Biomedical subjects

Carlos Gamallo

Publications and source records attributed to Carlos Gamallo.

16 recordsLinked to original sources

PubMed2007

Elective neck dissection in early-stage oral squamous cell carcinoma--does it influence recurrence and survival?

BACKGROUND: This study investigates the influence on survival and regional control rates of neck dissection therapy at the time of surgery of the primary tumor in early stages of squamous cell carcinoma (SCC) of the oral cavity. METHODS: A series of 154 patients with pT1N0M0 and pT2N0M0 intraoral carcinomas was analyzed retrospectively. Neck dissection was associated with tumor ablation in 87 patients (56.5%), although 67 patients (43.5%) were treated with local resection exclusively. Survival and relapse rates were studied with the Kaplan-Meier curves and the log-rank test for univariate analysis and Cox proportional model for multivariate analysis (p < .05). RESULTS: Regional recurrences occurred in 25 cases (16.2%), 7 cases (8%) with primary neck dissection and 18 cases (26.8%) with local excision alone. Neck dissection therapy was a significant prognostic factor for recurrences and survival (p < .05). The 5-year regional control rate was of 92.5% for patients with elective lymph node ablation versus 71.2% for patients without primary neck dissection. Neck dissection was also significant for recurrences in stage I and for survival and recurrences in stage II. Neck dissection therapy also showed independent prognostic value in the Cox analysis. CONCLUSIONS: In patients with intraoral carcinomas, elective neck treatment should be considered even in cases with a small primary tumor and negative clinical examination because of the high incidence of occult nodal metastases and the tendency to regional recurrences.

Adolescent↗

PubMed2006

Intratumoral lymphatic vessels and VEGF-C expression are predictive factors of lymph node relapse in T1-T4 N0 laryngopharyngeal squamous cell carcinoma.

BACKGROUND: The presence of intratumoral lymphatic vessels (ILVs) and the expression of vascular endothelial growth factor-C (VEGF-C) in tumour cells have been studied as markers of lymphangiogenesis in order to evaluate their role in metastatic dissemination in laryngopharyngeal squamous cell carcinoma. METHODS: A retrospective study was performed in 76 patients of N0 laryngopharyngeal carcinoma. with variable tumour size (T1-T4), histological grade, and location (supraglottic, glottic and hypopharyngeal). The presence of ILVs, as revealed by the expression of PA2.26 antigen and VEGF-C expression, were determined by immunohistochemistry (IHC). Low-grade and high-grade lymphangiogenesis were defined by qualitative and quantitative criteria. RESULTS: Multivariate analysis revealed low-grade ILV and VEGF-C expression to be associated respectively with 30.3- and 16.2-fold higher probabilities of cervical lymph node relapse (P = 0.005 and P = 0.032) and with 16.2- and 8.44-fold shorter disease-free survival (P = 0.009 and P = 0.045). CONCLUSIONS: Low-grade ILV and VEGF-C expression are independent predictive factors of cervical lymph node relapse and shortening of time to relapse in N0 laryngopharyngeal carcinoma.

Adenosine-5'-(N-ethylcarboxamide)↗

PubMed2006

Role of c-Src in human MCF7 breast cancer cell tumorigenesis.

To study the role of c-Src in breast cancer tumorigenesis, we generated a cell line derived from MCF7 carrying an inducible dominant negative c-Src (c-SrcDN: K295M/Y527F) under tetracycline control (Tet-On system). c-SrcDN expression caused phenotypic changes, relocation of c-Src, Fak, and paxillin, and loss of correct actin fiber assembly. These alterations were coupled to increased Fak-Tyr(397) autophosphorylation and to inhibition of Fak-Tyr(925), p130(CAS), and paxillin phosphorylation. An increased association of total Src with Fak and a decreased interaction of p130(CAS) and p85-PI3K with Fak were also observed. SrcDN inhibited cell attachment, spreading, and migration. Serum and EGF-induced stimulation of cell proliferation and Akt phosphorylation were also significantly reduced by SrcDN, whereas p27(Kip1) expression was increased. Consistently, silencing c-Src expression by siRNA in MCF7 cells significantly reduced cell migration, attachment, spreading and proliferation. Inoculation of MCF7 cells carrying inducible SrcDN to nude mice generated tumors. However, doxycycline administration to mice significantly reduced tumorigenesis, and when doxycycline treatment was installed after tumor development, a significant tumor regression was observed. In both situations, inhibition of tumorigenesis was associated with decreased Ki67 staining and increased apoptosis in tumors. These data undoubtedly demonstrate the relevance of the Src/Fak complex in breast cancer tumorigenesis.

Animals↗

PubMed2006

Mast cell quantification in normal peritoneum and during peritoneal dialysis treatment.

CONTEXT: Mast cells (MCs) have been implicated in fibrogenesis, angiogenesis, and immunity against bacteria. These 3 mechanisms participate in the peritoneal pathology secondary to peritoneal dialysis (PD) treatment. Despite their potential relevance to PD-related pathology, few studies have focused on MCs. OBJECTIVE: To evaluate possible variations in the number of MCs during PD treatment. DESIGN: A quantitative study of tissue MCs in normal and pathologic peritoneum. Parietal peritoneal biopsies were collected from 4 groups: (1) normal controls (n = 9), (2) uremic non-PD patients (n = 16), (3) uremic patients on PD (n = 26), and (4) non-renal patients with inguinal hernia (n = 20). MCs were evaluated using immunohistochemistry for the detection of tryptase. The total number of cross sections of vessels per peritoneal field was examined in 22 of the 26 peritoneal biopsies of PD patients. RESULTS: PD tissue samples showed fibrosis, mesothelial cell loss, and variable hyalinizing vasculopathy. The number of MCs was similar in normal controls and non-PD uremic patients (mean +/- SE: 7.13 +/- 0.67 and 7.74 +/- 0.74 MCs/mm2, respectively). Peritoneal dialysis patients showed a reduction (4 +/- 0.38 MCs/mm2, P < .001), whereas hernia sac samples showed an increase (10.59 +/- 3.48 MCs/mm2). MC reduction showed no correlation with time on dialysis, fibrosis, number of vessels, or previous episodes of peritonitis. CONCLUSIONS: The peritoneum of patients receiving PD treatment shows a reduction of MCs. Despite such a reduction, fibrosis takes place, suggesting that MCs do not play a critical role in fibrosis genesis. Mast cell loss may be a contributory factor to peritonitis episodes in PD patients.

Adult↗

PubMed2006

Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil.

Several variables associated to thymidylate synthase (TS), the biological target of 5-fluorouracil (5FU) have been studied for their possible role as predictors of the clinical outcome and response to chemotherapy in colorectal cancer (CRC) patients. The level of protein expression and the number of variable tandem-repeats of a 28-bp sequence within the gene promoter have been proposed as predictive and/or prognostic factors with variable agreement, while consensus seems to be achieved with respect to the value of a single nucleotide polymorphism (SNP) described within this same region. More recently, an association between TS expression pattern and survival has been disclosed. Paraffin-embedded sections from 140 CRC patients were analyzed by immuno-histochemistry (Mab TS106) for TS levels and expression pattern. Also, VNTR and SNP were determined by polymerase-chain reaction (PCR) and restriction-length-fragment polymorphism (RFLP) in 123 and 112 patients, respectively. Cytoplasmic expression pattern tended to be associated to C SNP (p=0.06). Low TS expression levels, cytoplasmic expression pattern and C SNP arose as variables associated to longer progression-free survival (PFS) in patients treated with 5FU. Accordingly, patients having at least two favourable or unfavourable variables were classified respectively as 'low risk' and 'high risk', the former showing significantly longer PFS (p=0.0299). The possibility for designing a selection method for subsequent therapies is suggested on the basis of a probable combined effect of the above mentioned parameters but further studies in larger populations are needed to confirm these results.

Aged↗

PubMed2005

Chromosomal instability and phenotypic plasticity during the squamous-spindle carcinoma transition: association of a specific T(14;15) with malignant progression.

In mouse epidermal carcinogenesis, the latest stage of malignant progression involves the transition from squamous cell carcinoma to a highly aggressive type of tumor with spindle morphology. In this work, we have isolated a minor epithelial cell subpopulation (CarC-R) contained in the highly malignant spindle carcinoma cell line CarC. CarC-R exhibited a drastic reduction in tumorigenicity when compared with CarC, but CarC-R-induced tumors were mainly sarcomatoid, although they subsequently reverted to the epithelial phenotype when tumor explants were recultured in vitro. Several single-cell clones with either stable epithelial or fibroblastic phenotypes were isolated from an explanted CarC-R tumor (CarC-RT). All these cell lines contained the same specific point mutation in H-Ras codon 61, but while CarC spindle cells had lost the normal H-Ras allele, it was retained in CarC-R- and CarC-RT-derived cell lines. Furthermore, CarC cells have inactivated p16INK4a and p19INK4a/ARF transcription, while CarC-R and CarC-RT clones expressed p19 mRNA and protein but not p16. Altogether, these results suggest that CarC-R represents a precursor stage to CarC in malignant progression. Spectral karyotyping analysis revealed that CarC-R was highly aneuploid and contained many chromosomal abnormalities. In contrast, CarC had a diploid or tetraploid modal chromosome number and contained a specific T(14;15) translocation in all of the analysed metaphases. The T(14;15) translocation was present in only a minority (1.9%) of CarC-R cells, but it was widely spread in CarC-RT and its derived cell clones, regardless of their epithelial or fibroblastic phenotype, indicating that T(14;15) segregates with malignancy.

Animals↗

PubMed2005

P-cadherin expression reduced in squamous cell carcinoma of the oral cavity: an indicatior of poor prognosis.

BACKGROUND: The loss of cadherin expression has been shown to correlate to the invasion and metastasis of many types of carcinomas. The purpose of the current study was to evaluate whether the impaired expression of E-cadherin (E-cad) and P-cadherin (P-cad) correlated with the clinical evolution and prognosis of oral squamous cell carcinoma (OSCC). METHODS: The authors used immunohistochemical methods to analyze the expression pattern of E-cad and P-cad in healthy oral mucosa, in oral carcinoma in situ (CIS), and in surgical samples of 50 patients with the early stages (Stages I-II) of OSCC. RESULTS: E-cad showed weak expression in the basal layer of the healthy oral mucosa and reduced expression in patients with oral CIS. P-cad expression was conserved on the basal and suprabasal layers of the healthy mucosa and, also, in the CIS. In the group of patients with OSCC, univariate analysis demonstrated that reduced expression of E-cad or P-cad correlated significantly with locoregional disease recurrence in the follow-up (P=0.03 and P=0.01, respectively). However, only the reduction in the expression of P-cad emerged as an independent prognostic marker in the multivariate analysis (P=0.04, hazard ratio =8.06). CONCLUSIONS: These findings suggested that a decrease in E-cad and/or P-cad expression may contribute to the invasive potential of early OSCC. According to the current data, P-cad expression may be a potential independent prognostic factor in patients with OSCC.

Cadherins↗

PubMed2005

Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas.

We report the full cDNA sequence encoding the human homologue of murine PA2.26 (T1alpha-2, podoplanin), a small mucin-type transmembrane glycoprotein originally identified as a cell-surface antigen induced in keratinocytes during mouse skin carcinogenesis. The human PA2.26 gene is expressed as 2 transcripts of 0.9 and 2.7 kb in several normal tissues, such as the placenta, skeletal muscle, heart and lung. Using a specific polyclonal antibody raised against a synthetic peptide of the protein ectodomain, PA2.26 was immunohistochemically detected in about 25% (15/61) of human early oral squamous cell carcinomas. PA2.26 distribution in the tumours was heterogeneous and often restricted to the invasive front. Double immunofluorescence and confocal microscopy analysis showed that PA2.26 colocalized with the membrane cytoskeleton linker ezrin at the surface of tumour cells and that its presence in vivo was associated with downregulation of membrane E-cadherin protein expression. Ectopic expression of human PA2.26 in HeLa carcinoma cells and immortalized HaCaT keratinocytes promoted a redistribution of ezrin to the cell edges, the formation of cell-surface protrusions and reduced Ca(2+)-dependent cell-cell adhesiveness. These results point to PA2.26 as a novel biomarker for oral squamous cell carcinomas that might be involved in migration/invasion.

Amino Acid Sequence↗

PubMed2004

The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer.

Several non-hypercalcemic analogs of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) show antitumor activity in a subset of cancer patients. High vitamin D receptor (VDR) expression, which is associated with good prognosis but is lost during tumor progression. We show that the SNAIL transcription factor represses VDR gene expression in human colon cancer cells and blocks the antitumor action of EB1089, a 1,25(OH)(2)D(3) analog, in xenografted mice. In human colon cancers, elevated SNAIL expression correlates with downregulation of VDR.

Animals↗

PubMed2004

Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions.

Accumulating evidences indicate that p120 catenin, a member of the E-cadherin (E-CD)/catenin adhesion complex, plays a role in tumor invasion. To establish the expression pattern of p120 in breast cancer, we analysed 326 breast tissue biopsies by tissue microarray. Most of the lobular tumors (88%) showed exclusive cytoplasmic localization, and 6% of them also had p120 nuclear staining. Cytoplasmic p120 strongly associated with complete loss of E-CD and beta-catenin not only in lobular carcinoma and its metastases but also in atypical lobular hyperplasias. In the latter, loss of heterozygosity of E-CD gene was also observed. Complete loss of E-CD and cytoplasmic and nuclear p120 staining was also observed in primary lobular cancer cell cultures generated by us. In ductal tumors, by contrast, reduction of p120 and E-CD in membrane was very common (57 and 53%, respectively), whereas cytoplasmic p120 staining was rarely seen. This simultaneous reduction of membranous E-CD and p120 was not associated with increased Src kinase activity. To demonstrate that cytoplasmic p120 localization was a consequence of the absence of E-CD, the endogenous E-CD was re-expressed in MDA-231 cells by 5-Aza-2'-deoxycytidine (5Aza) treatment. After treatment, p120 shifted from the cytoplasm to the membrane, where it colocalized with endogenous E-CD. Additionally, suppressing E-CD expression in Madin-Darby canine kidney cells by stable transfection of the transcriptional repressors Snail, E47 or Slug, provokes p120 cytoplasmic localization and p120 isoform switching. In conclusion, abnormal cytoplasmic and nuclear localization of p120, which are mediated by the absence of E-CD, characteristically occur in the early stages of lobular breast cancer and are maintained during tumor progression to metastasis. Consequently, p120 may be an important mediator of the oncogenic effects derived from E-CD inactivation, including enhanced motility and invasion, in lobular breast cancer.

Breast Neoplasms↗

PubMed2004

Prognostic significance of intratumoral lymphangiogenesis in squamous cell carcinoma of the oral cavity.

BACKGROUND: Clinicopathologic data demonstrated that the lymphatic system is the main route for solid tumor metastasis. However, the effect of intratumoral lymphangiogenesis (IL) on prognosis in oral carcinoma is still unknown because, until recently, no reliable markers for lymphatic endothelium were available. The current study analyzed the lymphatic vessels in tumor tissue specimens of patients with primary oral carcinoma using the new marker, PA2.26. METHODS: The authors investigated IL in surgical tissue samples of 61 patients with early-stage (Stages I-II) oral carcinoma. The tissue specimens were stained for PA2.26 and the correlation between IL and relevant parameters was analyzed by the Pearson chi-square test. In a univariate analysis using the Kaplan-Meier method, IL was analyzed against survival and disease-free period. Statistical significance of differences between distributions was studied by the log-rank test. Clinicopathologic parameters, including IL, were entered in a multivariate analysis to determine independent prognostic significance. RESULTS: Thirty-three patients had IL. In the follow-up, a strong association was found between IL and locoregional recurrence (30.3 % of the patients with IL and 7.1% of the patients without IL). The presence of IL did not correlate significantly with the pT classification, primary location, or tumor differentiation. IL was found to have no influence on overall survival in univariate analysis, but there was significant association between IL and disease-free survival (P=0.03). Multivariate analysis revealed IL to be the sole independent factor influencing disease-free interval (P=0.02). CONCLUSIONS: These results suggested that IL is associated with locoregional disease recurrence in early-stage oral carcinoma. The presence of IL was a useful discriminator in predicting the outcome of patients with absence of lymph node metastasis.

Biopsy, Needle↗

PubMed2004

Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis.

Peritoneal fibrosis is one of the most common morphological changes observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Both resident fibroblasts and new fibroblast-like cells derived from the mesothelium by epithelial-to-mesenchymal transition are the main cells involved fibrogenesis. In order to establish markers of peritoneal impairment and pathogenic clues to explain the fibrogenic process, we conducted an immunohistochemical study focused on peritoneal fibroblasts. Parietal peritoneal biopsies were collected from four patient groups: normal controls ( n = 15), non-CAPD uremic patients ( n = 17), uremic patients on CAPD ( n = 27) and non-renal patients with inguinal hernia ( n = 12). To study myofibroblastic conversion of mesothelial cells, alpha-smooth muscle actin (SMA), desmin, cytokeratins and E-cadherin were analyzed. The expression of CD34 by fibroblasts was also analyzed. Fibroblasts from controls and non-CAPD uremic patients showed expression of CD34, but no myofibroblastic or mesothelial markers. The opposite pattern was present during CAPD-related fibrosis. Expression of cytokeratins and E-cadherin by fibroblast-like cells and alpha-SMA by mesothelial and stromal cells supports that mesothelial-to-myofibroblast transition occurs during CAPD. Loss of CD34 expression correlated with the degree of peritoneal fibrosis. The immunophenotype of fibroblasts varies during the progression of fibrosis. Myofibroblasts seem to derive from both activation of resident fibroblasts and local conversion of mesothelial cells.

Adult↗

PubMed2004

Thymidylate synthase expression pattern is a prognostic factor in patients of colorectal cancer treated with 5-fluorouracil.

High intratumoral expression of thymidylate synthase (TS) has been reported as a factor of poor prognosis in patients with advanced colorectal cancer (CRC), but such association is unclear in some studies. Also, TS has been stated as a typical cytosolic enzyme, but nuclear location has been occasionally reported, and data on the clinical meaning of TS intracellular location are scarce. A retrospective study was performed in paraffin-embedded sections of primary tumor from 77 CRC patients treated with surgical resection and adjuvant 5-FU-based chemotherapy. TS levels and expression patterns were determined by immunohistochemistry (IHQ) using TS-106 antibody. Qualitative and quantitative variables were compared respectively by chi2 and Kruskal-Wallis tests; overall survival (OS) and disease-free survival (DFS) were analyzed with the Kaplan-Meier method and compared using the log-rank and Wilcoxon tests. TS was cytoplasmic in 27.1% of positive tumors and both, nuclear and cytoplasmic in 72.9%; specimens from seven patients (9.1%) lacked TS expression. TS levels were high in 21.6% of tumors with nuclear expression and low in 5.6%, whereas 68.4% of cytoplasmic ones showed low immunostaining intensity (p=0.02); cytoplasmic pattern was also associated to longer OS (p<0.009) and DFS (p=0.003). In patients with nuclear expression, low TS expression was associated to shorter OS (p<0.003) and DFS (p<0.04). These results indicate that, in our study, TS immunostaining patterns were related with OS and DFS, the best prognostic corresponding to cytoplasmic one, and, within the subset of patients with nuclear expression, low TS levels were associated to worse clinical outcome.

Aged↗

PubMed2003

Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: relationships with abnormal E-cadherin and catenin expression and microsatellite instability.

The causes and functional consequences of E-cadherin (E-CD) loss in breast cancer are poorly understood. E-CD loss might act in concert with alterations in the APC/beta-catenin pathway to permit oncogenic beta-catenin signaling. To test this hypothesis, we have analyzed the presence of genetic and epigenetic alterations affecting E-CD (CDH1), APC and beta-catenin (CTNNB1) genes and the immunohistochemical expression of E-CD, beta- and gamma-catenin in a series of 46 infiltrating lobular breast carcinomas (ILCs). Since 80% of ILCs featured complete loss of E-CD expression, we analyzed the molecular alterations responsible for E-CD inactivation in these tumors. We found that 10 of 46 (22%) cases harbored mutations in CDH1, including 1 case with 2 different mutations (1 of which was germline). CDH1 was also inactivated by loss of heterozygosity (LOH; 30/41, 73%) and promoter hypermethylation (19/46, 41%). Interestingly, LOH and mutations were also detected in the corresponding in situ lesions of the ILCs, implying that these alterations are early events in lobular cancer tumorogenesis. Additionally, the presence of a polymorphism in the CDH1 promoter was found to be inversely correlated with CDH1 mutations, but not with E-CD levels. We next examined whether alterations in the APC/beta-catenin pathway also occurred in the same series of ILCs. Although no CTNNB1 or APC mutations were detected, promoter methylation (25/46, 52%) and LOH (7/30, 23%) of APC were found. Moreover, methylation of APC and CDH1 occurred concordantly. However, beta- and gamma-catenin were severely reduced or absent in 90% of these tumors, implying that alterations in CDH1 and APC genes do not promote beta-catenin accumulation in ILC. These molecular alterations were not associated with microsatellite instability. In summary, several different mechanisms (mutations, LOH, methylation) are involved in the frequent CDH1 inactivation in invasive and in situ lobular breast cancer. The same tumors also show genetic and epigenetic alterations of APC gene. However, altered CDH1 and APC genes do not promote beta-catenin accumulation in this tumor type.

Adenomatous Polyposis Coli Protein↗

PubMed2003

Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells.

BACKGROUND: During continuous ambulatory peritoneal dialysis, the peritoneum is exposed to bioincompatible dialysis fluids that cause denudation of mesothelial cells and, ultimately, tissue fibrosis and failure of ultrafiltration. However, the mechanism of this process has yet to be elucidated. METHODS: Mesothelial cells isolated from effluents in dialysis fluid from patients undergoing continuous ambulatory peritoneal dialysis were phenotypically characterized by flow cytometry, confocal immunofluorescence, Western blotting, and reverse-transcriptase polymerase chain reaction. These cells were compared with mesothelial cells from omentum and treated with various stimuli in vitro to mimic the transdifferentiation observed during continuous ambulatory peritoneal dialysis. Results were confirmed in vivo by immunohistochemical analysis performed on peritoneal-biopsy specimens. RESULTS: Soon after dialysis is initiated, peritoneal mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype with a progressive loss of epithelial morphology and a decrease in the expression of cytokeratins and E-cadherin through an induction of the transcriptional repressor snail. Mesothelial cells also acquire a migratory phenotype with the up-regulation of expression of alpha2 integrin. In vitro analyses point to wound repair and profibrotic and inflammatory cytokines as factors that initiate mesothelial transdifferentiation. Immunohistochemical studies of peritoneal-biopsy specimens from patients undergoing continuous ambulatory peritoneal dialysis demonstrate the expression of the mesothelial markers intercellular adhesion molecule 1 and cytokeratins in fibroblast-like cells entrapped in the stroma, suggesting that these cells stemmed from local conversion of mesothelial cells. CONCLUSIONS: Our results suggest that mesothelial cells have an active role in the structural and functional alteration of the peritoneum during peritoneal dialysis. The findings suggest potential targets for the design of new dialysis solutions and markers for the monitoring of patients.

Cell Movement↗

PubMed2002

Enhanced intrahepatic inducible nitric oxide synthase expression and nitrotyrosine accumulation in primary biliary cirrhosis and autoimmune hepatitis.

BACKGROUND/AIMS: Nitrosative stress resulting from increased nitric oxide (NO) synthesis contributes to the pathogenesis of chronic inflammatory diseases, including chronic viral hepatitis. Our goal was to assess the expression of inducible nitric oxide synthase (iNOS) and the formation of nitrotyrosine (NTY), as a marker of nitrosative stress, in liver biopsies from primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) patients. METHODS: Intrahepatic expression of iNOS and NTY was measured immunohistochemically and compared to histological scores of the severity of liver disease. RESULTS: Hepatocellular iNOS expression was observed in liver sections from PBC patients (with a diffuse lobular distribution) and from AIH patients (marked staining in areas of pronounced inflammation and necrosis), but not in control liver sections, including non-autoimmune cholestatic liver disease. Liver samples from PBC and AIH patients, but not from controls, showed NTY accumulation in clusters of hepatocytes and Kupffer cells. Increased iNOS expression and NTY accumulation correlated with the histological severity of PBC or AIH, especially with the degree of inflammation. CONCLUSIONS: Patients with PBC and AIH showed an enhanced intrahepatic iNOS expression and NTY accumulation, related to the histological severity of liver disease, consistent with NO-mediated nitration of hepatocellular proteins contributing to liver damage in both diseases.

Adult↗