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Background: Metachronous liver metastasis (MLM) occurs in 20-40% of colorectal cancer (CRC) patients following surgical treatment. The aim of the present study was to determine the risk factors affecting the development of MLM in CRC patients following curative resection. Methods: A total of 1,356 patients who underwent curative intent resection for CRC were retrospectively studied. Of these patients, those who with 30 days postoperative mortality ( n = 23), incomplete medical record ( n = 32), synchronous liver metastasis ( n = 148) and UICC stage IV ( n = 54) were excluded, and finally 1,099 patients were analyzed, including 977 patients without liver metastasis and 122 patients with MLM-only. Clinical and pathological records for each patient were reviewed from medical charts. The clinicopathologic characteristics of 1,099 patients were investigated. Results: The median timing of developing MLM was 13 months with a range of 4 to 79 months. Univariate analysis identified that preoperative serum carcinoembryonic antigen (CEA) level, depth of invasion, lymph nodes metastasis, vascular invasion, and perineural invasion were significantly correlated with the development of MLM (all P < 0.05). Meanwhile, a multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) level > 5 ng/ml (Odds Ratio [OR] = 1.591; 95% Confidence Interval [CI], 1.065-2.377; P = 0.024), tumor depth (OR = 2.294; 95% CI, 1.103-4.768; P = 0.026), positive lymph node metastasis (OR = 2.004; 95% CI, 1.324-3.031; P = 0.001) and positive vascular invasion (OR = 1.872; 95% CI, 1.225-2.861; P = 0.004) were independent prognostic factors contributing to the occurrence of MLM. Conclusions: The present study demonstrates that preoperative serum CEA level, tumor depth, lymph node metastasis, and positive vascular invasion could affect the occurrence of MLM in CRC patients following curative resection, and thus could help to define these high-risk patients who would benefit from enhanced surveillance and therapeutic program(s). [ABSTRACT FROM AUTHOR]

Background Surgical intervention for internal jugular phlebectasia is occasionally necessary in cases of phlebitis, thrombus formation, rupture of the lesion, and some cosmetic deformity. However, the resultant neck scar can be of suboptimal cosmesis, with consequent psychological distress, particularly for children. Methods We described a 3-port transaxillary endoscopic technique performed under the fascia of the pectoralis major for excision of the dilated right internal jugular vein in an 8-year-old girl. Results The preservation of the upper tributaries of the right internal jugular vein was helpful in draining the cerebral blood to the collaterals and in preventing postoperative craniofacial swelling immediately. Six months later, there were no signs of recurrence of other jugular veins, and the patient showed a correct hemodynamic compensation. Conclusion This technique offered an effective way to surgically manage internal jugular phlebectasia while avoiding the potential for poor cosmesis from any neck scar. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

Laparoscopy is an alternative procedure for pediatric inguinal hernia; however, reported techniques necessitate two or three trocars and excellent intra-abdominal skills. This study was designed to describe and evaluate the preliminary result of one-trocar laparoscopic-assisted transperitoneal closure for inguinal hernia in children. A total of 33 children with inguinal hernia (body weight range, 2270 g to 58 kg) were included in this study from March to November 2007. Under a 5-mm laparoscopic guidance, the hernia defect was enclosed by a nonabsorbable suture, which was introduced into the abdomen by an 18-gauge vascular access on one side of the hernia defect and withdrawn on the opposite side by a homemade hook-pin through a needle puncture wound. Then, extracorporeal knot tying was performed. A total of 52 procedures were performed, and the mean operating time was 46.2 ± 16.2 (range, 18–87) minutes. No cauterization was used during the operations and there was no serious operative morbidity. The mean follow-up period was 7.6 ± 2.5 (range, 4–12) months. No recurrence was observed during this period. This easy technique provides the benefits of laparoscopic herniorrhaphy and combines the advantages derived from the novel use of a hook-pin and vascular access simplicity, low cost, safety, minimized tissue trauma, and improved cosmetics. In addition, only one umbilical trocar wound and another needle puncture point were made. Therefore, this procedure is recommended for pediatric inguinal hernia. [ABSTRACT FROM AUTHOR]

Background: Approximately 20%–45% of colorectal cancer (CRC) patients ultimately develop local recurrence or metastasis following curative surgical resection. The latter is caused by tumor cells shed from the primary carcinoma prior to or during operation, currently undetected by standard clinical staging. Fortunately, the presence of tumor cells in peripheral blood can be detected by molecular methods and is being regarded increasingly as a clinically relevant prognostic factor. Materials and Methods: To detect the presence of circulating tumor cells and evaluate their relationship to postoperative metastatic relapse, we simultaneously examined human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20), and carcinoembryonic antigen (CEA) mRNA (messenger RNA) in the peripheral blood of 72 CRC patients and 30 healthy individuals. Using a reverse-transcriptase polymerase chain reaction (RT-PCR), these tumor-related mRNAs were amplified; in addition, analyses were carried out for their correlation with patients' clinicopathologic features, as well as the occurrence of postoperative metastasis. Results: In RT-PCR analysis of the peripheral blood, 69.4% (50 out of 72), 66.7% (48 out of 72), 52.8% (38 out of 72), and 72.2% (52 out of 72) of CRC patients were positive for hTERT, CK-19, CK-20, and CEA mRNA respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA expression, while 2 were positive for either CK-19 mRNA or CK-20 mRNA expression. The detection of CEA mRNA was significantly correlated with depth of tumor invasion (P = 0.012), vessel invasion (P = 0.035), TNM stage (P < 0.0001), and postoperative metastasis (P < 0.0001), while positive hTERT mRNA was correlated with TNM stage (P = 0.037) and CK-19 was correlated with depth of tumor invasion (P = 0.039) and postoperative metastasis (P = 0.017). In addition, multivariate logistic regression showed that only CEA mRNA was an independent and significant predictor of postoperative metastasis (P = 0.006). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19, and CK-20 for the detection of circulating cancer cells in the peripheral blood of CRC patients. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the outcomes between the LigaSure vessel sealing system and the conventional closed Ferguson hemorrhoidectomy procedure performed by diathermy. Methods: A series of 84 patients with grades III and IV hemorrhoids were randomized into two groups: (1) LigaSure hemorrhoidectomy with submucosal dissection (42 patients) and (2) Ferguson hemorrhoidectomy (42 patients). The patient demographics, operative details, parenteral analgesic requirement, postoperative pain score (assessed by an independent assessor), operating time, intraoperative blood loss, hospital stay, early and delayed complications, and time off from work or normal activity were recorded. The patients were regularly followed up at 1, 2, 4, 6, and 8 weeks after surgery. Results: There were no statistically significant differences between the two groups in terms of age, gender, duration of symptoms, grade of the hemorrhoid(s), or number of hemorrhoids resected. The mean operating time for LigaSure hemorrhoidectomy with submucosal dissection was significantly shorter than that for the Ferguson hemorrhoidectomy (11.3 ± 0.4 vs. 34.2 ± 0.7 minutes; P < 0.0001). Patients treated with the LigaSure method had significantly less blood loss (P < 0.0001), a better pain score (P < 0.0001), less parenteral analgesic requirement (P < 0.0001), shorter hospital stay (P < 0.0001), and less time off from work or normal activity (P < 0.0001). There was no difference in the early and delayed postoperative complications between the two groups. Conclusions: LigaSure hemorrhoidectomy with submucosal dissection is a safe, effective procedure for grade III and IV hemorrhoids. Patients derive greater short-term benefits: reduced intraoperative blood loss, operating time, and postoperative pain as well as earlier resumption of work or normal activity. Long-term follow-up with a larger number of patients is required to confirm the long-term results of this procedure. [ABSTRACT FROM AUTHOR]

Early detection of tumor DNA in serum/plasma prior to the development of recurrence or metastases could help improve the outcome of patients with colorectal cancer (CRC) after tumor resection. Recent advances in the detection of tumor DNA in the serum/plasma has opened up numerous new areas for investigation and new possibilities for molecular diagnosis.APCand K-rasmutations are considered to be early-stage developments of CRCs, whereasp53mutations are thought to be relatively late events in the tumorigenesis of CRCs. The aim of this study was to search for the presence of genetic mutations in the DNA extracted from the serum of CRC patients and healthy subjects. We simultaneously evaluate the significance ofAPC, K-ras,andp53gene mutations in cancer tissues and their paired serum samples of 104 CRC patients by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) followed by direct sequencing. Additionally, analysis was carried out to detect the serum carcinoembryonic antigen (CEA) levels in CRC patients. Overall, we found at least one of the gene mutations in tumor tissues from 75% (78/104) of the CRC patients. Comparison of the three molecular markers showed that the detection rates in the serum were 30.4%, 34.0%, and 34.2% forAPC, K-ras,andp53genes, respectively. Of these patients, 46.2% (36/78) were identified as having positive serum results, whereas all healthy controls remained negative. The overall positive tumor DNA detection rates in the serum were 0% (0/7) for Dukes’ A classification, 22.4% (11/49) for Dukes’ B, 48.7% (19/39) for Dukes’ C, and 66.7% (6/9) for Dukes’ D. The detection rate increased as the tumor stage progressed (p= 0.012). Concurrently, a significant difference was observed between lymph node metastases and positive serum tumor DNA detection (p<0.001). A significantly higher postoperative metastasis/recurrence rate in patients harboring gene mutations with serum tumor DNA than those without serum tumor DNA was also demonstrated (p<0.001). However, no significant correlation between the postoperative metastasis/recurrence and serum CEA levels was observed (p= 0.247). These data suggest that the identification of circulating tumor DNA using the molecular detection ofAPC, K-ras,andp53gene mutations is a potential tool for early detection of postoperative recurrence/metastases. Moreover, these genes may be potential molecular markers of poor clinical outcome in CRC patients. [ABSTRACT FROM AUTHOR]

The role of a massive spontaneous portosystemic shunt (MSPSS) in cirrhotic patients with portal hypertension remains unclear. The aim of this study was to investigate clinical outcomes and portal hemodynamic changes following ligation of the MSPSS during devascularization surgery. Portography and gastroendoscopy were performed before and after surgery for hemodynamic and follow-up studies. Three types of MSPSS were demonstrated portographically: 22 portoumbilical shunts, 18 splenorenal shunts, and 2 inferior mesenteric-caval shunts. A total of 40 MSPSS patients with esophagogastric variceal (EGV) bleeding underwent surgery: 26 had ligation of the MSPSS, and the remaining 14 served as the nonligation group. Neither the preoperative mean portal pressure (MPP) nor the postoperative MPP were significantly different between the ligation and nonligation groups ( p > 0.1), and there was no significant difference regarding surgical mortality, recurrent varices, or cumulative survival rate for the two groups in the follow-up study. However, postoperative portography demonstrated persistent drainage of portal flow and decreased intrahepatic portal perfusion in the nonligation patients. Clinical signs of hepatic encephalopathy subsided after ligation of the MSPSS in three patients. Therefore ligation of the MSPSS, which may be responsible for the development of encephalopathy, is recommended during devascularization surgery for EGV in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Colorectal carcinogenesis is regarded as a multistep process resulting from accumulation of genetic alterations, including activation of protooncogenes and inactivation of tumor suppressor genes via signal transduction trigger the stage-wise progression to malignancy. The reported incidence of K-ras mutation detected in general tissue samples ranges from 21–60% in primary colorectal cancers (CRC). To assess the prevalence and spectrum of K-ras mutations in Taiwanese patients with CRC, we analyzed 65 CRC patients by polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing. K-ras mutations were detected in 43.1% (28 of 65) of the tumors. The mutational hot spots were located at codons 12, 13, 15 and 20, especially with the highest frequency at codon 15. To understand whether the codon 15 mutations in CRC were associated with activation of K-ras oncogene and the alterations of its biocharacteristics, mutant K-ras genes were cloned from tumor tissues and then inserted into expression vector pBKCMV to construct the prokaryotic expression plasmid pK15MCMV. Mutant K-ras genes were expressed at high levels in E. coli and the mutant K-ras proteins were shown to be functional with respect to their well-known specific, high-affinity, GDP/GTP binding. The purified K-ras protein from E. coli was then measured for its intrinsic GTPase activity and the extrinsic GTPase activity in the presence of GTPase-activating protein for ras. We found that the extrinsic GTPase activity of the codon 15 mutant K-ras proteins (p21K-ras15M) in the presence of GAP is much lower than that of the wild-type K-ras protein (p21 BN), whereas the intrinsic GTPase activity is nearly the same as that of the wild-type K-ras protein. The results indicated that mutation at the codon 15 of K-ras gene indeed decreased GTPase activity in CRC, however, its association with tumorigenesis of CRC needs be clarified by further studies. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Nature utilizes various styles of architecture for DNA-binding proteins to recognize diverse DNA sequences, a process facilitated by a complementary surface between protein and DNA. However, the extent and ways this ‘shape complementarity’ occurs at the protein–DNA interface have yet to be characterized. Here, by analyzing a set of diverse protein–DNA complexes of known three-dimensional structures, we investigated whether the normal vectors of a protein surface at the interface exhibited any relationship with DNA conformation. Generally, the normal vectors of a DNA-contacting protein surface distinctly preferred certain angles, enabling them to align with certain axes characterizing the conformation of DNA. Thus, a new geometric property of DNA-binding protein is demonstrated, i.e. the ‘shape complementarity’ of protein–DNA recognition clearly bears the property of ‘directionality’. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Due to refractory symptoms of gastric outlet obstruction and gastrointestinal bleeding, she received total gastrectomy with Roux-en-Y reconstruction (Figure 1C) where the pathology report showed consistency with Menetrier's disease. A case report of diffuse hyperplastic gastropathy with multiple polypoid formations in a patient with pernicious anemia, helicobacter pylori infection, hypergastrinemia and hypoalbuminaemia: do not forget of Ménétrier's disease. The laboratory data demonstrated severe anemia, hypochlorhydria and hypoalbuminemia, with edema of her four limbs also noted. [Extracted from the article]

Colorectal cancer is a major public health problem worldwide, and locally advanced rectal cancer (LARC) is known for its poor prognosis. A multimodal treatment approach is the only method to achieve satisfactory local recurrence and survival rates in LARC. Determining which therapeutic modality for LARC has the most satisfactory influence on quality of life and disease outcome is still controversial. LARC treatment is subject to continuous advancement due to the development of new and better diagnostic tools, radiotherapy techniques, and chemotherapeutic agents. Herein, we review various therapeutic modalities for LARC from several aspects. In addition to radiotherapy techniques such as neoadjuvant chemoradiotherapy (NCRT), we discuss the progress of chemotherapy, appropriate time interval between NCRT and surgery, relationship between tumor location and NCRT efficacy/safety, wait‐and‐watch policy, and predictors of treatment response following NCRT. Because of the controversies and unanswered questions regarding NCRT treatments for LARC, additional investigations are required to determine which therapeutic approach is the most feasible for LARC patients. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 4 article‐registration‐date‐day 11 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_234.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> The chemical composition of fucoidan, a kind of sulfated polysaccharide mainly derived from brown seaweed, includes a substantial percentage of l‐fucose. Fucoidan has various biological and pharmacological activities, such as anti‐cancer/anti‐tumor, anti‐proliferation, anti‐inflammatory and immune‐modulatory functions, and fucoidan‐related dietary supplements and nutraceuticals have recently drawn considerable attention. In this review, we aim to provide a current view of different aspects of fucoidan biological activity, with a focus on the anti‐cancer regulatory effects of fucoidan on growth signaling mechanisms. First, we discuss historical aspects of fucoidan and fucoidan products, as well as the anti‐cancer effects of fucoidan on various cancer cells. Second, we discuss fucoidan's biological activities and induction of cell death in cancer cells, including multiple mechanisms and signal transduction pathways related to its anti‐cancer effects. Next, we focus on fucoidan and fucoidan‐derived products that have been marketed as dietary supplements or nutraceuticals for cancer, including anti‐cancer effects of fucoidan when combined as an adjuvant with clinical drugs. Finally, case studies of fucoidan in complementary therapy and as an alternative medicine in animal and mouse models and human clinical trials to alleviate side effects of anti‐cancer chemotherapy are discussed. Combining fucoidan with clinical therapeutic agents in the treatment of cancer patients, dissecting the related signal transduction pathways and investigating their dynamic interactions may reveal potential molecular targets in cancer prevention, therapies and key obstacles in the current development of anti‐cancer strategies. [ABSTRACT FROM AUTHOR]

Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well‐tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier. [ABSTRACT FROM AUTHOR]

Fecal microbiota transplantation (FMT) had been an ancient remedy for severe illness several centuries ago. Under modern medical analysis and evidence‐based research, it has been proved as an alternative treatment for recurrent Clostridium difficile infection and recent randomized control study also showed that FMT could be an adjuvant treatment for inflammatory bowel disease. As we get a better understanding of the relationship between gut microbiota and systemic disease, FMT became a potential treatment to explore. This article summarized procedures such as donor selection, fecal material preparation, transplantation delivery methods, and adverse events. We also review the present evidence about FMT in clinical practice. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is correlated with angiogenesis and early relapse of colorectal cancer (CRC). This study investigated the role of miR‐148a in the regulation of VEGF/angiogenesis and early relapse of CRC. We established a stable clone with miR‐148a expression in HCT116 and HT29 cell lines and created a hypoxic condition by using CoCl2 to determine the underlying mechanism of miR‐148a. The effects of miR‐148a on the phosphoryl‐ERK (pERK)/hypoxia‐inducible factor‐1α (HIF‐1α)/VEGF pathway were evaluated through Western blotting and the inhibitory effect of miR‐148a on angiogenesis was demonstrated through a tube formation assay. Sixty‐three CRC tissues (28 early relapse and 35 non‐early relapse) were analysed to assess the relationship between miR‐148a and HIF‐1α/VEGF. The protein expression of pERK/HIF‐1α/VEGF in HCT116 and HT29 cells was significantly decreased by miR‐148a (all P < 0.05). The protein expression of VEGF/HIF‐1α was strongly inversely associated with the expression of miR‐148a in the 63 CRC tissue samples (all P < 0.05). Tube formation assay demonstrated that miR‐148a significantly obliterated angiogenesis. miR‐148a suppresses VEGF through down‐regulation of the pERK/HIF‐1α/VEGF pathway and might lead to the inhibition of angiogenesis; miR‐148a down‐regulation increased the early relapse rate of CRC. This demonstrates that miR‐148a is a potential diagnostic and therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Platinum resistance enhances DNA damage repair through nucleotide excision repair mechanisms involving the excision repair cross-complementing group 1 ( ERCC1), X-ray cross-complementing group 1 ( XRCC1), and excision repair cross-complementing group 2 ( ERCC2). We evaluated the correlation between the expression of these three DNA repair genes and clinical outcomes in patients with rectal cancer receiving FOLFOX-based preoperative chemoradiotherapy (CRT). Methods: Using immunohistochemistry, we examined the expression of ERCC1, ERCC2, and XRCC1 in pre-CRT cancer tissues from 86 patients with rectal cancer who had undergone curative resection and preoperative CRT with FOLFOX-4 to identify potential predictors of clinical outcomes. Results: Following CRT, 57 and 29 patients were classified as responders (pathological tumor regression grade TRG 0 and TRG 1) and poor responders (TRG 2 and TRG 3), respectively. The multivariate analysis revealed that ERCC1 overexpression was correlated with a poor CRT response [ p < 0.0001; odds ratio (OR), 9.397; 95% confidence interval (CI) 2.721-32.457]. Furthermore, a poor response to CRT (pathological TRG of 2-3) ( p = 0.18; OR 5.685; 95% CI 1.349-23.954) and abnormal pre-CRT serum carcinoembryonic antigen levels (>5 ng/mL) ( p = 0.03; OR 6.288; 95% CI 1.198-33.006) were independent predictors of postoperative relapse. By contrast, ERCC2 and XRCC1 expression did not play predictive roles in the analyzed patients. Conclusions: ERCC1 overexpression is associated with a poor preoperative CRT response in patients with rectal cancer receiving FOLFOX-based preoperative CRT. ERCC1 is a potential biomarker for identifying patients who can benefit from customized treatment programs. [ABSTRACT FROM AUTHOR]

We are grateful to the following reviewers for their contributions during 2022. Consistent high-quality of papers published in "Kaohsiung Journal of Medical Sciences" can only be maintained with the cooperation and dedication of a number of expert referees. [Extracted from the article]

Background: The aim of the present study was to determine which aspects of tumor histology influence postoperative early relapse and overall survival rates after radical resection of stage II colorectal cancer (CRC). Methods: Data were collected for 425 patients with stage II CRC who began treatment at a single institution between January 2006 and October 2013. All the enrolled patients were followed up on until death or until December 2014. Clinically significant factors affecting postoperative early relapse and overall survival rates were analyzed. Results: Using a multivariate analysis, tumor invasion depth ( P = 0.008), vascular invasion ( P = 0.029), postoperative carcinoembryonic antigen (CEA) level ( P = 0.001), and retrieval of less than 12 lymph nodes ( P = 0.002) were found to be independent predictors for postoperative early relapse. A combination of tumor invasion depth, vascular invasion, postoperative CEA level, and number of lymph nodes retrieved showed that the greater the number of predictors involved, the higher the likelihood of postoperative early relapse and the poorer the overall survival. Conclusions: This study revealed that T4 invasion, vascular invasion, postoperative CEA level, and the number of examined lymph nodes may significantly affect the prognosis of stage II CRC patients after radical resection. The risks of postoperative early relapse and worse clinical outcome increase in proportion to the values of these four parameters. [ABSTRACT FROM AUTHOR]

ABSTRACT Lead ions (Pb2+) are toxic industrial pollutants associated with chronic inflammatory diseases in humans and animals. Previously, we found that Pb2+ ions induce COX-2 gene expression via the EGF receptor/nuclear factor-κB signal transduction pathway in epidermoid carcinoma cell line A431. In this study, to see whether Pb2+ ions affect COX-2 expression by epigenetic mechanisms, we looked at the mRNAs of DNA methyltransferases (DNMTs) using real-time PCR of total RNA from these cells. Cells exposed to Pb2+ had low levels of DNMT3a mRNA, whereas the levels of DNMT1 and DNMT3b mRNAs remained unchanged. Pretreatment of cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5 μM) followed by Pb2+ (1 μM) significantly increased levels of COX-2 mRNA compared with cells treated with Pb2+ alone. Overexpression of tumor suppressor gene Rb correlated with an increase in COX-2 mRNA and a decrease in DNMT3a mRNA. Conversely, overexpression of transcription factor E2F1 correlated with a decrease in COX-2 mRNA and an increase in DMNT3a mRNA. Pretreatment with EGFR inhibitors AG1478 and PD153035 significantly limited Pb2+-induced reduction in DNMT3a mRNA. In addition, gene knockdown of DNMT3a with short hairpin RNA correlated with increased COX-2 mRNA induced by Pb2+. Our findings suggest Pb2+ ions induce COX-2 expression indirectly by reducing DNMT3a methylation of the COX-2 promoter via transcription factors Rb and E2F1. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1024-1032, 2015. [ABSTRACT FROM AUTHOR]

Tumor micro-environment is a critical factor in the development of cancer. The aim of this study was to investigate the inflammatory cytokines secreted by tumor-associated dendritic cells (TADCs) that contribute to enhanced migration, invasion, and epithelial-to-mesenchymal transition (EMT) in colon cancer. The administration of recombinant human chemokine (C-C motif) ligand 5 (CCL5), which is largely expressed by colon cancer surrounding TADCs, mimicked the stimulation of TADC-conditioned medium on migration, invasion, and EMT in colon cancer cells. Blocking CCL5 by neutralizing antibodies or siRNA transfection diminished the promotion of cancer progression by TADCs. Tumor-infiltrating CD11c+ DCs in human colon cancer specimens were shown to produce CCL5. The stimulation of colon cancer progression by TADC-derived CCL5 was associated with the up-regulation of non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), which subsequently increased the expression of Snail. Blocking MALAT-1 significantly decreased the TADC-conditioned medium and CCL5-mediated migration and invasion by decreasing the enhancement of Snail, suggesting that the MALAT-1/Snail pathway plays a critical role in TADC-mediated cancer progression. In conclusion, the inhibition of CCL5 or CCL5-related signaling may be an attractive therapeutic target in colon cancer patients. J. Cell. Physiol. 230: 1883-1894, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: SMAD3, which is accumulated in the nucleus, transcriptionally regulates TGF-β target genes, playing a significant role in mediating the activities of TGF-β. In this study, we assessed the roles of TGF-β1, SMAD3, and phosphorylated SMAD3 expressions in patients with locally advanced rectal cancer following preoperative fluoropyrimidine-based chemoradiotherapy. Methods: Using immunohistochemistry, we examined TGF-β1, SMAD3, and phosphorylated SMAD3 expressions in pre-chemoradiotherapy cancer tissues from 86 locally advanced rectal cancer patients. After chemoradiotherapy, 64 of 86 (74.4 %) locally advanced rectal cancer patients were classified as responders (pathological tumor regression grades of 2-4). Results: A multivariate analysis showed that phosphorylated SMAD3 overexpression correlated to poor preoperative chemoradiotherapy responses ( P = 0.015; OR 7.218; 95 % CI 1.479-35.229). Furthermore, a poor response (pathological tumor regression grades of 0-1) was an independent predictor of postoperative relapse ( P = 0.021; OR 5.452; 95 % CI 1.286-23.113). Additionally, patients with phosphorylated SMAD3 overexpression were found to have a worse disease-free survival ( P = 0.023). Conclusions: Our data suggested that analyzing pre-chemoradiotherapy tumors for phosphorylated SMAD3 overexpression would assist physicians in identifying locally advanced rectal cancer patients who may have a poor response risk to preoperative fluoropyrimidine-based chemoradiotherapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Divalent lead (Pb2+) is a common industrial pollutant epidemiologically associated with gastric cancers. Pb2+ was found to promote tumorigenesis, which may include interleukin (IL)-8, a pro-inflammatory chemokine that promotes angiogenesis and tumor metastasis. Given that the gastrointestinal tract is a major route of Pb2+ exposure, we investigated the ability of Pb2+ to induce IL-8 expression in gastric carcinoma cells and its underlying mechanism. At a concentration of 0.1 μM, Pb2+ induced IL-8 gene activation in gastric carcinoma AGS cells. Using a IL-8 promoter-deletion analysis, transcription factor activator protein 1 (AP-1) was identified as a necessary component of Pb2+-induced IL-8 gene activation. Upregulation of the IL-8 gene was abrogated by the MEK inhibitor, PD98059, and partially suppressed by the epidermal growth factor receptor inhibitors, AG1478 and PD153035. Furthermore, c-Jun protein expression was induced in cells treated with Pb2+, and overexpression of c-Jun enhanced Pb2+-induced IL-8 activation. Collectively, our findings highlight the pivotal roles of AP-1 and extracellular signal-regulated kinase in signal transduction of Pb2+-induced IL-8 gene activation. These molecules may be potential therapeutic targets for Pb2+-related inflammation leading to stomach carcinogenesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 315-322, 2015. [ABSTRACT FROM AUTHOR]

ABSTRACT Divalent lead ions (Pb2+) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb2+ from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb2+ affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 μM lead nitrate. We found that Pb2+ induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb2+. MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb2+-induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb2+ also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb2+ on gastrin gene activity in cell culture. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 129-136, 2015. [ABSTRACT FROM AUTHOR]

People whom the author would like to thank for reviewing papers for the periodical from September 1, 2013, through August 31, 2014 is presented including Robin Jones, Moran Amit, and Ruben Mesa.

Objectives We aimed to evaluate the performance of fecal occult blood tests (FOBT) for the screening of colorectal cancer (CRC). Methods We selected participants from a medical center in Taiwan, China from November 2009 to June 2011. All participants underwent screening colonoscopy and were asked to provide their stool samples for qualitative immunochemical FOBT ( qlFIT), quantitative immunochemical FOBT ( qnFIT) and the guaiac-based FOBT( GT). The receiver operating characteristic curve was utilized to determine the optimal cut-off value of qnFIT. We measured the detection ability of the FOBT for colonic polypoid lesions. Results In all, 699 participants were enrolled in this study. For qnFIT, we found increased levels of fecal hemoglobin in participants with polyps ≥10 mm (251.0 ng/mL), villous-containing adenomas (98.7 ng/mL) and advanced adenomas (187.9 ng/mL). The optimal cut-off value for qnFIT was 25 ng/mL for detecting advanced colorectal neoplasms ( ACRN). All three FOBT had a similar but low estimate in detecting small and tubular adenomatous polyps. The qnFIT had a better detection ability for large adenomas (positive likelihood ratio [ PLR], 5.6 vs 3.1 vs 0.3) and adenomas with villous-components ( PLR 3.7 vs 3.3 vs 0.3) than qlFIT and GT. For the ACRN group, qnFIT also showed the best screening ability with a sensitivity of 56.8%, accuracy of 86.7% and PLR 5.0. Conclusions Both qnFIT and qlFIT perform better than GT in detecting advanced adenomas and CRC in the Taiwanese population. [ABSTRACT FROM AUTHOR]

Aims OV-6 is among the best available markers of liver stem cells. The aim of this study was to investigate OV-6 expression and its clinical implications in colorectal cancer. Methods and results Expression of OV-6 and its clinical implications were investigated in 94 patients with American Joint Committee on Cancer ( AJCC) stage I- III primary colorectal cancer and in 37 rectal cancer patients who had received preoperative chemoradiotherapy. The two main expression patterns of OV-6 were cytoplasmic and membranous. Overexpression of OV-6, which was identified on the basis of overall staining intensity, was associated with perineural invasion, lymphovascular invasion, and early relapses. Membranous OV-6 overexpression was also significantly associated with depth of tumour invasion, AJCC stage, lymphovascular and perineural invasion, and postoperative early relapse. Disease-free survival and overall survival were significantly poorer in patients with high overall OV-6 expression than in those with low overall OV-6 expression ( P = 0.015 and P = 0.029, respectively), and significantly poorer in patients with high membranous OV-6 expression than in those with low membranous OV-6 expression ( P < 0.001 and P < 0.001, respectively). Membranous OV-6 expression was a more reliable prognostic marker than overall expression. Conclusions OV-6 is not unique to the hepatobiliary system, and may be a novel prognostic marker in colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated that laparoscopic surgery is safe and effective for urgent and emergent colectomy in adulthood. The aim of the present study was to evaluate the feasibility of laparoscopic colectomy for children in emergent settings. Methods: Between March 2008 and August 2011, 10 consecutive children with acute colonic perforations and fibropurulent peritonitis secondary to infectious colitis underwent emergency laparoscopic colectomy. Simultaneously, we reviewed and recorded the same data from another consecutive 10 patients who underwent standard laparotomy between November 2004 and February 2008. The two groups were compared with regard to operative time, length of hospital stay (LOS), and complications. Results: The gender, age, body weight, serum C-reactive protein, number of involved bowel segments, operative time, and LOS were not significantly different ( P = 0.36, 0.50, 0.33, 0.62, 0.81, 0.14 and 0.23, respectively). In the laparoscopy group, one patient required conversion to open surgery because of extensive bowel involvement, and another patient with solitary colonic perforation required reoperation for anastomostic leakage. However, patients who underwent laparotomy had a higher incidence of later complications, including wound infection, incisional hernia, and adhesion ileus ( P = 0.03, 0.06, and 0.03, respectively) and thus required more additional unplanned operations ( P = 0.05). Conclusions: Emergency laparoscopic surgery is technically feasible in most children with acute colonic perforations and fibropurulent peritonitis. However, extensive intestinal involvement with multiple perforations should be an indication for converting to open surgery. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 48-year-old woman presented with hematemesis. It discusses that Esophagogastroduodenoscopy revealed a submucosal tumor with vessel exposure near the cardiac area. It mentions that computed tomography revealed a homogeneous, hyper-enhanced tumor. It notes that treatment initiated by considering the manifestation of an advanced tumor with subserosa and lymph node invasion.

A letter to the editor is presented in response to the article "Clinico-pathological characteristics and long-term outcome in patients with distant metastases from differentiated thyroid carcinoma," by C. A. Benbassat and others in the May 2006 issue.

A response to a letter to the editor about their article "Randomized Controlled Trial of Ligasure with Submucosal Dissection versus Ferguson Hemorrhoidectomy for Prolapsed Hemorrhoids" in the 2006 issue is presented.