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The objectives of the present study were to investigate the role of K-Cl cotransporter 3 (KCC3) in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT) was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN), and the survival rate of patients with a CN > MT score was lower than that of patients with a CN ⩽ MT score. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the efficacy of a hypotonic treatment for peritoneal dissemination from gastric cancer cells using an in vivo model. We firstly evaluated the toxicity of a peritoneal injection of distilled water (DW) (2mL for 3 days) in mice. Macroscopic and microscopic examinations revealed that the peritoneal injection ofDWdid not severely damage the abdominal organs of these mice. MKN45 gastric cancer cells preincubated with NaCl buffer or DW for 20 minutes in vitro were then intraperitoneally injected into nude mice, and the development of dissemination nodules was analyzed. The total number, weight, and volume of the dissemination nodules were significantly decreased by the DW preincubation. We then determined whether the peritoneal injection of DW inhibited the establishment of peritoneal dissemination. After a peritoneal injection of MKN45 cells into nude mice, NaCl buffer or DW was injected into the abdominal cavity for 3 days. The total volume of dissemination nodules was significantly lower in DW-injected mice than in NaCl-injected mice. In conclusion, we demonstrated the safeness of a peritoneal injection of DW. Furthermore, the development of dissemination nodules from gastric cancer cells was prevented by a preincubation with or peritoneal injection of DW. [ABSTRACT FROM AUTHOR]

Respiratory morbidity is the most frequent complication following an esophagectomy. This study was designed to determine the efficacy of middle and lower esophagectomies preceded by the hand-assisted laparoscopic transhiatal approach (LTHA) regarding the perioperative outcomes of distal esophageal cancer. The esophageal hiatus was opened and carbon dioxide was introduced into the mediastinum. Dissection of the distal esophagus was performed up to the level of the tracheal bifurcation. Enbloc dissection of the posterior mediastinal lymph nodes was performed using the LTHA. Subsequently, a small thoracotomy (10 cm) was performed to divide the thoracic esophagus and allow middle mediastinal lymphadenectomy. Finally, reconstruction via the posterior mediastinal route with a gastric tube and anastomosis in the thoracic cavity were performed using a circular stapler. The treatment outcomes of 10 patients who underwent LTHA-preceded middle and lower esophagectomy were compared to those of 11 patients treated without prior LTHA (thoracotomy, 20 cm). The total operative time, the duration of one-lung ventilation and total operative blood loss were significantly decreased in the LTHA group. The number of resected lymph nodes did not differ significantly between the two groups. Postoperative respiratory complications occurred in 10.0% of patients treated with, and 36.3% of those treated without LTHA. The extubation time following surgery, the duration of thoracic drainage and postoperative hospital stay were significantly decreased by this method. In conclusion, middle and lower esophagectomies preceded by LTHA provides a good surgical view of the posterior mediastinum, markedly shortens the duration of one-lung ventilation and improves the perioperative outcome. [ABSTRACT FROM AUTHOR]

Background/Aims: Our previous study revealed that cytosolic Cl- affected neurite elongation promoted via assembly of microtubule in rat pheochromocytoma PC12D cells and Cl--induced blockade of intrinsic GTPase enhanced tubulin polymerization in vitro. Paclitaxel (PTX) is a microtubule-targeted chemotherapeutic drug and stabilizes microtubules resulting in mainly blockade of mitosis at the metaphase-anaphase transition and induction of apoptosis. In the present study, we tried to clarify whether the cytosolic Cl- affected PTX ability to inhibit cell growth in the gastric cancer cell line, MKN28. Methods: To clarify the cytosolic Cl- action on PTX-induced cell death and metaphase-anaphase transition in the gastric cancer cell line, MKN28 cell, and PTX-induced tubulin polymerization, we performed cell proliferation assay, cytosolic Cl- concentration measurement, immunofluorescence microscopy, and in vitro tubulin polymerization assay. Results: The decline of cytosolic Cl- weakened the cytotoxic effect of PTX on cell proliferation of MKN28 cells, which could pass through the metaphase-anaphase transition. Moreover, in vitro PTX-induced tubulin polymerization was diminished under the low Cl- condition. Conclusions: Our results strongly suggest that the upregulation of cytosolic Cl- concentration would enhance the antitumor effect of PTX, and that the cytosolic Cl- would be one of the key targets for anti-cancer therapy. [ABSTRACT FROM AUTHOR]

Zuotin-related factor 1 (ZRF1) is a recently characterized epigenetic factor involved in transcriptional regulation and is highly overexpressed in several malignancies, but it is not known whether it plays a role in gastric cancer (GC). In this study, we investigated whether ZRF1 acts as a cancer-promoting gene through its activation/overexpression in GC. We analyzed five GC cell lines and 133 primary tumors, which had been curatively resected in our hospital between 2001 and 2003. Overexpression of ZRF1 was detected in GC cell lines (four out of five lines, 80.0%) and was detected in primary tumor samples of GC (52 out of 133 cases, 39.1%) and significantly correlated with differentiated histological type, venous invasion, lymphatic invasion, advanced stage and a higher recurrence rate. ZRF1-overexpressing tumors had a worse survival rate than those with non-expressing tumors (P < 0.01, log-rank test). ZRF1 positivity was independently associated with a worse outcome in the multivariate analysis (P < 0.01; hazard ratio 4.92; 95% confidence interval: 1.6-21.1). In ZRF1-overexpressing GC cells, knockdown of ZRF1 using specific siRNAs inhibited the cell proliferation, migration and invasion and induced apoptosis in a p53-dependent manner. These findings suggest that ZRF1 plays a crucial role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC. [ABSTRACT FROM AUTHOR]

Background: The pathophysiological mechanisms of cisplatin nephrotoxicity include the reduction of renal blood flow, as well as tubular epithelial cell toxicity. The objective of this study was to investigate the influence of lower blood pressure and decreased food intake on the incidence of cisplatin nephrotoxicity.Methods: We conducted a retrospective cohort study at a university hospital between 2011 and 2012. We identified hospitalized adult patients with head and neck cancer, esophageal cancer, or gastric cancer, who received intravenous cisplatin administration. The primary outcome was the incidence of cisplatin nephrotoxicity defined as the increase in serum creatinine after cisplatin administration more than 1.5 times from baseline.Results: The study participants included 182 patients, in whom we observed a total of 442 cycles of cisplatin chemotherapy. The incidence of cisplatin nephrotoxicity was observed in 41 of 182 cycles with initial administration. Multivariate logistic regression analysis showed that systolic blood pressure was independently associated with cisplatin nephrotoxicity (adjusted odds ratio 0.75, 95% confidence interval 0.57 to 0.95 for each 10 mmHg). The use of renin-angiotensin system (RAS) inhibitors was also associated with cisplatin nephrotoxicity (3.39, 1.30 to 8.93). Among quartiles of systolic blood pressure in all cycles of chemotherapy, the incidence of nephrotoxicity in the lower blood pressure group was significantly higher than that in the higher blood pressure group for patients taking non-solid food (P = 0.037), while there was no significant difference for patients taking solid food (P = 0.67).Conclusions: Lower blood pressure and the use of RAS inhibitors were associated with the incidence of cisplatin nephrotoxicity, and lower blood pressure had a greater influence on nephrotoxicity in patients who could not take solid food. Discontinuation of antihypertensive medication including RAS inhibitors before cisplatin chemotherapy should be considered, which may be beneficial for patients with lower blood pressure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recent clinical trials, such as JCOG9912 and SPIRITS, excluded geriatric patients aged ≥75 years. The clinical significance of intensive chemotherapy for geriatric patients with advanced or recurrent gastric cancer remains unclear. Between 2002 and 2010, 54 consecutive advanced or recurrent gastric cancer patients aged ≥75 years were enrolled in this study. We analyzed the predictors of chemotherapy administration and evaluated the survival benefit of chemotherapy for geriatric patients with advanced or recurrent gastric cancer. A total of 23 geriatric patients received no chemotherapy (GP), whereas the remaining 31 patients were administered chemotherapy (GPC). Of the 54 patients, 20 had severe concomitant illnesses, such as cardiorespiratory disease. Lymph node involvement (P=0.044) and the absence of cardiorespiratory disease (P<0.001) were found to be independently associated with chemotherapy administration. The GPC group exhibited a significantly better prognosis compared to the GP group (median survival time, 19.4 vs. 13.6 months, respectively; P=0.043). GPC patients without cardiorespiratory disease tended to have a better prognosis compared to GP patients without cardiorespiratory disease (P=0.106), whereas there were no significant differences between GP and GPC patients with cardiorespiratory disease. However, administration of chemotherapy was identified as an independent prognostic factor by the Cox proportional hazards model (hazard ratio = 2.609; 95% confidence interval: 1.173-5.761; P=0.019). Therefore, chemotherapy appears to provide a survival benefit in geriatric patients with advanced or recurrent gastric cancer, particularly those without concomitant cardiorespiratory disease. [ABSTRACT FROM AUTHOR]