Endoplasmic reticulum stress induces 5-fluorouracil resistance in human colon cancer cells

Colon cancer can be treated with 5-fluorouracil (5-FU), but 5-FU resistance frequently occurs. We determined whether 5-FU resistance arises as a result of endoplasmic reticulum (ER) stress. 5-FU–resistant SNUC5 colon cancer cells (SNUC5/FUR cells) expressed higher levels of ER stress–related proteins than drug-sensitive SNUC5 cells. SNUC5/FUR cells also exhibited more intense ER staining and higher level of mitochondrial Ca²⁺ overload. SNUC5/FUR cells transfected with siRNA against GRP78, ATF6, ERK, or AKT were more sensitive to 5-FU than siControl RNA-transfected cells. These results suggested that 5-FU resistance was associated with ER stress in colon cancer.     

Effect of benzophenone-1 and octylphenol on the regulation of epithelial-mesenchymal transition via an estrogen receptor-dependent pathway in estrogen receptor expressing ovarian cancer cells

Epithelial-mesenchymal transition (EMT) is an important process in embryonic development and cancer progression and metastasis. EMT is influenced by 17β-estradiol (E2), an endogenous estrogen. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and 4-tert-octylphenol (OP) are suspected endocrine disrupting chemicals (EDCs) because they can exhibit estrogenic properties. In this study, we examined whether BP-1 and OP can lead to EMT of BG-1 ovarian cancer cells expressing estrogen receptors (ERs). A wound healing assay and western blot assay were conducted to show the effect of BP-1 and OP on the migration of BG-1 cells and protein expression of EMT-related genes. BP-1 (10⁻⁶ M) and OP (10⁻⁶ M) significantly enhanced the migration capability of BG-1 cells by reducing the wounded area in the cell monolayer relative to the control, similar to E2 (10⁻⁹ M). However, when BG-1 cells were co-treated with ICI 182,780, an ER antagonist, the uncovered area was maintained at the level of the control. N-cadherin, snail, and slug were increased by BP-1 and OP while E-cadherin was reduced compared to the control. However, this effect was also restored by co-treatment with ICI 182,780. Taken together, these results indicate that BP-1 and OP, the potential EDCs, may have the ability to induce ovarian cancer metastasis via regulation of the expression of EMT markers and migration of ER-expressing BG-1 ovarian cancer cells.     

Lesion regression rate based on RECIST: prediction of treatment outcome in patients with head and neck cancer treated with chemoradiotherapy compared with FDG PET-CT

The aim of this study was to evaluate whether the lesion regression rate (ΔLR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria could be used for the prediction of treatment outcome in head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiotherapy (CRT) compared with FDG PET-CT. A total of 33 patients underwent MRI and PET-CT at pretreatment and at 8 weeks after CRT. We assessed the treatment outcome by analyzing the following parameters: the RECIST criteria, ΔLR, the European Organization for Research and Treatment of Cancer (EORTC) criteria, and pretreatment SUV_max of the primary tumor and node. The correlation between the analysis of the parameters and the results of the long-term follow-up of the patients was determined. The RECIST did not significantly correlate with locoregional control (LRC) or survival. The ΔLR was significantly lower for the lesions with locoregional failure (LRF) than for those with LRC. A threshold ΔLR of 48% revealed a sensitivity of 72.7% and specificity of 77.3% for the prediction of LRF. Progression-free survival (PFS) of patients with ΔLR ≥ 48% was significantly better than that of patients with ΔLR < 48% (P = 0.001), but not overall survival. There was a significant correlation between LRC and the EORTC (P = 0.02). The patients who achieved a complete response by the EORTC criteria showed significantly better PFS and overall survival (P = 0.01 and 0.04, respectively). The ΔLR was inferior to FDG PET-CT with respect to the prediction of patient survival; however, it may be useful for selecting patients in need of more aggressive monitoring after CRT.     

CA19-9在三种胆囊良恶性疾病中的表达研究

【】 目的 研究血清CA19-9在胆囊良性疾病急性结石性胆囊炎、黄色肉芽肿性胆囊炎和恶性疾病胆囊癌患者血清中的异常表达，讨论CA19-9在上述三种疾病的鉴别诊断价值。方法 回顾性研究血清CA19-9异常的急性结石性胆囊炎、黄色肉芽肿性胆囊炎和胆囊癌病例各50例，分别设为研究1、2、3组。比较三组治疗前后血清CA19-9值，使用统计学方法判断差异。结果 研究1组治疗后1个月血清CA19-9基本恢复正常，存在显著差异（P﹤0.05）；研究2组治疗后6个月血清CA19-9基本恢复正常，存在显著差异（P﹤0.05）；研究3组治疗后随访12个月仅少数血清CA19-9恢复正常，无显著差异（P﹥0.05）。结论 三种胆囊良恶性疾病的血清CA19-9都能异常表达，但各自有其特点和临床意义，血清CA19-9是肿瘤指标，也可以是炎性指标，可以根据其表达特点加以鉴别疾病。     

Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence,progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.     

Small renal mass management in the elderly and the calibration of risk

Due to the increased utilization of cross-sectional imaging and prolonged life expectancy, the incidence of incidentally diagnosed renal tumors continues to rise. While partial nephrectomy is currently recommended as the gold standard treatment of cT1a small renal mass whenever technically feasible, the perceived benefits of partial nephrectomy may not be applicable to all patient groups. Selecting between treatment options in elderly and the infirm can present a significant challenge. Informed and thoughtful small renal mass management decisions require consideration and balance of patient, tumor, and procedural risks to maintain oncological efficacy while minimizing treatment associated morbidity. Herein we review the comparative effectiveness of partial versus radical nephrectomy in the elderly and the role of standardized tools to quantify risk.