Browsing by Department "Anatomy and Cell Biology"

Objective: Aberrant glycosylation affects many cellular properties in cancers. The core 1 β1,3-galactosyltransferase (C1GALT1), an enzyme that controls the formation of mucintype O-glycans, has been reported to regulate hepatocellular and mammary carcinogenesis. This study aimed to explore the role of C1GALT1 in ovarian cancer. Methods: C1GALT1 expression was assessed in a public database based on microarray data from 1287 ovarian cancer patients and ovarian cancerous tissues. Lectin blotting and flow cytometry analysis were conducted to detect changes in O-glycans on ovarian cancer cells. Effects of C1GALT1 on cell growth, migration, and sphere formation were analyzed in C1GALT1 knockdown or overexpressing ovarian cancer cells in vitro. Expression of cancer stemnessrelated genes was analyzed by quantitative reverse transcription polymerase chain reaction. Results: High C1GALT1 expression shows a trend toward association with poor survival in ovarian cancer patients. C1GALT1 modifies O-glycan expression on surfaces and glycoproteins of ovarian cancer cells. Knockdown of C1GALT1 decreased cell growth, migration, and sphere formation of ES-2 and OVTW59-p4 cells. Conversely, overexpression of C1GALT1 promoted such malignant properties of SKOV3 cells. Furthermore, C1GALT1 regulated the expression of several cancer stemness-related genes, including CD133, CD24, Oct4, Nanog, and SNAI2, in ovarian cancer cells. Conclusions: C1GALT1 modifies O-glycan expression and enhances malignant behaviors in ovarian cancer cells, suggesting that C1GALT1 plays a role in the pathogenesis of ovarian cancer and targeting C1GALT1 could be a promising approach for ovarian cancer therapy. Copyright ? 2017 by IGCS and ESGO.

A variety of oncogenic and environmental factors alter tumor metabolism to serve the distinct cellular biosynthetic and bioenergetic needs present during oncogenesis. Extracellular acidosis is a common microenvironmental stress in solid tumors, but little is known about its metabolic influence, particularly when present in the absence of hypoxia. In order to characterize the extent of tumor cell metabolic adaptations to acidosis, we employed stable isotope tracers to examine how acidosis impacts glucose, glutamine, and palmitate metabolism in breast cancer cells exposed to extracellular acidosis.

High expression of either β4 integrin or focal adhesion kinase (FAK) has been reported in human colon cancer. However, it remains unclear how β4 integrin together with FAK contributes to the tumorigenicity of colon cancer. Here, we demonstrate that the co-overexpression of β4 integrin and FAK positively correlates with advanced stages of human colon cancer. Activated β4 integrin interacts with FAK and subsequently induces FAK phosphorylation at Tyr397. Furthermore, ablation of the β4 integrin/FAK complex and/or FAK activation impair colon cancer cell proliferation, anchorage-independent growth, and tumorigenicity. Our data indicate that the β4 integrin/FAK complex and subsequent FAK activation are essential regulators during the tumorigenicity of colon cancer, and we suggest an alternative strategy for colon cancer therapy. ? 2016 Federation of European Biochemical Societies

Background: Acute-disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system, whose epidemiology, clinical presentations and functional outcome are incompletely understood in Asian populations. Objective: To assess the clinical presentations, predisposing factors and functional outcome of ADEM in Taiwan. Methods: 50 patients initially diagnosed with ADEM (male, 19; female, 31) were enrolled from 1991 to 2005. Diagnosis of ADEM or multiple sclerosis was established during a follow-up period of 2-120 months. 8 adult patients were noted to have taken the immunomodulatory drug, levamisole, within 3 months before onset of symptoms. The remaining 42 patients (male, 17; female, 25) were categorised by age as children (<16 years, n = 12), young adults (16-49 years, n = 21) and elderly adults (?50 years, n = 9). The clinical manifestations, predisposing factors and radiological findings were compared between different age groups and adult patients with or without levamisole use. Functional outcome was compared by a log-rank test. Results: Preceding upper respiratory tract infection was evident in 21 (50%) patients and only one young-adult patient had received Rubella vaccine immunisation. The frequency of fever was higher in children (p = 0.04) and psychiatric symptoms were more prevalent in elderly patients (p = 0.03). Functional recovery was faster in children than in adults (p = 0.002). Initial Expanded Disability Status Scale score (odds ratio (OR) 1.9, p = 0.03) and no fever (OR 0.04, p = 0.06) were associated with poor outcome (modified Rankin scale ?2). After a mean (SD) follow-up of 31.8 (9.9) months, 4 (9.5%) patients developed multiple sclerosis (3 (25%) children, 1 (4.7%) young adult, p = 0.03). The neurological disability, radiological and cerebrospinal fluid findings did not differ between patients with and without levamisole use. One elderly adult patient previously receiving levamisole developed multiple sclerosis of relapse-remitting type after a mean follow-up period of 36.9 months. Conclusion: The clinical presentations, functional outcome and risk of developing multiple sclerosis differed between different age groups. Functional recovery was faster in children than in adults. Poor functional outcome was related to initial high Expanded Disability Status Scale score and absence of fever.

The authors describe two patients with acute sensory ataxic neuropathy. Both had a profound loss of proprioception and generalized areflexia. High titers of monospecific anti-GD1b IgG antibody were detected in their sera during the acute phase. Sensory ataxia resolved within 2 weeks after the onset. Taken together with the induction of experimental sensory ataxic neuropathy sensitized with GD1b ganglioside, GD1b may be a target molecule for autoantibody in some patients with acute sensory ataxic neuropathy.

Background/Aims: Emergency abdominal surgery is associated with high morbidity and mortality rates, especially in the elderly patients, but prompt diagnoses and treatment should not be delayed. We conducted a retrospective review (1) to identify risk factors for morbidity and mortality among elderly patients admitted for emergent surgery of perforated peptic ulcers; and (2) to determine whether there were any differences between those who are 70-79 years old and those 80 years old and older. Methodology: 94 patients who were older than 70 years old and underwent emergency surgery for perforated peptic ulcer between 2000 and 2004 in our institution were reviewed retrospectively. The following variables were followed: age, sex, comorbidity, previous medications, time from onset of symptoms/signs to surgery, time from arrival in emergent room to surgery, perioperative risks, operative findings, type of operation, morbidity, mortality and length of hospital stay. Results: The age, morbidity, mortality and the length of intensive care unit stay were increased in Group 2 (>80 yrs) than Group 1 (70 to 79 yrs), but they did not achieve significant differences statistically. Time from symptoms/signs to emergency room over 24 hours, American Society of Anesthesiologist grade over IV and limited procedure showed significant contributions to postoperative morbidity on univariate analysis. Comorbidity, time from emergency room to operation room over 12 hours, American Society of Anesthesiologists grade over IV, peri-operative blood transfusion, postoperative morbidity and duration of ICU stays over 5 days were significant factors contributed to mortality on univariate analysis. Further analysis showed comorbidity, peri-operative blood transfusion, and postoperative morbidity were independent and predictive factors of mortality on multivariate model. Conclusions: Although perforated peptic ulcer in the elderly patients is associated with high morbidity and mortality, we should not delay the surgical intervention for patients with advanced age. Timely diagnosis and early surgical management of perforated peptic ulcers was imperative for elderly patients. The abdominal computer tomography was recommended in elderly patients for who had vague and atypical clinical symptoms/signs of perforated peptic ulcer. In addition, more attention should be paid to patients with preoperative comorbidities, peri-operative blood transfusion and post-operative morbidity for which were associated with high post-operative mortality. ? H.G.E. Update Medical Publishing S.A.

Flap necrosis is the most frequent postoperative complication encountered in reconstructive surgery. We elucidated whether adipose-derived stem cells (ADSCs) and their derivatives might induce neovascularization and protect skin flaps during ischemia/reperfusion (I/R) injury. Flaps were subjected to 3 hours of ischemia by ligating long thoracic vessels and then to blood reperfusion. Qtracker-labeled ADSCs, ADSCs in conditioned medium (ADSC-CM), or ADSC exosomes (ADSC-Exo) were injected into the flaps. These treatments led to significantly increased flap survival and capillary density compared with I/R on postoperative day 5. IL-6 levels in the cell lysates or in conditioned medium were significantly higher in ADSCs than in Hs68 fibroblasts. ADSC-CM and ADSC-Exo increased tube formation. This result was corroborated by a strong decrease in skin repair after adding IL-6–neutralizing antibodies or small interfering RNA for IL-6 ADSCs. ADSC transplantation also increased flap recovery in I/R injury of IL-6–knockout mice. IL-6 was secreted from ADSCs through signal transducer and activator of transcription phosphorylation, and then IL-6 stimulated angiogenesis and enhanced recovery after I/R injury by the classic signaling pathway. The mechanism of skin recovery includes the direct differentiation of ADSCs into endothelial cells and the indirect effect of IL-6 released from ADSCs. ADSC-CM and ADSC-Exo could be used as off-the-shelf products for this therapy. ? 2017 The Authors

Background: Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated. Methods: Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups. Results: From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted. Conclusions: This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.