Analysis of Ethylene Copolymers with Long-Chain α-Olefins (1-Dodecene, 1-Tetradecene, 1-Hexadecene): A Transition between Main Chain Crystallization and Side Chain Crystallization.

A series of ethylene copolymers with long-chain α-olefins [LCAOs, 1-dodecene (DD), 1-tetradecene (TD), 1-hexadecene (HD)] and various LCAO contents were prepared, and their thermal properties, including effects of LCAO content and side chain length, were explored. The Cp*TiCl2(O-2,6- i Pr2-4-SiEt3-C6H2)-MAO catalyst system afforded rather high-molecular-weight copolymers with unimodal molecular weight distributions and uniform compositions (confirmed by DSC thermograms). In addition to the melting temperatures (T m values) corresponding to the so-called main chain crystallization (samples with low LCAO contents, the T m value decreased upon increasing the LCAO content) and the side chain crystallization [polymer samples with high LCAO contents, by intermolecular interaction of side chains as observed in poly(DD), poly(TD), and poly(HD)], the other T m value was observed, especially in poly(ethylene-co-HD)s (assumed to be due to co-crystallization of the branch and the main chain through an interaction of the main chain and the long side chains). The presence of another crystalline phase in poly(ethylene-co-HD)s was also suggested by a wide-angle X-ray diffraction (WAXD) analysis. These T m values in poly(ethylene-co-TD)s and poly(ethylene-co-DD)s with rather high TD or DD contents were affected by the heating conditions in the measurement of DSC thermograms (5 or 10 °C/min), suggesting that the driving force for formation of the crystal packing (observed as T m) is weak and affected by the alkyl side chain lengths.

Augmented Self-Association by Electrostatic Forces in Thienopyrrole-Fused Thiadiazoles that Contain an Ester instead of an Ether Linker.

During the self-assembly of π-conjugated molecules, linkers and substituents can potentially add supportive noncovalent intermolecular interactions to π-stacking interactions. Here, we report the self-assembly behavior of thienopyrrole-fused thiadiazole (TPT) fluorescent dyes that possess ester or ether linkers and dodecyloxy side chains in solution and the condensed phase. A comparison of the self-association behavior of the ester- and ether-bridged compounds in solution using detailed UV-vis, fluorescence, and NMR spectroscopic studies revealed that the subtle replacement of the ether linkers by ester linkers leads to a distinct increase in the association constant (ca. 3-4 fold) and the enthalpic contribution (ca. 3 kcal mol-1 ). Theoretical calculations suggest that the ester linkers, which are in close proximity to one another due to the π-stacking interactions, induce attractive electrostatic forces and augment self-association. The self-assembly of TPT dyes into well-defined 1D clusters with high aspect ratios was observed, and their morphologies and crystallinity were investigated using SEM and X-ray diffraction analyses. TPTs with ester linkers exhibit a columnar liquid crystalline mesophase in the condensed phase.

[A Case of Gastric Cancer Invading the Pancreas with Pathological Complete Response Treated by Preoperative S-1 plus Oxaliplatin Therapy].

A 66-year-old man with severe anemia was diagnosed with gastric cancer. CT examination revealed primary gastric tumor, which involved the pancreas body, with regional lymph nodes that were enlarged(T4b[panc], cN2, cM0, cStage ⅣA). He received three courses of preoperative S-1 plus oxaliplatin therapy. Primary tumor and metastatic lymph nodes were reduced remarkably. We performed a curative distal gastrectomy(D2)without pancreas resection. Histopathological examination revealed Grade 3 pathological complete response in both primary tumor and metastatic lymph nodes.

[A Case of Intraductal Pancreatic Mallignant Tumor with Difficulty in Differentiating between IPMN and ITPN].

The patient was a male in his early 60s. Diabetes had aggravated 6 months earlier, and the patient was referred to our hospital for close examination. On contrast CT, enhanced mass shadows filling the lumen of the main pancreatic duct, which was dilated throughout the pancreas, were observed, and the mass was diagnosed as an adenocarcinoma on EUS-FNA. Based on these findings, main-duct IPMN was suspected and total pancreatectomy was performed. On macroscopic observation of the resected specimen, outgrowth of a solid tumor was observed in the main pancreatic duct, whereas only low-level mucus retention was noted in the pancreatic duct. Histopathological examination revealed a papillary/tubular tumor growth, suggesting interstitial infiltration throughout the pancreas. On immunostaining, the tumor was partially positive for MUC5AC, based on which the patient was diagnosed with an intraductal pancreatic mallignant tumor, with difficulty in differentiating between IPMC and ITPC. Clinicopathologically, many aspects regarding ITPN remain unclear. Further accumulation of such cases and investigation of the tumor pathology are necessary.

Preoperative evaluation of accessory hepatic ducts by drip infusion cholangiography with CT.

BACKGROUND: This retrospective study aimed to investigate the incidence of each type of accessory hepatic duct by drip infusion cholangiography with CT (DIC-CT). METHODS: Five hundred sixty nine patients who underwent preoperative DIC-CT and laparoscopic cholecystectomy were reviewed. Accessory hepatic ducts were classified as follows: type I (accessory hepatic ducts that merged with the common hepatic duct between the confluence of the right and left hepatic ducts and the cystic duct confluence), type II (those that merged with the common hepatic duct at the same site as the cystic duct), type III (those that merged with the common bile duct distal to the cystic duct confluence), type IV (the cystic duct merged with the accessory hepatic duct), and type V (accessory hepatic ducts that merged with the common hepatic or bile duct on the left side). RESULTS: Accessory hepatic ducts were observed in 50 patients. Type I, II, III, IV, and V accessory hepatic ducts were detected in 32, 3, 1, 11, and 3 patients, respectively. Based on their drainage areas, the accessory hepatic ducts were also classified as follows: a posterior branch in 22 patients, an anterior branch in 9 patients, a combination of posterior and anterior branches in 16 patients, a left-sided branch in 2 patients, and a caudate branch in 1 patient. None of the patients with accessory hepatic ducts suffered bile duct injuries. CONCLUSION: There are a number of variants of the accessory hepatic duct. DIC-CT is useful to detect the accessory hepatic duct.

[Metastatic Pancreatic Carcinoma from Renal Cell Carcinoma Indistinguishable from Primary Pancreatic Endocrine Tumor - A Case Report].

A hypervascularized tumor was detected in a 65-year-old man who had underwent a nephrectomy for a right renal cell carcinoma at the age of 55 years. We diagnosed the tumor as a non-functioning pancreatic neuroendocrine tumor or a metastatic tumor from the renal cell carcinoma. We performed distal pancreatectomy with splenectomy and lymph node dissection. The tumor was histopathologically diagnosed as metastatic renal cell carcinoma.

Circulating MicroRNAs: A Next-Generation Clinical Biomarker for Digestive System Cancers.

MicroRNAs (miRNAs) are short noncoding RNAs that post-transcriptionally regulate gene expression and play important roles in various physiological and developmental processes such as oncogenic or tumor suppressive regulators. Specific miRNA expression signatures have been identified in a number of human cancers. Cell-free miRNAs have recently been stably detected in plasma and serum (circulating miRNAs), and their presence in blood has attracted the attention of researchers due to their potential as non-invasive biomarkers. Circulating miRNAs have emerged as tumor-associated biomarkers that reflect not only the existence of early-stage tumors, but also the dynamics and status of advanced stage tumors, tumor recurrence, and drug sensitivities. This methodology for liquid biopsy may provide non-invasive and reproductive biomarkers and individualized therapeutic strategies for cancer patients. We herein review the current phase of biological and clinical research on the circulating miRNAs of solid cancers, particularly digestive tract cancers, and discuss future perspectives. The present review may be beneficial for future research on miRNAs used to detect various cancers.

Plasma microRNA profiles: identification of miR-23a as a novel biomarker for chemoresistance in esophageal squamous cell carcinoma.

BACKGROUND: This study aims to explore novel microRNAs in plasma for predicting chemoresistance in preoperative chemotherapy of patients with esophageal squamous cell carcinoma (ESCC) using a microRNA array-based approach. RESULTS: (1) Four candidate microRNAs (miR-223, 103a, 23b and 23a), which were highly expressed in the pretreatment plasma of patients with a low histopathologic response, were selected. (2) In a large-scale validation analysis by quantitative RT-PCR, plasma levels of miR-223, miR-23b and miR-23a were significantly higher in patients with a low histopathologic response than in those with a high histopathologic response (p = 0.0345, p = 0.0125 and p = 0.0114). (3) Of all candidate microRNAs, miR-23a expression of pretreatment ESCC tumor tissues was significantly higher in ESCC patients with a low histopathologic response than in those with a high histopathologic response (p = 0.0278). (4) After overexpressing each candidate in ESCC cells, miR-23a induced significant chemoresistance to both 5-fluorouracil and cisplatin, and miR-223 to cisplatin in vitro. (5) A high level of plasma miR-23a, which tended to correlate with lymphatic invasion (p = 0.0808) and deep depth of invasion (p = 0.0658), was an independent risk factor for chemoresistance in ESCC (p = 0.0222; odds ratio: 12.4; range 1.46-105). MATERIALS AND METHODS: We used the Toray® 3D-Gene microRNA array-based approach to compare plasma microRNA levels between patients with a high or a low histopathologic response to chemotherapy. All patients underwent a preoperative chemotherapy regimen with cisplatin plus 5-fluorouracil. CONCLUSIONS: Plasma miR-23a might be a useful biomarker for predicting chemoresistance in ESCC patients.

Impact of age on early surgical outcomes of laparoscopy-assisted gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer.

BACKGROUND/AIM: Although laparoscopy-assisted gastrectomy (LAG) is widely used for the treatment of gastric cancer, its safety and feasibility for elderly patients remains controversial. We herein examined the impact of age on the early surgical outcomes of LAG with suprapancreatic nodal dissection for elderly patients with clinical stage I gastric cancer. PATIENTS AND METHODS: This retrospective study included 292 patients undergoing LAG with suprapancreatic nodal dissection for clinical stage I gastric cancer. We divided patients into an elderly group (age ≥ 75 years; n=55) and non-elderly group (age <75 years; n=237). Preoperative conditions, operative findings and postoperative outcomes, including complications, were compared between these two groups. RESULTS: The elderly group had a higher incidence of co-morbidities (61.8%) and lower forced expiratory volume in 1 second/forced vital capacity (74.8%). Preoperative levels of hemoglobin (Hb) and serum albumin (Alb), as well as the total lymphocyte count (TLC) were lower in the elderly group (p<0.001, <0.001 and =0.018, respectively). No significant differences were observed in intraoperative findings between the two groups. The incidence of overall and surgical complications in the elderly group (21.8% and 14.5%, respectively) did not significantly differ from those in the non-elderly group. The frequency of non-surgical complications in the elderly group (9.1%) was significantly higher (p =0.018), whereas no critical complications or mortality were observed. No significant differences were noted in the severity of complications or hospital courses between the groups. CONCLUSION: LAG with suprapancreatic nodal dissection appears to be safe and feasible for elderly patients with clinical stage I gastric cancer.

Circulating miR-18a in plasma contributes to cancer detection and monitoring in patients with gastric cancer.

BACKGROUND: Recently, circulating microRNAs have been reported to be stably detectable in plasma/serum and to function as potent non-invasive biomarkers in various cancers. We hypothesized that miR-18a could contribute to a novel plasma biomarker in patients with gastric cancer (GC). METHODS: We focused on miR-18a, which is a component of miR-17-92 cluster and has been reported as highly expressed in GC tissues. The study involved three steps: (1) confirmation of the higher miR-18a expression in primary GC tissues and GC cell lines than in normal gastric tissues and a fibroblast cell line; (2) evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing 104 GC patients and 65 healthy volunteers; (3) evaluation of monitoring tumor dynamics by the plasma miR-18a assay. RESULTS: (1) The miR-18a expressions were significantly higher in GC tissues than in normal gastric tissues (P = 0.0286) and higher in all examined GC cell lines than in the fibroblast cell line. (2) The plasma miR-18a concentrations were significantly higher in GC patients than in healthy controls (P < 0.0001). The value of the area under the receiver-operating characteristic curve was 0.8059. (3) The plasma miR-18a levels were significantly reduced in postoperative samples compared to in preoperative samples (P = 0.0002). In an miR-18a overexpressing cell line, the miR-18a concentration of cultured medium increased in both cell number and time-course dependent manners, suggesting microRNA might be released from cancer cells into the surrounding environment. CONCLUSIONS: Circulating miR-18a could be a useful biomarker for screening GC and monitoring tumor dynamics.

Circulating miR-18a: a sensitive cancer screening biomarker in human cancer.

MicroRNAs have been reported to be stably detectable in plasma/serum and to exhibit resistance to endogenous ribonuclease activity because of binding to proteins such as Argonaute-2 and high-density lipoprotein, or being packed by secretory particles such as exosomes. These secretory particles include specific microRNAs and can function as intercellular transmitters. These findings could open-up a new and promising field in the use of circulating microRNAs for cancer treatment. In particular, miR-18a, which is located in the potentially oncogenic miR-17-92 cluster, is a highly expressed microRNAs in several types of cancers. The concentration of miR-18a in plasma/serum of patients with cancer such as esophageal (AUC=0.944), pancreatic (AUC=0.936), hepatocellular (AUC=0.881), colorectal and other types of cancers is much higher than that of healthy volunteers. Such reports provide evidence that circulating miR-18 might be a next-generation biomarker and contribute to cancer screening in non-invasive liquid biopsy, to a clinically-satisfactory degree of sensitivity and specificity.

Clinical impact of predicting CCND1 amplification using plasma DNA in superficial esophageal squamous cell carcinoma.

BACKGROUND: This study was designed to evaluate the clinical benefit of predicting the cyclin D1 (CCND1) status using cell-free plasma DNA in superficial esophageal squamous cell carcinoma (ESCC) patients. METHODS: The ratio of the CCND1 (11q13) dosage to the DRD2 (11q22-23) dosage (C/D ratio) as the CCND1 copy number was evaluated. This study was divided into three steps: (1) demonstration of the feasibility, (2) evaluation of whether the plasma C/D ratio assay could monitor tumor dynamics, and (3) a validation study in 63 consecutive superficial ESCC (pTis-T1) patients and 40 healthy volunteers. RESULTS: (1) The plasma C/D ratio was significantly higher (p = 0.0369) in superficial ESCC patients than in the controls in a preliminary test. (2) The high plasma C/D ratio appeared to reflect the tumor levels of the CCND1 status and was reduced in postoperative plasma samples (p = 0.1154) and samples following endoscopic resection (p = 0.0845). (3) Validation analysis revealed that the plasma C/D ratio was significantly higher in superficial ESCC patients than in controls (p < 0.0001). The frequency of recurrence was significantly higher (p = 0.0198), and recurrence-free survival was significantly shorter (p = 0.0075) in patients with a high plasma C/D ratio. Moreover, a high C/D ratio was shown to be an independent risk factor for recurrence on multivariate analysis [p = 0.0334; odds ratio 10.58 (range 1.203-93.23)]. CONCLUSION: The prediction of CCND1 amplification by plasma DNA may be a new complementary clinical biomarker for recurrence in patients with superficial ESCC.

xCT, component of cysteine/glutamate transporter, as an independent prognostic factor in human esophageal squamous cell carcinoma.

BACKGROUND: xCT is a component of the cysteine/glutamate transporter, which plays a key role in glutathione synthesis. The objectives of the present study were to investigate the role of xCT in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). METHODS: xCT expression in human ESCC cell lines was analyzed by Western blotting and immunofluorescent staining. Knockdown experiments were conducted with xCT siRNA, and the effect on cell cycle was analyzed. The cells' gene expression profiles were analyzed by microarray analysis. An immunohistochemical analysis of 70 primary tumor samples obtained from ESCC patients that had undergone esophagectomy was performed. RESULTS: xCT was highly expressed in TE13 and KYSE170 cells. In these cells, the knockdown of xCT using siRNA inhibited G1-S phase progression. Microarray analysis identified 1652 genes whose expression levels in TE13 cells were altered by the knockdown of xCT. Pathway analysis showed that the top-ranked canonical pathway was the G1/S checkpoint regulation pathway, which involves TP53INP1, CDKN1A, CyclinD1/cdk4, and E2F5. Immunohistochemical staining showed that xCT is mainly found in the nuclei of carcinoma cells, and that its expression is an independent prognostic factor. CONCLUSIONS: These observations suggest that the expression of xCT in ESCC cells might affect the G1/S checkpoint and impact on the prognosis of ESCC patients. As a result, we have a deeper understanding of the role played by xCT as a mediator and/or biomarker in ESCC.

Surgical outcomes of gastrectomy for elderly patients with gastric cancer.

BACKGROUND: This study was designed to determine the surgical outcomes of gastric cancer in elderly patients. This information can help establish appropriate treatment for these patients. METHODS: A total of 1,193 patients with gastric cancer who underwent gastrectomy between 1995 and 2010 were enrolled in this retrospective study. The clinicopathologic features of 104 elderly patients (aged ≥80 years) were compared with those of 1,089 nonelderly patients. RESULTS: (1) Tumors located in the lower-third of the stomach, differentiated cancer, and surgery with limited lymph node dissection were more common in elderly patients. However, there was no difference in the proportion of laparoscopic gastrectomy between elderly and nonelderly patients. (2) Although surgical complication rates were similar in the two groups, the operative mortality rate was higher in elderly patients (1.9 %) than in nonelderly patients (0.7 %). (3) Elderly patients had a significantly poorer overall survival rate, whereas the disease-specific survival rates of the two groups were similar. Limited lymph node dissection did not influence the disease-specific survival rate of elderly patients. (4) The median life expectancy of elderly gastric cancer survivors was 9.8 years in patients aged 80-84 years and 6.0 years in those ≥85 years. The patients with limited lymph node dissection had slightly better prognosis. CONCLUSIONS: The treatment results in elderly patients were comparable to those in nonelderly patients. These findings suggest that R0 resection with at least limited lymph node dissection according to Japanese guidelines should be considered, even for elderly patients.

XB130, a new adaptor protein, regulates expression of tumor suppressive microRNAs in cancer cells.

XB130, a novel adaptor protein, promotes cell growth by controlling expression of many related genes. MicroRNAs (miRNAs), which are frequently mis-expressed in cancer cells, regulate expression of targeted genes. In this present study, we aimed to explore the oncogenic mechanism of XB130 through miRNAs regulation. We analyzed miRNA expression in XB130 short hairpin RNA (shRNA) stably transfected WRO thyroid cancer cells by a miRNA array assay, and 16 miRNAs were up-regulated and 22 miRNAs were down-regulated significantly in these cells, in comparison with non-transfected or negative control shRNA transfected cells. We chose three of the up-regulated miRNAs (miR-33a, miR-149 and miR-193a-3p) and validated them by real-time qRT-PCR. Ectopic overexpression of XB130 suppressed these 3 miRNAs in MRO cells, a cell line with very low expression of XB130. Furthermore, we transfected miR mimics of these 3 miRNAs into WRO cells. They negatively regulated expression of oncogenes (miR-33a: MYC, miR-149: FOSL1, miR-193a-3p: SLC7A5), by targeting their 3' untranslated region, and reduced cell growth. Our results suggest that XB130 could promote growth of cancer cells by regulating expression of tumor suppressive miRNAs and their targeted genes.

Prognostic impact of circulating miR-21 in the plasma of patients with gastric carcinoma.

BACKGROUND: MicroRNAs (miRNAs) such as miR-17-5p, miR-21, miR-106a and miR-106b are reported to be highly expressed in gastric carcinoma (GC) tissues. Recently, we reported that these miRNAs were consistently detectable in plasma and reflected tumor dynamics of GC. We hypothesized that these plasma miRNA concentrations could be used as prognostic markers in patients with GC. MATERIALS AND METHODS: Between 2008 and 2009, preoperative plasma samples were collected from 69 consecutive patients with GC at our hospital. We retrospectively examined the association between plasma miRNA concentrations and prognosis. RESULTS: The postoperative cause-specific survival rate of patients with high plasma miR-21 concentration was significantly poorer than those with a low concentration (p=0.0451), as was that of those with high plasma concentration of miR-106a (p=0.1132). There were no prognostic differences according to the plasma concentration of miR-17-5p and miR-106b. Those with high miR-21 concentration had also a slightly higher incidence of vascular invasion (p=0.0311). Multivariate analysis revealed that the presence of a high miR-21 concentration in plasma was an independent prognostic factor (p=0.0133, hazard ratio: 13.4 (95% CI: 1.72-104.4)). CONCLUSION: The level of circulating miR-21 could be a reliable prognostic marker in the plasma of patients with GC. These findings contribute to the stratification of patients in order to identify those who need meticulous follow-up for early detection of recurrence and additional or alternative treatments of GC.

Overexpression of TRIM44 contributes to malignant outcome in gastric carcinoma.

Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family, which is characterized by a conserved RING finger, B-box, and coiled-coil domains, function as important regulators for carcinogenesis. In this study, we tested whether TRIM44 (11p13) acts as a cancer-promoting gene through overexpression in gastric cancer. We analyzed seven gastric cancer cell lines and 112 primary tumors, which were curatively resected in our hospital between 2001 and 2003. Expression of the TRIM44 protein was detected in gastric cancer cell lines (2/7 cell lines; 29%) and primary tumor samples of gastric cancer (29/112 cases; 25%). Knockdown of TRIM44 expression using several specific siRNAs inhibited the proliferation, migration, and invasion of TRIM44-overexpressing cells. Overexpression of the TRIM44 protein was significantly correlated with an advanced type of macroscopic appearance, lymphatic invasion, and higher recurrence rate. TRIM44-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.0038, log-rank test) in both intensity and proportion expression-dependent manner. TRIM44 positivity was independently associated with worse outcome in multivariate analysis (P = 0.0233, hazard ratio 3.37 [1.18-9.64]). These findings suggest that TRIM44 plays a crucial role in tumor cell proliferation through its overexpression, and highlight its usefulness as a predictor and potential therapeutic target in gastric cancer.

Claudin 1 mediates TNFα-induced gene expression and cell migration in human lung carcinoma cells.

Epithelial-mesenchymal transition (EMT) is an important mechanism in carcinogenesis. To determine the mechanisms that are involved in the regulation of EMT, it is crucial to develop new biomarkers and therapeutic targets towards cancers. In this study, when TGFß1 and TNFα were used to induce EMT in human lung carcinoma A549 cells, we found an increase in an epithelial cell tight junction marker, Claudin 1. We further identified that it was the TNFα and not the TGFß1 that induced the fibroblast-like morphology changes. TNFα also caused the increase in Claudin-1 gene expression and protein levels in Triton X-100 soluble cytoplasm fraction. Down-regulation of Claudin-1, using small interfering RNA (siRNA), inhibited 75% of TNFα-induced gene expression changes. Claudin-1 siRNA effectively blocked TNFα-induced molecular functional networks related to inflammation and cell movement. Claudin-1 siRNA was able to significantly reduce TNF-enhanced cell migration and fibroblast-like morphology. Furthermore, over expression of Claudin 1 with a Claudin 1-pcDNA3.1/V5-His vector enhanced cell migration. In conclusion, these observations indicate that Claudin 1 acts as a critical signal mediator in TNFα-induced gene expression and cell migration in human lung cancer cells. Further analyses of these cellular processes may be helpful in developing novel therapeutic strategies.

Prognostic impact of circulating miR-21 and miR-375 in plasma of patients with esophageal squamous cell carcinoma.

BACKGROUND: miR-21 and miR-375 are reported to be highly and poorly expressed in esophageal squamous cell carcinoma (ESCC) tissues, respectively. Recently, we demonstrated that circulating miR-21 and miR-375 were stably detectable in plasma and reflected tumor dynamics as a tumor marker for ESCC. We hypothesized that these plasma miRNA concentrations contributed to prognostic markers in patients with ESCC. METHODS: Between 2008 and 2010, 50 preoperative plasma samples were collected from consecutive patients with ESCC, who underwent curative esophagectomy in our hospital. We examined the association between plasma miRNA concentrations and prognosis retrospectively. RESULTS: i) The postoperative cause-specific survival rate of patients with high plasma miR-21 concentration tended to be poorer than low group (3-yr survival rate: 53.4 and 81.5%, p = 0.1038), while that of high plasma miR-375 group was better than low group (3-yr survival rate: 100 and 65.2%). ii) Patients with high miR-21 and low miR-375 concentrations in plasma had significantly poorer prognosis than other patients (3-yr survival rate: 48.4 and 83.1%, p = 0.039). Multivariate analysis revealed that the presence of high miR-21 and low miR-375 concentrations in plasma was an independent prognostic factor (p = 0.029, hazard ratio 3.8 (1.14-12.5)). CONCLUSION: Circulating miR-21 and miR-375 could be reliable prognostic markers for ESCC. These plasma markers might facilitate clinical decision-making to select prospective candidates, which need meticulous follow-up for early detection of recurrences and additional treatments such as neo-adjuvant chemotherapy and postoperative chemotherapy in ESCC.

Pleural lavage with distilled water during surgery for esophageal squamous cell carcinoma.

This study aimed to investigate cytocidal effects of hypotonic shock on esophageal squamous cell carcinoma (ESCC) cell lines, and to apply pleural lavage with distilled water to surgery for ESCC. Three human ESCC cell lines, TE5, TE9 and KYSE170 were exposed to distilled water, and morphological changes in ESCC cells were closely observed under a differential interference contrast microscope connected to a high-speed digital video camera. Further, serial cell volume changes after hypotonic shock were measured using a high-resolution flow cytometer. To investigate the cytocidal effects of hypotonic shock on ESCC cells, re-incubation of ESCC cells was performed after hypotonic shock. Additionally, the effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), a Cl- channel blocker, during hypotonic shock were analyzed. Video recordings by high-speed digital camera demonstrated that hypotonic shock with distilled water induced cell swelling followed by cell rupture. Measurements of cell volume changes using a high-resolution flow cytometer indicated that severe hypotonicity with distilled water increased broken fragments of ESCC cells within 5 min. Re-incubation experiments demonstrated cytocidal effects of hypotonic shock on ESCC cells. Treatment of cells with NPPB increased cell volumes by the inhibition of regulatory volume decrease, which is observed during hypotonic shock, and enhanced cytocidal effects. These findings demonstrated the cytocidal effects of hypotonic shock on ESCC cells, and clearly support the efficacy of pleural lavage with distilled water during surgery for ESCC.