The cancer-preventive potential of cruciferous vegetables has drawn public and research interests, primarily due to their unique phytochemicals, dietary isothiocyanates (ITCs). Cruciferous vegetables consist of a diverse group of vegetables containing glucosinolates, the precursors of ITCs (Holst & Williamson, 2004). Glucosinolates are segregated from the endogenous enzyme myrosinase in intact plants. When vegetables are chopped or chewed, glucosinolates are hydrolyzed due to the released myrosinase (Higdon, Delage, Williams, & Dashwood, 2007). ITCs are one of the hydrolyzed products from glucosinolates and have long been known to be biologically active because of its chemical structure of-N=C=S group (Fenwick, Heaney, Mullin, & VanEtten, 1983). The anticancer property of dietary ITCs, which was not recognized until the early 1990s, has been supported by a rapid growth of preclinical evidence in various cancer models (Chung, Morse,

Accumulating evidence insists that circular RNAs (circRNAs) play important roles in the development of human cancers, including gastric cancer. This study aimed to investigate the role of circ-SFMBT2 and provide a potential mechanism to explain its function. The expression of circ-SFMBT2, miR-885-3p and chromodomain-helicase-DNA-binding protein 7 (CHD7) mRNA was determined by quantitative real-time PCR (qRT-PCR), and the protein level of CHD7 was determined by western blot. To investigate the function of circ-SFMBT2 in vitro, the effects of circ-SFMBT2 on cell viability, colony formation, apoptosis, migration and invasion were assessed using cell counting kit-8 assay, colony formation assay, flow cytometry assay, wounding healing assay and transwell assay, respectively. The indicators of oxidative stress were assessed using matched kits. Besides, the function of circ-SFMBT2 was also investigated in animal models. The relationship between miR-885-3p and circ-SFMBT2 or CHD7 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ-SFMBT2 and CHD7 were upregulated, whereas miR-885-3p was downregulated in gastric cancer tissues and cells. In functional assay, circ-SFMBT2 knockdown suppressed gastric cancer cell viability, colony formation ability, migration, invasion and oxidative stress but induced apoptosis, and circ-SFMBT2 downregulation also blocked tumor growth in vivo. In mechanism analysis, circ-SFMBT2 regulated CHD7 expression by sponging its target miRNA, miR-885-3p. Rescue experiments manifested that miR-885-3p inhibition reversed the effects of circ-SFMBT2 knockdown, and CHD7 overexpression abolished the antitumor role of miR-885-3p overexpression. Moreover, circ-SFMBT2 knockdown inactivated the Wnt/β-catenin signaling pathway. Circ-SFMBT2 downregulation repressed the development of gastric cancer partially by controlling the miR-885-3p/CHD7 axis, which might be a novel strategy to inhibit gastric cancer progression. Anti-Cancer Drugs 33: e247-e259

ImportanceTobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear.ObjectiveTo examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non–muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions.Design, Setting, and ParticipantsThe Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022.ExposuresUse of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records.Main Outcomes and MeasuresHazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression.ResultsA total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003).Conclusions and RelevanceThese findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.

Scope Dietary isothiocyanates (ITCs) from cruciferous vegetables have shown potent anti‐breast cancer activities in preclinical models, but their anticancer effects in vivo in breast cancer patients remain elusive. A proof‐of‐principle, presurgical window of opportunity trial is conducted to assess the anticancer effects of dietary ITCs in breast cancer patients. Methods and Results Thirty postmenopausal breast cancer patients are randomly assigned to receive ITC‐rich broccoli sprout extract (BSE) (200 µmol ITC per day) or a placebo for 2 weeks. Expression of biomarkers related to ITCs functions are measured in breast cancer tissue specimens at pre‐ and post‐interventions using immunohistochemistry staining. First morning urine samples are collected at both timepoints for proteomic analysis. Overall, the study shows high compliance (100%) and low toxicity (no grade 4 adverse event). Trends of increase in cleaved caspase 3 and tumor‐infiltrating lymphocytes (TILs) and trends of decrease in Ki‐67 and nuclear to cytoplasm ratio of estrogen receptor (ER)‐α are observed in the BSE arm only, consistent with the significantly altered signaling pathways identified in urinary proteomic analysis. Conclusions Anticancer activities of ITCs are observed in breast cancer patients, supporting the potential beneficial roles of ITC‐containing cruciferous vegetables in breast cancer prognosis.

Background: Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCO) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AA) and European Americans (EA).Methods: SNPs in 11 SLCO members were selected, with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1,045 SNPs were genotyped and analyzed in 993 AAs and 1,057 EAs from the North Carolina-Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using qRT-PCR, IHC, and in situ RNA hybridization in independent sets of prostate cancer cases.Results: Significant associations with prostate cancer characteristics were found for SNPs in SLCO2A1 and SLCO5A1. The associations differed by race (P interaction < 0.05). SNPs in SLCO2A1 were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in SLCO5A1 were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively.Conclusions: SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs.Impact: The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer.

Laparoscopic colorectal resection has been extensively accepted for treatment of colorectal cancer. There are several reports about surgeon's age as a factor to have influence on learning laparoscopic approach, and there is no consensus on this point. This study was designed to evaluate the outcomes of laparoscopic colorectal resection in period of learning curve completed by surgeons with different age in order to make clear whether older surgeons may learn laparoscopic approach with more difficulty than younger. From July 2010 to August 2012, the first twenty patients underwent laparoscopic colorectal resection completed by each surgeon were selected for analysis. A total of 240 patients treated by 5 older surgeons with median age of 51 years (range 47-54 years) and 7 younger surgeons with median age of 37 years (range 34-43 years) were divided into group 1 (n = 100) and group 2 (n = 140). The short-term outcomes of laparoscopic surgery of the two groups were compared. Two groups were matched in age, gender, body mass index, American Society of Anesthesiologists (ASA), etc. The median number of lymph nodes harvested was 18 (range 7-63) in group 1 and 16 (range 3-66) in group 2 (P = 0.003); The median operative time in group 1 was 185 min (range 105-480 min) compared to 235 min (range 120-470 min) in group 2 (P < 0.001), and blood loss were 150 ml (range 50-400 ml) and 200 ml (range 50-800 ml), respectively (P < 0.001); Conversion rate in group 2 was lower than in group 1 (12.0 vs 18.6 %, P = 0.196). The mean time to passing of first flatus was 3 day (range 2-5 day) in group 1 and 4 day (range 2-6 day) in group 2 (P = 0.001). Older surgeons can master the laparoscopic skill more easily and quickly. Age is not an obstacle for older surgeons to learn laparoscopic approach for colorectal cancer.

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Approximately 80% of patients with advanced bladder cancer do not respond to immune checkpoint inhibitor (ICI) immunotherapy. Therefore, there is an urgent unmet need to develop clinically relevant preclinical models so that factors governing immunotherapy responses can be studied in immunocompetent mice. We developed a line of mouse triple knockout (TKO: Trp53, Pten, Rb1) urothelial carcinoma organoids transplanted into immunocompetent mice. These bladder tumors recapitulate the molecular phenotypes and heterogeneous immunotherapy responses observed in human bladder cancers. The TKO organoids were characterized in vivo and in vitro and compared to the widely used MB49 murine bladder cancer model. RNAseq analysis of the TKO tumors demonstrated a basal subtype. The TKO xenografts demonstrated the expression of urothelial markers (CK5, CK7, GATA3, and p63), whereas MB49 subcutaneous xenografts did not express urothelial markers. Anti-PD-1 immunotherapy resulted in a mixed pattern of treatment responses for individual tumors. Eight immune cell types were identified (basophils, B cells, dendritic cells, macrophages, monocytes, neutrophils, NK cells, and T cells) in ICI-treated xenografts. Responder xenografts displayed significantly increased immune cell infiltration (15.3%, 742 immune cells/4861 total cells) compared to the non-responder tumors (10.1%, 452 immune cells/4459 total cells, Fisher Exact Test p < 0.0001). Specifically, there were more T cells (1.0% vs. 0.4%, p = 0.002) and macrophages (8.6% vs. 6.4%, p = 0.0002) in responder xenografts than in non-responder xenografts. In conclusion, we have developed a novel preclinical model that exhibits a mixed pattern of response to anti-PD-1 immunotherapy. The higher percentage of macrophage tumor infiltration in responders suggests a potential role for the innate immune microenvironment in regulating ICI treatment responses.