Association of Preoperative and Postoperative Plasma Syndecan-1 and Colorectal Cancer Outcome.

Background/aim: A three-dimensional network constructed using glycocalyx (GCX) extends throughout the cancer cell nest in human colorectal cancer (CRC). GCX was found to be closely related to cancer. We examined the prognostic correlation and potential of syndecan-1 (SDC1), a representative proteoglycan of GCX, as a biomarker.

Antitumor effects of chemically modified miR-143 lipoplexes in a mouse model of pelvic colorectal cancer via myristoylated alanine-rich C kinase substrate downregulation.

Replenishing tumor-suppressor miRNAs (TS-miRNAs) is a potential next-generation nucleic acid-based therapeutic approach. Establishing an effective miRNA delivery system is essential to successful TS-miRNA therapy. To overcome vulnerability to RNA nucleases, we previously developed a chemically modified miRNA143-3p (CM-miR-143).

Application of an artificial intelligence-based system in the diagnosis of breast ultrasound images obtained using a smartphone.

Background: Breast ultrasound (US) is useful for dense breasts, and the introduction of artificial intelligence (AI)-assisted diagnoses of breast US images should be considered. However, the implementation of AI-based technologies in clinical practice is problematic because of the costs of introducing such approaches to hospital information systems (HISs) and the security risk of connecting HIS to the Internet to access AI services. To solve these problems, we developed a system that applies AI to the analysis of breast US images captured using a smartphone.

Accelerated glycolysis in tumor microenvironment is associated with worse survival in triple-negative but not consistently with ER+/HER2- breast cancer.

Metabolic reprogramming to sustain immortality is a hallmark of cancer and glycolysis is an important way to attain this. Thus, we investigate the association of glycolysis and associated pathways in the survival of breast cancer. A total of 5,176 breast cancer patients from multiple independent cohorts were analyzed.

Detection of high-risk patients resistant to CDK4/6 inhibitors with hormone receptor-positive HER2-negative advanced and metastatic breast cancer in Japan (KBCSG-TR-1316).

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve the prognosis of hormone receptor-positive HER2-negative advanced/metastatic breast cancer (HR+/HER2- mBC). However, some cancers show resistance to CDK4/6i and have a poor prognosis. The non-luminal disease score (NOLUS) was developed to predict non-luminal disease using immunohistochemical analysis.

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04).

Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC).

Methods: In this multicenter phase II clinical trial (January 2019-July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC.

Elevated bile acid metabolism and microbiome are associated with suppressed cell proliferation and better survival in breast cancer.

Bile acids are metabolized by the gut microbiome and are involved in fat absorption. Contrary to their carcinogenic role in gastrointestinal cancers, bile acids have been reported to inhibit cancer cell proliferation in breast cancer. The microbiome of breast cancer tissues may also influence cancer proliferation.

The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer.

The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of therapeutic responses, there has been an explosion of research into the mechanisms of microbial effects on CRC. Harnessing and reprogramming the microbiome may allow for the expansion of these successes to broader categories of CRC, the prevention of CRC in high-risk patients, and the enhancement of standard treatments.

High miR-99b expression is associated with cell proliferation and worse patient outcomes in breast cancer.

Although miR-99b is a known suppressive microRNA (miRNA) in several cancers, its role in breast cancer has not been elucidated. In this study, we examined the clinical relevance of miR-99b expression in breast cancer. We analyzed miRNA and mRNA expression and their relationships with clinical parameters in 1,961 breast cancer samples from two independent large cohorts, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA).

Low adipocyte hepatocellular carcinoma is associated with aggressive cancer biology and with worse survival.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and non-alcoholic fatty liver disease is strongly associated with its development. To explore the role of adipocytes in HCC, we investigated intratumoral adipocytes, also known as cancer-associated adipocytes (CAA). Based on our prior breast cancer findings, we hypothesized that low intratumoral adipocytes would be associated with aggressive cancer biology, worse tumor microenvironment (TME), and clinical outcomes.

Higher intra-tumoral expression of pro-coagulation genes is a predictor of angiogenesis, epithelial mesenchymal transition and worse patient survival in gastric cancer.

Coagulation regulates angiogenesis in cancer, and is associated with tumor development and metastasis. To date, there have been no studies quantifying the state of intra-tumoral coagulation. We measured intra-tumoral coagulation gene expression using the "Hallmark-COAGULATION" gene set in the MSigDB, performing gene set variation analysis and then assigning a "coagulation score" to quantify gene expression.

The mechanism underlying resistance to 5-fluorouracil and its reversal by the inhibition of thymidine phosphorylase in breast cancer cells.

Fluoro-deoxyuridine monophosphate (FdUMP) is an active metabolite of 5-fluorouracil (5-FU) synthesized through two hypothesized pathways: The orotate phosphoribosyl transferase-ribonucleotide reductase (OPRT-RR) pathway and the thymidine phosphorylase-thymidine kinase (TP-TK) pathway. In the present study, the mechanism underlying 5-FU resistance was investigated, focusing on changes in 5-FU metabolism using MCF-7, 5-FU-resistant MCF-7/5-FUR, MDA-MB-231 and 5-FU-resistant MDA-MB-231/5-FUR breast cancer cells. The amount of FdUMP present following treatment with 5-FU was determined by the density of the upper band of thymidylate synthase detected by western blotting, and its changes were investigated.

Enhanced immune response outperform aggressive cancer biology and is associated with better survival in triple-negative breast cancer.

Although the value of tumor-infiltrating lymphocytes is well known, the clinical relevance of an increased immune response, specifically in breast cancer, has not been investigated across large cohorts of patients using computational algorithms. Our hypothesis stated that an enhanced immune response is associated with an improvement in outcomes. To quantify the immune response, we utilized the allograft rejection score correlated with cytolytic activity and with all the other Hallmark immune-related gene sets.

The clinical relevance of unfolded protein response signaling in breast cancer.

Protein homeostasis regulated by the Endoplasmic Reticulum (ER) is a recognized process involved in cancer progression. ER stress activates the Unfolded Protein Response (UPR) and has been implicated in a variety of cancers. Given the role of the UPR activation in carcinogenesis, we hypothesized that UPR activation could be associated with pathological progression, higher clinical stage, and worse survival in breast cancer.

Intratumoral PDGFB gene predominantly expressed in endothelial cells is associated with angiogenesis and lymphangiogenesis, but not with metastasis in breast cancer.

Purpose: Platelet-derived growth factor B (PDGFB) is known to play essential roles in angiogenesis and lymphangiogenesis during development, and tumor growth and vessel stabilization in experimental models. However, whether these findings could be translated to breast cancer patients remains unclear. We hypothesized that PDGFB gene expression is associated with angiogenesis, cell proliferation, and clinical outcomes in breast cancer patients.

NR2F1, a Tumor Dormancy Marker, Is Expressed Predominantly in Cancer-Associated Fibroblasts and Is Associated with Suppressed Breast Cancer Cell Proliferation.

Background: Tumor dormancy is a crucial mechanism responsible for the late recurrence of breast cancer. Thus, we investigated the clinical relevance of the expression of , a known dormancy biomarker.

Methods: A total of 6758 transcriptomes of bulk tumors from multiple breast cancer patient cohorts and two single-cell sequence cohorts were analyzed.

Clinical Relevance of Estrogen Reactivity in the Breast Cancer Microenvironment.

Purpose: Estrogen signals play an important role in the phenotype of estrogen receptor-positive breast cancer. However, comprehensive analyses of the effect of responsiveness to estrogen signals on the tumor microenvironment and survival in large cohorts of primary breast cancer patients have been lacking. We aimed to test the hypothesis that estrogen reactivity affects gene expression and immune cell infiltration profiles in the tumor microenvironment and survival.

Abundance of reactive oxygen species (ROS) is associated with tumor aggressiveness, immune response, and worse survival in breast cancer.

Purpose: Reactive oxygen species (ROS) are oxygen-containing molecules that have high reactivity and play roles in protection or harm the cancer cells. We aimed to clarify the clinical relevance of ROS in breast cancer (BC) tumor microenvironment (TME). We hypothesized that it is associated with worse BC patient outcomes.

APOBEC3F expression in triple-negative breast cancer is associated with tumor microenvironment infiltration and activation of cancer immunity and improved survival.

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) causes a point mutation from cytidine to uracil in DNA and/or RNA. The role of APOBEC3A and APOBEC3B in breast cancer has been well described, whereas that of APOBEC3F remains unknown. To investigate the clinical relevance of APOBEC3F expression, we analyzed a total of 3000 breast cancer cases from multiple independent large patient cohorts including METABRIC, TCGA, GSE75688, and GSE114725.

Intratumoral lymphatic endothelial cell infiltration reflecting lymphangiogenesis is counterbalanced by immune responses and better cancer biology in the breast cancer tumor microenvironment.

Lymphangiogenesis, the generation of new lymphatic vessels from existing ones, results from the dynamic interactions of lymphatic endothelial cells and the tumor microenvironment (TME). It is well known that lymphangiogenesis occurs during the initial stage of metastasis in various types of malignant tumors. However, it is currently not used as a biomarker partially because gold standard method to quantify it is labor and cost intensive.

Intratumoral density of regulatory T cells is a predictor of host immune response and chemotherapy response in colorectal cancer.

Regulatory T cells (Tregs) are a subset of CD4+ T lymphocytes known to dampen the host immune response against cancer cells. Within the tumor microenvironment, Tregs are potent facilitators of immune tolerance, and a higher proportion of Tregs compared to cytotoxic T cells predicts a worse outcome in most solid tumors. We studied the association between Treg density, and cancer biology and clinical outcome in colorectal cancer (CRC).

High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer.

Purpose: Although the DNA repair mechanism is important in preventing carcinogenesis, its activation in established cancer cells may support their proliferation and aggravate cancer progression. RAD51 cooperates with BRCA2 and is essential in the homologous recombination of DNA repair. To this end, we hypothesized that RAD51 gene expression is associated with cancer cell proliferation and poor prognosis of breast cancer (BC) patients.

Evaluation of the SYNAPSE VINCENT for lateral lymph node dissection in rectal cancer with robotic surgery: a preliminary report.

Background: Even if 3D angiographic images of preoperative contrast-enhanced computed tomography (CT) are created, the coronal and axial sections can be unclear, and thus, it is difficult to achieve projection awareness similar to that of actual laparoscopic images. In recent years, the technology of analyzing and applying medical images has advanced, and surgical simulation and navigation have been widely used to improve the safety of surgical operations. It is important to understand pelvic anatomy in the area of rectal cancer, and use of the SYNAPSE VINCENT makes it possible to simulate the anatomy before surgery, which is very useful in educating surgeons and their assistants.

, a p53-downstream gene, is associated with suppression of breast cancer cell proliferation and better survival.

Mitochondria-eating protein (; also known as ), a p53-downstream gene, is involved in mitochondrial quality control (MQC). Enforced MIEAP expression induces caspase-dependent cell death in vitro, and impairment of the p53/-regulated MQC pathway is frequently observed in breast cancer (BC), resulting in poor disease-free survival (DFS). To investigate the clinical significance of in BC, we identified 2,980 patients from two global, large-scale primary BC cohorts: the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=1,904) and the Cancer Genome Atlas (TCGA; n=1,076).

Breast reconstruction using a tissue expander after enucleation of a giant fibroadenoma: A case report.

Introduction: Fibroadenomas are among the most common benign tumors in women. Juvenile giant fibroadenomas account for nearly 0.5% of all fibroadenomas.