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New Targets in Advanced Thyroid Cancer Refractory Iodine 晚期甲状腺癌难治碘的新靶点
Cancer Research Journal Pub Date : 2019-04-23 DOI: 10.11648/J.CRJ.20190702.12
Lynda Marianela Vásconez Proaño
{"title":"New Targets in Advanced Thyroid Cancer Refractory Iodine","authors":"Lynda Marianela Vásconez Proaño","doi":"10.11648/J.CRJ.20190702.12","DOIUrl":"https://doi.org/10.11648/J.CRJ.20190702.12","url":null,"abstract":"The majority of deaths due to thyroid cancer occur in patients with advanced DTC refractory to radioactive iodine. The spectacular advances in molecular medicine of recent years have opened new therapeutic possibilities. Currently, there is general agreement that treatment with Tyrosine Kinase Inhibitors (TKI) should only be considered in patients with differentiated thyroid carcinoma refractory to radioactive iodine, with progressive and / or symptomatic metastatic disease that can not otherwise be treated locally. Most of these \"new molecules\" are multichannel inhibitors with varied action, which interact on different proteins such as RET, BRAF, cKIT, MET, EGFR, MAPK, PDGFR, etc. In addition, they have the additional advantage that they markedly prevent angiogenesis by acting on VEGFR 1, 2, and 3. TKI are associated with progression-free survival but not curative. Also, causes adverse effects that can affect the quality of life.The prolongation of progression-free survival has been demonstrated with sorafenib and lenvatinib compared with placebo in two phase III trials. These two drugs have been approved by the FDA and the European Medicines Agency for use in patients refractory to radioactive iodine with metastatic disease. Based on the Phase II Trials there are other Tyrosine Kinase Inhibitors (TKI) available such as sunitinib, axitinib or pazopanib that can produce some kind of clinical benefit and therefore need further investigation.","PeriodicalId":9422,"journal":{"name":"Cancer Research Journal","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85659125","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}
引用次数: 0
Effect of Second Cycle Pre-induction Chemotherapy in Critically Ill Burkitt’s Lymphoma Children 第二周期诱导前化疗治疗危重儿童伯基特淋巴瘤的效果
Cancer Research Journal Pub Date : 2019-04-18 DOI: 10.11648/J.CRJ.20190701.14
E. Moussa, A. Hamoda, S. Semary, Marwa Romeih, R. Amin, Omneya Hassanin
{"title":"Effect of Second Cycle Pre-induction Chemotherapy in Critically Ill Burkitt’s Lymphoma Children","authors":"E. Moussa, A. Hamoda, S. Semary, Marwa Romeih, R. Amin, Omneya Hassanin","doi":"10.11648/J.CRJ.20190701.14","DOIUrl":"https://doi.org/10.11648/J.CRJ.20190701.14","url":null,"abstract":"Advanced stage Burkiit’s lymphoma (BL) is associated with tumor burden. Toxicities from intensive therapies are significant. The objectives of this study were to analyze the outcome of patients who could not receive induction chemotherapy on time, and were given a 2nd pre-phase (CVP), and to measure the impact of delay on disease outcome. It is a retrospective non randomized study included pediatric patients, suffering from Burkitt’s Lymphoma over 8 years period in CCHE. The result showed that, four hundred and eight patients were diagnosed as Burkitt’s Lymphoma from July 2007 till October 2015, 286 patients (70.1%) received induction on time as per protocol, while 122 patients (29.9%) were not fit to receive their induction chemotherapy on due time. The delay ranged from 6-45 days. While forty five patients (36.88%) out of the delayed patients received 2nd CVP, 16 patients (13.1%) showed relapse/progression. OS among delayed patients who received 2nd CVP versus those who were delayed and were able to receive full induction chemotherapy was (76.1%), (88.7%) respectively. OS in patients who were delayed versus those who were not delayed was (84%), (85.9%) respectively. In conclusion, in critically ill patients delay of chemotherapy in induction phase is important to reduce morbidity and mortality. The delay of chemotherapy has no impact on OS in Burkitt’s lymphoma children. A second pre-phase therapy in our opinion should not be adopted for all critical ill patients who will not tolerate intensive therapy during early phases of treatment, but instead we recommend a recovery from organ toxicity and starting intensive therapy (COPADM) rather than giving 2nd CVP with careful surveillance of disease progression.","PeriodicalId":9422,"journal":{"name":"Cancer Research Journal","volume":"83 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77521435","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}
引用次数: 0
Treatment Efficiency and Problems of Local Control in Localized Bladder/Prostate Rhabdomyosarcoma 局限性膀胱/前列腺横纹肌肉瘤的治疗效果及局部控制问题
Cancer Research Journal Pub Date : 2019-04-18 DOI: 10.11648/J.CRJ.20190702.11
H. Hafez, E. E. Nadi, A. Younes, Gehad Ahmed, M. Zaghloul, H. Taha, Rania M Labib, S. Fadel, Soha Ahmed
{"title":"Treatment Efficiency and Problems of Local Control in Localized Bladder/Prostate Rhabdomyosarcoma","authors":"H. Hafez, E. E. Nadi, A. Younes, Gehad Ahmed, M. Zaghloul, H. Taha, Rania M Labib, S. Fadel, Soha Ahmed","doi":"10.11648/J.CRJ.20190702.11","DOIUrl":"https://doi.org/10.11648/J.CRJ.20190702.11","url":null,"abstract":"Objectives: To assess the treatment efficiency, outcome and factors affecting the local control of localized bladder/prostate RMS. Patients and methods: Retrospective analysis of 54 patients with localized bladder/prostate RMS treated at Children Cancer Hospital, Egypt between August 2007 and Jan 2017. All patients were treated according to Intergroup Rhabdomyosarcoma Study (IRS -V) and subsequent Children’s Oncology Group COG guidelines. Results: The median age at diagnosis was 3.28 years (range 0.4–13.6). Fifty-one patients (94%) underwent initial biopsy. Complete surgical resection (primary or delayed) was performed in 7 patients (13%). Local control started before/at week 12 in 29 patients (61.7%). Local control methods were: Radiotherapy in 43 patients (79.2%), radiotherapy with surgery in 4 patients (9%), surgery in 1 patient and four patients did not receive local control. With a median follow up of 38.12 months, the 5-year failure-free survival (FFS) and overall (OS) of the whole patients were 60.4 ± 14.5% and 75.4 ± 14.1% respectively. A better 5-year FFS was experienced by those who had early local control (79.2 ± 17% vs. 43.8 ± 25% p= 0.005). Conclusions: Timing of local control and local radiotherapy is crucial and shouldn’t be delayed waiting for further response to the systemic chemotherapy.","PeriodicalId":9422,"journal":{"name":"Cancer Research Journal","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91542334","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}
引用次数: 0
Localised Prostate Versus Whole Pelvic Irradiation in High Risk Prostate Cancer, Single Institute Experience 高危前列腺癌的局部前列腺照射vs全盆腔照射,单个研究所的经验
Cancer Research Journal Pub Date : 2019-04-01 DOI: 10.11648/J.CRJ.20190701.13
R. Latif, Ghada Ezzat Eladawei
{"title":"Localised Prostate Versus Whole Pelvic Irradiation in High Risk Prostate Cancer, Single Institute Experience","authors":"R. Latif, Ghada Ezzat Eladawei","doi":"10.11648/J.CRJ.20190701.13","DOIUrl":"https://doi.org/10.11648/J.CRJ.20190701.13","url":null,"abstract":"Objectives: Whole pelvic irradiation [WPRT] versus prostate only radiation [PO-RT] in node negative high risk disease is controversial. This study aims to assess survival benefit of PO-RT against WPRT in high risk negative nodes prostate cancer. Patients and Methods: Patients with high risk prostate cancer and negative pelvic lymph nodes treated randomly either with WPRT [arm1] or PORT [arm2] from June-2014-June-2017. Eligible patients were ˃18 years, risk factors selected are ≥T3, GS≥8, or PSA≥20nglml. All patients received hormonal therapy as neo-adjuvant and concurrent with radiation and followed to 2-3 years. Univariate and multivariate analysis are performed. The primary end point was progression free survival [PFS], and the secondary was OAS and toxicity assessment. Results: Ninety four patients included, 48 received WPRT arm and 46 received PORT. With median follow up 26 months there was no significant difference in PFS, or OAS [P=0.994 and 0.505] respectively between both arms. On univariate analysis PFS was significantly better in lower stage [P=0.014], lower GS [P=0.000], lower number of risk factors [P=0.016]. Only 2 cases with late grade 3 gastrointestinal toxicity in observed in WPRT [P=0.044], and one case late grade 3 genitourinary in PORT with no significance [P=0.096]. Conclusion: Addition of pelvic irradiation in high risk node negative prostate cancer has no impact on survival in comparison to PORT.","PeriodicalId":9422,"journal":{"name":"Cancer Research Journal","volume":"26 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73239498","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}
引用次数: 0
High Expression of C-reactive Protein Increases the Risk of Poor Prognosis in Patients with Gastric Cancer: A Meta-analysis c反应蛋白高表达增加胃癌患者预后不良的风险:一项荟萃分析
Cancer Research Journal Pub Date : 2016-12-25 DOI: 10.11648/j.crj.20190703.16
Jing Yang, Fulun Li, Ruijie Chang, Yong-bin Lu
{"title":"High Expression of C-reactive Protein Increases the Risk of Poor Prognosis in Patients with Gastric Cancer: A Meta-analysis","authors":"Jing Yang, Fulun Li, Ruijie Chang, Yong-bin Lu","doi":"10.11648/j.crj.20190703.16","DOIUrl":"https://doi.org/10.11648/j.crj.20190703.16","url":null,"abstract":"Objective: To investigate the correlation between the expression level of C-reactive protein (CRP) and the prognosis of patients with gastric cancer, and its dose-response relationship. Methods: A computer-based online search was performed by using China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and Web of Science database. The cohort studies on the relationship between CRP and the risk of poor prognosis in patients with gastric cancer were selected according to the inclusion and exclusion criteria, and the data were extracted and evaluated. Then Meta-analysis was performed by using STATA 11.0 software. The pooled hazard ratio (HR) and its 95% confidence interval (CI) were calculated. Furthermore, the subgroup analysis, multivariate analysis, sensitivity analysis and publication bias test were performed, respectively. Results: A total of eighteen cohort studies were included, involving 3 656 patients with gastric cancer. Meta-analysis showed a significant association between the expression of CRP and prognosis in patients with gastric cancer (HR = 1.50, 95% CI: 1.24-1.81, P 10 mg/L. Subgroup analysis showed no significant difference when the included studies were divided by the number of samples, follow-up time, TNM staging, and treatment methods (all P > 0.05). According to multivariate analysis, the peritoneal metastasis and recurrence were the independent factors associated with poor prognosis of patients with gastric cancer (both P > 0.05). Conclusion: The level of CRP was significantly associated with the prognosis of patients with gastric cancer in different clinical stages, and the risk of poor prognosis was significantly increased when CRP level > 10mg/L. DOI:10.3781/j.issn.1000-7431.2016.33.662","PeriodicalId":9422,"journal":{"name":"Cancer Research Journal","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81597181","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}
引用次数: 0
Reactive Oxygen Species and Serous Epithelial Ovarian Adenocarcinoma. 活性氧与浆液上皮性卵巢腺癌。
Cancer Research Journal Pub Date : 2016-11-01 Epub Date: 2017-01-09 DOI: 10.11648/j.crj.20160406.13
Shakeria Cohen, Sharifeh Mehrabi, Xuebiao Yao, Stephanie Millingen, Felix O Aikhionbare
{"title":"Reactive Oxygen Species and Serous Epithelial Ovarian Adenocarcinoma.","authors":"Shakeria Cohen,&nbsp;Sharifeh Mehrabi,&nbsp;Xuebiao Yao,&nbsp;Stephanie Millingen,&nbsp;Felix O Aikhionbare","doi":"10.11648/j.crj.20160406.13","DOIUrl":"https://doi.org/10.11648/j.crj.20160406.13","url":null,"abstract":"<p><p>Serous ovarian cancer (SOC) is usually diagnosed at late stage and stage-adjusted five year survival rate is low. Mortality is relatively heavy on African-Americans/Black (AA) affected with SOC compared to their Caucasian counterparts, though the cause for the disparity remains unclear. DNA damage induced by oxidative stress has been linked to ovarian cancer, but the role of oxidative stress in distinguishing differences in aggressive SOC tumors among patients is yet to be determined. This study aims to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reactive carbonyl groups and antioxidants in primary SOC normal, precancerous (cystadenoma, borderline) and invasive (III/IV) tissue samples obtained from AA and Caucasian subgroups. Additionally, the study seeks to investigate significant changes in the level of ROS between AA and Caucasian SOC samples. A fluorogenic probe, dichlorodihydrofluorescein (DCFH-DiOxyQ), was used to scavenge reactive oxygen species in SOC normal, precancerous and malignant stages III/IV tissue samples. Malondialdehyde (MDA), a lipid peroxidation marker, and reactive carbonyl groups were measured as indicators of oxidative injury. Moreover, antioxidant status was assessed by estimating glutathione peroxidase 3 (GPX3) enzyme levels. Results indicate ROS concentration was approximately 96% higher in the malignant tissues in comparative to the normal non-diseased controls. In addition, ROS concentration among AA women was approximately 9% higher than Caucasian women. MDA levels increased exponentially from non-disease control and precancerous tissues relative to malignant tissues. Furthermore, malignant serous ovarian samples showed significantly higher reactive carbonyl content compared to the non-disease controls (p=0.009), while GPX3 levels decreased considerably in serous cystadenoma and malignant tissue samples, and non-diseased control compared to borderline disease. The results suggest accumulation of ROS and MDA levels may be a causative factor for SOC. Elevated levels of MDA and reactive carbonyl proteins could override the GPX3 enzyme capacity therefore, initiating serous ovarian neoplasm.</p>","PeriodicalId":9422,"journal":{"name":"Cancer Research Journal","volume":"4 6","pages":"106-114"},"PeriodicalIF":0.0,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427055/pdf/nihms852990.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34993802","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}
引用次数: 17
Investigating Molecular Mechanisms of Activation and Mutation of the HER2 Receptor Tyrosine Kinase through Computational Modeling and Simulation. 通过计算模型和模拟研究HER2受体酪氨酸激酶激活和突变的分子机制。
Cancer Research Journal Pub Date : 2011-01-01
Shannon E Telesco, Andrew Shih, Yingting Liu, Ravi Radhakrishnan
{"title":"Investigating Molecular Mechanisms of Activation and Mutation of the HER2 Receptor Tyrosine Kinase through Computational Modeling and Simulation.","authors":"Shannon E Telesco,&nbsp;Andrew Shih,&nbsp;Yingting Liu,&nbsp;Ravi Radhakrishnan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human epidermal growth factor receptor 2 (HER2)/ErbB2 is a receptor tyrosine kinase belonging to the EGFR/ErbB family and is overexpressed in 20-30% of human breast cancers. Since there is a growing effort to develop pharmacological inhibitors of the HER2 kinase for the treatment of breast cancer, it is clinically valuable to rationalize how specific mutations impact the molecular mechanism of receptor activation. Although several crystal structures of the ErbB kinases have been solved, the precise mechanism of HER2 activation remains unknown, and it has been suggested that HER2 is unique in its requirement for phosphorylation of Y877, a key tyrosine residue located in the activation loop (A-loop). In our studies, discussed here, we have investigated the mechanisms that are important in HER2 kinase domain regulation and compared them with the other ErbB family members, namely EGFR and ErbB4, to determine the molecular basis for HER2's unique mode of activation. We apply computational simulation techniques at the atomic level and at the electronic structure (quantum mechanical) level to elucidate details of the mechanisms governing the kinase domains of these ErbB members. Through analysis of our simulation results, we have discovered potential regulatory mechanisms common to EGFR, HER2, and ErbB4, including a tight coupling between the A-loop and catalytic loop that may contribute to alignment of residues required for catalysis in the active kinase. We further postulate an autoinhibitory mechanism whereby the inactive kinase is stabilized through sequestration of catalytic residues. In HER2, we also predict a role for phosphorylated Y877 in bridging a network of hydrogen bonds that fasten the A-loop in its active conformation, suggesting that HER2 may be unique among the ErbB members in requiring A-loop tyrosine phosphorylation for functionality. In EGFR, HER2, and ErbB4, we discuss the possible effects of activating mutations. Delineation of the activation mechanism of HER2 in the context of the other ErbB members is crucial for understanding how the activated kinase might interact with downstream molecules and couple to signaling cascades that promote cancer. Our comparative analysis furthers insight into the mechanics of activation of the HER2 kinase and enables us to predict the effect of an identified insertion mutation on HER2 activation. Further understanding of the mechanism of HER2 kinase activation at the atomic scale and how it couples to downstream signaling at the cellular scale will elucidate predictive molecular phenotypes that may indicate likelihood of response to specific therapies for HER2-mediated cancers.</p>","PeriodicalId":9422,"journal":{"name":"Cancer Research Journal","volume":"4 4","pages":"1-35"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208668/pdf/nihms294756.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32773328","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}
引用次数: 0
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