Targeting Amino Acid Metabolic Reprogramming via L-Type Amino Acid Transporter 1 (LAT1) for Endocrine-Resistant Breast Cancer.

The PI3K/Akt/mTOR pathway has been well known to interact with the estrogen receptor (ER)-pathway and to be also frequently upregulated in aromatase inhibitor (AI)-resistant breast cancer patients. Intracellular levels of free amino acids, especially leucine, regulate the mammalian target of rapamycin complex 1 (mTORC1) activation. L-type amino acid transporters such as LAT1 and LAT3 are associated with the uptake of essential amino acids. LAT1 expression could mediate leucine uptake, mTORC1 signaling, and cell proliferation. Therefore, in this study, we explored amino acid metabolism, including LAT1, in breast cancer and clarified the potential roles of LAT1 in the development of therapeutic resistance and the eventual clinical outcome of the patients. We evaluated LAT1 and LAT3 expression before and after neoadjuvant hormone therapy (NAH) and examined LAT1 function and expression in estrogen deprivation-resistant (EDR) breast carcinoma cell lines. Tumors tended to be in advanced stages in the cases whose LAT1 expression was high. LAT1 expression in the EDR cell lines was upregulated. JPH203, a selective LAT1 inhibitor, demonstrated inhibitory effects on cell proliferation in EDR cells. Hormone therapy changed the tumor microenvironment and resulted in metabolic reprogramming through inducing LAT1 expression. LAT1 expression then mediated leucine uptake, enhanced mTORC1 signaling, and eventually resulted in AI resistance. Therefore, LAT1 could be the potential therapeutic target in AI-resistant breast cancer patients.

[Thymic carcinoid associated with multiple endocrine neoplasia type 1].

We report a case of a thymic carcinoid associated with multiple endocrine neoplasia type 1( MEN-1). A 37-year-old man was referred to our hospital for further examination of an abnormal chest shadow. A chest computed tomography (CT) showed an anterior mediastinal mass measuring 6.5 cm in diameter. A pathological diagnosis of thymic carcinoid was made from a CT-guided needle biopsy specimen. Preoperative workup including endocrinological examination revealed a pituitary adenoma and hyperparathyroidism, and MEN-1 was clinically diagnosed. We performed total parathyroidectomy with autotransplantation and thymectomy with lymph node dissection through cervical collar incision and median sternotomy. The diagnosis of MEN-1 was confirmed by the genomic analysis postoperatively. Since 25% of thymic carcinoids are MEN-1 related and 95% of MEN-1 patients develop hyperparathyroidism, it should be kept in mind that this condition can be treated by thymectomy and concurrent parathyroidectomy.

Comparison of screen-film and full-field digital mammography in Japanese population-based screening.

PURPOSE: To investigate how the greater contrast of full-field digital mammography (FFDM) affects the detection of suspicious lesions in Japanese population-based screening. MATERIALS AND METHODS: Screen-film mammography (SFM) and FFDM were performed in 480 women aged 50 years or more. A set of mediolateral oblique views was obtained with each modality. All mammograms were independently double-read. The five-scale category assessment and type of finding using the Breast Imaging Reporting and Data system (BI-RADS) nomenclature were given. Intraobserver variance, recall rates, and positive predictive value were calculated. RESULTS: The findings between the two modalities were discordant. kappa-values for each reader were 0.619 and 0.385, respectively. Almost half of the microcalcifications were called with both modalities. The detection of masses was less concordant between the readers (27%). The masses were detected more frequently with FFDM (73%). Other findings were only detected with one modality. The recall rate was not significantly different (2.9% with SFM vs. 4.2% with FFDM; p=0.253). The positive predictive value was not significantly different (14% with SFM vs. 10% with FFDM; p=0.69), either. Two patients with breast cancer were detected with both modalities. CONCLUSION: Recall rates and positive predictive value were not significantly different between SFM and FFDM. Cancers were detected with both modalities.