Activated platelets promote tumor cell growth, angiogenesis, and invasion. Platelet activity can be inferred by platelet volume indices (PVIs), which include platelet distribution width (PDW), mean platelet volume (MPV), platelet distribution width-to-platelet count ratio (PDW/P), and mean platelet volume-to-platelet count ratio. Platelets and platelet-related markers, such as the platelet-to-lymphocyte ratio, have been found to be significant prognostic factors in patients with breast cancer. However, the role of PVIs for predicting survival in breast cancer remains unknown; hence, we performed this retrospective analysis of 275 patients with breast cancer. PVIs were compared with clinicopathological variables, and were assessed to identify independent indicators associated with disease-free survival (DFS) using the Cox proportional hazards model. An elevated PDW/P significantly correlated with age and HER2 status. Univariate analysis revealed that elevated PDW, MPV, and PDW/P as well as tumor size, nuclear grade, and lymph node involvement were significantly associated with inferior DFS rates (tumor size: p<0.01; nuclear grade, lymph node involvement, PDW, MPV, and PDW/P: p<0.05). On multivariate analysis, a large tumor size and elevated PDW/P were significant prognostic factors for DFS, with hazard ratios of 3.24 (95% confidence interval [CI]: 1.24–8.47) and 2.99 (95% CI: 1.18–7.57), respectively (p<0.05). Our study is the first to reveal that an elevated PDW/P significantly reduces DFS in patients with breast carcinoma. Measuring the PDW/P is simple, relatively inexpensive, and almost universally available using routine blood counts; this makes it an attractive biomarker for improved risk assessment.

Red cell distribution width (RDW) to platelet ratio (RPR) is a prognosticator in acute pancreatitis and myocardial infarction; however, the prognostic values of RDW and RPR in breast cancer have not been studied. This retrospective analysis of 299 breast cancer patients investigated the association between RDW and RPR and clinicopathological characteristics and prognosis, compared to platelet distribution width to platelet count ratio (PDW/P) which is a known independent prognostic factor in patients with breast cancer. We found a significant correlation between RPR, and age and HER2 status. An elevated RPR significantly correlated with age and HER2 status. After a median follow-up duration of 48 months, tumour size, nuclear grade, PDW/P, and RPR were recgnized to be significantly associated with lower disease-free survival rates (tumour size: p < 0.01; nuclear grade, PDW/P, and RPR: p < 0.05) in univariate analysis. Tumour size and RPR were significant prognostic factors for lower disease-free survival rates, with hazard ratios of 4.31 (95% confidence interval: 1.76–10.53) (p < 0.01)] and 2.79 [95% confidence interval: 1.01–87.69) (p < 0.05)], respectively, in a multivariate analysis using the Cox proportional hazards model. This is the first study showing that an elevated RPR could independently predict poor prognosis in patients with breast carcinoma. Thus, RPR could be a novel biomarker for prognostic estimation.

We herein report a 50-year-old Japanese woman with breast cancer who complained of blurred vision and central scotoma in her left eye on the 12th day after surgery. Subsequently, the sudden-onset binocular visual disorder progressed, and she was diagnosed with cancer-associated retinopathy (CAR) based on the clinical findings. Although her visual acuity temporarily improved following the start of adjuvant chemotherapy, reductions in her visual acuity progressed once again. After two courses of steroid pulse therapy initiated from the 59th day following the onset of CAR, although her visual field was still constricted, her binocular visual acuity improved from finger movement to 0.8 2 months later. The shorter the period from onset to treatment, the better the prognosis of the visual function. However, a diagnosis is often delayed because the incidence of this disease is very rare. Therefore, it is important to suspect CAR whenever a sudden visual disorder develops in cancer patients. Furthermore, treatment is believed to be effective even if steroid therapy is started up to 2 months from onset.

Abstract. Background Lung cancer, which is a leading cause of cancer death worldwide, is associated with a poor survival, even when the tumor is surgically removed. In terms of histology, lung squamous cell carcinoma, which accounts for 22% of the cases of resected lung cancer, is associated with poorer overall survival, with a five-year survival rate of approximately 60% in comparison to adenocarcinoma, which is the most common histological type (68%) and which has a five-year survival rate of approximately 75% (1). Molecular targeting therapies have recently been developed and have shown promising results against advanced lung cancer. Among the various types of lung cancer, lung squamous cell carcinoma has fewer treatment options because it is driven by alterations of tumor suppressor genes and subsequent chromosomal instability rather than oncogenic mutations (2). The chromosomal instability results in accumulation of somatic mutations and DNA damage response (3). This may explain why carcinogen-induced cancer, like lung squamous cell carcinoma and melanoma, is often accompanied by inflammation, as the DNA damage response is a major trigger activating the innate immune response. This consequence has been closely examined in the immune elimination process during viral infection and recently in the cancer immunity cycle (4).The activation of the innate immune response leads to activation of immune checkpoint molecules as a mechanism of immune escape. Programmed death-ligand 1 (PD-L1) is one of the immune checkpoint molecules that are expressed on the surface of tumor cells. Once it is expressed on the tumor cells, PD-L1 binds to its receptor, PD-1, on the membrane of the cytotoxic T cell and inhibits T cell activity, resulting in the escape of the tumor cell from the immune system (5). The recent development of therapies against immune checkpoint molecules, namely, CTLA-4, PD-1 and PD-L1 has shown that PD-1/PD-L1 blockade can improve overall survival in patients with cancer including malignant melanoma, lung squamous cell carcinoma, and lung adenocarcinoma (6-13).During the DNA damage response process, γH2AX, a unique histone subunit, serves as a sensor of double-stranded DNA damage, thereby gathering other proteins to form DNA damage repair complex foci (14). γH2AX foci are formed through irradiation, UV exposure, and cytotoxic chemotherapy, and the overexpression of γH2AX is common among various types of cancer. We hypothesized that the 171 This article is freely accessible online.Correspondence to: Ass. Prof.

Background Acquired resistance (AR) to an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is a common event, and several underlying mechanisms, including T790 M, MET amplification and PTEN downregulation, have been reported for the common EGFR mutations. EGFR G719X is an uncommon mutation that has been reported to show sensitivity to EGFR-TKIs. However, no established cell lines harboring the EGFR G719X have been reported in the literature. Materials and Methods G719S-GR cells were established from malignant pleural effusion of a patient whose tumor developed AR from gefitinib treatment. G719S-GR cells were then genotyped and tested for drug sensitivities. Multiplex ligation-dependent probe amplification (MLPA) was used to compare the clinical tumor samples with G719S-GR. Results G719S-GR cells were resistant to EGFR-TKIs with an LC50 of around 10 μM. A genomic analysis showed that G719S-GR cells harbor the EGFR G719S mutation as well as the amplification of EGFR locus. The homozygous deletion of CDKN2A and the loss of PTEN and TSC1 were also detected. On comparing the copy number of tumor suppressor genes using MLPA, G719S-GR cells were found to lack one copy of PTEN, which was not observed in a tumor obtained before gefitinib treatment. Loss of PTEN may result in AKT activation. The mTORC1/2 inhibitor Torin-1 was able to inhibit the downstream signaling when combined with osimertinib. Discussion The newly established G719S-GR cell line may be useful for investigating the mechanism underlying the development of AR in the G719X mutation; the loss of PTEN may be one such mechanism.