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Abstract Background Postoperative neurogenic bladder (PONB) frequently occurs as a complication after rectal cancer surgery. This study aimed to analyze risk factors for developing PONB after rectal cancer surgery, particularly the association between pelvic anatomy and visceral fat mass. Methods We included 138 patients who underwent rectal resection for lower rectal cancer in our department between 2017 and 2021. PONB was defined as the need for urethral catheter reinsertion or oral medication administration for urinary retention after catheter removal with severe NB that required treatment for ≥ 60 days. We obtained visceral fat area (VFA) at the umbilical level based on a CT scan and measured five pelvic dimensions. Results Of the 138 patients, 19 developed PONB, with 16 being severe cases. PONB more frequently occurs in patients with a height of

Abstract Background This study aims to explore novel microRNAs in urine for screening and predicting clinical characteristics in pancreatic cancer (PC) patients using a microRNA array-based approach. Methods We used the Toray® 3D-Gene microRNA array-based approach to compare urinary levels between PC patients and healthy volunteers. Results (1) Four oncogenic microRNAs (miR-744-5p, miR-572, miR-210-3p, and miR-575) that were highly upregulated in the urine of PC patients compared to healthy individuals were identified by comprehensive microRNA array analysis. (2) Test-scale analysis by quantitative RT-PCR for each group of 20 cases showed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P = 0.009). (3) Validation analysis (58 PC patients and 35 healthy individuals) confirmed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P

Objectives: A total mesenteric excision (TME) with lateral pelvic lymph node dissection (LLND) is the standard treatment for advanced low rectal cancer in Japan. Recently, neoadjuvant (chemo)radiotherapy (n(C)RT) has been used with LLND to improve outcomes at multiple Japanese institutes. This study evaluates the benefits of adding nCRT to TME with LLND. Methods: Seventy-two consecutive patients who underwent TME and LLND with or without nCRT between 2006-2019 to treat advanced low rectal cancer were retrospectively reviewed. The clinicopathological data were compared and the risk factors for local recurrence were evaluated. Results: Fifty-seven patients (79.1%) underwent TME and LLND with nCRT, and 15 patients (20.9%) without nCRT. There was no significant difference in the clinicopathological characteristics except the clinical T stage. The occurrence of postoperative complications was statistically insignificant. The 5-year local recurrence rate of patients with nCRT was significantly lower than those without (4.0% versus 26.6%, in all patients, p=0.002). Multivariate analysis revealed that the absence of nCRT was an independent risk factor for local recurrences in patients who underwent TME with LLND (hazard ratio: 6.04, p=0.04). Conclusions: The administration of nCRT prevented local recurrences more effectively in patients with advanced low rectal cancer who underwent TME with LLND.

Abstract Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with gastric cancer (GC). This study aimed to identify the risk factors for postoperative liver dysfunction and their clinical impact after GC surgery. We retrospectively analyzed the data of 124 patients with GC who underwent laparoscopic or robotic surgery at Kyoto Prefectural University of Medicine between 2017 and 2019. Twenty (16.1%) patients with GC developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 ≥ Grade 3). Univariate analyses identified robotic surgery as a risk factor for postoperative liver dysfunction (P = 0.005). There was no correlation between the postoperative liver dysfunction status and postoperative complications or postoperative hospital stays. Patients with postoperative liver dysfunction did not have significantly worse overall survival (P = 0.296) or recurrence-free survival (P = 0.565) than those without postoperative liver dysfunction. Robotic surgery is a risk factor for postoperative liver dysfunction; however, postoperative liver dysfunction does not affect short or long-term outcomes.

Abstract Background Lymphovascular invasion (LVI) is a poor prognostic factor in various malignancies. However, its prognostic effect in remnant gastric cancer (RGC) remains unclear. We examined the correlation between LVI and disease prognosis in patients with T1N0-3 or T2-3N0 RGC in whom adjuvant chemotherapy was not indicated and a treatment strategy was not established. Methods We retrospectively analyzed patients with T1N0-3 and T2-3N0 RGC who underwent curative surgery at the Kyoto Prefectural University of Medicine between 1997 and 2019 and at the Kyoto Chubu Medical Center between 2009 and 2019. Results Fifteen of 38 patients (39.5%) with RGC were positive for LVI. Patients with LVI had a significantly poorer prognosis for both overall survival ([OS]: P = 0.006) and recurrence-free survival ([RFS]: P = 0.001) than those without LVI. Multivariate analyses using the Cox proportional hazards model revealed LVI as an independent prognostic factor affecting OS (P = 0.024; hazard ratio 8.27, 95% confidence interval:1.285–161.6) and RFS (P = 0.013; hazard ratio 8.98, 95% confidence interval:1.513–171.2). Conclusions LVI is a prognostic factor for patients with T1N0-3 or T2-3N0 RGC. Evaluating LVI may be useful for determining treatment strategies for RGC.

Abstract Introduction Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported that the formation of the GCX is promoted on cancer cells and is associated with tumor growth and metastasis. Heparan sulfate proteoglycan glypican‐1 (GPC1) is a core protein of the GCX that is overexpressed in esophageal squamous cell carcinoma (ESCC) and is involved in the development and progression of cancer cells. The purpose of the present study is to analyze the utility of GPC1 as a new biomarker ralated to glycocalyx that reflects therapeutic effect and prognosis of ESCC. Methods We measured the concentration of GPC1 protein in preoperative plasma from advanced esophageal cancer patients and examined its relationships with clinicopathological factors and therapeutic efficacy, and the effects of extracellular GPC1 were investigated. Results The following clinical factors were significantly correlated with the preoperative high GPC1 concentration: male, tumor size ≥30 mm, venous invasion, pT factor ≥2, pStage ≥3, residual tumor, and distant metastatic recurrence. Both overall and recurrence‐free survival were significantly worse in the high GPC1 group. Extracellular GPC1 protein concentration reflected intracellular GPC1 expression. Furthermore, we examined the effects of extracellular recombinant human (rh)GPC1 on ESCC cells, and found that extracellular rhGPC1 affects cell motility, including migration and invasion. Conclusions These results demonstrated the utility of extracellular GPC1 as a biomarker, which can be assayed from a less invasive blood sample‐based liquid biopsy. Extracellular GPC1 protein plays a role in both tumor cell motility and cancer progression. Thus, plasma GPC1 is a useful biomarker for esophageal cancer progression and may be a potential candidate of therapeutic target.

Abstract Background Although a 3–5 cm surgical margin distance is recommended for advanced gastric cancer (GC) in Japanese guidelines, little is known about the clinical effects of the surgical margin, especially the distal resection margin (DM). This study aims to clarify the clinical significance of DM in GC. Methods A total of 415 GC patients who underwent curative distal gastrectomy between 2008 and 2018 were analyzed retrospectively. Results The DM significantly stratified recurrence-free survival (P = 0.002), and a DM 50 mm), the number (P

Abstract Although the average life span differs between males and females, little is known about differences in clinical features and short and long-term outcomes between elderly male and female gastric cancer patients. This study was designed to clarify these issues to identify the possibility for sex-based treatment strategies in elderly gastric cancer patients. This study included 295 consecutive elderly gastric cancer patients (75 years or older) who underwent curative gastrectomy between 1997 and 2016. We defined postoperative complications as Clavien–Dindo classification grade II or higher. Comorbidities were present in 67% of all patients. Males tended to have more comorbidities than females (P = 0.077). Male patients had significantly more upper gastric cancers (P = 0.001), a higher incidence of postoperative complications (P = 0.045), and poorer prognoses than females (P = 0.003). Multivariate analysis revealed that being male was an independent risk factor for postoperative complications (Odds ratio 2.5, P = 0.045) and a poor prognostic factor (Hazard ratio 1.81, P = 0.008). Patients who underwent limited surgery without postoperative complications tended to have a better prognosis than patients receiving standard surgery with postoperative complications (3-year overall survival: 78% vs. 55%, P = 0.156). Male was an independent risk factor for postoperative complications and an independent poor prognostic factor in elderly gastric cancer patients. To avoid postoperative complications, the limited surgery might be justified for high-risk elderly male patients.

Abstract The obesity paradox is reported to exist in various diseases. However, obesity is a pivotal issue in gastric cancer (GC) patients because of the surgical difficulty related to postoperative abdominal infectious complications (PAIC). This study clarified the existence of the obesity paradox in GC. Between 1997 and 2015, 1536 consecutive patients underwent curative gastrectomy. Of all patients, 18.6% (285/1536) were obese and tended to have a better prognosis (P = 0.073). In patients without PAIC, obesity was a significant prognostic factor for 5-year overall survival (P = 0.017). PAIC was an independent poor prognostic factor in both obese and non-obese patients (P

Abstract Background Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery. Methods We retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I–IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction. Results Forty-eight (13.3%) colorectal cancer patients (Stages I–IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P

Abstract Background Adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Lymph node metastasis is an important clinical issue in AEG patients. This study investigated the usefulness of a positive lymph node ratio (PLNR) to stratify prognosis and evaluate stage migration. Methods We retrospectively analysed 117 consecutive AEG patients (Siewert type I or II) who received a lymphadenectomy between 2000 and 2016. Results A PLNR cut-off value of 0.1 most effectively stratified patient prognosis into two groups (P

Abstract Background Esophagectomy is the standard adjuvant treatment for superficial esophageal squamous cell carcinoma (SESCC) following noncurative endoscopic submucosal dissection (ESD). However, recent reports have also shown that ESD with adjuvant chemoradiotherapy (CRT) has promising results. This retrospective study aimed to elucidate the efficacy of CRT compared to surgery in patients with SESCC after noncurative ESD. Methods This study retrospectively compared the long-term outcomes of patients who received adjuvant treatment with surgery or CRT after noncurative ESD for SESCC. Results Data were collected from 60 patients who developed SESCC after noncurative ESD, 34 of whom received adjuvant chemoradiotherapy (CRT) and 26 underwent esophagectomy. The median follow-up periods were 46 and 56 months in the CRT and esophagectomy groups, respectively. The median patient age was significantly higher in the CRT group than in the esophagectomy group (69 vs. 65 years, p = 0.0054). CRT was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The overall and disease-free survival did not significantly differ between the two groups. Conclusions CRT following ESD seems a promising nonsurgical strategy for optimizing the selection of therapies for high-risk SESCC and warrant further investigation.

Abstract Background Calcifying fibrous tumors (CFTs) are rare benign tumors. Because CFTs sometimes relapse, radical resection with adequate margins is necessary. We report a case of ileal CFT resected using single-port laparoscopic surgery. Case presentation A 33-year-old man presented with chief complaints of abdominal pain and vomiting. Computed tomography demonstrated a 45-mm-sized pelvic mass with partial calcification in the ileum. The patient was diagnosed with an ileal tumor, and partial resection of the ileum was performed using the single-port laparoscopic technique. Pathologic findings revealed hypocellular spindle cells with dense hyalinized collagen, interspersed calcification, and infiltration of lymphoplasmacytic cells. Immunohistochemical analysis showed that the factor XIIIa was positive and other tumor-specific markers were negative. Based on these findings, the tumor was finally diagnosed as a CFT. Conclusions Although CFT is benign, multifocal and recurrent CFTs have been reported. Therefore, careful intraperitoneal observation and curative resection are necessary. Single-port laparoscopic surgery is acceptable, both in terms of curability and minimal invasiveness.

Abstract Background Since inflammation and the immune system contribute to the development and progression of malignancies, parameters that reflect a host’s immune-inflammatory status may be useful prognostic indicators of gastric cancer (GC). The present study examined the clinical significance of a preoperative systemic immune-inflammation index (SII) for predicting postoperative survival outcomes in GC. Methods A total of 447 patients who underwent curative gastrectomy for GC were included in the present study. SII was calculated as platelet count × neutrophil count/lymphocyte count. The prognostic impact of preoperative SII was examined using univariate and multivariate analyses. Results Preoperative SII ranged between 105 and 4455 (median 474), and the optimal cutoff value for predicting overall survival (OS) was 395 based on a receiver operating characteristic curve. The 5-year OS rate of the SII ≥ 395 group was 80.0%, which was significantly worse than that (92.7%) of the SII < 395 group (p < 0.001). The multivariate analysis identified SII ≥ 395 (hazard ratio [HR] 2.95; 95% confidence interval [CI] 1.49–6.39; p = 0.001), heart disease (HR 2.14, 95% CI 1.07–4.07), C-reactive protein ≥ 0.5 (HR 2.45, 95% CI 1.15–4.94), pT4 (HR 4.46, 95% CI 2.44–8.14), and pN+ (HR 4.02, 95% CI 2.10–7.93) as independent predictors of worse OS. Peritoneal recurrence was more frequent in the high SII group than in the low SII group (p = 0.028). Conclusion Preoperative SII may be a useful predictor of postoperative survival outcomes in GC. The meticulous surveillance of GC relapse, particularly peritoneal dissemination, is necessary for patients with SII ≥ 395 even after curative gastrectomy.

Objective:. Late dumping syndrome is a common postgastrectomy complication characterized by reactive hypoglycemia. This study aimed to explore the glycemic trend in patients who underwent gastrectomy for gastric cancer and clarify its changes over time in association with postgastrectomy symptoms. Summary Background Data:. Changes over time in glycemic trend in association with postgastrectomy symptoms have not been evaluated. Methods:. We conducted a prospective study of 71 patients who underwent curative gastrectomy for gastric cancer between November 2017 and April 2020. The patients underwent continuous glucose monitoring twice—at 1- and 12-month postgastrectomy—and were assessed using the Post-Gastrectomy Syndrome Assessment Scale 37-item questionnaire (PGSAS-37) at 1-, 6-, and 12-month postgastrectomy. Results:. Our results revealed that hypoglycemia (

Abstract Background Precise staging is indispensable to select the appropriate treatment strategy for gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be improved. This study investigated the clinical significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) for the prediction of pathological lymph node metastasis (pN+) in GC. Methods This was a retrospective study of 429 patients with GC who underwent curative gastrectomy. The predictive ability of NLR for pN+ was examined in comparison with that of computed tomography. Results The preoperative NLR ranged from 0.6 to 10.8 (median, 2.0), and the optimal cut-off value for predicting pN+ was 1.6 according to the receiver operating characteristic curve with the maximal Youden index. Multivariate analysis identified a NLR ≥ 1.6 (odds ratio (OR) 3.171; 95% confidence interval (CI) 1.448–7.235, p = 0.004) and cN+ (OR 2.426; 95% CI 1.221–4.958, p = 0.011) to be independent factors associated with pN+ in advanced GC (cT2-T4). On the other hand, a NLR ≥ 1.6 was not useful for predicting pN+ in early GC (cT1). In advanced GC, a NLR ≥ 1.6 detected pN+ with a higher sensitivity (84.9%) and negative predictive value (NPV) (63.9%) than conventional modalities (50.0 and 51.7%, respectively). When the subjects were limited to those with advanced GC with cN0, the sensitivity and NPV of a NLR ≥ 1.6 for pN+ increased further (90.7 and 81.0%, respectively). Conclusion The preoperative NLR may be a useful complementary diagnostic tool for predicting pN+ in advanced GC because of its higher sensitivity and NPV than conventional modalities.

Abstract Recent studies identified that low levels of tumour suppressor microRNAs (miRNAs) in plasma/serum relate to tumour progression and poor outcomes in cancers. We selected six candidates (miR-126, 133b, 143, 203, 338-3p, 655) of tumour suppressor miRNAs in oesophageal squamous cell carcinoma (ESCC) by a systematic review of NCBI database. Of these, miR-655 levels were significantly down-regulated in plasma of ESCC patients compared to healthy volunteers by test- and validation-scale analyses. Low levels of plasma miR-655 were significantly associated with lymphatic invasion, lymph node metastasis and advanced stage. Univariate and multivariate analysis revealed that the low level of plasma miR-655 was an independent risk factor of lymphatic progression and a poor prognostic factor. Overexpression of miR-655 in ESCC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. Increased plasma miR-655 levels by the subcutaneous injection significantly inhibited lymph node metastasis in mice. Low levels of miR-655 in plasma relate to lymphatic progression and poor outcomes, and the restoration of the plasma miR-655 levels might inhibit tumour and lymphatic progression in ESCC.

Ion and water channels were recently shown to be involved in cancer cell functions, and various transporter types have been detected in upper gastrointestinal tract (UGI) cancers. Current information on the expression and roles of these channels and transporters in the death and survival of UGI cancer cells was reviewed herein, and the potential of their regulation for cancer management was investigated. Esophageal cancer (EC) and gastric cancer (GC) cells and tissues express many different types of ion channels, including voltage-gated K+, Cl–, and Ca2+, and transient receptor potential (TRP) channels, which regulate the progression of cancer. Aquaporin (AQP) 1, 3, and 5 are water channels that contribute to the progression of esophageal squamous cell carcinoma (ESCC) and GC. Intracellular pH regulators, including the anion exchanger (AE), sodium hydrogen exchanger (NHE), and vacuolar H+-ATPases (V-ATPase), also play roles in the functions of UGI cancer cells. We have previously conducted gene expression profiling and revealed that the regulatory mechanisms underlying apoptosis in ESCC cells involved various types of Cl– channels, Ca2+ channels, water channels, and pH regulators (Shimizu et al., 2014; Ariyoshi et al., 2017; Shiozaki et al., 2017, 2018a; Kobayashi et al., 2018; Yamazato et al., 2018; Konishi et al., 2019; Kudou et al., 2019; Katsurahara et al., 2020, 2021; Matsumoto et al., 2021; Mitsuda et al., 2021). We have also previously demonstrated the clinicopathological and prognostic significance of their expression in ESCC patients, and shown that their pharmacological blockage and gene silencing had an impact on carcinogenesis, indicating their potential as targets for the treatment of UGI cancers. A more detailed understanding of the molecular regulatory mechanisms underlying cell death and survival of UGI cancers may result in the application of cellular physiological methods as novel therapeutic approaches.

Abstract Background The standard treatment for superficial esophageal cancer (SEC) involving muscularis mucosal (T1a-MM) or submucosal (T1b) invasion has been the surgical resection of the esophagus. However, esophagectomy with extended lymph node dissection is highly invasive. Recent reports have shown that endoscopic submucosal dissection (ESD) followed by chemoradiotherapy (CRT) has promising results and might become a new therapeutic approach. This retrospective study aimed to elucidate the efficacy and safety of this new treatment. Methods Patients with clinical stage T1b tumor without apparent metastasis treated with ESD followed by CRT from 2014 to 2017 (the CRT group) were included. The outcomes on disease-free survival (DFS) of this group were compared with those of consecutive patients in a historical control group who underwent ESD followed by esophagectomy (the esophagectomy group) between 2008 and 2015. Results Of 32 patients analyzed, 16 were in the CRT group and 16 with similar stage cancer were in the esophagectomy group. Radiotherapy was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The 2-year overall survival rates were 100%, and locoregional control was achieved in all patients in the CRT group, and the 2-year DFS rates were 88 and 100% for the CRT and esophagectomy groups, respectively, without significant differences. Conclusions Our data confirmed our new approach as being safe and effective for locoregional control and may provide a nonsurgical treatment option for patients with clinical stage T1b tumors.

Abstract Background Although adjuvant chemotherapy with S-1 after curative gastrectomy has been performed as a standard treatment for Stage II and III gastric cancer (GC) in Japan, patients with Stage III GC still have a high incidence of recurrence and a poor prognostic outcome. The aim of this study was to investigate risk factors for recurrence in patients with Stage III GC despite of curative gastrectomy followed by adjuvant chemotherapy, suggesting an indicator for more intensive management. Methods A total of 97 patients with pathological Stage III GC underwent adjuvant chemotherapy after curative gastrectomy between 2001 and 2014, were enrolled in this study. We retrospectively analyzed their hospital records from our hospital. Results The 5-year relapse-free survival (RFS) rates of patients with pStage III GC were 42.0%. Univariate and multivariate analyses for RFS revealed that venous invasion (v+) was an independent factor predicting a shorter RFS (v + vs. v-, 36.5% vs. 47.4%, P = 0.034, HR 1.82, 95% CI: 1.01–3.37). Venous invasion also predicted a shorter overall survival (OS) (v + vs. v-, 33.7% vs. 50.4%, P = 0.027). Regarding the patterns of recurrence, hematogenous recurrence was significantly occurred in patients with v + GC than those without (P = 0.022). Conclusions Stage III GC with venous invasion is a high-risk subgroup for hematogenous recurrence after curative surgery followed by adjuvant chemotherapy. More intensive and effective adjuvant chemo and/or molecular targeted therapy for Stage III GC patients with venous invasion should be considered to improve their outcomes.

A lymphocele is one of the complications of systematic pelvic or para-aortic lymphadenectomy. Although most patients are entirely asymptomatic, our patient exhibited an obstructive ileus at the jejunum compressed by a lymphocele. We report here a case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection. A 68-year-old woman with sigmoid colon cancer (T3N2bM1a) underwent laparoscopic sigmoidectomy. After 4 courses of chemotherapy (CapeOX + Bmab), para-aortic lymphadenectomy was additionally performed. One month later, an obstructive ileus occurred suddenly due to a lymphocele. A drainage catheter was placed into the lymphocele and a total of 35 mL of autologous peripheral blood was injected in 4 divided doses through the catheter. The volume of the lymphocele gradually reduced and the ileus improved after blood injection. This is the first report of a successful case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection without any complications.

Abstract This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in pancreatic cancer (PCa) patients to clarify their potential as novel biomarkers and therapeutic targets. We used the microRNA array-based approach to select candidates by comparing plasma levels between PCa patients and healthy volunteers. Six down-regulated miRNAs (miR-107, miR-126, miR-451, miR-145, miR-491-5p, and miR-146b-5p) were selected. Small- and large-scale analyses using samples from 100 PCa patients and 80 healthy volunteers revealed that miR-107 was the most down-regulated miRNA in PCa patients compared with healthy volunteers (P

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.

Recent studies have shown that some members of the tripartite motif-containing protein family function as important regulators for carcinogenesis. In this study, we investigated whether tripartite motif-containing protein 44 acts as a cancer-promoting gene through its overexpression in esophageal squamous cell carcinoma. We analyzed esophageal squamous cell carcinoma cell lines to evaluate malignant potential and also analyzed 68 primary tumors to evaluate clinical relevance of tripartite motif-containing protein 44 protein in esophageal squamous cell carcinoma patients. Expression of the tripartite motif-containing protein 44 protein was detected in esophageal squamous cell carcinoma cell lines (8/14 cell lines; 57%) and primary tumor samples of esophageal squamous cell carcinoma (39/68 cases; 57%). Knockdown of tripartite motif-containing protein 44 expression in esophageal squamous cell carcinoma cells using several specific small interfering RNAs inhibited cell migration and invasion, but not cell proliferation. Immunohistochemical analysis demonstrated that the overexpression of the tripartite motif-containing protein 44 protein in the tumor infiltrated region was associated with the status of lymph node metastasis ( p = 0.049), and the overall survival rates were significantly worse among patients with tripartite motif-containing protein 44–overexpressing tumors than those with non-expressing tumors ( p = 0.029). Moreover, multivariate Cox regression model identified that overexpression of the tripartite motif-containing protein 44 protein was an independent worse prognostic factor (hazard ratio = 2.815; p = 0.041), as well as lymphatic invasion (hazard ratio = 2.735; p = 0.037). These results suggest that tripartite motif-containing protein 44 protein could play a crucial role in tumor invasion through its overexpression and highlight its usefulness as a predictor and potential therapeutic target in esophageal squamous cell carcinoma.

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.

XB130, a novel adaptor protein, mediates RET/PTC chromosome rearrangement-related thyroid cancer cell proliferation and survival through phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway. Recently, XB130 was found in different cancer cells in the absence of RET/PTC. To determine whether RET/PTC is required of XB130-related cancer cell proliferation and survival, WRO thyroid cancer cells (with RET/PTC mutation) and A549 lung cancer cells (without RET/PTC) were treated with XB130 siRNA, and multiple Akt down-stream signals were examined. Knocking-down of XB130 inhibited G(1)-S phase progression, and induced spontaneous apoptosis and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Knocking-down of XB130 reduced phosphorylation of p21Cip1/WAF1, p27Kip1, FOXO3a and GSK3β, increased p21Cip1/WAF1protein levels and cleavages of caspase-8 and-9. However, the phosphorylation of FOXO1 and the protein levels of p53 were not affected by XB130 siRNA. We also found XB130 can be phosphorylated by multiple protein tyrosine kinases. These results indicate that XB130 is a substrate of multiple protein tyrosine kinases, and it can regulate cell proliferation and survival through modulating selected down-stream signals of PI3K/Akt pathway. XB130 could be involved in growth and survival of different cancer 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 TGFβ1 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 TGFβ1 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.

Background/Aim: Esophagectomy for esophageal carcinoma (EC) is known to lead to deterioration of respiratory function (RF) due to thoracotomy and mediastinal lymph node dissection. This study aimed to evaluate the impact of transmediastinal esophagectomy (TME) on pulmonary function. Patients and Methods: We retrospectively analyzed the data of 102 patients with EC who underwent transthoracic esophagectomy (TTE) or TME and underwent RF tests within three months postoperatively at Kyoto Prefectural University of Medicine between 2014 and 2022. Perioperative pulmonary functions were evaluated based on vital capacity (VC) and forced expiratory volume in one second (FEV1.0). Results: Among 102 patients undergoing esophagectomy, 12 (11.8%) patients were included in the TTE group, and the remaining 90 (88.2%) patients were included in the TME group. Neoadjuvant treatments were significantly more common in the TTE group (p=0.011), with more advanced tumor stages (p=0.017). The TME group had significantly lower estimated blood loss (p=0.015). RF after esophagectomy showed a decrease in VC, and VC of predicted (%VC). The decrease rate in VC, %VC, and FEV1.0 was significantly greater in the TTE group than in the TME group. Conclusion: TME is a surgical procedure with a less severe postoperative decline in RF than TTE. [ABSTRACT FROM AUTHOR]

Background/Aim: Pancreatic cancer is one of the most lethal malignant cancers worldwide and the seventh most common cause of cancer-related death in both sexes. Herein, we analyzed open access data and discovered that expression of a gene called deoxynucleotidyltransferase terminal-interacting protein 2 (DNTTIP2) is linked to prognosis of pancreatic ductal adenocarcinoma (PDAC). We then elucidated the role of DNTTIP2 in the proliferation of pancreatic cancer cells in vitro. Materials and Methods: A WST-8 assay, cell cycle analysis, Annexin-V staining, quantitative reverse transcription-PCR, and western blot analysis were conducted to assess cell proliferation, cell cycle, apoptosis, and expression of DNTTIP2 mRNA and protein, respectively, in DNTTIP2-depleteted MIA-PaCa-2 and PK-1 cells. Results: Depletion of DNTTIP2 induced G1 arrest in MIA-PaCa-2 cells by decreasing expression of special AT-rich sequence binding protein 1 (SATB1) and cyclin-dependent kinase 6 (CDK6). In addition, depletion of DNTTIP2 induced G2 arrest in PK-1 cells by decreasing expression of CDK1. Depletion of DNTTIP2 did not induce apoptosis in MIA-PaCa-2 or PK-1 cells. Conclusion: DNTTIP2 is involved in proliferation of pancreatic cancer cells. Thus, DNTTIP2 is a potential target for inhibiting progression of pancreatic cancers. [ABSTRACT FROM AUTHOR]