Wen-Shih Huang

The nodular form of hepatic tuberculosis: a review with five additional new cases.

Background: Tuberculosis presenting as an isolated liver tumour, without active pulmonary or miliary tuberculosis, or other clinical evidence of tuberculosis, is distinctly rare. A greater awareness of this rare clinical entity may prevent needless surgical intervention. Aims: To help characterise this distinctly rare presentation of tuberculosis, five new cases are presented, together with a review of the world literature. The clinical, laboratory, radiological, and pathological features of these patients are described. Methods: Polymerase chain reaction (PCR) assay of the liver tissue was carried out in all cases to confirm an aetiological diagnosis of Mycobacterium tuberculosis infection. Results: All five patients (44–71 years old; two women, three men) underwent surgery, and had a preoperative diagnosis of malignant hepatic neoplasm and a postoperative histological diagnosis of chronic granulomatous inflammation, suggestive of tuberculosis. None of them had a known previous history of tuberculosis. All of them were positive for M tuberculosis by PCR analysis of the liver tissue. Conclusions: This report illustrates the difficulty in reaching a correct preoperative diagnosis. It is usually unsuspected and confused with primary or metastatic carcinoma of the liver, especially when it coexists with other malignancies. A high index of suspicion is required for diagnosis, which can be made only by histological and bacteriological studies, and PCR analysis.

The oncologic benefit of high ligation of the inferior mesenteric artery in the surgical treatment of rectal or sigmoid colon cancer

PurposeIt remains controversial as to whether high ligation of the inferior mesenteric artery (IMA) should be performed during surgical treatment for sigmoid colon or rectal cancer. The purpose of this study is to attempt to clarify the extent of the oncologic benefit of high ligation of the IMA.Materials and methodsFrom January 1995 to July 2001, a total of 1,389 patients underwent high ligation of the IMA; 387 patients featured non-disseminated sigmoid colon cancer and 1,002 patients had rectal cancer. Pathology of the primary tumors, IMA nodes, and clinical outcome were reviewed.ResultsForty-three patients (3.1%) revealed IMA node metastasis. Of these 43 patients, 29 (67.4%) featured tumor recurrences/metastases. After a minimum 5-year follow-up, 11 of these 43 patients (25.6%) were alive and disease free. Of these 43 patients, the 5-year disease-free survival rate for patients featuring sigmoid cancer was 50% and for patients with rectal cancer 13.8%. The beneficial rate of high ligation of the IMA for non-disseminated sigmoid colon cancer and rectal cancer was 0.8%, for non-disseminated sigmoid colon cancer 1.8%, and for non-disseminated rectal cancer, the rate was only 0.4%. The rates of IMA metastasis in patients with T stage tumors were 0% (pT1), 1.0% (pT2), 2.6% (pT3), and 4.3% (pT4).ConclusionsAlthough patients afflicted with IMA node metastasis revealed a rather high incidence of tumor recurrence/metastasis, 25.6% of these patients remained disease free following IMA node dissection after a minimum 5-year follow-up. We consider that IMA node dissection is more beneficial in patients with non-disseminated sigmoid pT4 tumor.

Metastatic lymph node ratio is a more precise predictor of prognosis than number of lymph node metastases in stage III colon cancer

ObjectiveThe objective of this study is to assess the value of metastatic lymph node ratio (LNR) in predicting disease-free survival (DFS) in patients with stage III adenocarcinoma of the colon.Materials and methodsFrom 1995 to 2003 inclusively, a total of 624 patients featuring stage III adenocarcinoma of the colon underwent curative resection. Of the 624 patients, an adequate number of lymph nodes (n ≥ 12) had been harvested in 490 patients. These patients were stratified into LNR groups 1 (LNR ≤ 0.4), 2 (0.4 < LNR ≤ 0.7), and 3 (LNR > 0.7). Kaplan–Meier survival curve and log-rank test were used to evaluate the prognostic value of LNR. A Cox regression model was used for multivariate analyses.ResultsThe 5-year DFS rate was 66.7% for patients with LNR1, 35.1% for those with LNR2, and 0% for patients with LNR3 (p < 0.0001). In T3/4LNR1 patients (n = 411), there was no difference in survival between those with N1 stage and those with N2 stage. Cox proportional hazards regression analysis revealed that N stage (number of positive lymph nodes) was not a significant factor when LNR was taken into consideration.ConclusionsLNR is a more precise predictor of 5-year DFS than number of positive lymph nodes (N stage) in patients with stage III colon cancer.

Endometrial cyst of the liver: a case report and review of the literature

The occurrence of pelvic endometriosis is not uncommon but hepatic endometriosis is extremely rare. Only five such cases of hepatic endometriosis have been described in the literature. This report concerns another patient with hepatic endometriosis forming a large cystic mass. The clinicopathological features and the possible pathogenesis are discussed. Endometriosis should be considered in the differential diagnosis of a cystic liver mass, particularly in patients with known endometriosis.

Proteomic analysis of the effects of baicalein on colorectal cancer cells.

Baicalein is the flavonoids with multiple pharmacological activities. The aim of our study was to investigate the effects of baicalein on colorectal cancer (CRC) and to recognize the targets of baicalein treatment. To better understand baicaleins target, proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS‐PAGE) to elucidate proteins differential display. Results from this study investigate that baicalein treatment of CRC cells results in reduced cell proliferation. As a result, differential protein displays between baicalein‐treated and untreated CRC were determined and validated. There were 11 differentially expressed proteins between baicalein‐treated and untreated CRC. Furthermore, we demonstrate that baicalein inhibits cancer cell proliferation and reduced reactive oxygen species (ROS) by up‐regulating the levels of peroxiredoxin‐6 (PRDX6). Knockdown of PRDX6 in baicalein‐treated CRC cells by specific small interfering RNA resulted in ROS production and proliferation, opposite of the baicalein treatment scenario as indicated by cell cycle distribution. These results illustrate that baicalein up‐regulates the expression of PRDX6, which attenuates the generation of ROS and inhibits the growth of CRC cells, whereas baicalein treatment have no effect on normal epithelial cells.

Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells

BackgroundStromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells.ResultsHuman gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity.ConclusionsResistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer.

Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine.

Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

Stromal cell‐derived factor‐1/CXC receptor 4 and β1 integrin interaction regulates urokinase‐type plasminogen activator expression in human colorectal cancer cells

The stromal cell‐derived factor‐1 (SDF‐1)/CXC receptor 4 (CXCR4) axis has been shown to play a role in colorectal cancer progression. In addition, the protease urokinase‐type plasminogen activator (uPA) is an important factor in tumor cell invasion and metastasis. However, the mechanism by which SDF‐1 mediates uPA expression in human colorectal cancer cells remains unknown. We investigated the molecular mechanism governing the interaction between SDF‐1 stimulation and uPA expression in three human colon cancer cell lines (DLD‐1, SW48, and COLO 205). We found that SDF‐1 stimulation led to an increase in the expression and secretion of uPA in these cells. Experiments involving specific inhibitors and small interfering RNA demonstrated that the activation of p38 mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase (PI3K)/Akt pathways are critical for SDF‐1‐induced uPA expression. Analysis of transcription factor binding using ELISA and chromatin immunoprecipitation assays revealed that SDF‐1 increased Sp1‐ and AP‐1‐DNA‐binding activities in DLD‐1 cells. Inhibition of Sp1 and AP‐1 activation blocked the SDF‐1‐induced expression and activity of the uPA promoter. The effect of SDF‐1 on DLD‐1 signaling and uPA expression was mediated by the CXCR4/β1 integrin axis. In summary, our findings elucidate the mechanisms of SDF‐1/CXCR4 downstream signaling and provide insights into the function of SDF‐1 in colon cancer cells. J. Cell. Physiol. 227: 1114–1122, 2012.

Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade

BackgroundHericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved.MethodsMice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination.ResultsTreatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax.ConclusionThese physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.

High glucose-treated macrophages augment E-selectin expression in endothelial cells

E-selectin expression by endothelial cells (ECs) is crucial for leukocyte recruitment during the inflammatory response. Macrophage accumulation and serum E-selectin elevation are features of type 2 diabetes mellitus. However, the interactions between macrophages and ECs in regulating vascular endothelial function are not clearly understood. We investigated the mechanisms underlying the modulation of EC E-selectin expression by high glucose (HG)-treated macrophages. Macrophage-conditioned media (MCM) were prepared from HG-treated macrophages. EC stimulation with HG-MCM induced increases the expression and secretion of E-selectin. By using specific inhibitors and small interfering RNAs, we demonstrate that the activation of the JNK and p38 MAPK pathways are critical for HG-MCM-induced E-selectin expression. Transcription factor ELISA and chromatin immunoprecipitation assays further showed that HG-MCM increases the NF-κB- and AP-1 DNA-binding activities in ECs. The inhibition of NF-κB and AP-1 activation by specific siRNAs blocks the HG-MCM-induced E-selectin promoter activity and expression. Protein arrays and blocking assays using neutralizing antibodies demonstrated that macrophage inflammatory protein 1α and 1β in HG-MCM are major mediators for the induction of EC E-selectin expression. These data support the hypothesis that E-selectin up-regulation stimulated by macrophages may play an active role in atherogenesis in the HG condition and suggest a new mechanism by which arterial disease is accelerated in diabetes.