Option of the surgical mode for breast cancer based on the effect of neoadjuvant chemotherapy

Neoadjuvant chemotherapy has become standard treatment for breast cancer patients to avoid mastectomy in larger tumors. Neoadjuvant chemotherapy permits more breast-conserving surgery to be performed. The treatment outcome is favorable in women whose tumors show a complete pathological response. Histological grade, HER-2, p53, and hormone receptor status are significant predictive factors of a good pathological response to neoadjuvant chemotherapy. In addition, computed tomography and/or magnetic resonance imaging are useful tools in determining the optimal resection area for breast cancer.     

Serum C-reactive protein levels predict survival in hepatocellular carcinoma.

BACKGROUND/AIMS: C-reactive protein (CRP) was recently identified as a prognostic factor for patients with hepatocellular carcinoma (HCC) after surgical resection. We investigated the relationship between the serum levels of high sensitivity CRP (H-CRP) and the prognosis of HCC patients. METHOD: We conducted a cohort study of 90 HCC patients enrolled from 1997 to 1998. All patients were treated and followed for a mean period of 3.2 years. Clinical variables were compared between patients positive for H-CRP (serum H-CRP levels >/=3.0 mg/L, n=47) and those negative for H-CRP (serum H-CRP levels <3.0 mg/L, n=43). We also determined the relationship between serum H-CRP and prognosis in HCC patients. RESULTS: The survival rate of patients of the H-CRP-positive group was lower than that of H-CRP-negative patients. Tumour stage (stages 3 or 4), total bilirubin >/=1.2 mg/dL, albumin (Alb) <3.5 g/dL, des-gamma-carboxy prothrombin >/=40 mAU/mL, positive H-CRP and initial treatment (transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy or best supportive care) were identified as significant poor prognostic factors by univariate analysis, while positive H-CRP [hazard ratio (HR), 1.58; P=0.048], Alb<3.5 g/dL (HR, 2.10; P=0.004), tumour stage (stages 3 or 4; HR, 3.05; P=0.001) and initial treatment (HR, 1.88; P=0.029) were considered to be significant determinants of poor prognosis by multivariate Cox proportional hazards analysis. CONCLUSIONS: The prognosis of H-CRP-positive patients was poorer compared with H-CRP-negative patients. This study confirmed that H-CRP, like CRP, is a marker of poor prognosis in HCC patients.     

Lysophosphatidylcholine potentiates the mitogenic effect of various vasoactive compounds on rabbit aortic smooth muscle cells

We examined the mechanism of action of lysophosphatidylcholine (lyso-PC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflamatory disorders, and its interaction with well-known vasoactive compounds such as hydrogen peroxide (H2O2), thromboxane A2 (TX-A2), serotonin (5-HT), angiotensin II (Ang-II), endothelin-1 (ET-1), or urotensin II (U-II) on VSMC proliferation. Growth-arrested rabbit VSMCs were incubated with given concentrations of lyso-PC with H202, TX-A2, 5-HT, Ang-II, ET-1, or U-II. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. Lyso-PC induced a maximal effect on [3H]thymidine incorporation at a concentration of 15 microM (156%), and its effect was significantly inhibited by the phospholipase C inhibitor U73122 (10 microM), the intracellular antioxidant NAC (400 microM), and the NADPH oxidase inhibitor diphenylene iodonium (1 microM), but not by the MAPK kinase inhibitor (10 microM). H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II also stimulated [3H]thymidine incorporation in a dose-dependent manner. A non-mitogenic concentration of lyso-PC (5 microM) significantly potentiated the effect of low concentrations of H2O2 (0.1 microM, 110 to 222%), TX-A2 (5 microM, 120 to 202%), 5-HT (5 microM, 182 to 259%), Ang-II (0.5 microM, 167 to 304%), ET-1 (0.01 microM, 139 to 297%), or U-II (0.025 microM, 120 to 332%) on [3H]thymidine incorporation. The results suggest that lyso-PC acts synergistically with the vasoactive compounds H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II in inducing VSMC proliferation, which may play an important role in the progression of atherosclerosis.     

Notch-Hes1 pathway is required for the development of IL-17-producing γδ T cells

Unlike conventional T cells, which are exported from the thymus as naive cells and acquire effector functions upon antigen encounter in the periphery, a subset of γδ T cells differentiates into effectors that produce IL-17 within the fetal thymus. We demonstrate here that intrathymic development of the naturally occurring IL-17-producing γδ T cells is independent of STAT3 and partly dependent on RORγt. Comparative gene-expression analysis identified Hes1, one of the basic helix-loop-helix proteins involved in Notch signaling, as a factor specifically expressed in IL-17-producing γδ T cells. Hes1 is critically involved in the development of IL-17-producing γδ T cells, as evidenced by their severe decrease in the thymi of Hes1-deficient fetal mice. Delta-like 4 (Dll4)-expressing stromal cells support the development of IL-17-producing γδ T cells in vitro. In addition, conditional Hes1 ablation in peripheral γδ T cells decreases their IL-17 production but not their IFN-γ production. These results reveal a unique differentiation pathway of IL-17-producing γδ T cells.     

Work and family characteristics as socioeconomic determinants in long sickness absence: the Japanese civil servants study

Long sickness absence is more common among low socioeconomic status (SES) groups than high SES groups. This study aimed to evaluate whether work and family characteristics contribute to SES and sex differences in long sickness absence (7 days or more). The participants were 3080 civil servants working for a local Japanese government. In both sexes, low-grade employees were likely to take long sickness absence, with a statistically significant association for men (age-adjusted OR of lowest-grade employees for long sickness absence: 2.30 (95% Confidence Interval (CI): 1.32–4.02)). After adjusting for all variables, SES differences in long sickness absence in men decreased to OR 1.98 (CI 1.10–3.55) but remained significant; in men, being without a spouse was significantly associated with long sickness absence. Employees working long hours had lower OR for long sickness absence after adjusting for all variables in both sexes. Conversely, poor sleep quality and longstanding illness significantly increased OR for long sickness absence. In conclusion, SES differences in sickness absence were explained partly by work and family characteristics, longstanding illness, and poor sleep quality; however, other factors that were not evaluated in this study may also be associated with SES differences.     

Safety and Applicability of Continuous Retrograde Cardioplegia in Minimally Invasive Aortic Valve Replacement: New Approaches

Purpose: To discuss minimally invasive cardiac surgery aortic valve replacement (MICS-AVR) approach via anterior thoracotomy using continuous retrograde cardioplegia. Continuous retrograde cardioplegia facilitates excellent continuous homogeneous cooling of the heart during cardiac arrest.Methods: We performed AVR using the proposed method in nine patients between June 2018 and September 2019. The median age of the patients was 73 (range: 43–84) years. The pleural space was entered via anterior thoracotomy. After opening of the right atrium, a retrograde cardioplegic cannula was inserted into the coronary sinus with a purse-string suture. Continuous cold blood retrograde cardioplegia was initiated at 700 mL/h.Results: Extubation in the operating room was performed in five (56%) patients. No new decreased function of the left and right ventricles was observed in intraoperative transesophageal echography or transthoracic echocardiogram.Conclusion: MICA-AVR through continuous retrograde cardioplegia is a safe technique.     

Immunolocalization of CD80 and CD86 in Non-Small Cell Lung Carcinoma: CD80 as a Potent Prognostic Factor

It has been demonstrated that tumor cells express programed cell death protein 1 (PD-L1) to escape T lymphocytes that express programed cell protein 1 (PD-1), and PD-1/PD-L1 immune checkpoint inhibitors have been regarded in lung cancer patients. CD80 and CD86 are members of B7 superfamily which regulates T lymphocyte activation and tolerance. However, immunolocalization of CD80 and CD86 has not been examined in the lung carcinoma tissues and their clinical significance remains unknown. Therefore, to clarify clinical significance of CD80 and CD86, we immunolocalized these in 75 non-small cell lung carcinomas (NSCLC) in this study. Immunoreactivities of CD80 and CD86 were mainly detected in tumor-infiltrating macrophages. Immunohistochemical CD80 status was high in 56% of NSCLC, and it was positively associated with stage, pathological T factor, distant metastasis, histological type and PD-L1 status. Moreover, multivariate analysis turned out that the CD80 status was an independent worse prognostic factor. CD86 status was high in 53% of the cases, but it was not significantly associated with any clinicopathological parameters. These findings suggest that CD80 is a potent worse prognostic factor possibly in association with escape from immune attack in NSCLC.     

microRNA‐99a‐5p induces cellular senescence in gemcitabine‐resistant bladder cancer by targeting SMARCD1

Patients with advanced bladder cancer are generally treated with a combination of chemotherapeutics, including gemcitabine, but the effect is limited due to acquisition of drug resistance. Thus, in this study, we investigated the mechanism of gemcitabine resistance. First, gemcitabine‐resistant cells were established and resistance confirmed in vitro and in vivo. Small RNA sequencing analyses were performed to search for miRNAs involved in gemcitabine resistance. miR‐99a‐5p, selected as a candidate miRNA, was downregulated compared to its parental cells. In gain‐of‐function studies, miR‐99a‐5p inhibited cell viabilities and restored sensitivity to gemcitabine. RNA sequencing analysis was performed to find the target gene of miR‐99a‐5p. SMARCD1 was selected as a candidate gene. Dual‐luciferase reporter assays showed that miR‐99a‐5p directly regulated SMARCD1. Loss‐of‐function studies conducted with si‐RNAs revealed suppression of cell functions and restoration of gemcitabine sensitivity. miR‐99a‐5p overexpression and SMARCD1 knockdown also suppressed gemcitabine‐resistant cells in vivo. Furthermore, β‐galactosidase staining showed that miR‐99a‐5p induction and SMARCD1 suppression contributed to cellular senescence. In summary, tumor‐suppressive miR‐99a‐5p induced cellular senescence in gemcitabine‐resistant bladder cancer cells by targeting SMARCD1.