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An investigation to standardize the protocol for in vitro application of colchicine for enhancing the doubled haploid production in wheat was done. Two tetraploid (PDW-314 and A-9-30-1); and two hexaploid (DH-40 and C-306) wheat genotypes were used as maternal parents, whereas, the pollen sources involved Zea mays (cv. Bajaura Makka) and Imperata cylindrica. During the rabi seasons of years 2013–14 and 2014–15, wheat × maize and wheat × I. cylindrica hybridization was carried out followed by treatment of their haploids produced as a result of elimination of chromosomes of maize and I. cylindrica respectively, with varied doses of colchicine for different durations The various doses of colchicine were categorized into two groups: lower doses for longer durations (0.01, 0.025, 0.05% each for 5, 7, 9, 11 hrs) and higher doses for shorter durations (0.05, 0.075, 0.10, 0.15, 0.20, 0.25% each for 5, 4, 3, 2 hrs). The response of different concentrations of colchicine applied for varied durations revealed significant differences for various doubled haploidy parameters viz., per cent survived plants, per cent doubled haploid formation and per cent doubled haploid seed formation. In hexaploid and tetraploid wheats, colchicine doses of 0.075% for 4 hrs and 0.15% for 4 hrs, respectively were established as optimum for enhanced doubled haploid production. [ABSTRACT FROM AUTHOR]

Targeting a T-cell inhibitory checkpoint with the anti-CTLA-4 monoclonal antibody, ipilimumab, represents a scientific breakthrough in immunotherapy for the treatment of cancer. However, ipilimumab therapy is also associated with unique side effects, known as immune-related adverse events (irAEs), which need to be recognized and managed with immunosuppressive agents. To date, the majority of our knowledge regarding ipilimumab-associated side effects is based upon clinical studies in melanoma. Here we provide a review of ipilimumab-induced irAEs and our experience in a cohort of 44 patients with prostate cancer who were treated at the MD Anderson Cancer Center on two different clinical trial protocols. [ABSTRACT FROM AUTHOR]

Background Melanoma cell lines treated with decitabine show upregulation of cancer antigens, and interferon-α upregulates MHC Class I antigens in cancer cells, leading to enhanced T-cell recognition and T-cell mediated tumor apoptosis. We evaluated the synergy between the hypomethylating effects of decitabine and the immunomodulatory effects of interferon in a combination regimen administered to advanced melanoma patients in a phase 1 trial. Methods Patients with one prior systemic therapy were eligible. Using a modified 3 + 3 design, patients received escalating doses of decitabine and pegylated interferon α-2b (PEG-IFN) during every 28-day treatment cycle. Global DNA methylation was measured on days 1 and 5 of cycles 1 and 3. Cytokine profiling and quantification of T-cell subpopulations by FACS were performed at baseline and cycle 3. Results Seventeen patients were assigned to one of four dose levels. Decitabine 15 mg/m2/d + PEG-IFN 3 μg/kg was the maximum tolerated dose (MTD). Grade 3/4 cytopenias were seen across all dose levels: anemia (1), neutropenia (7), and thrombocytopenia (2). One patient remained progression-free for 37 weeks. The other 16 patients progressed at or before 12 weeks. Median overall survival was 39 weeks. Hypomethylation was seen at all dose levels. Due to treatment-induced lymphocytopenia, absolute changes in T-cell populations post-treatment were too small to be meaningfully interpreted. Conclusions The response to this combination regimen was characterized by significant myelosuppression, particularly neutropenia. Although disappointing efficacy and slow accrual led to early closure of the trial, hypomethylation showed pharmacodynamic evidence of a therapeutic effect of decitabine at all dose levels. [ABSTRACT FROM AUTHOR]