- 作者列表："Oba, Atsushi","Inoue, Yosuke","Ono, Yoshihiro","Irie, Shoichi","Sato, Takafumi","Mise, Yoshihiro","Ito, Hiromichi","Takahashi, Yu","Saiura, Akio
Purpose This study aimed to clarify the key factors for minimizing unsuitable surgical interventions for patients with radiologically occult metastatic pancreatic cancer (ROMPC), defined as a distant metastasis detected during surgery or within 6 months after resection. Methods This study involved 502 patients planned to undergo curative resection for pancreatic cancer between 2008 and 2015. Patients were divided into ROMPC and non-ROMPC groups and evaluated preoperative factors associated with ROMPC. Results Overall survival (OS) was significantly lower in the ROMPC group ( n = 145) than the non-ROMPC group ( n = 357, median survival time [MST] 10.8 vs. 35.3 months, P < 0.001). In the ROMPC group, OS tended to be worse for patients who had pancreatectomies ( n = 84) than those who did not ( n = 61, MST 10.1 vs. 13.2 months, P = 0.057), and the next chemotherapy started significantly later in patients who had pancreatectomies ( P < 0.001). Moreover, OS was significantly lower for patients with ( n = 82) than without ( n = 63) liver metastases (MST 9.7 vs. 13.0 months, respectively, P = 0.020). The best indicator for patients at higher risk of ROMPC was a combination of carbohydrate antigen 19-9 concentration ≥ 300 U/ml and tumor size ≥ 30 mm. Conclusions In the ROMPC group, patients who underwent pancreatectomy had a poorer prognosis than patients not undergoing pancreatectomy. Given that the liver was the most frequent distant metastatic site for ROMPC and had the poorest prognosis, establishing a strategy featuring new imaging modalities to detect radiologically occult liver metastases is necessary.
目的本研究旨在阐明减少放射学隐匿性转移性胰腺癌 (ROMPC) 患者不适当手术干预的关键因素, 定义为手术期间或切除后 6 个月内发现的远处转移。方法本研究共纳入 502 例计划于 2015 和 2008年进行胰腺癌根治性切除术的患者。将患者分为 ROMPC 组和非 ROMPC 组，评估与 ROMPC 相关的术前因素。结果 ROMPC 组 (n = 145) 的总生存期 (OS) 明显低于非 ROMPC 组 (n = 357, 中位生存时间 [MST] 10.8 vs. 35.3 个月，P
METHODS::Pancreatic ductal adenocarcinoma (PDAC) is a disease of aging. The TP53 gene product regulates cell growth, aging, and cancer. To determine the important targets of TP53 in PDAC, we examined the expression of 440 proteins on a reverse phase protein array (RPPA) in PDAC-derived MIA-PaCa-2 cells which either had WT-TP53 or lacked WT-TP53. MIA-PaCa-2 cells have a TP53 mutation as well as mutant KRAS and represent a good in vitro model to study PDAC. RPPA analysis demonstrated expression of tumor promoting proteins in cells that lacked WT-TP53; and this feature could be reversed significantly when the cells were transfected with vector encoding WT-TP53 or treated with berberine or a modified berberine (BBR). Expression of miR-34a-associated signaling was elevated in cells expressing WT-TP53 compared to cells expressing mTP53. Results from in vivo studies using human PDAC specimens confirmed the in vitro results as the expression of miR-34a and associated signaling was significantly decreased in PDAC specimens compared to non-cancerous tissues. This study determined SERPINE1 as a miR-34a target with relevance to the biology of PDAC. Thus, we have identified a key target (SERPINE1) of the TP53/miR-34a axis that may serve as a potential biomarker for early detection of pancreatic cancer.
METHODS::Background: SLC6A14 (ATB0,+), a Na+/Cl-coupled transporter for neutral/cationic amino acids, is overexpressed in many cancers; It has been investigated as a target for improved liposomal drug delivery to treat liver cancer.Research design and methods: Here we explored the mechanism of ATB0,+-mediated entry of such liposomes. As ATB0,+ is highly-expressed in pancreatic cancer, we also examined the therapeutic utility of ATB0,+-targeted liposomal drug delivery to treat this cancer.Results: The uptake of lysine-conjugated liposomes (LYS-LPs) was greater in ATB0,+-positive MCF7 cells. The uptake process consisted of two steps: binding and internalization. The binding of LYS-LPs to MCF7 cells was higher than that of bare liposomes, and the process was dependent on Na+ and Cl-, and inhibitable by ATB0,+ substrates or blocker. In contrast, the internalization step was independent of lysine. The cellular entry of LYS-LPs facilitated by ATB0,+ occurred via endocytosis with transient endosomal degradation of ATB0,+ protein with subsequent recovery. Moreover, LYS-LPs also enhanced the uptake and cytotoxicity of gemcitabine in these cells in an ATB0,+-dependent manner.Conclusions: We conclude that ATB0,+ could be exploited for targeted drug delivery in the form of lysine-conjugated liposomes and that the approach represents a novel strategy for enhanced pancreatic cancer therapy.
METHODS:PURPOSE:Pre-operative prediction of histological response to neoadjuvant therapy aids decisions regarding surgical management of borderline resectable pancreatic cancer (BRPC). We elucidate correlation between pre-/post-treatment whole-tumor apparent diffusion coefficient (ADC) value and rate of tumor cell destruction. We newly verify whether post-treatment ADC value at the site of vascular contact predicts R0 resectability of BRPC. METHODS:We prospectively reviewed 28 patients with BRPC who underwent diffusion-weighted magnetic resonance imaging before neoadjuvant chemotherapy and surgery. Correlation between the percentage of tumor cell destruction and various parameters was analyzed. Strong parameters were assessed for their ability to predict therapeutic histological response and R0 resectability. RESULTS:Pre-/post-treatment whole-tumor ADC value correlated with tumor cell destruction rate by all parameters (R = 0.630/0.714, P 50% was determined at 1.40 × 10-3 mm2/s. It predicts histological response with 100% sensitivity, 81% specificity, and 89% accuracy. It predicts R0 with 88% sensitivity, 70% specificity, and 75% accuracy. CONCLUSIONS:Post-treatment whole-tumor ADC value may be a predictor of R0 resectability in patients with BRPC. Tumor cell destruction rate is indicated by the difference between pre-/post-treatment ADC values. This difference is strongly affected by the pre-treatment ADC value. The cutoff value of ADC at the site of vascular contact could not discriminate R0 resectability.