Induction of breast cancer stem cells by M1 macrophages through Lin-28B-let-7-HMGA2 axis.

Proinflammatory macrophage (M1) is now being suggested as a potential therapeutic strategy for cancer because of its tumoricidal capacity. However, few studies have been focused directly on the effects of M1 macrophages on cancer cells. Here, we found that M1 induced a subpopulation of CD44high/CD24-/low or ALDH1+ cells with CSC-like phenotypes from different types of breast cancer cells (BCCs) in a paracrine manner. Stat3/NF-κB pathways in BCCs were activated by proinflammatory cytokines, igniting Lin-28B-let-7-HMGA2 axis to induce CSC through epithelial-mesenchymal transition (EMT). Previously, we reported that Stat3-coordinated Lin-28B-let-7-HMGA2 axis initiated EMT in BCCs. Here, inhibition of Stat3/NF-κB pathways or Lin-28B-let-7-HMGA2 axis suppressed EMT/CSCs program. Notably, HMGA2 knockdown directly repressed M1-induced CSC formation and expression of Klf-4 and Nanog. Meanwhile, prolonged coculture with BCCs endowed M1 with M2 properties. M1 supernatant induced CSC from non-stem cancer cells, while M2 supernatant sustained a higher proportion of ALDH1+ cells. Our data suggest that macrophages might modulate CSC formation and maintenance by transferring between M1/M2 phenotype. Given that M1 are being considered as a promising immunotherapy tool, it is important to inhibit their CSC-inducing potential by targeting key molecules and pathways.

[Establishment of mouse model of bone metastasis of prostate cancer and breast cancer via femoral artery injection of tumor cells].

OBJECTIVE: To explore an efficient and reliable method for establishing an animal model of bone metastasis of tumors. METHODS: Male C57BL/6J mice were randomized into 4 equal groups to receive injections of normal saline or prostate cancer RM-1 cell suspension via the femoral artery or the external iliac artery, and breast cancer 4T1-luc cells were injected in 15 female BALB/c mice via the femoral artery. The operation time, postoperative survival rate, and the tumor formation rates in the mice with two different injection methods were compared. The tumor metastasis in the mice was evaluated with in vivo imaging. RESULTS: The mean time for hemostasis time was 2.53∓1.75 min in mice receiving tumor cell injection via the femoral artery, significantly shorter than that in mice with injections via the external iliac artery (4.70∓1.63 min; P<0.05); the mean operation time was 14.67∓2.16 min and 22.47∓3.50 min in the two groups, respectively (P<0.05). At 21 days after the operation, the survival rate was 93.3% in femoral artery injection group, significantly higher than that in external iliac artery injection group (66.7%;P<0.05). The tumor metastasis rate was 100% in both groups. CONCLUSION: Injection of the tumor cells via the femoral artery is more suitable for establishing mouse models of bone metastasis of cancers.

[Establishment of a human bladder cancer cell line stably co-expressing hSPRY2 and luciferase genes and its subcutaneous tumor xenograft model in nude mice].

Objective To establish a human bladder cancer cell line stably co-expressing human sprouty2 (hSPRY2) and luciferase (Luc) genes simultaneously, and develop its subcutaneous tumor xenograft model in nude mice. Methods The hSPRY2 and Luc gene segments were amplified by PCR, and were cloned into lentiviral vector pCDH and pLVX respectively to produce corresponding lentivirus particles. The J82 human bladder cancer cells were infected with these two kinds of lentivirus particles, and then further screened by puromycin and G418. The expressions of hSPRY2 and Luc genes were detected by bioluminescence, immunofluorescence and Western blot analysis. The screened J82-hSPRY2/Luc cells were injected subcutaneously into BALB/c nude mice, and the growth of tumor was monitored dynamically using in vivo fluorescence imaging system. Results J82-hSPRY2/Luc cell line stably expressing hSPRY2 and Luc genes was established successfully. Bioluminescence, immunofluorescence and Western blot analysis validated the expressions of hSPRY2 and Luc genes. The in vivo fluorescence imaging system showed obvious fluorescence in subcutaneous tumor xenograft in nude mice. Conclusion The J82-hSPRY2/Luc bladder cancer cell line and its subcutaneous tumor xenograft model in nude mice have been established successfully.

Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS-induced colitis model.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition. Psychological stress has been postulated to affect the clinical symptoms and recurrence of IBD. The exact molecular mechanisms are not fully understood. In the present study, we demonstrate that psychological stress promotes neutrophil infiltration into colon tissues in dextran sulfate sodium (DSS)-induced colitis model. The psychological stress resulted in abnormal expression of the proinflammatory cytokines (IL-1ß, IL-6, IL-17A, and IL-22) and neutrophil chemokines (CXCL1 and CXCL2) and overactivation of the STAT3 inflammatory signaling pathway. Under chronic unpredictable stress, the adrenergic nervous system was markedly activated, as the expression of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, in bone marrow and colonic epithelium was enhanced, especially in the myenteric ganglia. The ß-AR agonist isoproterenol mimicked the effects of psychological stress on neutrophilia, neutrophil infiltration, and colonic damage in DSS-induced colitis. The ß1-AR/ß2-AR inhibitor propranolol reduced the numbers of the neutrophils in the circulation, suppressed neutrophil infiltration into colonic tissues, and attenuated the colonic tissue damage promoted by chronic stress. Propranolol also abolished stress-induced upregulation of proinflammatory cytokines and neutrophil chemokines. Our data reveal a close linkage between the ß1-AR/ß2-AR activation and neutrophil trafficking and also suggest the critical roles of adrenergic nervous system in exacerbation of inflammation and damage of colonic tissues in experimental colitis. The current study provides a new insight into the mechanisms underlying the association of psychological stress with excessive inflammatory response and pathophysiological consequences in IBD. The findings also suggest a potential application of neuroprotective agents to prevent relapsing immune activation in the treatment of IBD.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Prostate Cancer: A Systematic Review and Meta-analysis.

Inflammation is increasingly reported to be associated with the prognosis of patients with cancers. And the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in patients with prostate cancer (PCa) remains inconsistent. Therefore, we conducted this systematic review and meta-analysis to obtain a more reliable assessment of prognostic significance of NLR in PCa.A comprehensive literature research regarding the association of NLR and prognosis of PCa was performed through PubMed, Embase, Cochrane Central, and Web of Science. The hazard ratios (HRs) and its 95% confidence intervals (CIs) for overall survival (OS), progression-free survival, or recurrence-free survival were extracted and pooled using fix-effects model or random-effects model.A total of 14 studies that met our criterion were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was not significantly associated with the poor OS (HR = 1.45; 95% CI 0.77-2.71; P = 0.248) or recurrence-free survival (HR = 1.34; 95% CI 0.89-2.02; P = 0.155) of patients with localized PCa. Although elevated NLR predicted poorer OS (HR = 1.57; 95% CI 1.41-1.74; P < 0.001) and progression-free survival (HR = 1.97; 95% CI 1.28-3.04; P = 0.002) of patients with metastatic castration resistant prostate cancer (mCRPC).Elevated NLR is a strong indicator of poorer prognosis of patients with mCRPC, whereas the NLR is not significantly associated with prognosis of patients with localized PCa. Therefore, NLR could be used in patients with mCRPC for risk stratification and decision making of individual treatment.

Lateroconal fascia suspension for management of peritoneal tear and "curtain" effect during retroperitoneal laparoscopic operations.

PURPOSE: To describe the method of lateroconal fascia suspension for the management of peritoneal tear and curtain effect during retroperitoneal laparoscopic operations. MATERIALS AND METHODS: Between May 2013 and October 2014, we performed lateroconal fascia suspension in 30 cases of retroperitoneal laparoscopic operations. Peritoneal tear occurred and retroperitoneal space collapsed in 18 cases of them during the operation, and free edge of the lateroconal fascia caused curtain effect and sheltered the field of view in another 12 cases after the lateroconal fascia was incised longitudinally. RESULTS: The curtain effect of lateroconal fascia was eliminated successfully, and the sheltered field of view got normal in all the 12 cases. The collapsed retroperitoneal space due to peritoneal tear got enlarged effectively and was sufficient for the following operations in 15 patients of the overall 18 cases, while the collapsed retroperitoneal space did not get enlarged significantly in the other three cases. After the insertion of an extra 5-mm trocar into peritoneal space, the collapsed retroperitoneal space got enlarged eventually. Finally, retroperitoneal laparoscopic operations were continued and completed successfully in all these 30 patients. It took 4 min to complete the suspension procedure, and no related complications occurred during the whole suspension process. CONCLUSION: Lateroconal fascia suspension method could manage most peritoneal tears and curtain effect effectively during retroperitoneal laparoscopic operations.

Radiofrequency Ablation Versus Partial Nephrectomy in Treating Small Renal Tumors: A Systematic Review and Meta-Analysis.

Radiofrequency ablation (RFA) has emerged as an alternative treatment to surgical partial nephrectomy (PN) in the treatment of small renal tumors (SRTs). But its safety and oncological efficacy are still controversial. We conducted this systematic review and meta-analysis to compare the peritoperative and oncological outcomes of RFA and PN in the treatment of SRTs. Pubmed, EMBASE, Cochrane CENTRAL, and Web of Science were searched to identify eligible studies that compared the RFA and PN in the treatment of SRTs. Twelve retrospective studies that compared RFA with PN in the treatment of SRTs met our selection criterion and were included in this meta-analysis. The pooled results indicated that the local recurrence rate (4.14% vs 4.10%, RR: 1.18, 95% CI: 0.68, 2.07, P = 0.550) and distant metastases rate (2.76% vs 1.89%, RR: 1.31, 95% CI: 0.70, 2.46, P = 0.686) were not significantly different between the RFA group and the PN group. In terms of perioperative outcomes, RFA was associated with shorter length of stay (LOS) (WMD: -2.02 days, 95% CI: -2.77, -1.27, P < 0.001), lower eGFR decline after treatment (WMD: -3.90, 95% CI: -6.660, -1.140, P = 0.006). However, the overall perioperative complication rate (7.5% vs 6.2%, RR:1.10, 95% CI: 0.64, 1.87, P = 0.740) and the major complication rate (3.7% vs 4.4%, RR: 0.83, 95% CI: 0.43, 1.60, P = 0.579) were both similar between RFA and PN groups. Compared with PN, RFA achieves an equal oncological outcome for SRTs with similar local recurrence rate and distant metastases rate. Additionally, RFA is associated with a similar perioperative complication rate, lower decline of eGFR, and shorter LOS. Therefore, RFA is an effective option in the treatment of SRTs for selected patients.

[Association between obesity-related plasma hemodilution and the concentration of prostate specific antigen].

OBJECTIVE: To determine the effect of obesity on prostate specific antigen (PSA) in men with benign prostatic hyperplasia (BPH) and develop a PSA-related parameter that can eliminate the effect of obesity. METHODS: We reviewed the clinical data of 706 patients with BPH. Two PSA-related parameters, namely PSA mass (total circulating PSA protein) and PSA mass ratio (total circulation PSA protein per prostate volume), were calculated for all the patients and the association of BMI with PSA, PSA mass, and PSA mass ratio was assessed. RESULTS: A higher BMI was significantly associated with a greater plasma volume and prostate volume (P<0.05). Linear regression analysis revealed a greater adjusted R2 of BMI versus plasma volume than of BMI PSA (0.569 vs 0.027). PSA was positively associated with the prostate volume and negatively with BMI and plasma volume (P<0.05). PSA mass was positively associated with prostate volume (P<0.05) but was not associated with BMI or plasma volume (P>0.05). PSA mass ratio was not associated with prostate volume (P>0.05) but negatively associated with BMI and plasma volume. Plasma volume and prostate volume, PSA, and PSA mass ratio (P<0.05), but not PSA mass (P>0.05), differed significantly among normal-weight, overweight, and obese patients. CONCLUSION: A higher BMI is associated with a greater plasma volume in BPH patients. In obese patients with BPH, a lower PSA concentration may result from hemodilution caused by a greater plasma volume, and PSA mass can eliminate the effect of obesity on PSA.