大阪大学 · 医学
佐々田健二郎教授の研究室は、卵巣がんの発症・進行メカニズムの解明を柱とし、特に腫瘍マイクロ環境や細胞接着分子、シグナル伝達経路に注目した基盤研究を展開しています。E-cadherinやα5β1インテグリン、c-Met、CD47、IL-6Rといったがん関連分子の機能解明を通じて、転移・再発のメカニズムを解き明かし、がん治療の新たな標的を模索しています。また、アルエンドロン酸のような既存薬の再利用可能性についても実験的に検証しており、翻訳的医療応用への道を模索しています。
Figures are computed from collected data and may differ slightly.
E-cadherin loss is frequently associated with ovarian cancer metastasis. Given that adhesion to the abdominal peritoneum is the first step in ovarian cancer dissemination, we reasoned that down-regulation of E-cadherin would affect expression of cell matrix adhesion receptors. We show here that inhibition of E-cadherin in ovarian cancer cells causes up-regulation of alpha(5)-integrin protein expression and transcription. When E-cadherin was blocked, RMUG-S ovarian cancer cells were able to attac
The hepatocyte growth factor receptor c-Met is a receptor tyrosine kinase that plays an important role in tumor growth by activating mitogenic signaling pathways. The goal of this study was to evaluate the role of c-Met in the biology of ovarian cancer and to determine its potential as a therapeutic target. c-Met protein expression was detected by immunohistochemistry in 138 advanced-stage ovarian cancers using a tissue microarray annotated with disease-specific patient follow-up. Fifteen of 138
Ovarian cancer is the most lethal of malignant gynecological tumors. Its lethality may be due to difficulties in detecting it at an early stage and lack of effective treatments for patients with an advanced or recurrent status. Therefore, there is a strong need for prognostic and predictive markers to diagnose it early and to help optimize and personalize treatment. MicroRNAs are noncoding RNAs that regulate target genes posttranscriptionally. They are involved in carcinogenesis, cell cycle, apo
Alendronate, a nitrogen-containing bisphosphonate, is a potent inhibitor of bone resorption used for the treatment and prevention of osteoporosis. Recent findings suggest that alendronate and other nitrogen-containing bisphosphonates inhibit the mevalonate pathway and thereby inhibit the synthesis of products derived from this metabolite. This, in turn, prevents the prenylation of a number of small GTPases, which regulate cell growth, motility, and invasion. We studied the effect of alendronate
Ovarian cancer is largely diagnosed at advanced stages upon detection of multiple peritoneal dissemination, resulting in poor outcomes. CD47 is overexpressed in tumors, facilitates tumor immune evasion, and is located on exosomes. We aimed to investigate the role of exosomal CD47 in ovarian cancer progression. Prognostic significance of CD47 expression in ovarian cancer was examined using a public database including 1,435 patients and validated with 26 patients at our institution. CD47 expressio
Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in
Peritoneal dissemination is a distinct form of metastasis in ovarian cancer that precedes hematogenic or lymphatic metastasis. Exosomes are extracellular vesicles of 30-150 nm in diameter secreted by different cell types and internalized by target cells. There is emerging evidence that exosomes facilitate the peritoneal dissemination of ovarian cancer by mediating intercellular communication between cancer cells and the tumor microenvironment through the transfer of nucleic acids, proteins, and
Epithelial ovarian cancer is a fatal disease, with a cure rate of only 30%. Several recent studies have targeted integrins for cancer treatment. Preclinical studies have shown the effectiveness of several integrin inhibitors for blocking cancer progression, especially by blocking angiogenesis. Because the initial critical step in ovarian cancer metastasis is the attachment of cancer cells to the peritoneum or omentum and because clinical trials have provided positive results for anti-angiogenic
Ovarian cancer is a deadly disease, with a cure rate of only 30%. Despite aggressive treatments, relapse remains almost inevitable in patients with advanced-stage disease. In recent years, great progress has been made towards targeting integrins in cancer treatment, and clinical studies with various integrin inhibitors have demonstrated their effectiveness in blocking cancer progression. Given that the initial critical step of ovarian cancer metastasis is the attachment of cancer cells onto the
Intrauterine balloon-tamponade could successfully control severe hemorrhage from a lower uterine segment of a patient with placenta previa. This technique is simple to use, scarcely invasive, and available at a low cost to all maternity wards, and should be considered as one of the first management options to reduce the risk of undesirable hysterectomy.
Exosomes are extracellular vesicles involved in several biological and pathological molecules and can carry many bioactive materials to target cells. They work as important mediators of cell-cell communication and play essential roles in many diseases, especially in cancer. Ovarian cancer is one of the most common gynecological malignancies. Most patients are diagnosed at advanced stages involving widespread peritoneal dissemination, resulting in poor prognosis. Emerging evidence has shown that
In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous
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