Biomedical subjects

Shiu-Feng Huang

Publications and source records attributed to Shiu-Feng Huang.

At least 19 recordsLinked to original sources

PubMed2007

Identification of NV-F virus DNA in hepatocellular carcinoma.

A fragment of DNA sequence derived from a hepatotropic virus, named NV-F was isolated recently. The aim of this study was to examine whether this virus was associated with hepatocellular carcinoma (HCC). Total cellular DNA was extracted from hepatocellular carcinoma tissues. NV-F virus DNA was detected by PCR. The PCR products were subjected to sequence analysis. Of the 78 HCC samples included, 12 (15.4%) were positive for NV-F virus DNA. Sequence analysis of the 12 amplified DNA fragments revealed a point mutation in one of them. The clinicopathological parameters between patients with and without NV-F virus infection were compared. It was found that patients with NV-F virus infection were older than those without NV-F virus infection (mean ages, 61.5 versus 52.5 years; P = 0.032). Otherwise, no difference was observed between the two groups. Of the 12 HCC patients positive for NV-F virus DNA, 11 patients were co-infected by either hepatitis B or C virus. The remaining patient was a Taiwanese aboriginal inhabitant with cryptogenic cirrhosis. In conclusion, NV-F virus DNA was identified in 15.4% of HCC tissues. HCC patients with NV-F virus infection were significantly older than those without NV-F virus infection.

Carcinoma, Hepatocellular↗

PubMed2006

Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer.

Mutational analysis was performed in the kinase domain (exons 18-21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p=0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p=0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness.

Adenocarcinoma↗

PubMed2006

Different responses to gefitinib in lung adenocarcinoma coexpressing mutant- and wild-type epidermal growth factor receptor genes.

Response to gefitinib is strongly associated with the status of the epidermal growth factor receptor gene. Here we report the different treatment responses in a case of lung adenocarcinoma coexpressing mutant-type gene in the primary lung mass and a wild-type gene in the metastatic bone lesions. This case demonstrated that at least two strains of tumor cells were present in a single patient. This may be one of the mechanisms of gefitinib resistance.

Adenocarcinoma↗

PubMed2006

Fulminant pulmonary calciphylaxis and metastatic calcification causing acute respiratory failure in a uremic patient.

Calciphylaxis is a rare and life-threatening disorder characterized by small-vessel mural calcification with intimal proliferation, fibrosis, and thrombosis, resulting in tissue ischemic necrosis. Although it has been viewed as a systemic disease involving mainly the dermis, subcutaneous fat, or muscle, calciphylaxis of other organs rarely is reported. We describe the case of a 25-year-old uremic woman who rapidly developed massive pulmonary calcification that led to acute respiratory failure after the initiation of hemodialysis therapy. Chest radiography and high-resolution computed tomography showed typical pulmonary calcification. Pulmonary calciphylaxis and metastatic calcification were confirmed further by lung tissue biopsy. No skin or muscle calciphylaxis was discovered. Despite multiple factors precipitating pulmonary calciphylaxis in this patient, we speculate that hemodialysis was the main culprit in accelerating the development of fulminant pulmonary calciphylaxis and metastatic calcification. Alteration in the local environment from an acid to an alkaline condition and a relatively high dialysate calcium level in the presence of systemic hyperphosphatemia are believed to have facilitated the deposition of calcification. This case highlights the importance of "visceral calciphylaxis" and early identification of its causes.

Acute Disease↗

PubMed2006

Open lung biopsy in early-stage acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has heterogeneous etiologies, rapid progressive change and a high mortality rate. To improve the outcome of ARDS, accurate diagnosis is essential to the application of effective early treatment. The present study investigated the clinical effects and safety of open lung biopsy (OLB) in patients with early-stage ARDS of suspected non-infectious origin. METHODS: We undertook a retrospective study of 41 patients with early-stage ARDS (defined as one week or less after intubation) who underwent OLB in two medical intensive care units of a tertiary care hospital from 1999 to 2005. Data analyzed included baseline characteristics, complication rate, pathological diagnoses, treatment alterations, and hospital survival. RESULTS: The age of patients was 55 +/- 17 years (mean +/- SD). The average ratio of arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) was 116 +/- 43 mmHg (mean +/- SD) at biopsy. Seventeen patients (41%) were immunocompromised. Postoperative complications occurred in 20% of patients (8/41). All biopsies provided a pathological diagnosis with a diagnostic yield of 100%. Specific pathological diagnoses were made for 44% of patients (18/41). Biopsy findings led to an alteration of treatment modality in 73% of patients (30/41). The treatment alteration rate was higher in patients with nonspecific diagnoses than in patients with specific diagnoses (p = 0.0024). Overall mortality was 50% (21/41) and was not influenced by age, gender, pre-OLB oxygenation, complication rate, pathological results, and alteration of treatment. There was no surgery-related mortality. The survival rate for immunocompromised patients was better than that for immunocompetent patients (71% versus 33%; p = 0.0187) in this study. CONCLUSION: Our retrospective study suggests that OLB was a useful and acceptably safe diagnostic procedure in some selected patients with early-stage ARDS.

Adult↗

PubMed2006

Global gene expression profiling of dimethylnitrosamine-induced liver fibrosis: from pathological and biochemical data to microarray analysis.

The development of hepatocellular carcinoma (HCC) is generally preceded by cirrhosis, which occurs at the end stage of fibrosis. This is a common and potentially lethal problem of chronic liver disease in Asia. The development of microarrays permits us to monitor transcriptomes on a genome-wide scale; this has dramatically speeded up a comprehensive understanding of the disease process. Here we used dimethylnitrosamine (DMN), a nongenotoxic hepatotoxin, to induce rat necroinflammatory and hepatic fibrosis. During the 6-week time course, histopathological, biochemical, and quantitative RT-PCR analyses confirmed the incidence of necroinflammatory and hepatic fibrosis in this established rat model system. Using the Affymetrix microarray chip, 256 differentially expressed genes were identified from the liver injury samples. Hierarchical clustering of gene expression using a gene ontology database allowed the identification of several stage-specific characters and functionally related clusters that encode proteins related to metabolism, cell growth/maintenance, and response to external challenge. Among these genes, we classified 44 potential necroinflammatory-related genes and 62 potential fibrosis-related markers or drug targets based on histopathological scores. We also compared the results with other data on well-known markers and various other microarray datasets that are available. In conclusion, we believe that the molecular picture of necroinflammatory and hepatic fibrosis from this study may provide novel biological insights into the development of early liver damage molecular classifiers than can be used for basic research and in clinical applications. A public accessible website is available at http://LiverFibrosis.nchc.org.tw:8080/LF.

Animals↗

PubMed2005

Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct--an immunohistochemical study of 110 cases of hepatolithiasis.

BACKGROUND/AIMS: Two types of neoplastic lesions preceding invasive intrahepatic cholangiocarcinoma (ICC) are identified: a flat-type neoplastic lesion called 'biliary intraepithelial neoplasia (BilIN)' and an intraductal papillary neoplasm of the bile duct (IPN-B). Multi-step carcinogenesis has been suggested in both lesions, although phenotypic changes during this process remain unclarified. METHODS: We immunohistochemically examined expression patterns of MUC1, MUC2, MUC5AC, cytokeratin 7 (CK7), and CK20 in BilIN, IPN-B, and ICC in 110 cases of hepatolithiasis. RESULTS: Thirty-seven cases of ICC in hepatolithiasis were divided into 18 tubular adenocarcinomas with BilIN, 10 tubular adenocarcinomas with IPN-B and nine colloid carcinomas with IPN-B. Carcinogenesis via BilIN was characterized by MUC2-/CK7+/CK20-with increasing MUC1 expression. IPN-B was characterized by the intestinal phenotype (MUC2+/CK20+), and carcinogenesis leading to tubular adenocarcinoma was associated with increasing MUC1 expression and that to colloid carcinoma with MUC1-negativity. Pathological stages of tubular adenocarcinoma of ICC with BilIN or IPN-B were more advanced than those of colloid carcinoma with IPN-B. CONCLUSIONS: Immunophenotypes of MUCs and cytokeratins might characterize three cholangiocarcinogenetic pathways in hepatolithiasis. Increased expression of MUC1 in BilIN and also IPN-B is associated with tubular adenocarcinoma, while colloid carcinoma in IPN-B is characterized by MUC1-negativity and less advanced pathologic stages.

Adenocarcinoma, Papillary↗

PubMed2005

Invasive pulmonary aspergillosis and pulmonary cryptococcosis really coexist in immunocompromised host.

Fungal infections develop slowly in immunocompetent patients and rarely a severe disease, however, they progress rapidly and usually prove fatal in immunocompromised patients. Early diagnosis and treatment of fungal infections is essential to survival of immunocompromised patients. We report a 33-year-old woman with systemic lupus erythematosus undergoing immunotherapy infected with combined invasive pulmonary aspergillosis and pulmonary cryptococcosis diagnosed by video-assisted thoracic surgery lung biopsy and she was successfully treated as a result of early diagnosis and treatment.

Adult↗

PubMed2005

High-frequency Alu-mediated genomic recombination/deletion within the caspase-activated DNase gene in human hepatoma.

The Alu repetitive elements, which constitute 10% of human genome, may serve as bridges for genomic recombination. However, their roles in tumorigenesis remain to be elucidated. Caspase-activated DNase (CAD), whose gene (hCAD) is mapped at chromosome 1p36, a region frequently displaying hemizygote deletion in many human cancers, is the key enzyme for nucleosome fragmentation during apoptosis. Recently, we detected many aberrant mRNAs for hCAD in many human hepatoma cells. To elucidate the genetic basis leading to the mRNA aberration, we used PCR-based chromosome walking to clone the corresponding genomic DNA identifying a novel Alu/Alu homologous recombination/deletion within hCAD in HepG2 and Hep3B cells. We then detected similar recombination events in 13 out of the 20 hepatoma tissues and in eight of the para-cancerous cirrhotic livers. The recombination was inclined to occur in males (P=0.031) and had marginal association with high-grade hepatoma (P=0.070) and tumor recurrence (P=0.070). The recombination caused exon-3 deletion, which in turn led to exon-3 skipping or replacement with a partial Alu-sequence, and consequential C-truncation of CAD. Our findings of high frequency of Alu-mediated hCAD deletion in human hepatoma not only underscore the implication of hCAD in hepatocarcinogenesis, but also highlight the potential roles of human repetitive sequences in mediating genome instability in human cancers.

Alu Elements↗

PubMed2005

Type II collagen gene variants and inherited osteonecrosis of the femoral head.

BACKGROUND: Avascular necrosis of the femoral head (ANFH) causes disability that often requires surgical intervention. Most cases of ANFH are sporadic, but we identified three families in which there was autosomal dominant inheritance of the disease and mapped the chromosomal position of the gene to 12q13. METHODS: We carried out haplotype analysis in the families, selected candidate genes from the critical interval for ANFH on 12q13, and sequenced the promoter and exonic regions of the type II collagen gene (COL2A1) from persons with inherited and sporadic forms of ANFH. RESULTS: We identified a G-->A transition in exon 50 of COL2A1 in affected members of a four-generation family with ANFH. This transition predicts the replacement of glycine with serine at codon 1170 in a GXY repeat of type II collagen. Another pedigree was shown to harbor the same transition, but the mutant allele occurred on a different haplotype background. In a third family, a G-->A transition in exon 33 of the gene, causing a glycine-to-serine change at codon 717, was detected. No mutation was found in the COL2A1 coding region in sporadic cases of ANFH. CONCLUSIONS: All the patients with familial ANFH whom we studied carried COL2A1 mutations. In families with ANFH, haplotype and sequence analysis of the COL2A1 gene can be used to identify carriers of the mutant allele before the onset of clinical symptoms, allowing the initiation of measures that may delay progression of the disease.

Adult↗

PubMed2005

Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer.

Epidermal growth factor receptor (EGFR) has been detected in the nucleus of cancer cells and primary tumors for decades. While localized in the nucleus, EGFR functions as a transcriptional regulator resulting in the activation of the cyclin D1 gene. Despite nuclear accumulation of EGFR is linked to increased DNA synthesis and proliferative potential, the pathological significance of nuclear EGFR, however, remains uninvestigated. Furthermore, expression of EGFR has not provided a consistent predictive value for survival of breast cancer patients. Here, we analyzed 130 breast carcinomas via immunohistochemical analyses for the levels of nuclear and non-nuclear EGFR. We found 37.7% of the cohort immunostained positively for nuclear EGFR and 6.9% with high levels of expression. Importantly, Kaplan-Meier survival analysis and log-rank test revealed a significant inverse correlation between high nuclear EGFR and overall survival (P = 0.009). Expression of nuclear EGFR correlated positively with increased levels of cyclin D1 and Ki-67, both are indicators for cell proliferation. In contrast, expression of non-nuclear EGFR did not significantly correlate with those of cyclin D1 and Ki-67 or the overall survival rate. In addition, we analyzed 37 oral squamous carcinomas for EGFR expression and found 24.3% of the cases to contain moderate/high levels of nuclear EGFR. Taken together, our findings indicate pathological significance of nuclear EGFR and may have important clinical implication.

Breast Neoplasms↗

PubMed2005

Intrahepatic cholangiocarcinoma escapes from growth inhibitory effect of transforming growth factor-beta1 by overexpression of cyclin D1.

Transforming growth factor-beta1 (TGF-beta1) is involved in tumor progression by promoting angiogenesis or suppressing the immune system; yet TGF-beta1 also has a growth-inhibitory effect on epithelial cells including carcinoma cells. Several mechanisms of impaired TGF-beta1 responsiveness of carcinoma cells have been reported. In this study, we examined how TGF-beta1 participates in the development and progression of intrahepatic cholangiocarcinoma (ICC) associated with hepatolithiasis, and how ICC cells escape from growth inhibitory effect of TGF-beta1. A total of 40 cases of hepatolithiasis were studied, including 16 cases of ICC, and in vitro studies were conducted with cultured murine non-neoplastic biliary epithelial cells (MBEC) and three ICC cell lines. Immunohistochemically, TGF-beta1 was expressed in mononuclear cells and mesenchymal cells around the stone-containing bile ducts and invasive ICC, and also in biliary epithelial cells (hyperplastic and precursor lesions, and ICC). TGF-beta type II receptor (TbetaR-II) was constantly expressed on biliary epithelial cells irrespective of biliary lesions. In cell culture studies, TGF-beta1 significantly inhibited proliferation of MBEC via downregulation of cyclin D1, cdk4, and cdk6, while TGF-beta1 did not influence the proliferation of ICC cells. After suppression of cyclin D1 expression in one ICC cell line using cyclin D1 small interfering RNA, TGF-beta1 significantly inhibited the proliferation of ICC cells. In conclusion, high levels of TGF-beta1 around ICC or its precursors may be involved in development and progression of ICC in hepatolithiasis. ICC cells could escape the growth inhibitory effect of TGF-beta1 by overexpression of cyclin D1.

Cell Division↗

PubMed2005

Recurrent panniculitis associated with generalized lipodystrophy and growth hormone deficiency.

Generalized lipodystrophy (GLD) is characterized clinically by an almost complete lack of fat in adipose tissue. Traditionally, GLD can be divided into congenital and acquired types according to the clinical course and underlying etiologies. Here, we describe a boy with a probable diagnosis of acquired GLD. He showed recurrent panniculitis since early infancy, and short stature with delayed skeletal age (3 years less) and low levels of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3. Growth hormone (GH) deficiency was confirmed by GH provocative tests (peak GH below 5 microg/L). In addition to slow progressive loss of subcutaneous fat tissue, he also suffered from hepatosplenomegaly, recurrent febrile episodes in association with painful nodular skin lesions and abdominal pain. The diagnosis of lipodystrophic panniculitis was confirmed after skin biopsy. The febrile episodes and skin lesions responded to oral corticosteroid with the progression of time. Acquired GLD with GH deficiency (e.g., recurrent panniculitis) may occur as a result of chronic inflammation over the pituitary stalk and pituitary gland. The use of steroid and GH replacement may alleviate this disorder.

Adolescent↗

PubMed2004

High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan.

PURPOSE: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer. EXPERIMENTAL DESIGN: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. RESULTS: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. CONCLUSIONS: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.

Adenocarcinoma↗

PubMed2004

Evaluation of prognosis for malignant rectal gastrointestinal stromal tumor by clinical parameters and immunohistochemical staining.

PURPOSE: The aim of this study was to identify associated prognostic factors influencing the outcome of curative resection of rectal gastrointestinal stromal tumor. PATIENTS AND METHODS: Diagnostic immunohistochemical staining with CD34, CD117, S-100, desmin, and muscle-specific actin was performed in 46 consecutive patients with previously diagnosed rectal leiomyosarcoma who underwent curative resection from 1979 to 1999. CD44, Bcl-2, P53, and Ki-67 staining were performed on tumors rediagnosed as gastrointestinal stromal tumor for the prognostic evaluation. RESULTS: There were 42 (91.3 percent) patients with rectal gastrointestinal stromal tumor (18 females and 24 males; mean age, 58.4 years). Twenty-nine patients underwent radical surgical resections, such as abdominoperineal resection or low anterior resection, whereas the other 13 patients underwent wide local excision, such as transrectal excision or Kraske's operation. Sixteen tumors were classified as high-grade gastrointestinal stromal tumors, and 26 as low-grade. No tumor had a positive P53 stain. Twenty-seven patients (64.3 percent) developed recurrence or metastasis postoperatively (median follow-up, 52 months). The one-year, two-year, and five-year disease-free survival rates were 90.2 percent, 76.7 percent, and 43.9 percent, respectively. Of these patients with recurrence, subsequent resections in 12 patients with local recurrence, transarterial tumor embolism or STI-571 chemotherapies in 3 patients with distant mestastases were performed. The one-year, two-year, and five-year overall survival rates were 97.4 percent, 94.3 percent, and 83.7 percent, respectively. Bcl-2 (P = 0.007) and histologic grade (P = 0.05) in disease-free survival analysis and age < 50 years (P = 0.03) and tumor size > 5 cm (P = 0.02) in overall survival analysis were independent prognostic factors. The group with wide local excision had a higher local recurrence rate than that of the radical resection group (77 percent vs. 31 percent, P = 0.006), despite smaller tumors (4.5 vs. 7.2 cm, P = 0.05). There was no difference in the incidence of distant metastasis between the two groups. CONCLUSION: Younger age (< 50 years), higher histologic tumor grade, positive Bcl-2 status, and larger tumors (> 5 cm) were factors associated with significantly poorer prognoses for rectal gastrointestinal stromal tumor. Radical resection was superior to wide local excision in the prevention of local recurrence, but not that of distant metastases.

Adult↗

PubMed2004

Correlation of MYCN amplification with MCM7 protein expression in neuroblastomas: a chromogenic in situ hybridization study in paraffin sections.

Amplification of the MYCN oncogene in neuroblastomas is generally associated with a more aggressive clinical course. Recently, 1 of the minichromosome maintenance proteins, MCM7, was found to be a direct target of the MYCN transcription factor in neuroblastoma. To confirm this correlation, chromogenic in situ hybridization (CISH) to detect MYCN amplification and immunohistochemical staining for MCM7 protein expression were performed on paraffin tissue sections of 26 neuroblastomas cases and of 4 recurrences of these tumors. Seven of the primary tumors showed MYCN amplification, and all were stage 3 or 4 tumors. Only 4 of these showed MCM7 overexpression. However, 11 primary tumors overexpressed MCM7. The 4 patients with MCM7 expression associated with MYCN amplification all died from the tumor. In contrast, the 7 patients with MCM7 overexpression but no MYCN amplification were all younger than 1 year of age and have shown good survival. This suggests that MCM7 overexpression by itself is not related to a poorer prognosis as is MYCN amplification. In addition, the 4 pairs of primary and recurrent tumors all showed changes in MCM7 expression from negative to positive, whereas none of them had MYCN amplification. This study showed that MCM7 overexpression is not necessarily correlated with MYCN amplification or an aggressive clinical course. Interpretation of the results of CISH was quite easy and straightforward because the preparations were viewed with an ordinary light microscope with good preservation of the tissue morphology.

Adolescent↗

PubMed2004

Frequent p16ink4a inactivation is an early and frequent event of intraductal papillary neoplasm of the liver arising in hepatolithiasis.

Intraductal papillary neoplasm of the liver (IPNL) is a precursor lesion of intrahepatic cholangiocarcinoma (ICC) arising in hepatolithiasis. In this study, 98 foci of IPNL identified in 39 surgically resected hepatolithiatic livers were investigated for expression of p16INK4a, cyclin D1, p21WAF1/CIP1, p53, mouse double-minute 2 (MDM2), and pRb. In addition, methylation-specific polymerase chain reaction (MSP) for p16 INK4a promoter region was performed in these foci. Nonneoplastic bile ducts from 11 hepatolithiatic livers, 5 histologically normal livers, and 9 cases of nonpapillary conventional ICC were used as controls. Decreased expression of p16INK4A was seen in IPNL group 1 with mild dysplasia and continued along the progression of IPNL to ICC. The expression of cyclin D1, p21WAF1/CIP1,and pRb gradually increased along the progression of IPNL to ICC and became significantly high in IPNL of group 3 (carcinoma in situ). The expression of p53 and MDM2 was increased in IPNL group 3 and group 4 with evident invasive carcinoma. MSP revealed that 54.6% of 44 IPNL foci harbored p16INK4a promoter hypermethylation, and such foci were significantly correlated with decreased expression of p16INK4a protein. Ki-67 labeling index exhibited a stepwise increase from IPNL group 1 to group 4. We conclude that p16INK4a inactivation, due mainly to its promoter hypermethylation, is a frequent and early event of IPNL and may be responsible for genetic and epigenetic alterations of other cell cycle regulators in IPNL.

Adenoma, Bile Duct↗

PubMed2004

Thalidomide salvages lethal hepatic necroinflammation and accelerates recovery from cirrhosis in rats.

BACKGROUND/AIMS: The authors investigated the feasibility of thalidomide employed to treat liver fibrosis. METHODS: A cirrhotic model was established using Sprague-Dawley rats fed thioacetamide. Thalidomide-treated group was given thalidomide (10mg/kg/day) intraperitoneally for 10 consecutive days. Mortality, histopathological changes, TNFalpha, TGFbeta1, TIMP-1 and TIMP-2 were determined. Expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from the experimental rats were determined. RESULTS: The mortality rates of thalidomide-treated group and vehicle-treated group were 8 and 32%, respectively. The total Knodell score of thalidomide-treated rats was lower than those of vehicle-treated rats. Micro-nodular cirrhosis resolved grossly in thalidomide-treated rats on day 28; while vehicle-treated rats continued to display uneven liver surface on day 28. Expression of TNFalpha, TGFbeta1, TIMP-1, and TIMP-2 was decreased in thalidomide-treated rats compared to those treated with vehicles. Finally, the expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from rats treated with thalidomide were much lower than those treated with vehicle. CONCLUSIONS: Thalidomide salvages lethal hepatic necroinflammation, accelerates recovery from cirrhosis in rats, and works by suppressing of TNFalpha and TGFbeta1 production of Kupffer's cells.

Animals↗