The complications of clinical metastatic disease are responsible for the majority of breast cancer related deaths, and fewer therapies substantially prolong survival. Nitidine chloride (NC), a natural polyphenolic compound, has been shown to exhibit potent anticancer effects in many cancer types, including breast cancer. The epithelial-mesenchymal transition (EMT) and the acquisition of cancer stem cells (CSCs)-like properties emerge as critical steps in the metastasis of human cancers. However, the effects of NC on the EMT and the CSCs-like properties in breast cancer cells, and the underlying molecular mechanisms are not fully understood. In the present study, MDA-MB-468 and MCF-7 cancer cells were treated with NC. Scratch and Transwell assays were performed to determine whether NC could attenuate the migratory and invasive capability of cancer cells; Mammosphere formation and flow cytometry analysis were performed to confirm that NC decreased CSCs-like phenotype; RT-PCR and western blot analysis were used to examine the expression level of EMT and CSC related markers in both cells. Mechanistically, NC could inhibit the components of Hedgehog pathway (smoothened, patched, Gli1 and Gli2), subsequently inhibited the expression of Snail, Slug and Zeb1, which were correlated with the significant changes of the expression of EMT related markers (N-cadherin, E-cadherin, and Vimentin) to reverse EMT. On the other hand, NC could also inhibit the expression of CSCs related factors such as Nanog, Nestin, Oct-4 and CD44 via Hedgehog pathway. Furthermore, transforming growth factor-β1 (TGF-β1)-induced increment of EMT and CSCs properties could be reversed by NC. Taken together, these data indicated that NC suppressed breast cancer EMT and CSCs-like properties through inhibiting Hedgehog signaling pathway. Our study suggested that NC may be a potential anticancer agent for breast cancer.

Purpose: To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments. Patients and Methods: Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate, and drug safety profile. Results: Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (CI), 69.6–87.8, 67 patients], with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (95% CI, 9.3–15.9). The median PFS was 13.4 months (95% CI, 11.1–16.7). The 12-month OS rate was 91.4% (95% CI, 82.7–95.8) and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events Grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%). Conclusions: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory patients with FL who had received at least two prior systemic therapies.

Background: Recent studies identified an increased risk of prostate cancer (PCa) in Caucasian men harboring polymorphisms of genes involved in innate immunity and inflammation. This study was designed to assess whether single nucleotide polymorphisms in the IL-10 promoter play a role in predisposing individuals to PCa in a Chinese population. Methods: We genotyped three SNPs of the IL-10 promoter (-1082A/G, -819T/C and -592A/C) using polymerase chain reaction-restriction fragment length polymorphism analysis in 262 subjects with PCa and 270 age-matched healthy controls. Odds ratio and 95% confidence interval were determined by logistic regression for the associations between IL-10 genotypes and haplotypes with the risk of PCa and advanced PCa grade. Results: No significant differences in allele frequency or genotype distribution were observed for any of the IL-10 SNPs between PCa patients and control subjects. Significantly higher frequencies of -1082G, -819C and -592C allele and GCC haplotype were observed, however, in early stage patients in comparison to advanced PCa patients (for -1082 G, 13.9% vs 6.1%, OR = 2.48, P = 0.005; for -819 C 40.3% vs 30.8%, OR = 1.51, P = 0.043; for -512C, 40.3% vs 30.8%, OR = 1.51, P = 0.043; and for haplotype GCC 11.1%vs 5.1%, OR = 2.66, P = 0.008, respectively). Conclusions: Our results identify that IL-10 promoter polymorphisms might not be a risk factor for PCa in Chinese cohorts, but rather incidence of polymorphisms associates with PCa grade, suggesting that IL-10 expression may impact PCa progression.

Purpose: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas. Patients and Methods: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II dose (RP2D) based on the findings during dose escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCL. Results: Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (CI), 41–78]. Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI, 7.4–not reached). Median progression-free survival was 11.1 months (95% CI, 5.3–22.0), and 12-month overall survival rate was 92% (95% CI, 72–98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count [nine (32%)] as well as decreased white blood cell count, decreased neutrophil count, and anemia [four (14%) for each]. No treatment-related deaths were reported. Conclusions: This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.