000525","url":null,"abstract":"Like all other great Prophets (as) of Allah (God), statements of the Prophet (peace be upon him) of Islam are divinely inspired. Prophet Muhammad (PBUH) never spoke a single lie in his lifetime. Whatever he spoke was under divine inspiration. Concerning his statements and utterances Allah says in the Qur'an: “He does not speak anything on his own. It is but a Revelation which is sent down to him” (An-Najm 53:3-4). “And if Muhammad had made up about Us some [false] sayings, we would have seized him by the right hand; then We would have cut from him the aorta” (Al-Haqqah, 69: 44-46). So, traditions of the Prophet (PBUH) on healing are also true, which modern science proves through research after 14 centuries. Although the Prophet’s mission was neither as a physician or pharmacist, he was inspired by God to make nearly 1000 statements on healing for the benefit of humankind because man needs to remain well free from sickness to fulfill his brief mission on earth. About Nigella sativa Abu Hurayrah (ra) narrates that the Prophet (PBUH) said: \"Hold on (use this seed regularly)! Because it is a remedy (cure) for every disease except death.\" (Bukhari, Muslim) This amazing statement of the Prophet (PBUH) generated tremendous interest among the world scientific community, which finally led them to carry out extensive biological and phytochemical investigations on the plant seed. However, the researchers after carrying out hundreds of studies in various countries finally concluded that black seed can effectively cure 129 different types of ailments including 17 types of cancers. This large number of diseases curable by black seed demonstrates the authenticity of the Prophet’s statement. In this paper the learned readers will be informed about the beneficial pharmacological effects of Nigella sativa in the treatment of most human ailments as well as the findings of modern scientific researches on how Prophetic chemo isolated from Nigella sativa can effectively cure numerous cancers without any side effects.","PeriodicalId":15170,"journal":{"name":"Journal of Cancer Science & Therapy","volume":"52 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73664719","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}