Genomic profiles of Japanese patients with vulvar squamous cell carcinoma.

The incidence of vulvar carcinoma varies by race; however, it is a rare disease, and its genomic profiles remain largely unknown. This study examined the characteristics of vulvar squamous cell carcinoma (VSCC) in Japanese patients, focusing on genomic profiles and potential racial disparities. The study included two Japanese groups: the National Cancer Center Hospital (NCCH) group comprised 19 patients diagnosed between 2015 and 2023, and the Center for Cancer Genomics and Advanced Therapeutics group comprised 29 patients diagnosed between 2019 and 2022. Somatic mutations were identified by targeted or panel sequencing, and TP53 was identified as the most common mutation (52-81%), followed by HRAS (7-26%), CDKN2A (21-24%), and PIK3CA (5-10%). The mutation frequencies, except for TP53, were similar to those of Caucasian cohorts. In the NCCH group, 16 patients of HPV-independent tumors were identified by immunohistochemistry and genotyping. Univariate analysis revealed that TP53-mutated patients were associated with a poor prognosis (log-rank test, P = 0.089). Japanese VSCC mutations resembled those of Caucasian vulvar carcinomas, and TP53 mutations predicted prognosis regardless of ethnicity. The present findings suggest potential molecular-targeted therapies for select VSCC patients.

Copper-catalyzed reaction of aziridine for the synthesis of substituted imidazolidine and imidazolidinone.

Herein we report a copper-catalyzed synthesis of imidazolidine by employing the reaction of aziridine with imine. The reaction smoothly provided a diverse range of 2-substituted imidazolidines with high compatibility with various functional groups. Moreover, during our investigation, we discovered that isocyanate also reacted with aziridine to yield substituted imidazolidinones efficiently. The versatility of these reactions was further demonstrated by their application in the synthesis of hybrid molecules derived from two pharmaceutical compounds. This approach opens new possibilities for the discovery of novel classes of bioactive molecules.

Copper-Catalyzed Heterocyclic Recombination of Aziridine and Diazetidine for the Synthesis of Imidazolidine.

The discovery of new catalytic applications for metals remains an important goal in organic synthesis. If a catalyst has multiple functions, such as inducing bond cleavage and formation, it can streamline multi-step transformations. Herein, the Cu-catalyzed synthesis of imidazolidine through heterocyclic recombination between aziridine and diazetidine is reported. Mechanistically, Cu catalyzes the conversion of diazetidine into the corresponding imine, which then reacts with aziridine to form imidazolidine. The scope is sufficiently wide to form various imidazolidines, as many functional groups are compatible with the reaction conditions.

[Ovarian Carcinosarcoma Associated with Cowden Syndrome-A Case Report].

Cowden syndrome is a rare autosomal dominant disorder characterized by multiple hamartomas in various tissues, including the skin, mucous membranes, and gastrointestinal tract. Germline mutations of the PTEN tumor suppressor gene are responsible for Cowden syndrome. Cowden syndrome is associated with an increased risk of breast, thyroid, renal and uterine cancers; however, ovarian cancer rarely develops in women with Cowden syndrome, although somatic PTEN mutation often occurs in some types of ovarian carcinomas. Herein we report the first case of ovarian carcinosarcoma that developed in a woman with Cowden syndrome. A 55-year-old woman with a history of breast cancer, thyroid goiter, and palatal papillomatosis presented with pelvic distention. CT scan revealed a pelvic tumor suggesting ovarian cancer. She underwent a total abdominal hysterectomy, a bilateral salpingo-oophorectomy, and an omentectomy, but the surgical cytoreduction was suboptima( l >2 cm residual disease). Pathological examination showed a mixed tumor composed of high-grade carcinoma and heterologous sarcoma. Immunohistochemically, tumor cells were positive for p53. She was diagnosed with stage ⅢC ovarian carcinosarcoma. Genetic testing detected a PTEN variant, confirming the diagnosis of Cowden syndrome. She received paclitaxel/ carboplatin chemotherapy. However, no response was observed and she died of disease 2 months postoperatively.

Evaluation of internal margins for prostate for step and shoot intensity-modulated radiation therapy and volumetric modulated arc therapy using different margin formulas.

PURPOSE: This feasibility study evaluated the intra-fractional prostate motion using an ultrasound image-guided system during step and shoot intensity-modulated radiation therapy (SS-IMRT) and volumetric modulated arc therapy (VMAT). Moreover, the internal margins (IMs) using different margin formulas were calculated. METHODS: Fourteen consecutive patients with prostate cancer who underwent SS-IMRT (n = 5) or VMAT (n = 9) between March 2019 and April 2020 were considered. The intra-fractional prostate motion was observed in the superior-inferior (SI), anterior-posterior (AP), and left-right (LR) directions. The displacement of the prostate was defined as the displacement from the initial position at the scanning start time, which was evaluated using the mean ± standard deviation (SD). IMs were calculated using the van Herk and restricted maximum likelihood (REML) formulas for SS-IMRT and VMAT. RESULTS: For SS-IMRT, the maximum displacements of the prostate motion were 0.17 ± 0.18, 0.56 ± 0.86, and 0.18 ± 0.59 mm in the SI, AP, and LR directions, respectively. For VMAT, the maximum displacements of the prostate motion were 0.19 ± 0.64, 0.22 ± 0.35, and 0.14 ± 0.37 mm in the SI, AP, and LR directions, respectively. The IMs obtained for SS-IMRT and VMAT were within 2.3 mm and 1.2 mm using the van Herk formula and within 1.2 mm and 0.8 mm using the REML formula. CONCLUSIONS: This feasibility study confirmed that intra-fractional prostate motion was observed with SS-IMRT and VMAT using different margin formulas. The IMs should be determined according to each irradiation technique using the REML margin.