Frontiers in oncology
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Cutaneous T cell lymphomas (CTCL) are a heterogeneous group of malignancies characterized by the expansion of a malignant T cell clone. Chimeric Antigen Receptor (CAR) T cell therapy has shown impressive results for the treatment of B-cell tumors, but several challenges have prevented this approach in the context of T cell lymphoma. These challenges include the possibilities of fratricide due to shared T-cell antigens, T cell immunodeficiency, and CAR transduction of malignant cells if CAR T are manufactured in the autologous setting. In this review, we discuss these and other challenges in detail and summarize the approaches currently in development to overcome these challenges and offer cellular targeting of T cell lymphomas.
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Frontiers in oncology · Jan 2019
ReviewUnderstanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies.
Taking advantage of the immune system to exert an antitumor effect is currently a novel approach in cancer therapy. Adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) targeting a desired antigen has shown extraordinary antitumor activity, especially in refractory and relapsed B-cell malignancies. ⋯ However, with the widespread use of CAR T-cell therapy, problems of resistance and relapse are starting to be considered. This review provides a comprehensive picture of the mechanisms of resistance to CAR T-cell therapy from three aspects, namely, CAR T-cell factors, tumor factors, and tumor microenvironment factors, offering insights for improving CAR T-cell therapy.
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Frontiers in oncology · Jan 2019
Combination of Intravesical Bacille Calmette-Guérin and Chemotherapy vs. Bacille Calmette-Guérin Alone in Non-muscle Invasive Bladder Cancer: A Meta-Analysis.
Background: About 75% of newly diagnosed bladder cancer cases suffer from non-muscle invasive bladder cancer (NMIBC), which used to recur and progress despite transurethral resection of bladder tumor (TURBT). This meta-analysis was conducted to examine if combined application of intravesical bacille Calmette-Guérin (BCG) with chemotherapy is associated with better prognosis. Methods: Systematic searches of randomized controlled trials (RCTs) concerning NMIBC were performed in PubMed, EMbase, CENTRAL, CNKI, WanFang, VIP, CBM databases, and some specialized websites. ⋯ The rate of fever (RR = 0.50, 95%CI: 0.27-0.91, P = 0.02), irritative bladder symptoms (RR = 0.69, 95%CI: 0.52-0.90, P = 0.007) and hematuria (RR = 0.50, 95%CI: 0.28-0.89, P = 0.02) were significantly decreased in patients treated with combination therapy compared to those with BCG alone. There were no statistically significant differences between combination therapy and BCG alone in toxicity (RR = 0.69, 95%CI: 0.34-1.40, P = 0.30), gastrointestinal reaction (RR = 2.54, 95%CI: 0.61-10.60, P = 0.20) or cystitis (RR = 0.67, 95%CI: 0.29-1.54, P = 0.34). Conclusions: Combined application of intravesical BCG and chemotherapy appears to be an effective treatment for patients with intermediate- to high-risk NMIBC, but not for those with tumor in situ alone or recurrent bladder cancer.
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Frontiers in oncology · Jan 2019
Prognostic Role of Platelet-to-Lymphocyte Ratio in Patients With Bladder Cancer: A Meta-Analysis.
Background: Many studies have been reported that platelet-to-lymphocyte ratio (PLR) may be associated with the prognosis of bladder cancer, but the results are inconsistent. Therefore, we performed a meta-analysis to evaluate the effect of pretreatment PLR on the prognosis of bladder cancer. Methods: The databases PubMed, Embase, Cochrane Library, and Web of Science were searched. ⋯ An elevated PLR was significantly associated with poorer overall survival (OS) (HR = 1.26, 95% CI = 1.03-1.54, p = 0.026), but not with cancer-specific survival (CSS) (HR = 1.15, 95% CI = 0.95-1.38, p = 0.149), or recurrence-free survival (RFS) (HR = 1.72, 95% CI = 0.79-3.75, p = 0.175). In addition, high PLR was correlated with age ≥ 65 years (OR = 1.82, 95% CI = 1.24-2.67, p = 0.002), whereas was not significantly correlated with sex, tumor grade, tumor stage, distant metastasis, or tumor size. Conclusions: The pretreatment PLR could serve as a predicative biomarker of poor prognosis for patients with bladder cancer.
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Frontiers in oncology · Jan 2019
Observational Studies on the Association Between Post-diagnostic Metformin Use and Survival in Ovarian Cancer: A Systematic Review and Meta-Analysis.
Objectives: To summarize and quantify the relationship between post-diagnostic metformin use and ovarian cancer (OC) survival. Methods: We systematically conducted an updated meta-analysis based on observational studies published up to December 31, 2018, identified from PubMed and Web of Science. Two team members independently extracted data and assessed the quality of each study. ⋯ No significant publication bias was detected in these analyses. Conclusions: Post-diagnostic metformin use is consistently associated with better survival of OC patients regardless of diabetes status. Studies with larger sample sizes and prospective designs are required to confirm these findings and obtain detailed information, including standardized references for comparison, intensity and dose of metformin use, and further adjustment for potential confounders.