Journal of cancer science and clinical therapeutics最新文献

{"title":"Identifying the Mutational Profile of ABCB5 Upregulation in Colorectal Cancer: A Comprehensive Database Analysis","authors":"R. Sexton, K. Danasekaran, H. Khan, H. Uddin, M. N. Al-Hallak, Y. Landesman, T. Kashyap, Yiwei Li, A. Aboukameel, A. Azmi","doi":"10.26502/jcsct.5079123","DOIUrl":"https://doi.org/10.26502/jcsct.5079123","url":null,"abstract":"Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide and the third leading cause of cancer related deaths in the United States with a 5-year survival rate of 63%. Depending on the stage of disease, there are differing rates of overall survival: Stage I (90%) vs. Stage IV (14%). There is a clear discrepancy between early and late stage disease due to a variety of factors including acquired genetic and tumor mutations and lack of initial symptoms leading to late stage detection. It is clear that further understanding into the mechanisms of CRC need to be explored in depth to improve overall survival rates. ATP binding cassette subfamily B member 5 (ABCB5) has been found to be pathogenic in a variety of diseases including melanoma and colorectal cancer but there has been few studies looking at the cellular consequences of ABCB5 upregulation in CRC cells. Using publicly accessible databases, we explored ABCB5 positivity in CRC cells and found novel interactions with 64 differentially expressed genes involved in cellular processes like modulation of inflammation, (XCL1, TNFSF4), enhanced cell signaling via interaction with serine protease inhibitors (SERPINB4, WFDC6) and downregulation of anti-apoptotic proteins (SPIN2A). Although ABCB5 upregulation is not currently targetable with pre-clinical compounds, our analysis revealed the genetic effects induced by ABCB5 upregulation are targetable, including evidence of sensitivity to the XPO1 inhibitor XPOVIO (selinexor). It is clear further pre-clinical investigation is needed to validate these findings.","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69367550","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 Experience using Osimertinib in Patients with Recurrent Malignant Gliomas Containing <i>EGFR</i> Alterations.","authors":"Marin Abousaud, Naqeeb M Faroqui, Glenn Lesser, Roy E Strowd, Shakti H Ramkissoon, Madan Kwatra, Kristin S Houston, Fang-Chi Hsu, Annette Carter, Robin Petro, Alisha T DeTroye","doi":"10.26502/jcsct.5079114","DOIUrl":"10.26502/jcsct.5079114","url":null,"abstract":"<p><strong>Background: </strong><i>EGFR</i> alterations are commonly observed in malignant gliomas (MG). Osimertinib, an irreversible EGFR-tyrosine kinase inhibitor, effectively penetrates the blood brain barrier and achieves therapeutic concentrations in brain tissue.</p><p><strong>Materials and methods: </strong>This retrospective chart review identified six patients with recurrent MG and <i>EGFR</i> alterations who received osimertinib.</p><p><strong>Results: </strong>Four patients were assessed for response. One patient had a partial response, two patients achieved stable disease and one was refractory. One patient with an <i>EGFR vIII</i> rearrangement remained on treatment for 236 days and a second patient with an <i>EGFR vIII</i> mutation remained on treatment for 294 days and continued on treatment at the time of analysis. Thrombocytopenia occurred in two patients, one patient developed grade 1 diarrhea and pneumonia, and another patient developed grade 1 mucositis.</p><p><strong>Conclusion: </strong>Osimertinib had a tolerable safety profile in this heavily pretreated brain tumor population. Osimertinib may benefit select patients with recurrent MG containing <i>EGFR</i> alterations.</p>","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"5 2","pages":"210-220"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9174799","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":"Epileptogenic Temporal lobe Intrinsic Epidermoid Tumor: A Rare Case Report and Review of the Literature","authors":"Mohammad Sujan Sharif, Tarikul Islam KM, Abdur Rahman, Abu Bakar Siddik, Masum Rahman","doi":"10.26502/jcsct.5079124","DOIUrl":"https://doi.org/10.26502/jcsct.5079124","url":null,"abstract":"Intracerebral epidermoid cysts are uncommon, accounting for only around 1.5 percent of intracranial tumors. Among these, Temporal lobe intracerebral epidermoid tumors are exceedingly rare. The great majority of these slow-growing tumors are asymptomatic, whereas few exhibit overt symptomatologies. We report a case of epidermoid tumors in a unique location, presented as a secondary complex partial seizure. A forty-year-old female presented with multiple episodes of convulsions followed by loss of consciousness for nine months, increasing in frequency over the last two months. MRI of the brain without contrast showed a well-circumscribed right temporal lobe mass, appearing hypointense on the T1 and hyperintense on the T2 sequence. In addition to our experience and review of existing literature demonstrate gross total resection of these lesions confers control of localization-related epilepsy.","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69367557","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":"Development and Management of Massive Subcutaneous Metastases with Unusual Clinical Course from Uterine Leiomyosarcoma","authors":"Filippin Dm, Nuvola G, Nannini M, S. M, Cammelli S, De Paolis M, Perrone Am, De Iaco P, De Leo A, A. A., Pan Ma","doi":"10.26502/jcsct.5079131","DOIUrl":"https://doi.org/10.26502/jcsct.5079131","url":null,"abstract":"Uterine leiomyosarcoma (U-LMS) is the most common histotype among all primary uterine sarcomas. The lung, peritoneum, pelvic or para-aortic lymph nodes, bone and liver are the most common metastatic sites involved. However, some case series of atypical sites of metastasis such as heart, brain and different endocrine glands have J Cancer Sci Clin Ther 2021; 5 (4): 459-467 DOI: 10.26502/jcsct.5079131 Journal of Cancer Science and Clinical Therapeutics 460 been described. Here we report the clinical presentation and therapeutic management of two patients affected by ULMS with a very atypical behavior, characterized by soft tissue metastases with an impressive and massive enlargement during chemotherapy despite a good control of the other sites of disease.","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69348090","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 Role of Radiation Therapy in Recurrent Ovarian Cancer","authors":"Yuichiro Hotta, Tamina Kino, H. Shigeta","doi":"10.26502/jcsct.5079143","DOIUrl":"https://doi.org/10.26502/jcsct.5079143","url":null,"abstract":"Recent remarkable technological advances in radiation therapy made the way for stereotactic body RT (SBRT), which can be used for oligometastatic tumors anywhere in the body. Oligometastases from gynecological malignancies have been considered as one of the most promising candidate for SBRT. It is suggested that SBRT was associated with high rates of local control, impressive survival, and minimal toxicity in ovarian cancer. It is also suggested that SBRT serves to destroy chemoresistant tumor clones, and help stimulate innate immune response or expose tumor neoantigens, and can be used in women who have had prior radiotherapy. Among the ovarian cancers, clear cell cancer might be a good candidate for radiation therapy because it is less sensitive to standard platinum-based chemotherapy. A patient was reported who had recurrent ovarian clear cell cancer and had been free from disease more than ten years after the discontinuation of proton beam therapy. Proton beam therapy provides superior dose distributions and a dosimetric advantages over photon beam therapy. Therefore, radiation therapy is considered to be an effective and safe option for oligometastatic ovarian cancer patients. Proton beam therapy is a good potential option for chemotherapy-resistant, localized, recurrent ovarian cancer including clear cell cancer. J Cancer Sci Clin Ther 2022; 6 (1): 25-30 DOI: 10.26502/jcsct.5079143 Journal of Cancer Science and Clinical Therapeutics 26","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69348225","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":"Stress-Induced Accumulation of HnRNP K into Stress Granules.","authors":"Jayoung Kim, Austin Yeon, Woong-Ki Kim, Khae-Hawn Kim, Takbum Ohn","doi":"10.26502/jcsct.5079129","DOIUrl":"10.26502/jcsct.5079129","url":null,"abstract":"<p><p>Stress granules (SGs) are cytoplasmic aggregates to reprogram gene expression in response to cellular stimulus. Here, we show that while SGs are being assembled in response to clotrimazole, an antifungal medication heterogeneous nuclear ribonucleoprotein (hnRNP) K, an RNA-binding protein that mediates translational silencing of mRNAs, is rapidly accumulated in SGs in U-2OS osteosarcoma cells. Forced expression of hnRNP K induces resistance to clotrimazole-induced apoptosis. Erk/MAPK is transiently activated in response to clotrimazole, and pharmacological suppression of the Erk/MAPK pathway sensitizes the cells to apoptosis. Inhibition of the Erk/MAPK pathway promotes the assembly of SGs. These results suggest that dynamic cytoplasmic formation of SGs and hnRNP K relocation to SGs may be defensive mechanisms against clotrimazole-induced apoptosis in U-2OS osteosarcoma cells.</p>","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"5 1","pages":"434-447"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49149480","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":"A Phase I dose escalation trial using Intensity-Modulated Radiotherapy with simultaneous integrated boost in Pelvic Chemoradiotherapy for Metastatic Rectal Cancer","authors":"T. Lizée, V. Seegers, J. Blanchecotte, E. Rio, O. Capitain, V. Guérin-Meyer, F. Legouté, D. Autret, M. Mahé, A. Paumier","doi":"10.21203/rs.3.rs-127929/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-127929/v1","url":null,"abstract":"\u0000 BackgroundIn unresectable metastatic rectal cancers, the surgery of the primitive tumor remains highly debated. Chemoradiotherapy (CRT) of the primitive could allow sufficient local control in order to avoid major and sometimes mutilating surgery. Dose escalation during CRT could increase this local control. The aim of this study was to evaluate the feasibility and tolerance of a CRT with radiation dose escalation delivered in intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB), in metastatic low and middle rectal cancers.MethodsThis multicenter phase I study included six patients treated for unresectable synchronous metastatic low and middle rectal adenocarcinoma in two dose levels. Radiotherapy was delivered using IMRT with SIB. The dose escalation was 52.5 Gy (level 1) and 56.25 Gy (level 2) in the primary tumor, in 25 fractions of 2.1 Gy and 2.25 Gy, respectively. High-risk clinical target volume (CTV) and low-risk CTV received respectively 50 Gy and 45 Gy in 25 fractions in the two levels. Concomitant chemotherapy was oral capecitabine and CRT was performed after four cycles of mFOLOX6 chemotherapy. The dose-limiting toxicity (DLT) was defined by a toxicity requiring the interruption of radiotherapy for more than five consecutive fractions.ResultsAll six patients received the full course of treatment at scheduled doses. No patients had acute toxicity requiring interruption of radiotherapy therefore no DLT has been reported. No patients had acute toxicity ≥ 3. Concerning late toxicity, three patients experienced grade 3. After CRT, four patients had a partial response and one patient had a complete clinical response. Two patients were considered in local progression at 9.4 months and 20.4 months of inclusion.ConclusionsDose escalation at 56.25 Gy in the tumor lesion was possible with good acute tolerance. It needs to be evaluated in a larger study. It could allow sufficient local control in order to avoid mutilating surgery in these metastatic patients.Trial registrationNCT03634202. Registered 16 August 2018 – retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03634202","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42453291","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":"Assessment of circulating VEGF as a predictive biomarker of peritoneal carcinomatosis in gastric cancer","authors":"","doi":"10.36879/jcst.20.000121","DOIUrl":"https://doi.org/10.36879/jcst.20.000121","url":null,"abstract":"Introduction: Early diagnosis of peritoneal carcinomatosis is difficult in patients with gastric cancer who are at high risk of developing\u0000peritoneal metastases. The measurement of serum Vascular Endothelial Growth Factor (VEGF) has proven to be a useful prognostic\u0000factor in gastric cancer, but it also could be a predictive factor for peritoneal metastases since the VEGF signalling pathway is directly\u0000involved in the development of peritoneal metastases.\u0000Methods: This is a retrospective study from 2005 to 2017. We reviewed the peritoneal recurrence pattern of a cohort of 59 gastric\u0000cancer patients in whom serum VEGF was measured before surgery and after completion of adjuvant treatment\u0000Results: Preoperative serum VEGF (pre-VEGF) level was identified as an independent prognostic factor for developing peritoneal\u0000metastases. The optimal cut-off value of pre-VEGF levels was 507 pg/mL, which presented a sensitivity of 66 % and a specificity of\u000078% to predict the development of peritoneal metastases. Patients with high pre-VEGF levels (>507 pg/mL) were at greater risk of\u0000developing peritoneal metastases than patients with low pre-VEGF levels (<507 pg/mL) (p=0.023).\u0000Conclusions: VEGF plays a crucial role in the development of peritoneal metastases, and serum VEGF meets the requirements of a\u0000potential predictive marker for peritoneal carcinomatosis. Therefore, the measurement of serum VEGF levels could be useful during\u0000the follow-up of patients with advanced gastric cancer.","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84402989","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":"Prognosis analysis of patients with resectable T4 colorectal cancer","authors":"Wei Chen, Xiao-ping Tan, Junwen Ye, Yan Zhang, Jing-lin Liang, Mei Huang","doi":"10.21203/rs.3.rs-37853/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-37853/v1","url":null,"abstract":"\u0000 Objective: To observe the factors related to survival and prognosis of patients with resectable stage T4 colorectal cancer. Methods : 148 patients with resectable stage T4 colorectal cancer who underwent surgery in the first Affiliated Hospital of Sun Yat-sen University between August, 1994 and December, 2005 were retrospectively analyzed. Univariate and multivariate analyses of associations between clinicopathological variables and survival were analyzed using the Cox regression model. Results: At the end of December of 2010 or death, the 5-year and 10 years OS rates were 49.0% and 32.2% respectively, the median OS was 25 months. The disease free survival rates (DFS) at 5 and 10 years were 44.2% and 30.3% respectively. In univariate analysis, patients with postoperative pathology lymph node metastasis was associated with the prognosis of patients with OS (all P< 0.01), postoperative adjuvant therapy failed to improve OS and DFS (P>0.05). Postoperative pathology lymph node metastasis was associated with DFS too (all P< 0.01). In multivariate analysis, postoperative pathology lymph node metastasis was independent factor affected OS and DFS in colorectal cancer patients. Conclusion: Postoperative prognosis of T4 colorectal cancer patients is poor, postoperative pathology lymph node positive was an independent factor affect OS and DFS.","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42894791","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":"PD-L1 regulation in colorectal cancer and role of DNA damage induced by chemotherapies","authors":"","doi":"10.36879/jcst.20.000120","DOIUrl":"https://doi.org/10.36879/jcst.20.000120","url":null,"abstract":"For patients with metastatic colorectal cancer (CRC), first-line therapy is based on chemotherapeutic agents, such as oxaliplatin,\u00005-fluorouracil and irinotecan. These drugs increase the overall survival, but resistance to therapy appears in almost 90% of patients,\u0000and the 5-year survival rate for patients with metastatic CRC is only about 12%.\u0000During the last few years, immune checkpoints blockade therapies have been developed and show good response in different cancers,\u0000including CRC with microsatellite instability (MSI). In this CRC subtype, the response rate to anti-PD-(L)1 antibodies is high thanks to\u0000the presence of neoantigens and tumor-infiltrating lymphocytes that are associated with the anti-tumor immune response. Nivolumab\u0000and pembrolizumab, two anti-PD-1 antibodies, have been approved for CRC MSI treatment. Moreover, it has been shown that the\u0000combination of chemotherapy and anti-PD-(L)1 molecules may convert cold tumors into hot tumors in which the immune system and\u0000T-cell infiltration are activated. In addition, recent studies found that DNA damage induces PD-L1 expression. ATM, ATR, DNA-PKcs\u0000and Chk1 are key sensors of the DNA damage response that regulate PD-L1 expression.\u0000This review summarizes the current knowledge on PD-L1 regulation at the genetic, epigenetic, transcriptional and translational\u0000levels. It also describes PD-L1 activation in response to chemotherapy and DNA damage. Then, it summarizes the current clinical\u0000trials that assess anti-PD-(L)1 therapies in combination with kinase inhibitors or chemotherapeutic agents in CRC.","PeriodicalId":73634,"journal":{"name":"Journal of cancer science and clinical therapeutics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84042792","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}