E-cadherin and c-Met expression in actinic cheilits and lip squamous cell carcinoma

Objective: The aim of this study was to assess epithelial expression of E-cadherin and c-Met in normal lip, in actinic cheilitis and lip squamous cell carcinoma. Study Design: Biopsies of normal lip vermillion (NL, n=18), actinic cheilitis (AC, n=37), and lip SCC (n=22) were processed for E-cadherin and c-Met immunodetection. Epithelial and tumor cell expression was scored for each sample considering staining intensity and percentage. Results: E-cadherin expression was significantly reduced in AC and lip SCC as compared to normal lip (P<0.05), with a significant reduction in lip SCC as compared to AC (P=0.003). Expression of c-Met was significantly higher in AC and lip SCC as compared to NL (P<0.05), with a significant increase in lip SCC as compared to AC (P<0.0001). Conclusion: The results showed that epithelial E-cadherin expression is reduced and c-Met expression is increased as lip carcinogenesis progresses, suggesting that these proteins may be useful markers of malignant transformation.

Single exposure of human oral mucosa fibroblasts to ultraviolet B radiation reduces proliferation and induces COX-2 expression and activation

The lip vermillion constitutes a transition tissue, between oral mucosa and skin, where oral mucosal cells from epithelial and connective tissue compartments are exposed to ultraviolet (UV) sunlight. Fibroblasts are abundant resident cells of the connective tissue which are key regulators of extracellular matrix composition, as well as, epithelial and endothelial cell function. UVB light, an inherent component of sunlight, causes several alterations in skin fibroblasts, including premature senescence and increased cyclooxygenase (COX)-2 expression. To assess if UVB irradiation had similar effects on fibroblasts derived from human oral mucosa (HOM), primary cultures of HOM fibroblasts were irradiated with a single dose of 30 or 60 mJ/cm²of UVB light or sham-irradiated. Fibroblast proliferation was assessed from 3 to 48 hrs after UVB-irradiation utilizing [³H]-thymidine incorporation and MTT assays. In addition, COX-2 mRNA expression was detected by RT-PCR, and PGE2 production was assessed using enzyme immunoassay from 0.5 to 24 hrs after UVB-irradiation. The results showed a significant decrease in proliferation of UVB-irradiated HOM fibroblasts as compared to controls as measured by both [³H]-thymidine incorporation and MTT assays (p<0.001). HOM fibroblasts had increased COX-2 mRNA expression at 0.5 and 12 hrs after irradiation, and PGE2 production was elevated at 12 and 24 hrs post-irradiation as compared to controls (p<0.05). The results showed an inhibitory effect of a single dose of UVB irradiation on HOM fibroblast proliferation with an increase in COX-2 expression and activation. Therefore, photodamaged fibroblasts may play and important role in the pathogenesis of UV-induced lesions of the lip.

Estudio comparativo: prevalencia patologías bucales en pacientes pediátricos oncológicos 1997-2007 / Comparative study: oral pathologies prevalence in pediatric oncology patients 1997- 2007

Los pacientes pediátricos oncológicos con frecuencia presentan lesiones orales debido a su neoplasia o como efecto colateral del tratamiento. El objetivo de este estudio fue comparar la prevalencia de patologías de la mucosa oral en niños con cáncer que fueron hospitalizados y tratados con quimioterapia en el Hospital Regional de Concepción, en los años 1997 y 2007. Se realizó un estudio descriptivo retrospectivo longitudinal en datas de 148 pacientes (74 cada año) con patologías neoplásicas en tratamiento con quimioterapia (Leucemias, linfomas, tumores del Sistema Nervioso Central y otros), registrando sus datos generales y la patología bucal (mucositis (M), candidiasis (C), lesiones por Virus Herpes tipo 1 (VHS) y síndromes hemorragíparos (H) . Los datos se resumieron en tablas anuales y fueron sometidos a análisis estadísticos. Se encontró una disminución significativa del número de pacientes con patologías bucales en el año 2007 en relación al año 1997 (P<0.05, Tet de Fisher). Además se encontró una tendencia a la baja en los pacientes con candidiasis y con mucositis en el año 2007 en comparación con 1997. Es necesario seguir estudiando medidas para prevenir, diagnosticar y/o tratar tempranamente las patologías orales de los pacientes en tratamiento antineoplásico.

Pediatric oncology patients frequently have oral lesions due to malignancy or as a side effect of treatment. The aim of this study was to compare the prevalence of oral pathologies in oncology patients hospitalized and treated at the Regional Hospital of Concepción, Chile, in the years 1997 and 2007. A retrospective study was carried out in 74 patients each year. Patients suffered from acute lymphoblastic leukemia, acute myeloblastic leukemia, central nervous system tumors, lymphomas and other neoplasms. General data (age, gender, oncologic disease) and presence of oral pathologies (candidiasis, mucositis post-chemotherapy, herpetic lesions and hemorrhage) were obtained from their clinical records. Data was analyzed for statistical differences. A significant reduction in the number of patients with oral pathologies was found in 2007 in comparison to 1997 (P<0.05, Fisher´s test). In addition, candidiasis and oral mucositis showed less prevalence in 2007 as compared to 1997, although no significant differences were found. For the relevance of oral pathologies in the chemotherapy it´s important to continue studies about prevention, early detection and treatment of oral pathologies.

Reduction of syndecan-1 expression during lip carcinogenesis.

BACKGROUND: Actinic cheilitis (AC) is an oral pre-cancerous lesion that sometimes develops into lip squamous cell carcinoma (SCC). Syndecan-1, a transmembrane heparan sulfate proteoglycan, modulates cell-proliferation, adhesion, migration and angiogenesis. Malignant epithelial cells often down-regulate their own syndecan-1 production, and are capable of inducing aberrant syndecan-1 expression in stromal cells. The aim of this study was to evaluate the variations in syndecan-1 expression during lip carcinogenesis, in normal lip (NL), AC and well-differentiated lip SCC. METHODS: Biopsies of NL vermillion (n = 19), AC (n = 23) and lip SCC (n = 24) were stained immunohistochemically for syndecan-1. RESULTS: Syndecan-1 expression was significantly reduced in AC and lip SCC as compared to NL (P < 0.05), with a significant reduction in lip SCC as compared to AC (P < 0.0001). In lip SCC lesions, syndecan-1 expression at the epithelium overlying the tumor was increased when compared to the tumor itself (P < 0.03), but was significantly reduced as compared to AC and NL (P < 0.001). CONCLUSION: The results showed that epithelial syndecan-1 expression is reduced as lip carcinogenesis progresses (NL>AC>lip SCC), suggesting that syndecan-1 could be a useful marker of malignant transformation in the lip.

Oxidative stress markers in plasma and urine of prepubertal patients with type 1 diabetes mellitus.

Markers of oxidative stress were studied in plasma and urine of prepubertal patients with type 1 diabetes mellitus (DM1) with less than 5 years of disease (n = 27). The results were compared to healthy, age- and sex-matched control children (n = 27). Oxidative stress parameters evaluated included advanced oxidation protein products (AOPP), total peroxyl radical-trapping antioxidant parameter (TRAP), and F2-isoprostanes (8-epi-prostaglandin-F2: 8-isoPGF2alpha). No statistically significant differences were found for any of the oxidative stress markers assessed between patients with DM1 and controls. In addition, weight, height, and routine metabolic tests, including creatininemia and cholesterol levels, were similar between the groups. The lack of significant differences between healthy controls and patients with DM1 suggests that treatment is able to counteract the increase in free radical production.

TNFa increases in vitro migration of human HPV18-positive SW756 cervical carcinoma cells

TNFa has been associated with both, tumor survival and apoptosis. This cytokine is also involved in promoting cell migration during wound healing and tumorigenesis. SW756 is a HPV18-positive cervical carcinoma cell line, which has been used to study different mechanisms of cervical cancer progression. An in vitro assay of scratch wound healing onto monolayers of SW756 cells was used to assess the effect of TNFa on cell migration into a wound space. It was found that SW756 cells have the ability to migrate, but not proliferate in response to scratch wounding in a serum-free medium supplemented with TNFa. RT-PCR analysis showed that SW756 cells express TNFa mRNA when incubated in medium with and without serum. Wound closure and migration rate of SW756 cells were significantly increased in the presence of serum-free media supplemented with TNFa (10 ng/mL) as compared to serum-free media, and media supplemented with either anti-TNFa antibody or both TNFa and anti-TNFa antibody (p<0.05). The results showed a stimulatory effect of TNFa on the migration of SW756 cervical carcinoma cells, suggesting a novel and important role for TNFa in cervical cancer progression.

Expression of apoptotic and cell proliferation regulatory proteins in actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation. The apoptotic proteins p53, bax, bcl-2, and the proliferation marker Ki-67, are known to play an important role in UV-exposed skin and carcinomas, therefore, these markers were assessed in AC and compared with normal lip and oral mucosa. METHODS: AC (n = 13), normal lip (n = 7) and oral mucosa (n = 6) biopsies were stained immunohistochemically for p53, bax, bcl-2 and Ki-67, to determine their expression and distribution. RESULTS: p53 was over-expressed in AC as compared with normal lip and oral mucosa (P < 0.003). Although bcl-2 expression was higher in AC than in oral mucosa (P < 0.002), it was significantly reduced as compared with normal lip (P < 0.04). Bax expression remained unchanged, and Ki-67 was significantly increased in AC and normal lip as compared with oral mucosa (P < 0.05). CONCLUSION: The results suggest that DNA-damaged cells by UV radiation in AC are eliminated by apoptosis.

Characterization of mast cell subpopulations in lip cancer.

BACKGROUND: Lip squamous cell carcinoma (SCC) is the most common form of oral cancer. Human mast cells (MCs), which are increased in lip SCC, are classified by their protease content in tryptase-positive (MC(T)) and tryptase/chymase-positive (MC(TC)). MC proteases are associated with tumor progression and angiogenesis. The aim of this study was to quantify and characterize MC subpopulations in lip SCC. METHODS: Serial sections from lip SCC (n = 21) and normal lip vermilion (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC subpopulation density and distribution. RESULTS: MC(T) and MC(TC) were increased in lip SCC when compared with normal lip (P < 0.0001), where MC(T) predominated over MC(TC) (P < 0.01). In lip SCC neither subpopulation predominated. Regarding distribution, MC(T) were higher than MC(TC) at the intratumoral stroma, whereas MC(TC) were higher than MC(T) at the peritumoral stroma (P < 0.01). CONCLUSIONS: The results suggest that MC subpopulations may contribute to lip SCC progression. While intratumoral MC(T) may stimulate angiogenesis, peritumoral MC(TC) may promote extracellular matrix degradation and tumor progression at the invasion front.

TNFalpha increases in vitro migration of human HPV18-positive SW756 cervical carcinoma cells.

TNFalpha has been associated with both, tumor survival and apoptosis. This cytokine is also involved in promoting cell migration during wound healing and tumorigenesis. SW756 is a HPV18-positive cervical carcinoma cell line, which has been used to study different mechanisms of cervical cancer progression. An in vitro assay of scratch wound healing onto monolayers of SW756 cells was used to assess the effect of TNFalpha on cell migration into a wound space. It was found that SW756 cells have the ability to migrate, but not proliferate in response to scratch wounding in a serum-free medium supplemented with TNFalpha. RT-PCR analysis showed that SW756 cells express TNFalpha mRNA when incubated in medium with and without serum. Wound closure and migration rate of SW756 cells were significantly increased in the presence of serum-free media supplemented with TNFalpha (10 ng/mL) as compared to serum-free media, and media supplemented with either anti-TNFalpha antibody or both TNFalpha and anti-TNFalpha antibody (p < 0.05). The results showed a stimulatory effect of TNFalpha on the migration of SW756 cervical carcinoma cells, suggesting a novel and important role for TNFalpha in cervical cancer progression.

TNFalpha increases in vitro migration of human HPV18-positive SW756 cervical carcinoma cells.

TNFalpha has been associated with both, tumor survival and apoptosis. This cytokine is also involved in promoting cell migration during wound healing and tumorigenesis. SW756 is a HPV18-positive cervical carcinoma cell line, which has been used to study different mechanisms of cervical cancer progression. An in vitro assay of scratch wound healing onto monolayers of SW756 cells was used to assess the effect of TNFalpha on cell migration into a wound space. It was found that SW756 cells have the ability to migrate, but not proliferate in response to scratch wounding in a serum-free medium supplemented with TNFalpha. RT-PCR analysis showed that SW756 cells express TNFalpha mRNA when incubated in medium with and without serum. Wound closure and migration rate of SW756 cells were significantly increased in the presence of serum-free media supplemented with TNFalpha (10 ng/mL) as compared to serum-free media, and media supplemented with either anti-TNFalpha antibody or both TNFalpha and anti-TNFalpha antibody (p < 0.05). The results showed a stimulatory effect of TNFalpha on the migration of SW756 cervical carcinoma cells, suggesting a novel and important role for TNFalpha in cervical cancer progression.

Increased mast cell density and protease content in actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation and characterized by epithelial and connective tissue alterations. Mast cells (MCs), key contributors to solar elastosis in murine UV-irradiated skin, were characterized in order to assess their potential contribution to connective tissue degeneration in AC. METHODS: Actinic cheilitis (n = 15) and normal lip (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC density and protease content. MC subpopulations (i.e. MC(T) containing only tryptase, and MC(TC) containing chymase and tryptase) and their distribution were also determined. RESULTS: Mast cells and their proteases were increased in AC as compared with normal lip (P < 0.0001), and appeared degranulated especially around elastotic areas. MC(T) predominated over MC(TC) in AC and normal lip (P < 0.05). However, in AC MC(T) were increased in the epithelium/connective junction and connective area (P < 0.05), while in normal lip MC(T) predominated in connective and submucosal areas (P < 0.05). CONCLUSION: The results suggest that increased MC density and protease content may contribute to elastosis formation in AC. In addition, changes in MC(T) distribution may favor AC malignization.

Uterine mast cells: a new hypothesis to understand how we are born

Birth is the result of complex, well-defined, and coordinated events, that are tightly regulated by endocrine, nervous, and immune responses, and take place primarily in the female reproductive tract. Various mechanisms and mediators involved in pregnancy, labor, and delivery, are highly conserved among different mammalian species and mast cells emerge as potential and crucial participants in these processes, as it is discussed in this review. (AU)

Uterine mast cells: a new hypothesis to understand how we are born

Birth is the result of complex, well-defined, and coordinated events, that are tightly regulated by endocrine, nervous, and immune responses, and take place primarily in the female reproductive tract. Various mechanisms and mediators involved in pregnancy, labor, and delivery, are highly conserved among different mammalian species and mast cells emerge as potential and crucial participants in these processes, as it is discussed in this review.

The role of protein kinase C and calcium in induction of human polymorphonuclear leukocyte IL-1 beta gene expression by GM-CSF.

At infection sites, synthesis of interleukin (IL-)1beta by polymorphonuclear leukocytes (PMNs) facilitates the recruitment of inflammatory cells and enhances the inflammatory response. We investigated the role of protein kinase C (PKC) and Ca2+ in the induction of PMN IL-1beta gene expression by GM-CSF. The PKC inhibitors chelerythrine and H7 blocked induction of IL-1beta mRNA expression in human PMNs. HA1004, an H7 analogue with little activity towards PKC, had no inhibitory effect. Similarly, H7 blocked IL-1beta transcription in nuclear run-on analysis, while HA1004 had little effect. The intracellular Ca2+ chelator BAPTA/AM inhibited induction of IL1beta mRNA accumulation and transcription by GM-CSF. At concentrations similar to those used to inhibit IL-1beta gene expression, H7, chelerythrine, and BAPTA all inhibited substrate phosphorylation by PKC isolated from PMN lysates. Thus, PKC and Ca2+ are potential targets for modulating an important PMN immunoregulatory function.