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Background: Recurrent/metastatic adenoid cystic carcinoma (ACC) is a rare, incurable disease. MYB is a putative oncogenic driver in ACC that is often overexpressed through an MYB‐NFIB rearrangement. The authors hypothesized that AKT inhibition with the allosteric inhibitor MK‐2206 could decrease MYB expression and induce tumor regression in patients with incurable ACC (ClinicalTrials.gov identifier NCT01604772). Methods: Patients with progressive, incurable ACC were enrolled and received MK‐2206 150 mg weekly; escalation to 200 mg was allowed. The primary end point was confirmed response. Secondary end points were progression‐free survival, overall survival, and safety. An exploratory analysis evaluating the effect of MK‐2206 on MYB expression was conducted in a subset of patients. Results: Sixteen patients were enrolled, and 14 were evaluable for efficacy. No confirmed responses were observed. Thirteen patients had stable disease, and one had disease progression as their best response. The median progression‐free survival was 9.7 months (95% CI, 3.8–11.8 months), and the median overall survival was 18.0 months (95% CI, 11.8–29.9 months). Nine of 16 patients (56%) had at least one grade 3 treatment‐related adverse event, and the most common were rash (38%), fatigue (19%), decreased lymphocyte count (13%), and hyperglycemia (13%). Twelve of 14 tumors (86%) had detectable MYB expression by immunohistochemistry, and seven of 14 tumors (50%) had an MYB‐NFIB gene rearrangement. Serial biopsies revealed decreased MYB levels with MK‐2206 in four of five patients. Conclusions: MK‐2206 failed to induce clinical responses in patients with incurable ACC. AKT inhibition may diminish MYB protein levels, although the effect was highly variable among patients. Novel approaches to target MYB in ACC are needed. This phase 2 clinical trial demonstrated that the AKT inhibitor MK‐2206 failed to induce clinical responses in patients with recurrent/metastatic adenoid cystic carcinoma. Tumor tissue analyses suggest that MK‐2206 treatment may have diminished intratumoral MYB protein levels. [ABSTRACT FROM AUTHOR]

Abstract Background Metastatic melanoma is an incurable disease with an average survival of less than one year. Talabostat is a novel dipeptidyl peptidase inhibitor with immunostimulatory properties. Methods This phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75–100 mg/m2 cisplatin combined with 300–400 mcg talabostat bid for 6, 21-day cycles. The primary endpoint was overall response. The rate of complete responses, duration of overall objective response, progression-free survival (PFS), and overall survival were the secondary endpoints. Results Six objective partial responses were recorded in the 74 patients (8.1%) in the intention-to-treat population. Five of these responses involved the 40 evaluable patients (12.5%). Thirty-one percent of patients reported SAEs to the combination of talabostat and cisplatin. Conclusion Acceptable tolerability was observed in the intention-to-treat population and antitumor activity was observed in 12.5% of evaluable patients, which is not greater than historical expectation with cisplatin alone.

Objective: This pilot study determined the profile of the oral bacterial flora in an outpatient cancer population before and after chemotherapy using molecular techniques. Study design: We recruited 9 newly diagnosed breast cancer patients scheduled for induction chemotherapy. All were seen immediately before chemotherapy, and 7 to 14 days later. At both visits, we performed oral evaluations and obtained mucositis grading (with the World Health Organization [WHO] scale), absolute neutrophil counts (ANC), and bacterial samples from the buccal mucosa. Bacterial DNA was isolated, and 16S ribosomal RNA gene clonal libraries were constructed. Sequences of genes in the library were used to determine species identity by comparison to known sequences. Results: After chemotherapy, WHO scores of 0 and 1 were in 3 and 6 patients, respectively, and mean ANC (±SD) dropped from 3326 ± 463 to 1091 ± 1082 cells/mm3. From pre- and post-chemotherapy samples, 41 species were detected, with a predominance of Gemella haemolysans and Streptococcus mitis. More than 85% of species have not been previously identified in chemotherapy patients. Seven species appeared exclusively before chemotherapy and 25 after chemotherapy. After chemotherapy, the number of species per patient increased by a mean of 2.6 (SD = 4.7, P = .052). Conclusion: We identified species not previously identified in chemotherapy patients. Our results suggest a shift to a more complex oral bacterial profile in patients undergoing cancer chemotherapy. [Copyright &y& Elsevier]

This investigation has confirmed the earlier reports that when aflatoxin B - DNA adducts are stored under physiological conditions some aflatoxin B - guanine adducts are converted to a secondary product in which fission of the imidazole ring of the adduct guanine has occurred. Incubation of DNA containing aflatoxin B - guanine adducts for an increasing number of hours under physiological conditions resulted in a progessive increase in the number of adducts in which the imidazole rings of guanines underwent fission. It was shown that the enzyme, formamidopyrimidine-DNA glycosylase exercises from the 6-day incubated DNA, an amount of imidazole ring opened guanines equivalent to 40% of the aflatoxin B - guanine adducts present in the DNA. The enzymatic excision of imidazole ring opened aflatoxin B - guanine adducts is inhibited by Cibacron Blue F3GA a strong inhibitor of formamidopyrimidine-DNA glycosylase. Treatment of afaltoxin B - DNA with mild alkali (pH 9.6), resulted in a 2-fold increase in the amount of aflatoxin B - guanines with opened imidazole rings; this was revealed by enzyme assays using this alkaline treated DNA substrate as well as by analysis of acid hydrolysates of the alkaline treated DNA. [ABSTRACT FROM PUBLISHER]