Browsing by Subject "Antineoplastic Combined Chemotherapy Protocols"
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Item Chronic lymphocytic leukemia: from "chemo"-therapy to "chronic" therapy(2020-07-24) Awan, Farrukh T.Item Mechanisms of Sensitization to Chemotherapy in Non-Small Cell Lung Cancer(2012-07-20) Greer, Rachel Marie; Minna, John D.Lung cancer is the leading cause of cancer-related deaths world-wide for men and women, due in part to late detection of disease and inherent resistance to treatment. This body of work focuses on resistance to treatment, specifically chemotherapy and understanding ways to sensitize non-small cell lung cancers to existing chemotherapies. Using a large panel of non-small cell lung cancers, response to common platinum-based doublet chemotherapy was tested, and compared in a statistical fashion to each chemotherapy as a single agent, to understand the breadth of responses, and have a baseline of response to improve upon. The rest of this work endeavors to make chemotherapies more effective at tumor kill by targeting tumor specific alterations. One such targeted approach focused on miR337, and its ability to influence paclitaxel sensitivity through introduction of miR337 mimics and antagomiRs was evaluated using MTS based assays; increasing miR337 levels in moderately paclitaxel-sensitive or completely paclitaxel resistant cells sensitized the cells at least ten-fold to paclitaxel. Non-small cell lung cancers have frequent mutations in p53 (>80%). Targeting of the p53 promoter region with agRNAs, in p53-mutant containing cell lines induces cytotoxicity that is reminiscent of wild type p53 activity and is associated with large increases of the non-coding RNA lincRNAp21, and can cause large sensitizations to p53-dependent chemotherapies such as doxorubicin, indicating that these agRNAp53s could be of therapeutic importance in p53-mutant lung cancers. Re-engagement of the apoptotic pathway by a small molecule (JP1201) sensitizes non-small cell lung cancers to a variety of chemotherapies. Anti-mitotic chemotherapies have the most frequent sensitization across a large panel of non-small cell lung cancers, and the largest degree of sensitization by combination with JP1201, and this sensitization is dependent on activation of the ER stress pathway. Xenograft models using cell lines recapitulate the ability of JP1201 to sensitize non-small cell lung cancers to chemotherapy, indicating that combinations with JP1201 might be effective in patients.Item Metastatic prostate cancer: current and emerging therapies(2014-12-05) Courtney, KevinItem Study of the Effect of Age on Toxicity During Treatment of Acute Lymphoblastic Leukemia (ALL)(2016-01-19) Wu, Amy; Leonard, David; Winick, NaomiBACKGROUND: Minimizing toxicity is critical to the safety and efficacy of therapy. There are data suggesting that adolescents and young adults experience greater toxicity than younger patients during the induction and delayed intensifications (DI) phases of therapy due to use of arparaginase and steroids. However, this data have reflected the use of an older asparaginase preparation, have been based on reviews, or do not address the potential role of BMI and ethnicity in the expression of toxicities. OBJECTIVE: We wanted to determine whether age influences the likelihood of a patient with ALL to experience a higher number or maximum grade of 3-5 chemotherapy-related toxicities during the induction and DI phases. We looked at what role BMI, ethnicity, and gender play in the effect of age on toxicity. METHODS: Patients with ALL aged <1 and >22 years at diagnosis, classified and treated as having high-risk disease on or as per the Children's Oncology group protocol AALL0232 over the past 10 years, were identified though the pediatric oncology registry at Children's Health System of Texas. We conducted a retrospective chart review; the data collected included type of leukemia, age at diagnosis, ethnicity, BMI, toxicities, WBC at diagnosis, CNS status, date of treatment, allergies to chemotherapy, and leukemia cytogenetics. We graded the toxicity severity using the CTCAEv4 system. Patient characteristics were summarized by quartile of age at diagnosis. Unadjusted trends between toxicity outcomes and age were tested using the Jonckheere-Terpstra nonparametric method. Trends between toxicity outcomes and age adjusted for BMI, ethnicity, and gender were tested using Poisson regression models. Febrile neutropenia was omitted as a toxicity. RESULTS: In the induction phase of the therapy with N=158, the unadjusted trend between age at diagnosis and maximum grade of toxicity is significant (p=0.011). The unadjusted trend between age at diagnosis and number of grade 3-5 toxicities is significant (p=0.009). The multiple regression results indicate that when the relationships between age at diagnosis and toxicity are adjusted for BMI, ethnicity and gender, the relationship between age and both maximum grade and number of grade 3-5 toxicities are no longer significant. BMI and ethnicity significantly influence the number of 3-5 toxicities. The relationship between age and toxicity during the DI phase is not significant. CONCLUSIONS: Conducting a retrospective chart review of the high-risk ALL patients at Children's Health System revealed that age is not a significant risk factor for higher number and severity of chemotherapy-related toxicity when adjusted for BMI, ethnicity, and gender. This will allow for better supportive care measure and counselling of patients and their parents with respect to the risks associated with ALL therapy.Item Well differentiated neuroendocrine tumors past, present and future(2017-12-08) Arriaga, Yull E.