A Radial Sclerosing Lesion Mimicking Breast Cancer on Mammography in a Young Woman

A spiculated mass on a mammogram is highly suggestive of malignancy. We report the case of a 32-year-old woman with a radial sclerosing lesion that mimicked breast cancer on mammography. She visited her physician after palpating a lump in her left breast. Mammography showed architectural distortion in the upper inner quadrant of the left breast. Ultrasonography showed a low echoic area with an ambiguous boundary. Core needle biopsy was performed because of the suspicion of malignancy. Histological examination did not reveal any malignant cells. After 6 months, the breast lump became larger and the patient was referred to our hospital. Mammography performed in our hospital showed a spiculated mass, and therefore mammotome biopsy was performed. Histological examination revealed dense fibroelastic stroma with a wide variety of mastopathic changes, leading to a diagnosis of a radial sclerosing lesion. One year after the biopsy, the lump on her left breast had disappeared and mammography showed no spiculated mass

Anti-TIM-3 Antibody Prevents Lymphocyte Apoptosis and Enhances Dendritic Cell Cancer Therapy

Currently, there is a strong unmet need for a new intervention therapy for hepatocellular carcinoma (HCC). One candidate therapy uses dendritic cells (DCs), which are professional antigen-presenting cells that are characterized by their potent ability to elicit immune responses to foreign antigens. DCs may be attractive adjuvant agents for cancer therapy but the effect of DCs therapy is restricted because of the immunosuppressive nature of the tumor microenvironment. T-cell immunoglobulin and mucin protein-3 (TIM-3) is a marker of this immunosuppressive tumor environment. Interaction of TIM-3 with its ligand, galectin 9, triggers cell death in activated T cells. In this study, we evaluated the antitumor effects of DC vaccine therapy in combination with TIM-3 blockade in a murine HCC system. In an animal cancer prevention model, BALB/c mice were immunized with DCs with or without anti-TIM-3 antibody before challenging with HCC tumor cells (BNL). In an animal cancer therapeutic model, BALB/c mice were inoculated with DCs with or without anti-TIM-3 antibody 10 days after injection with BNL cells. The mechanism of this combination therapy was investigated using immunohistologic staining of the treated tumors and flow cytometry of lymphocytes. DC and anti-TIM-3 antibody combination treatment prevented tumor development to a greater extent than DCs alone. In the therapeutic model, the outgrowth of the established tumors was significantly reduced in mice treated with the combination of DCs and anti-TIM-3 antibody. Immunohistological analyses of the therapeutic model showed marked infiltration of CD4+ cells and CD8+ T-cells in the established BNL tumors of mice treated with both DCs and anti-TIM-3 antibody. Anti-TIM-3 antibody treatment reduces lymphocyte apoptosis and enhances the antitumor effect of DC therapy in a murine HCC model

Effects of Interleukin-4-Transduced Tumor Cell Vaccines and Blockade of Programmed Cell Death 1 on the Growth of Established Tumors

Interleukin (IL)-4 exhibits strong antitumor effects and IL-4 gene therapy has been used clinically in the treatment of some types of cancer. In the present study, we evaluated the efficacy of IL-4-transduced tumor cell vaccines in combination with blockade of programmed cell death 1 (PD-1) and investigated the mechanisms underlying the antitumor effects of this therapy. A poorly immunogenic murine colorectal cancer cell line (i.e. MC38) was transduced to overexpress IL-4. In a therapeutic model, MC38-IL4 cells and anti-PD-1 antagonistic antibodies (Ab) were inoculated into parental tumor-bearing mice. Immunohistochemical analyses and tumor-specific lysis were also performed. Additive antitumor effects were observed when mice were treated with IL-4 in combination with an anti-PD-1 Ab. Immunohistochemical analysis of the therapeutic model showed marked infiltration of CD4+ and CD8+ cells into established MC38 tumors of mice treated with anti-PD-1 Ab. Significant tumor-specific cytolysis was detected when the splenocytes of mice treated with both IL-4 and anti-PD-1 Ab were used as effector cells. These results suggest that blockade of the interaction between PD-1 and programmed death ligand 1 (PD-L1) enhances the antitumor immune responses induced by IL-4. Thus, IL-4 gene-transduced tumor cell vaccines in combination with PD-1 blockade may be considered as possible candidates for clinical trials of new cancer vaccines

The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study

Introduction: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. Methods: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. Results: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 +/- 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). Conclusion: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD