Significance of MUC1 and β-Catenin Localization in Mucinous Carcinoma of the Breast.

Background/aim: There are two main subtypes of mucinous carcinoma (MC) based on the quantification of the mucinous component: the pure variant (pMC) and the mixed variant (mMC). pMC has been subdivided into pure A with a hypocellular variant, and pure B with a hypercellular variant.

Patients And Methods: We retrospectively analyzed the clinicopathological features of 99 patients with MC who were treated at our institution from January 2002 to December 2014.

Association Between High Expression of Phosphorylated-STMN1 and Mesenchymal Marker Expression and Cancer Stemness in Breast Cancer.

Background/aim: In patients with breast cancer, the expression of stathmin1 (STMN1) has been significantly related to a poor prognosis, cancer aggressiveness, and expression of cancer stem cell markers. The STMN1 protein is closely regulated by phosphorylation in four sites. However, few studies have investigated the relationship between the expression of phosphorylated STMN1 (pSTMN1) and clinicopathological findings, including tumor-aggressive biomarkers, in patients with breast cancer.

Conophylline Inhibits Hepatocellular Carcinoma by Inhibiting Activated Cancer-associated Fibroblasts Through Suppression of G Protein-coupled Receptor 68.

Treatment of hepatocellular carcinoma (HCC) is currently challenging. Cancer-associated fibroblasts (CAFs) promote the malignancy of HCC cells via production of cytokines. Conophylline (CnP), a vinca alkaloid obtained from leaves, has been reported to suppress activation of hepatic stellate cells and liver fibrosis in rats.

Inflammatory and immune checkpoint markers are associated with the severity of aortic stenosis.

Objective: Aortic stenosis (AS) is a disease characterized by narrowing of the aortic valve (AV) orifice. In relation to this disease, the purpose of this study was to elucidate the relationships among factors such as expression of programmed cell death-1 ligand (PD-L1, which is the ligand of PD-1 protein; together, they play a central role in the inhibition of T lymphocyte function), clinicopathologic characteristics, infiltrating immune cells, and disease severity.

Methods: We performed immunohistochemical analysis on the surgically-resected AVs of 53 patients with AS.

Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer.

Introduction: Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood.

Objective: This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa.

Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling.

Background: Wisteria floribunda agglutinin (WFA) Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness.

Diagnostic value of F-FDG-PET to predict the tumour immune status defined by tumoural PD-L1 and CD8tumour-infiltrating lymphocytes in oral squamous cell carcinoma.

Background: Lately, immune checkpoint proteins, such as programmed death 1 (PD-1) and its ligand-1 (PD-L1), have garnered attention as a new target in oral squamous cell carcinoma (OSCC). Reportedly, fluoro-D-glucose (FDG)-uptake alteration by anti-PD-1 antibody treatment depicts the response in patients with lung cancer. This study aims to elucidate the correlations between tumour immune status, clinicopathological factors, F-FDG-uptake and cold tumour phenotypes as low PD-L1 expression/low CD8tumour-infiltrating lymphocytes (TILs) in OSCC.

Nintedanib inhibits intrahepatic cholangiocarcinoma aggressiveness via suppression of cytokines extracted from activated cancer-associated fibroblasts.

Background: Intrahepatic cholangiocarcinoma (ICC) is a malignancy that is challenging to treat. Fibroblasts in ICC tissues have been identified as cancer-associated fibroblasts (CAFs) that promote the malignant behaviour of ICC cells. An antifibrotic drug nintedanib has been reported to suppress activated hepatic stellate cells in liver fibrosis.

FDG-PET reflects tumor viability on SUV in colorectal cancer liver metastasis.

Background: Liver resection is the most effective procedure for colorectal cancer liver metastasis (CRLM); however, early recurrence is an important problem that affects the postoperative prognoses of patients with CRLM. We previously suggested a therapeutic algorithm for CRLM using fluorodeoxyglucose-positron emission tomography (FDG-PET) and revealed the applicability of FDG-PET in predicting the prognosis after liver resection of CRLM. In this study, we assessed the correlation between FDG-PET and biological viability such as proliferation or metabolic activity.

High Stromal TGFBI in Lung Cancer and Intratumoral CD8-Positive T Cells were Associated with Poor Prognosis and Therapeutic Resistance to Immune Checkpoint Inhibitors.

Background: We investigated whether the expression of transforming growth factor-beta-induced protein (TGFBI) and intratumoral immune cells including CD8- and Forkhead box protein P3 (Foxp3)-positive T cells in clinical lung cancer patients could predict the therapeutic response to nivolumab.

Methods: Thirty-three patients who were treated with nivolumab were enrolled in this study. Immunohistochemical analyses of TGFBI, PD-L1, CD8, Foxp3, and vimentin expression were conducted.

Fluorodeoxyglucose uptake is associated with low tumor-infiltrating lymphocyte levels in patients with small cell lung cancer.

Objectives: Positron emission tomography (PET) using 2-deoxy-2-[F] fluoro-D-glucose (F-FDG) is a clinically useful modality for cancer evaluation. The mechanism of F-FDG uptake within cancer cells involves the glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1 α (HIF-1α). Although recent research has shown its clinical efficacy in small-cell lung cancer (SCLC), no suitable biomarker has been identified.

Carboxypeptidase A4 accumulation is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer.

Using whole transcriptome analysis and a lentiviral short hairpin RNA screening library, carboxypeptidase A4 (CPA4) was identified as a novel marker in breast cancer and a therapeutic target in triple‑negative breast cancer (TNBC) in the present study. Immunohistochemistry was used to evaluate the presence of CPA4, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki67, epidermal growth factor receptor, cytokeratin 5/6, aldehyde dehydrogenase 1, cluster of differentiation (CD)44, CD24, claudins, E‑cadherin, vimentin and androgen receptor in 221 cases of breast cancer, including 68 TNBC cases. The effects of CPA4 on the viability and migration ability of TNBC cells were analyzed using RNA interference methods.

Conophylline suppresses pancreatic cancer desmoplasia and cancer-promoting cytokines produced by cancer-associated fibroblasts.

Despite recent advances in cancer treatment, pancreatic cancer is a highly malignant tumor type with a dismal prognosis and it is characterized by dense desmoplasia in the cancer tissue. Cancer-associated fibroblasts (CAF) are responsible for this fibrotic stroma and promote cancer progression. We previously reported that a novel natural compound conophylline (CnP) extracted from the leaves of a tropical plant reduced liver and pancreatic fibrosis by suppression of stellate cells.

Mutant TP53 modulates metastasis of triple negative breast cancer through adenosine A2b receptor signaling.

Purpose: The identification of genes with synthetic lethality in the context of mutant TP53 is a promising strategy for the treatment of basal-like triple negative breast cancer (TNBC). This study investigated regulators of mutant TP53 (R248Q) in basal-like TNBC and their impact on tumorigenesis.

Experimental Design: TNBC cells were analyzed by RNA-seq, and synthetic-lethal shRNA knock-down screening, to identify genes related to the expression of mutant .

High stromal transforming growth factor β-induced expression is a novel marker of progression and poor prognosis in gastric cancer.

Background And Objectives: Transforming growth factor β-induced (TGFBI) protein is a secreted extracellular matrix protein with conflicting roles in cancer, acting as a tumour suppressor and a promoter, which appears to be tissue specific. The role of TGFBI in gastric cancer (GC) remains unclear, which we aimed to investigate using the clinical samples as well as an in vitro coculture model of GC.

Methods: The clinical significance of TGFBI was assessed in 208 GC samples using immunohistochemistry.

High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the major causes of tumor death; thus, the identification of markers related to its diagnosis and prognosis is critical. Previous studies have revealed that epithelial-to-mesenchymal transition (EMT) is involved in tumor invasion and metastasis, and the forkhead box protein C2 (FOXC2) has been shown to promote tumor cell proliferation, invasion, and EMT. In the present study, we examined the clinicopathological significance of FOXC2 and EMT-related markers in clinical HCC specimens and identified factors related to the diagnosis and prognosis of HCC.

Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma.

Background: Lymph node metastasis (LNM) is a standard mechanism of cancer progression in esophageal squamous cell carcinoma (ESCC). We aimed to clarify the anatomical mechanism of skip nodal metastasis to mediastinal zones by analyzing the relationship between LNM to sentinel zones and lymphatic vessel counts in the muscle layer adjacent to the outer esophagus.

Methods: We examined the surgical records of 287 patients with ESCC who underwent potentially curative surgery (three-field lymphadenectomy) and whole esophagi, including pharynges and stomachs from 10 cadavers, to determine the number of lymphatic vessels in the intra-outer longitudinal muscle layer adjacent to the outer esophagus of the cervical (Ce), upper thoracic, middle thoracic (Mt), lower thoracic (Lt), and abdominal esophagi (Ae).

High expression of carcinoembryonic antigen and telomerase reverse transcriptase in circulating tumor cells is associated with poor clinical response to the immune checkpoint inhibitor nivolumab.

The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified.

Re-evaluation of MIB-1 immunostaining for diagnosing hyalinizing trabecular tumour of the thyroid: semi-automated techniques with manual antigen retrieval are more accurate than fully automated techniques.

Hyalinizing trabecular tumour (HTT) immunohistochemically shows cell membranous immunoreactivity for MIB-1. This aberrant immunoreactivity is an important factor for the diagnosis of HTT. However, fully automated stainers frequently fail to confirm the immunoreactivity.

Small cholangiolocellular carcinoma that was difficult to distinguish from cholangiocellular carcinoma: a case report.

Background: Cholangiolocellular carcinoma (CoCC) is thought to be derived from hepatic progenitor cells. Because of its origin, CoCC has diverse clinicopathological and imaging findings. Here, we report a case of small CoCC that was difficult to diagnose preoperatively.

Stathmin1 expression is associated with aggressive phenotypes and cancer stem cell marker expression in breast cancer patients.

Stathmin1 (STMN1) regulates progression in various cancers. The present study aimed to determine the relationship between STMN1 expression and several cancer-related markers in breast cancer. Using immunohistochemistry, we evaluated STMN1, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, epidermal growth factor receptor (EGFR), CK5/6, CD44, CD24, aldehyde dehydrogenase 1, E-cadherin, epithelial cell adhesion molecule, and vimentin in 237 breast cancer patients and the clinical significance of STMN1.

Expression patterns of claudins in patients with triple-negative breast cancer are associated with nodal metastasis and worse outcome.

Claudins (CLDNs) are key cell adhesion molecules, which compose tight junctions (TJs), and the disruption of TJs is associated with cancer development. Here we immunohistochemically studied expression patterns of CLDNs in 222 primary invasive breast cancers including 68 triple-negative breast cancers (TNBCs), and examined their correlation with epithelial-to-mesenchymal transition (EMT)-related markers, breast cancer stem cell (BCSC) markers, and clinicopathological features including patients' clinical outcome. Tumor margins were classified as three infiltrating growth patterns (expanding, intermediate and infiltrating).

Caspase14 expression is associated with triple negative phenotypes and cancer stem cell marker expression in breast cancer patients.

Background And Objectives: The Caspase14 (CASP14) was reported that the low expression of CASP14 in ovarian cancer and colon cancer was associated with cancer progression, on the other hand, that the CASP14 expression in breast cancer was higher than that of non-cancerous tissues. The purpose of this study is to determine the clinical significance of CASP14 in breast cancer.

Methods: We performed immunohistochemistry for CASP14, ER, PgR, HER2, Ki67, EGFR, CK5/6, CD44, CD24, ALDH1, claudins, and androgen receptor in 222 breast cancer patients including 55 TNBC cases, and evaluated the relationship of CASP14, above-mentioned markers, and prognosis.

High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients.

Background: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases.

Association of RAB5 overexpression in pancreatic cancer with cancer progression and poor prognosis via E-cadherin suppression.

Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis.