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Lysosomal TMEM9-LAMTOR4-controlled mTOR signaling integrity is required for mammary tumorigenesis

Cancer Communications 2023年第1期43卷 159-163页

作者： Shengzhe Zhang Sung Ho Lee Litong Nie Yuanjian Huang Gengyi Zou Youn-Sang jung sohee jun Jie Zhang Esther MLien junjie Chen Jae-Il Park Department of Experimental Radiation Oncology Division of Radiation Oncologythe University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Graduate School of Biomedical Sciences the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Program in Genetics and Epigenetics the University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

Dear Editor,Accumulating evidence suggests that dysregulated lysosomal membrane proteins,including vacuolar ATPase(v-ATPase)and the mammalian target of rapamycin(mTOR),are involved in tumorigenesis[1].Therefore,lysosomal proteins were proposed as potential therapeutic targets in cancer[1].As one of the lysosome-related signaling pathways,mTOR signaling regulates cell proliferation,survival,motility,and metabolism[2].SincemTOR signaling activation promotes tumorigenesis,mTOR inhibitors(mTORi),AZD8055[3],MLN0128[4],and Rapalink-1(the latest third-generation mTORi)[4],have been applied to several ***,the limitations of mTORi include drug resistance and the lack of biomarkers.

关键词： tumorigenesis metabolism mTOR

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Leptomeningeal seeding after surgical resection or stereotactic radiosurgery for brain metastases: Analysis of risk factors

Leptomeningeal seeding after surgical resection or stereotac...

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第五届韩-中神经肿瘤会议

作者： jun Hyong Ahn Sang Hyun Lee Heon Yoo Seung Hoon Lee jungnam Joo sohee Kim Ho-Shin Gwak Department of Neurosurgery Seoul National University College of Medicine National Cancer Center Korea Department of diagnostic radiology National Cancer Center Korea Neuro-oncology Clinic and National Cancer Center Korea Department of Medical statistics National Cancer Center Korea

Background: Leptomeningeal seeding （LMS） is a devastating complication of malignancy. Among several pathogenesis, surgical spillage has been one of the iatrogenic factors for the development of LMS. We retrospectively analyzed various surgical factors affecting the development of LMS. Patients and Methods: We identified 294 patients with brain metastasis who had been treated using surgery between 2001 and 2009. We classified the tumor location into subcortical, pial, epipial, juxtaventricular and ventricular. The description of surgical resection was divided into piecemeal and en-bloc and the risk of using cavitron ultrasonic aspirator （CUSA） were investigated. Results: A total 44 of the 294 patients （15%） developed LMS after undergoing index procedure. The median time to LMS development was 6months （range, 1.0-42.0）. Among the 294 surgical patients, seven out of 101 en-bloc removal patients （6.9%） developed LMS, whereas 37 out of 193 piecemeal removal patients （19.2%） developed LMS, and the incidence of LMS was significantly different between these two surgical resection modes （p = 0.005）.The adjusted hazard ratio （HR） for patients whose tumors were resected by piecemeal compared to en-bloc was 3.12 （95% CI, 1.4-7.0;p = 0.006）. The incidence of LMS was significantly higher （p ＜ 0.001） in patients whose tumors were resected by CUSA, and the HR of using CUSA was 4.18 （95% CI, 1.9-9.4;p = 0.001）. The location of tumor at high-risk of CSF exposure （epipial and ventricular） conferred increased risk of LMS after the treatment compared to low-risk group with the HR 2.52 （95% CI, 1.4-4.7;p = 0.004）. On the other hand, the location of tumor at low-risk of CSF exposure （subcortical） showed significantly reduced risk of LSM compared to the other locations （HR=0.27;95% CI 0.12-0.65;p-value = 0.003）. Conclusion: The piecemeal resection mode and the use of CUSA were found to increase risk of LMS in this retrospective study. Therefore, the piecemeal resection using CUSA should be

关键词： Leptomeningeal carcinomatosis Neoplasm seeding surgery stereotactic radiosurgery

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