In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.

Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting.

Sarcopenia is defined as loss of skeletal muscle mass and strength. This can lead to adverse clinical outcomes in patients with advanced cancer. The lymphocyte-to-monocyte ratio (LMR), a converted inflammatory response, is associated with poor prognosis in patients with malignancies. Herein, we examined the prognostic influence of sarcopenia status assessed by pectoralis muscle area (PMA), inflammatory status calculated by LMR, and its association with disease-free survival (DFS) in a cohort of women diagnosed with nonmetastatic breast cancer. A total of 293 patients with nonmetastatic breast cancer who underwent primary mass resection and radiotherapy between January 2011 and December 2017 were enrolled. The cross-sectional area of the muscle (cm²) at PMA was measured using computed tomography before radiation therapy. Baseline monocyte and lymphocyte counts were obtained from the complete blood count to calculate the LMR. Most of the patients (248/293, 84.6%) underwent breast conservation surgery. Lymph node involvement at diagnosis (hazard ratio [HR], 5.08; P < .001), low LMR (HR, 2.79; P = .007), and low PMA (HR, 3.80; P < .001) were independent poor prognostic factors in multivariate analysis. The mean DFS of sarcopenic and nonsarcopenic patients was 89.8 months and 118.8 months, respectively (P < .001). Sarcopenic patients with low LMR showed the worst outcomes, whereas nonsarcopenic patients with high LMR showed the best outcomes. Low PMA and low LMR were independent poor prognostic factors for DFS in patients with nonmetastatic breast cancer.

The optimal treatment strategy for biliary tract cancer (BTC) after curative-intent resection remains controversial. The purpose of this study was to evaluate the efficacy of fluoropyrimidine-based adjuvant chemotherapy for BTC patients undergoing microscopically margin-negative (R0) resection. We retrospectively analyzed the clinical data of BTC patients who underwent curative-intent R0 resection. Patients were eligible if they received either fluoropyrimidine-based adjuvant chemotherapy or observation after R0 resection. A total of 153 patients were included. In the entire patient cohort, no significant differences were observed in 5-year overall survival (OS) rates (48.4% vs. 39.6%, P = 0.439) or 3-year recurrence-free survival (RFS) rates (49.1% vs. 39.5%, P = 0.299) between patients who received fluoropyrimidine-based adjuvant chemotherapy or observation. However, for patients with stages II and III BTC, chemotherapy significantly improved 5-year OS rate (52.4% vs. 35.6%, P = 0.002) and 3-year RFS rate (55.5% vs. 39.1%, P = 0.021) compared with observation. Fluoropyrimidine-based adjuvant chemotherapy may prolong the survival of patients with stages II and III BTC after R0 resection.

Primary immune thrombocytopenia (ITP) is an immune-mediated disease that is defined as increased platelet destruction and impaired platelet production. Treatment is recommended for highly selected patients, the standard regimen includes glucocorticoid, intravenous immunoglobulin (IVIG). The recombinant thrombopoietin (TPO) receptor agonists, romiplostim, stimulate platelet production and have approved for glucocorticoid or IVIG, splenectomy-refractory chronic ITP patients. A patient has been diagnosed with ITP, reftractory to steroid, IVIG, splenectomy, danazol, and cyclosporine. The patient received romiplostim to normalize his platelet count, however, over the course of the following year, his platelet counts progressively decreased despite increasing the romiplostim dosing. A peripheral blood smear showed a severe leukoerythroblastic reaction and bone marrow biopsy demonstrated myelofibrosis due to romiplostim. Since this diagnosis, romiplostim was discontinued for a while, after 3 months, romiplostim was re-administered to improve thrombocytopenia. His platelet count recovered to 70,000/mm3 after the administration of romiplostim at 2 μg/kg, and he did not experience complications for 6 months. This report represents the first evidence of romiplostim-induced myelofibrosis, which was associated with increased levels of bone marrow reticulin and Masson trichrome staining.