Published papers

Cervical cancer ranks high among the causes of female cancer mortalities and is an important disease in developing and developed countries. Current diagnosis of cervical cancer depends on colposcopy, pathological diagnosis and preoperative diagnosis using methods, including magnetic resonance imaging and computed tomography. Advanced cervical cancer has a poor prognosis. The tumor marker squamous cell carcinoma is conventionally used for screening, but recent studies have revealed the mechanisms of carcinogenesis and the factors associated with a poor prognosis in cervical cancer. These include epigenetic biomarkers, with the methylation level of the checkpoint with forkhead and ring finger gene being potentially useful for predicting the malignancy of cervical cancer and sensitivity to treatment with paclitaxel. The extent of methylation of the Werner DNA helicase gene is also useful for determining sensitivity to an anticancer agent, CPT-11. In addition to epigenetic changes, the expression levels of hypoxia-inducible factor 1alpha subunit, epidermal growth factor receptor and cyclooxygenase-2 have been reported as possible biomarkers in cervical cancer. Novel prognostic factors, including angiogenic factors, fragile histidine triad, thymidylate synthase, glucose-related protein 58 and mucin antigens, have also been described, and hemoglobin and platelets may also be significant prognostic biomarkers. Utilization of these biomarkers may facilitate personalized treatment and improved outcomes in cervical cancer.

Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen-dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of PTEN, beta-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR-124, miR-126, miR-137, miR-491, miR-129-2 and miR-152. Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes.

Positron-emission tomography (PET), a diagnostic imaging technique using an agent labeled with a positron-emitting radionuclide, may facilitate improved diagnosis and treatment in gynecological fields. A combined PET/computerized tomography (CT) scan can identify the precise anatomical location of a lesion based on accumulation of (18)F-fluoro-D-glucose (FDG). FDG-PET and PET/CT have been used for detecting metastatic lesions and predicting prognosis in uterine cancer. PET has higher reliability in diagnosing lymph node metastases of uterine cancer than CT or MRI, and is considered most useful among non-invasive diagnostic imaging methods. Accumulation of FDG in lesions is indicative of a poor prognosis. Due to its limited spatial resolution, PET is not suitable has lower utility for detecting small lesions, and is not suitable for early-stage screening, and diagnosing primary lesions. Further improvements in diagnostic technology, including PET/MRI, investigation of new positron tracers, and analysis of data from various combinations of tracers are likely to make PET particularly useful for diagnosis and therapeutic strategy planning.