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.

A 37-year-old woman was admitted with epigastric pain. Her abdomen was distended, and there was rebound tenderness. Abdominal enhanced computed tomography confirmed a poor contrast region in the ileocecal region to the ascending colon and a large amount of ascites. An urgent laparotomy was performed for acute peritonitis caused by bowel necrosis. There was a large amount of purulent ascites at the time of surgery, intra-peritoneal drainage was performed, and antibiotic therapy with tazobactam/ piperacillin was started. However, no causes of acute peritonitis, such as gastrointestinal perforation, were evident. On day 2 after the operation, Streptococcus pyogenes was detected from the culture of the intraabdominal white coat. Primary peritonitis caused by Streptococcus pyogenes was diagnosed. Ceftriaxone and clindamycin were given to treat the Streptococcus pyogenes ; the patient's general condition improved, and the inflammatory reaction decreased. On postoperative day 19, the patient was discharged in good condition. Primary peritonitis with Streptococcus pyogenes is a cause of acute peritonitis. It should be suspected in a patient with no obvious cause of acute peritonitis during the operation. Key words：Streptococcus pyogenes，primary peritonitis，streptococcal toxic shock like syndrome

No abstract