진행성 난소암을 진단 받은 환자에서 종양감축술을 받을 때 고령이 예후에 미치는 영향

학위논문(석사) -- 서울대학교대학원 : 의과대학 의학과, 2023. 2. 김희승.Although debulking surgery is a significant factor in improving the prognosis of advanced ovarian cancer, it may lead to increased surgical morbidity and mortality in elderly patients. However, some studies suggest that there are other stronger contributing factors to such risk. Through this study, we aim to explore the impact of old age on surgical outcomes and complications. We collected data of elderly patients aged 65 years and older who underwent debulking surgery for advanced ovarian cancer. A total of 120 patients were identified and classified as follows: group 1, 65–69 years (n = 58); group 2, 70–74 years (n = 38); group 3, 75–79 years (n = 17); group 4, ≥ 80 years (n = 7). There were no differences in most of the characteristics, surgical extent and outcomes, and postoperative complications between the four groups, whereas polypharmacy was more common (85.7% vs 27.6-34.2%, p = 0.02) and operation time was shorter (median, 194 vs. 285–330 min, p = 0.02) in group 4. Factors related to frailty rather than age, polypharmacy, preoperative albumin level, estimated blood loss, and transfusion increased the risk of postoperative complications. Thus, increased age is not the determining cause of increased morbidity and mortality in elderly patients. Instead, there are other aspects that can better predict prognosis. In conclusion, increasing old age is not a contraindication to performing debulking surgery in advanced ovarian cancer.진행성 난소암 환자의 예후를 개선하기 위해 종양감축술을 시행하는 것은 중요하다. 그러나, 고령 환자에서는 수술 후 합병증과 사망률이 높을 수 있다는 이유로 종양감축술을 시행하는 것이 쉽지 않다. 고령 자체보다는, 고령에 동반되는 기저질환이 종양감축술 후 예후의 위험인자라는 일부 연구결과가 있지만, 아직 근거가 부족하다. 따라서, 본 연구진은 진행성 난소암 환자에서 종양감축술 후 예후에 고령이 미치는 영향을 조사하고자 하였다. 진행성 난소암 진단을 받고 종양감축술을 받은 65세 이상의 환자에 대해 후향적으로 자료를 수집하였다. 총 환자수는 120명이었으며, 나이 에 따라 다음과 같은 네 그룹으로 나누었다: 그룹 1, 65-69세 (n = 58); 그룹 2, 70-74세 (n = 38); 그룹 3, 75-79세 (n = 17); 그룹 4, ≥ 80세 (n = 7). 수술 전 변수들은 그룹 간 유의한 차이를 보이지 않았다. 수술 전 변수, 수술 범위, 수술 결과, 수술 후 합병증에 대해서는 그룹 간 차이를 보이지 않았다. 반면, 그룹 4에서는 다른 그룹에 비해 다약제 복용 빈도 가 더 높았으며 (85.7% vs 27.6-34.2%, p = 0.02), 수술 시간은 더 짧았다 (중앙값, 194 vs 285-330분, p = 0.02). 노쇠를 반영하는 인자, 다약제 복용, 수술 전 알부민 수치, 추정실혈량 및 수혈량은 수술 후 합병증의 위험을 유의하게 증가시켰으나, 노년은 유의한 상관관계를 보이지 않았다. 따라서, 고령은 난소암 환자에서 종양감축술 후 합병증을 증가시키는 인자가 되지 않으며, 노쇠를 반영하는 수술 전 인자들이 더 많은 영향을 주는 것으로 생각된다. 결론적으로, 고령 자체는 진행성 난소암 환자에서 종양감축술의 금기가 되지 않는 것으로 보인다.Chapter 1. Introduction 1 1.1. Study of background 1 1.2. Purpose of research 1 Chapter 2. Methods 3 2.1. Patients 3 2.2. Surgical extents and outcomes 4 2.3. Postoperative complications 4 2.4. Statistical analysis 4 Chapter 3. Results 6 3.1. Characteristics 6 3.2. Surgical extents and outcomes 6 3.3. Postoperative complications 6 Chapter 4. Discussion 8 Bibliography 27 Abstract in Korean 31석

Mutation SVCT2 promotes cell proliferation, invasion and migration in colorectal cancer

The sodium-dependent vitamin C transporter 2 (SVCT2) surface glycoprotein regulates ascorbate accumulation in the plasma, often resulting in the induction of cancer cell death. Therefore, high expression of this gene associates with increased overall survival in several cancers. However, in colorectal cancer (CRC), high (likely mutated) SVCT2 expression relates to poor overall survival, and its functional significance has not been studied. Thus, we hypothesize that mutant SVCT2 expression could affect CRC patient survival. According to biological databases, SVCT2 has been found to be mutated frequently, and SVCT2 E264K has a particularly high pathogenic score (0.98), compared to other SVCT2 mutant sites, in CRC patients. Interestingly, our results reveal expression of SVCT2 E264K in many CRC tissues and cells. Also, we found wild-type SVCT2 expression to be largely localized to the cytoplasm and membrane, while SVCT2 E264K was restricted to the cytoplasm. We further found that SVCT2 E264K overexpression increases cell growth. By contrast, SVCT2 E264K knockdown significantly reduced cell proliferation and promoted cell apoptosis, resulting in inhibition of cell invasion and migration. Taken together, SVCT2 E264K plays a critical role in proliferation in CRC. Our results suggest that SVCT2 E264K could be a promising novel therapeutic target in CRC

Role of p53 in transcriptional repression of SVCT2

SVCT2, Sodium-dependent Vitamin C Transporter 2, uniquely transports ascorbic acid (also known as vitamin C and ascorbate) into all types of cells. Vitamin C is an essential nutrient that must be obtained through the diet and plasma levels are tightly regulated by transporter activity. Vitamin C plays an important role in antioxidant defenses and is a cofactor for many enzymes that enable hormone synthesis, oxygen sensing, collagen synthesis and epigenetic pathways. Although SVCT2 has various functions, regulation of its expression/activity remains poorly understood. We found a p53-binding site, within the SVCT2 promoter, using a transcription factor binding-site prediction tool. In this study, we show that p53 can directly repress SVCT2 transcription by binding a proximal- (similar to-185 to -171 bp) and a distal- (similar to-1800 to -1787 bp) p53-responsive element (PRE), Chromatin immunoprecipitation assays showed that PRE-bound p53 interacts with the corepressor-histone deacetylase 3 (HDAC3), resulting in deacetylation of histones Ac-H4, at the proximal promoter, resulting in transcriptional silencing of SVCT2. Overall, our data suggests that p53 is a potent transcriptional repressor of SVCT2, a critical transporter of diet-derived ascorbic acid, across the plasma membranes of numerous essential tissue cell types