Selective Inhibition of L-type Amino Acid Transporter 1 Suppresses Cell Proliferation in Ovarian Clear Cell Carcinoma.

BACKGROUND/AIM: Ovarian clear cell carcinoma (OCCC) is a histological type of ovarian cancer that is refractory to chemotherapy and has poor prognosis, which necessitates the development of novel treatment therapies. In this study, we focused on L-type amino acid transporter 1 (LAT1), which is involved in cancer growth, and investigated the effect of its selective inhibition on cell proliferation in OCCC. MATERIALS AND METHODS: The inhibitory effect of nanvuranlat (JPH203), a LAT1 selective inhibitor, on the cellular uptake of [3H] leucine was evaluated using the OCCC cell line JHOC9, which expresses the LAT1 protein. In addition, the kinetics of cell proliferation and changes in phosphorylation of the mTOR pathway were analyzed. The correlation between LAT1 expression and progression-free survival (PFS) was evaluated using clinical specimens of OCCC. RESULTS: Nanvuranlat inhibited [3H] leucine intracellular uptake and cell proliferation in a dose-dependent manner in JHOC9 cells. In addition, it suppressed the activity of the mTOR signaling pathway, which is thought to inhibit cancer cell proliferation. LAT1 expression was most frequent in OCCC among clinical specimens of epithelial ovarian cancer. A correlation between LAT1 expression and PFS was observed in OCCC. CONCLUSION: LAT1 selective inhibition suppresses cell proliferation via the mTOR pathway by inhibiting leucine uptake in OCCC. This study illustrates the potential of using LAT1 selective inhibition as a treatment strategy for OCCC.

Radiomic Analysis for Pretreatment Prediction of Recurrence Post-Radiotherapy in Cervical Squamous Cell Carcinoma Cancer.

BACKGROUND: The current study aims to predict the recurrence of cervical cancer patients treated with radiotherapy from radiomics features on pretreatment T1- and T2-weighted MR images. METHODS: A total of 89 patients were split into model training (63 patients) and model testing (26 patients). The predictors of recurrence were selected using the least absolute shrinkage and selection operator (LASSO) regression. The machine learning used neural network classifiers. RESULTS: Using LASSO analysis of radiomics, we found 25 features from the T1-weighted and 4 features from T2-weighted MR images, respectively. The accuracy was highest with the combination of T1- and T2-weighted MR images. The model performances with T1- or T2-weighted MR images were 86.4% or 89.4% accuracy, 74.9% or 38.1% sensitivity, 81.8% or 72.2% specificity, and 0.89 or 0.69 of the area under the curve (AUC). The model performance with the combination of T1- and T2-weighted MR images was 93.1% accuracy, 81.6% sensitivity, 88.7% specificity, and 0.94 of AUC. CONCLUSIONS: The radiomics analysis with T1- and T2-weighted MR images could highly predict the recurrence of cervix cancer after radiotherapy. The variation of the distribution and the difference in the pixel number at the peripheral and the center were important predictors.

Uterine leiomyosarcoma well-controlled with eribulin mesylate.

Uterine leiomyosarcoma is a rare type of malignant gynecological tumor and has a poor prognosis; therefore, this tumor is often difficult to treat. Some new drugs have been approved during the past several years in Japan and are expected to be efficacious. Eribulin, one of these drugs, is a natural product of halichondrin B, which is isolated from a marine sponge. A recent clinical trial comparing eribulin with dacarbazine to target liposarcoma and leiomyosarcoma indicated that overall survival (OS) was prolonged by treatment with eribulin. We report a case of uterine progressive leiomyosarcoma that responded to eribulin. A 57-year-old woman was suspected of having leiomyosarcoma based on an endometrial biopsy and imaging examinations. Although the tumor grew toward the uterine artery on the right side of the uterine cervix, we performed a total abdominal hysterectomy and bilateral salpingo-oophorectomy to obtain an outcome of no gross residual disease. However, the margin of the right side of the uterine cervix was histologically positive, so leiomyosarcoma stage IIB (pT2bcN0cM0, FIGO2008) was diagnosed. Gemcitabine and docetaxel therapy was administered postoperatively. However, after three cycles, the residual tumor progressed. Other anticancer drugs were administered but were ineffective. We administered eribulin (1.4 mg/m2) as a fourth-line regimen, and the mass decreased by 32% after four cycles. However, the residual tumor continued to grow after eight cycles. The only adverse event associated with eribulin treatment was mild, grade 2 neutropenia. For our patient, eribulin was effective for her recurrent leiomyosarcoma. In selecting chemotherapy, there are currently no fixed guidelines; we should consider the characteristics and adverse events associated with each drug and patient performance status and comorbidities. In this patient, eribulin was associated with few adverse events, an easy route of administration and a good quality of life. Therefore, eribulin is expected to be efficacious for the treatment of gynecologic sarcoma.