Keio University · Medicine
Professor Kohei Nakamura's research lab focuses on molecular oncology and precision medicine, with a particular emphasis on understanding the genetic and molecular mechanisms underlying gynecological and gastrointestinal cancers. The lab investigates oncogenic drivers, such as ERBB2 amplification and TP53 mutations, in high-grade serous carcinoma and other malignancies, aiming to improve diagnostic accuracy and therapeutic strategies. Using advanced genomic technologies like next-generation sequencing and functional modeling in immortalized epithelial cells, the lab explores tumorigenesis pathways and tumor heterogeneity to guide personalized treatment approaches. The work also extends to rare gynecologic sarcomas and hereditary cancer syndromes, including Lynch syndrome, to expand the scope of precision oncology.
Figures are computed from collected data and may differ slightly.
Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a
Fallopian tube secretory epithelial cells (FTSECs) have been suggested to be the source of high-grade serous ovarian carcinoma (HGSOC). Although several genetic alterations are known to be involved in HGSOC development, the minimal requirements remain unclear. We aimed to identify oncogenic mutations indispensable for HGSOC development in a stepwise model, using immortalized FTSECs. FTSECs were isolated from clinical samples and immortalized by overexpression of cyclin D1, CDK4<sup>R24C</sup>, a
A high pre-treatment plasma level of D-dimers represents an independent prognostic biomarker for CC that could assist in identifying high-risk populations for treatment decisions.
Lynch syndrome, a hereditary cancer syndrome, occurs because of germline mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1 (<i>MLH1</i>), MutS Homolog 2 (<i>MSH2</i>), MutS Homolog 6 (<i>MSH6</i>), and PMS1 Homolog 2 (<i>PMS2</i>)). The disorder is associated with colorectal, endometrial, and other epithelial malignancies, but not cervical cancer. We report a woman with Lynch syndrome with synchronous cervical cancer. This is the first report of Lynch syndrome-related c
Precision medicine, which includes comprehensive genome sequencing, is a potential therapeutic option for treating high-grade serous carcinoma (HGSC). However, HGSC is a heterogeneous tumor at the architectural, cellular, and molecular levels. Intratumoral molecular heterogeneity currently limits the precision of medical strategies based on the gene mutation status. This study was carried out to analyze the presence of 160 cancer-related genetic alterations in three tissue regions with different
A better understanding of the underlying genetic mechanisms will help to clarify the carcinogenesis of BG-ACC. In turn, this will enable treatment with novel targeting agents, as well as the initial exploration of gene-based precision oncological therapies, which aim to improve treatment outcomes for patients with this disease.
Low-grade endometrial stromal sarcoma (LGESS) is a rare malignancy. The tumor is reportedly responsive to hormonal therapy, most commonly with medroxyprogesterone acetate (MPA), but the effectiveness of aromatase inhibitors for recurrent LGESS remains unclear. The present study reports a case of stage IC LGESS presenting with abnormal uterine bleeding, and also provides a review of the literature. Following a total abdominal hysterectomy and bilateral salpingo-oophorectomy, MPA therapy was initi
High pretreatment D-dimer levels have an impact on prognoses independently of VTE, and also have potential as markers to predict surgical outcomes in patients with endometrial carcinoma. Pretreatment D-dimer levels may contribute to the identification of high-risk populations for treatment decisions.
This study aimed to describe the long-term outcomes of patients with menorrhagia treated with microwave endometrial ablation (frequency, 2.45 GHz), as well as to identify factors associated with recurrence or re-surgery. This retrospective cohort study was conducted from 2007 to 2015 at Shimane University Hospital in Japan. Patients with severe menorrhagia and a desire to preserve their uterus were included in the study. Clinical factors associated with recurrence of menorrhagia or re-surgery we
Tumor sensitivity to platinum (Pt)-based chemotherapy and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors is increased by homologous recombination deficiency-causing mutations; in particular, reversion mutations cause drug resistance by restoring protein function. Treatment response is predicted by breast cancer susceptibility gene 1/2 (BRCA1/2) mutations; however, BRCA1/2 reversion mutations have not been comprehensively studied in pan-cancer cohorts. We aimed to characterize BR
The aim of the present study was to assess the prognostic significance of the pre‑treatment neutrophil‑to‑lymphocyte ratio (NLR), the platelet‑to‑lymphocyte ratio (PLR) and other clinicopathological characteristics in patients with non‑surgically treated uterine cervical carcinoma. The correlations of clinicopathological characteristics with overall and progression‑free survival were determined in 98 Japanese patients who received non‑surgical treatment for uterine cervical carcinoma between Jan
Ovarian low-grade serous carcinoma is thought to begin as a serous cystadenoma or adenofibroma that progresses in a slow stepwise fashion. Among the low-grade serous carcinomas, there is a high frequency of activating mutations in the KRAS or BRAF genes; however, it remains unclear as to how these mutations contribute to tumor progression. This is the first report to track the histopathological progression of serous adenofibroma to low-grade serous carcinoma. Each stage was individually analyzed
Multiple MEA successfully controls menorrhagia from adenomyosis and achieves a higher satisfaction rate than single MEA.
We examined the usefulness of evaluating tumor size determined using preoperative magnetic resonance imaging (MRI) for prognosis in patients with endometrial carcinoma (EC). Patients (<i>N</i> = 184) with EC who underwent surgery at Shimane University Hospital between 1997 and 2013 were enrolled. We investigated the association between the tumor size of EC assessed prior to surgery by MRI (anteroposterior [AP], transverse [TV], and craniocaudal [CC] diameters) and various clinical parameters inc
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