As independent risk factors, cellular atypia may reconfirm the importance of morphological analysis, and the TAM number may indicate the significance of TAM function in gastric adenoma.

Aim: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. Patients and Methods: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. Conclusion: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.Lung cancer has the highest mortality rate worldwide of all cancer types (1, 2). In recent years, the emergence of molecular targeted drugs and immune checkpoint inhibitors (ICIs) has drastically changed the strategy for the treatment of advanced lung cancer. ICIs improve the overall survival (OS) of patients with lung cancer (3-5).The expression level of programmed death-ligand 1 (PD-L1) in tumor cells is determined through immunohistochemistry (IHC). PD-L1 is a significant predictive marker of ICIs; however, it is not a sufficient indicator of the efficacy of immunotherapy. Several serum-based parameters related to systemic inflammation and nutritional status of patients have been studied as predictive or prognostic markers during immunotherapy, such as the neutrophil-tolymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) (6-8). However, the unified cutoff points for these metrics and other parameters that are more sensitive than these markers are controversial.This study aimed to investigate factors of the efficacy of immunotherapy that are readily available via routine blood tests. We focused on the combination of hemoglobin (Hb) and serum albumin levels. Patients and MethodsThis retrospective study included consecutive patients with inoperable lung cancer who underwent monotherapy with ICIs,

Liver cirrhosis patients generally progress to liver failure. To cure this progressive disease, we developed a novel cell therapy using bone marrow cells; autologous bone marrow cell infusion (ABMi) therapy. We previously described the possible action mechanism of ABMi therapy in the cirrhotic liver, and showed the timeline and results of clinical studies of ABMi therapy. We have also carried out other clinical studies using bone marrow cells and granulocyte colony-stimulating factor. Here, we report a new randomized clinical trial to evaluate the effects of ABMi therapy. However, ABMi therapy may not be possible in patients who are unable to undergo general anesthesia; therefore, we have started to develop a next-generation stem cell therapy using cultured mesenchymal stem cells.

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BackgroundThe prognostic value and the best method of testing of topoisomerase II alpha (TOP2A) status have not been established in modern tailored therapy based on breast cancer subtype.ResultsThe frequencies of TOP2A overexpression and TOP2A amplified were 55.8% and 9.5%, respectively. TOP2A overexpression correlated strongly with non-luminal A subtype (χ2-test, p < 0.001). TOP2A overexpression was significantly associated with relapse-free survival in luminal B breast cancer (n = 316; log rank test, p < 0.001) but not in other breast cancer subtypes. Cox regression analysis showed that TOP2A overexpression is a significant prognostic factor in luminal B breast cancer (hazard ratio (HR) 4.00, 95% confidence interval (CI) 1.65–9.54, p = 0.002). TOP2A amplified was recognized in HER2 positive breast cancer (p < 0.001). In HER2 positive breast cancer, TOP2A amplified (HR 0.30, 95% CI 0.085–1.07, p = 0.063) appeared to be a better prognostic factor.ConclusionIn modern tailored therapy, TOP2A overexpression can be a poor prognostic factor in luminal B breast cancer. In contrast, TOP2A amplified could be a better prognostic factor in HER2 positive breast cancer.Materials and methodsBetween May 2005 and April 2015, a total of 643 consecutive non-metastatic invasive breast cancers were evaluated for TOP2A amplified using fluorescence in situ hybridization analysis (FISH) and for TOP2A overexpression using the immunohistochemistry assay. FISH ratios of 2 or higher were designated as TOP2A amplified, and TOP2A staining >10% was defined as TOP2A overexpression. The prognostic values of TOP2A amplified and TOP2A overexpression were retrospectively evaluated.

Gastric cancer (GC) is the third most common cause of cancer-related mortality. The diagnosis and treatment of early GC is a crucial strategy for prognostic improvement of GC. Annexin A10 (ANXA10), a calcium-/phospholipid-binding protein, is a member of the annexin family. The significance of ANXA10 expression in early GC remains unclear. This is the first report to investigate ANXA10 expression in early GC. We performed immunohistochemistry to evaluate ANXA10 expression in early GC, and the correlation between ANXA10 and clinicopathological factors. The loss of ANXA10 expression was detected in 63 (61.2%) of 103 early GC cases and significantly correlated with poor overall survival in patients. Sex, pT stage, pN stage, histology, and ANXA10 expression were associated with poor survival. Sex, histology, and ANXA10 expression were determined as independent predictors of survival in early GC patients. ANXA10 immunostaining could be a new decision-making biomarker in GC.

Background/Aim: Colorectal adenoma is well known as a precursor lesion of colorectal adenocarcinoma (ADC). We recently reported the significance of CD204 (+) tumor-associated macrophages (TAMs), a vital component of the tumor microenvironment, in the carcinoma development of gastric adenoma. The aim of the present study was to clarify the roles of TAM in the malignant transformation of colorectal adenoma. Materials and Methods: We immunohistochemically assessed the TAM number in 88 tubular or tubulovillous adenomas that were classified into L (low-grade adenomas) or H (high-grade adenomas). Results: Larger adenoma size, higher frequency of villous structure, loss of proliferation polarity, p53 expression, larger TAM numbers and larger microvessel density (MVD) were detected in Group H than in Group L adenomas. Positive relations were observed between TAM and MVD, proliferation polarity and the expression of p53. Conclusion: CD204 (+) TAM is a novel component in the malignant transformation of colorectal adenoma.Colorectal cancer (CRC) is one of the leading causes of cancer-associated death worldwide (1). Many CRCs arise from adenomatous polyps through a machinery that we call the "adenoma-carcinoma sequence" (2). Larger size, villous structure, and high-grade morphology are known to represent a higher frequency of potential as precursors of CRC (3). In recent studies, it is obvious that CRC arose from adenomas with an accumulation of mutations in tumor suppressor genes and oncogenes (4).Accumulating evidence supports the idea that the development and progression of tumor tissue is greatly influenced by the tumor microenvironment (5). Tumor cells and stromal cells, such as lymphocytes, fibroblasts, endothelial cells and macrophages are believed to intermingle with each other in a "tumor microenvironment". In particular, cancer-associated fibroblasts and tumor associated macrophages (TAMs) infiltrate tumor tissue and are believed to be one of the crucial components of the tumor microenvironment. TAMs are actually known to possess an angiogenic ability in the tumor microenvironment, which has been supported by the positive correlation between TAMs and MVD in several malignant tumors (6, 7). Several studies have reported significant correlations between TAM and poor outcomes in patients with many types of malignancies (8). According to the reports, TAM had the ability to polarize into M2 macrophages upon exposure to M2 macrophage-differentiation factors produced by the tumor microenvironment (5). CD204 is a class A scavenger receptor that is highly expressed in M2-polarized macrophages and CD204 (+) TAMs that are related to tumor progression in several types of cancers, such as lung cancer, pancreatic cancer, ovarian tumor and glioma (6,(9)(10)(11)(12). These previous studies mainly focused on the role of TAMs in further progression of the advanced tumor. To the best of our knowledge, research concerning the role of TAM in precancerous lesions is quite limited and our previous report on gastric adenoma (13) seems to ...

Background/Aim: Small bowel adenocarcinoma (SBA) is a relatively rare malignant epithelial neoplasm. Thus, little is known about prognostic biomarkers of SBA. Annexin A10 (ANXA10) is a member of the annexin family. The significance of ANXA10 expression in SBA is unclear. This is the first study to examine the expression of ANXA10 in SBA. Materials and Methods: We immunohistochemically evaluated ANXA10 expression of SBA and studied the relationship between ANXA10 expression and clinicopathological factors. Results: ANXA10 expression was detected in 17 (56.7%) of 30 SBA cases and was significantly associated with poor overall survival. Univariate predictors for poor prognosis were tumour size (p=0.017) and ANXA10 expression (p=0.026). In multivariate analysis, ANXA10 expression (p=0.038) and tumour size (p=0.024) were found to be independent predictors of poor prognosis. Conclusion: ANXA10 could be a new prognostic biomarker for SBA.