A5068725056- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Innovations in Medical Education
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Cell Adhesion Molecules Research
- Gastric Cancer Management and Outcomes
- Cancer Mechanisms and Therapy
- Anatomy and Medical Technology
- Chemokine receptors and signaling
- Lung Cancer Treatments and Mutations
- Ferroptosis and cancer prognosis
- Immune cells in cancer
- Global Health and Surgery
- Prostate Cancer Treatment and Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Endometriosis Research and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Hippo pathway signaling and YAP/TAZ
- Healthcare professionals’ stress and burnout
- Simulation-Based Education in Healthcare
- Global Health Workforce Issues
- Cultural Competency in Health Care
- Pancreatic and Hepatic Oncology Research
Tokyo Women's Medical University
2014-2025
Massachusetts General Hospital
2016-2023
Harvard University
1964-2023
Goethe University Frankfurt
1964-1965
An alternate route for metastatic cells Metastatic tumor are thought to reach distant organs by traveling through the blood circulation or lymphatic system. Two studies of mouse models now suggest a hybrid cell dissemination. Pereira et al. and Brown used distinct methodologies monitor fate in lymph nodes. They found that could invade local vessels within node, exit node entering circulation, then go on colonize lung. Whether this dissemination occurs cancer patients is unknown; answer...
Sorafenib, a broad tyrosine kinase inhibitor, is the only approved systemic therapy for advanced hepatocellular carcinoma (HCC) but provides limited survival benefits. Recently, immunotherapy has emerged as promising treatment strategy, its role remains unclear in HCCs, which are associated with decreased cytotoxic CD8 + T‐lymphocyte infiltration both murine and human tumors. Moreover, mouse models after sorafenib intratumoral hypoxia increased may fuel evasive resistance. Using orthotopic...
Background and Aims Activation of the antitumor immune response using programmed death receptor‐1 (PD‐1) blockade showed benefit only in a fraction patients with hepatocellular carcinoma (HCC). Combining PD‐1 antiangiogenesis has shown promise substantially increasing HCC who respond to treatment, but mechanism this interaction is unknown. Approach Results We recapitulated these clinical outcomes orthotopic—grafted or induced—murine models HCC. Specific vascular endothelial receptor 2...
Background and purpose Combining inhibitors of vascular endothelial growth factor the programmed cell death protein 1 (PD1) pathway has shown efficacy in multiple cancers, but disease-specific agent-specific mechanisms benefit remain unclear. We examined defined when combining regorafenib (a multikinase antivascular receptor inhibitor) with PD1 blockade murine hepatocellular carcinoma (HCC) models. Basic procedures used orthotopic models HCC mice liver damage to test effects...
Background Increasing evidence indicates that tumor endothelial cells (TEC) differ from normal (NEC). Our previous reports also showed TEC were different NEC. For example, have chromosomal abnormality and proangiogenic properties such as high motility proliferative activity. However, the mechanism by which acquire a specific character remains unclear. To investigate this mechanism, we focused on tumor-derived microvesicles (TMV). Recent studies shown TMV contain numerous types of bioactive...
Abstract Sorafenib is a RAF inhibitor approved for several cancers, including hepatocellular carcinoma (HCC). Inhibition of kinases can induce dose-dependent “paradoxical” upregulation the downstream mitogen-activated protein kinase (MAPK) pathway in cancer cells. It unknown whether ERK activation occurs after sorafenib therapy HCC, and if so, it impacts therapeutic efficacy. Here, we demonstrate that inhibition by rapidly leads to dimerization HCCs, which contributes treatment evasion. The...
Objective Intrahepatic cholangiocarcinoma (ICC)—a rare liver malignancy with limited therapeutic options—is characterised by aggressive progression, desmoplasia and vascular abnormalities. The aim of this study was to determine the role placental growth factor (PlGF) in ICC progression. Design We evaluated expression PlGF specimens from patients assessed effect genetic or pharmacologic inhibition orthotopically grafted mouse models. impact stimulation blockade cells cancer-associated...
A key goal of vaccine immunotherapy is the generation long-term memory CD8(+) T cells capable mediating immune surveillance. We discovered a novel intercellular pathway governing development potent cell responses against cell-associated Ags that mediated through cross-presentation by XCR1(+) dendritic (DCs). Generation tumor pulsed with an invariant NKT ligand depended on cross-talk between and plasmacytoid DCs was regulated IFN-α/IFN-αR signals. IFN-α production stimulated OX40 signal from...
Background: Although extensive resection improves the prognosis of gliomas, it risks impairing critical brain functions. Photodynamic therapy (PDT) utilizing talaporfin sodium (TS) targets tumor cells upon light activation. Despite its approval in Japan, TS application remains restricted, and factors influencing efficacy are unclear. We aimed to identify determinants optimize treatment outcomes. Methods: Data from 171 patients with grade 4 glioma who underwent surgery PDT at Tokyo Women’s...
The endometrium undergoes continuous repair and regeneration without scarring throughout the reproductive life of women. However, mechanisms responsible for this complete restoration remain mostly unexplored. We hypothesized that ischemic state local hypoxia present after parturition may create a special microenvironment endometrial healing, ischemia might be caused by reduction in organ volume via postpartum uterine contraction. Here, we developed mouse model using combination cesarean...
Vasohibin-2 (VASH2) has been identified as an endogenous and vascular endothelial growth factor (VEGF)-independent angiogenic that is highly expressed in tumor cells. In the present study, we aimed to determine whether pre-existing changes can be used predict transformation benign or malignant. We sought characterize microvascular development intestinal tract of ApcMin/+ mice ApcMin/+/Vash2-/- mice.ApcMin/+ provide a unique orthotopic model for spontaneous adenomatous polyposis subsequent...
Background: Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Angiogenesis and inflammation are hallmarks of HCC progression therapeutic targets. Methods: We retrospectively evaluated preoperative clinical variables circulating (plasma) biomarkers angiogenesis a cohort who underwent liver resection (LR) or transplantation (LT). Biomarker correlation with outcomes—freedom recurrence (FLR), disease-free survival (DFS) overall (OS)—was...
Abstract Radiotherapy is widely used to treat cancer because it has the advantage of physically and functionally conserving affected organ. To improve radiotherapy investigate molecular mechanisms cellular radioresistance, we established a clinically relevant radioresistant (CRR) cell line, SAS‐R, from SAS cells. SAS‐R cells continue proliferate when exposed fractionated radiation (FR) 2 Gy/day for more than 30 days in vitro. A xenograft tumor model was also resistant X‐rays days. The...
Radiotherapy (RT) is a standard treatment for patients with advanced prostate cancer (PCa). Previous preclinical studies showed that SDF1α/CXCR4 axis could mediate PCa metastasis (most often to the bones) and resistance RT. We found high levels of expression both SDF1α its receptor CXCR4 in primary metastatic tissue samples. In vitro analyses using cells revealed an important role cell invasion but not radiotolerance. Pharmacologic inhibition AMD3100 no efficacy orthotopic bone models....
The vasohibin ( VASH ) family consists of two genes, 1 and 2 . is mainly expressed in vascular endothelial cells suppresses angiogenesis an autocrine manner, whereas cancer exhibits pro‐angiogenic activity. Employing adenomatous polyposis coli gene mutant mice, we recently reported on the role Vash2 spontaneous formation intestinal tumors. In this study, used K19‐Wnt1/C2mE Gan mice examined gastric formation. spontaneously develop tumors by activation Wnt prostaglandin E2 signaling pathways...
Chloride flux from nutrient to secretory surface of frog gastric mucosa was observed be maximal with isotonic NaCl as the solution, and depressed in varying amounts by replacement other sodium salts or nonelectrolytes. In particular, bicarbonate ion solution lowered Cl flux, but not because an increase pH. On contrary, increasing partial pressure CO 2 maintain a normal pH produced further decrease flux. This decrement similar that due only, so effects were additive. The largest reduction...