Protective Effect of Tunisian Flaxseed Oil against Bleomycin-Induced Pulmonary Fibrosis in Rats.

The aims of this study are to investigate the preventive effect of flaxseed oil (FO) on bleomycin (BLM)-induced pulmonary fibrosis (PF). Thirty adult male Wistar rats (180-220 g) were randomly divided into three groups. The control group (G1) received no treatment, the group (G2) received only intratracheally BLM, and the group (G3) received FO (2 mL/kg body weight) once a day for 60 days + BLM (4 mg/kg body weight "bw"). Our results demonstrated that FO protected against BLM-induced PF, by increasing proline, fructose, glucose, glyceride, choline, lactate, and malate metabolites in bronchoalveolar lavage fluid (Balf) which are involved in anti-inflammatory reactions. Also, FO-treatment reduced the score of fibrosis and the inflammatory index and revealed a decrease in tumor growth factor beta (TGFß) density in alveoli, inflammatory infiltrate and fibrocytes, comparatively to the BLM group. As well, our data demonstrated that acute BLM-induced fibrosis was accompanied by an oxidative stress in lung tissue as assessed by an increase of lipid peroxidation as well as antioxidant enzyme activities depletion such as superoxide dismutase (SOD) and catalase (CAT). The FO treatment reversed all disturbances of BLM-induced oxidative stress parameters, and increased fatty acids levels promoting anti-inflammatory reactions especially in erythrocytes (linoleic, α-linolenic, docosapentaenoic acids).

Hypericum Humifusum Leaves Attenuates Hepatic Ischemia-Reperfusion Injury in a Rat Model.

INTRODUCTION: Effective prevention strategies require specific actions during the different phases of ischemia-reperfusion (I-R) injury. The objective of our study is to evaluate the effect of aqueous extract of Hypericum humifusum leaves (HHL) on liver I-R model in Rat. MATERIAL AND METHODS: Animals were subjected to 90 min of hepatic ischemia followed by reperfusion (120 min). HHL extract (25 mg/mL/kg) was injected 15 min before reperfusion. To evaluate the effect of HHL extract on I-R, we have monitored transaminases levels, Malondialdehyde (MDA) concentration, histological lesions (apoptosis and necrosis) and compared the results to a reference oxidant vitamin E. RESULTS: The determination of total phenol extracts of HHL was 59.91 ± 0.35 mg of Gallic Acid/g dry plant material with higher antioxidant activity (91.73% ± 1.67) compared to vitamin E (87.42%). Using aqueous extract of HHL, we noted a significant decrease of AST and ALT [1129 UI (585/1995) and 768 UI (335/1375)] compared to no-treated group [5,585.5 UI (5,035/12,070) and 8,099.5 UI (5,040/12,326)] as a decrease in MDA content [85.7% protection (50.9/91.5)]. HHL extract reduce the damage induced by I-R of 48.7% (27/48.7) and 96.1% (95.7/96.5) for necrosis and apoptosis lesions respectively. CONCLUSION: HHL aqueous extract have potential to protect liver from the damage effect induced by I-R better than vitamin E solution.

Protective Effect of Pistacia lentiscus Oil Against Bleomycin-Induced Lung Fibrosis and Oxidative Stress in Rat.

We aimed in the present study to investigate the protective effect of Pistacia lentiscus oil against bleomycin-induced lung fibrosis as well as the involvement of oxidative stress in such protection. In this respect, adult male Wistar rats were used and divided into three groups of twenty each: control (NaCl, 0.9%), bleomycin, and bleomycin (4 mg/kg b.w.) + P. lentiscus oil (3 g/kg, b.w.). Animals were pretreated for 30 days before the induction of fibrosis by bleomycin and 1 wk after the induction of fibrosis. The oil principal compounds detected by gas chromatography analysis are: Linoleic and palmitic acids (70.6 and 24.7%, respectively). Our data demonstrated that P. lentiscus oil protected against bleomycin-induced fibrosis as evidenced by TGFß immunostaining increase in lungs fibrocytes as well as inflammatory infiltrate. We also showed that acute bleomycin-induced fibrosis was accompanied by an oxidative stress in lung tissue as assessed by an increase of lipid peroxidation as well as antioxidant enzyme activities depletion such as superoxide dismutase (SOD) and catalase (CAT). More importantly, P. lentiscus oil treatment reversed all bleomycin-induced oxidative stress parameters disturbances. In conclusion, we suggest that P. lentiscus oil had potent protective effects against bleomycin-induced fibrosis due in part to its antioxidant properties.

Effect of Pistacia lentiscus oil on experimental pulmonary fibrosis.

Background - Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by histopathological lesions in lung tissue. This is the most common and most severe idiopathic interstitial pneumonias. Current treatments are based on the combination of corticosteroids and immunosuppressants, but their effectiveness is still debated. Purpose of work - Testing the preventive effect of Pistacia Lentiscus oil, known for its antioxidant, anti-mutagenic and anti-proliferative effects, on a model of experimental lung fibrosis. Methods - Two groups of rats received an intratracheal injection of bleomycin (4.5 mg / kg). The first group, control (n = 20 rats), has received no treatment. The second group was treated with Pistacia Lentiscus oil (n = 20 rats) for 30 days before fibrosis induction, by daily gavage oil Pistacia Lentiscus oil (3,33ml / kg). This treatment was continued for 10 days. At the end of the experimental period, all rats were sacrificed and the lung tissue was examined histopathologically and immunostained for TGFß. Results - The chromatographic profile oil Pistacia Lentiscus oil shows the dominance of two fatty acids that are linoleic acid and palmitic acid representing respectively 70.57 and 24.67%. Our results also show a decrease in the distribution of TGFß both at the level of the inflammatory infiltrate and at the level of the pulmonary parenchyma histiocytes of rats treated with Pistacia Lentiscus oil compared with control rats. However, these changes are not accompanied by statistically significant changes of fibrosis score and inflammatory index. Conclusion - Our results are interesting to consider. Further studies using higher doses of Pistacia Lentiscus oil are important to conduct.

Protective effect of Ulva lactuca extract during hepatic cold preservation in rats.

Introduction In recent years, many marine resources have drew attention in the research for bio-active compounds to develop new drugs and health foods. (1) Marine algae are now considered as a rich source of antioxidants (2). It is known that seaweeds contain numerous bioactive substances that have the ability to lower cholesterol, reduce blood pressure, promote healthy digestion; and antioxidant activity (3). Natural antioxidants are interesting compounds due to their properties which help prevent oxidative stress (4), among other potentially beneficial actions. For instance, several biological effects have been attributed to flavonoids, such as anti-tumoral, anti-inflammatory, anti-ischemic and anti-aggregate plaquetary activities. These activities are believed to be in part related to the antioxidant properties of the compounds, namely in scavenging radical oxygen species (ROS). (5, 6) The cold ischemia constitute a situation of oxidative stress in touch with liberation of oxygenated radicals, these situations incited the researchers to find means for the improvement of the conservation of organs allowing to prolong the durations of the cold ischemia of certain organs (in particular the liver) with conservation of the maximum functional value. However, the constant efforts led by the teams of transplantation to develop transplants, the conservation of organs remains a problem to be resolved. (7) Conservation solution of organ appears as being a stemming to remedy the fatal effects of the ischemia-reperfusion. For our part, we think that seaweeds have not delivered their secrets and yet especially that the marine environment of the Tunisian coast still remains little exploited in spite of the big variety of the fauna and the flora of the coast. We envisage in this work, to study a sort of seaweed collected on the Tunisian quotation in the region of "Chott Meriem" (North West of Tunisia). The purpose of our work is to estimate the capacity of extracts stemming from the green seaweed Ulva lactuca to improve the conservation solution of organs against the hepatic effects of ischemia.

Animal model of liver ischemia reperfusion: biochemical and histological evaluation.

INTRODUCTION: During last years, significant progress was made in the comprehension of the hepatic lesions after Ischemia-Reperfusion episode in order to improve the Results in practice clinical. AIM: To avoid or reduce the damage induced by Ischemia-Reperfusion, we developed a model of hepatic Ischemia-Reperfusion with variable periods of reperfusion from 0 to 24 hours.  METHODS: Our study related to rats Wistar males.  Six various groups were studied: the first reference group (without neither ischemia and reperfusion), the second group with ischemia of 90 min and without reperfusion and the 3end , 4end, 5end and 6end groups in addition to ischemia, underwent a reperfusion of 30 min, 2h, 6h and 24h respectively.  The damage of hepatic Ischemia-Reperfusion was evaluated by a biochemical test based on the proportioning of transaminases and an anatomopathologic study by optical microscopy for the determination of the degree of hepatic attack.  RESULTS: The RESULTS obtained seem to show an aggravation of the liver lesions and an increase in the plasmatic rates of AST and ALT in relation with the duration of the reperfusion.  Indeed, the maximum of damage was observed after 2 hours of reperfusion. We observed a reduction in the lesions after 6h and 24h of reperfusion.  CONCLUSION: Our work enabled us to describe a simple model of hepatic Ischemia-Reperfusion with functional, biochemical and anatomopathologic tests.

Positive link between variant Toll-like receptor 4 (Asp299Gly and Thr399Ile) and colorectal cancer patients with advanced stage and lymph node metastasis.

Toll-like receptors (TLRs) are considered as major endotoxin-signaling receptor and as crucial sensors of innate immunity. TLRs recognize pathogen-associated molecular patterns; induce effectors genes involving inflammatory cytokines and therefore initiation of adaptative immune responses against pathogens. Recently, it has been shown that TLRs are involved in tumor progression. In fact, increased level of TLR4 is associated with progression of colon malignancies. Even, TLR4 polymorphism has been shown associated with susceptibility to have colorectal cancer. Our study aimed to investigate an association between TLR4 Asp299Gly (D299G) and Thr399Ile (T399I) polymorphisms in Tunisian patients with colorectal cancer. Using a primer extension method (SNaPshot), we genotyped two variants of TLR4 D299G and T399I in 100 patients with colorectal cancer and 140 healthy controls in Tunisian population. Interesting, we noted a significant association between T399I polymorphism and tumor differentiation (p = 0.027) and tumor architecture (p = 0.02) in colorectal cancer (CRC) patients. We also showed a significant association of D299G with an increased risk of advanced stage (p = 0.03). Finally, we observed a positive link between D299G and T399I polymorphisms and CRC patients with lymph node (p = 0.00024; p = 0.0005, respectively) and metastasis (p = 0.001; p = 0.002, respectively). However, we found no evidence to support a significant association between TLR4 D299G and T399I polymorphisms and colorectal cancer susceptibility. Our findings suggest that TLR4 D299G and T399I polymorphisms are significantly associated with clinical features variables. TLR4 polymorphisms may serve as biomarker of disease progression. Therefore, our results need confirmation in even larger studies.

Significant association between interleukin-17A polymorphism and colorectal cancer.

Interleukin (IL) 17A is an inflammatory cytokine expressed by Th 17 cells and plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We have investigated the association between colorectal cancer and polymorphisms of IL17A (rs2275913. G197A). The study was performed in 241 subjects (102 with colorectal cancer and 139 healthy controls). Genotypes were determined by fluorescent-based restriction fragment length polymorphism method. The association between the molecular features at the gene in relation to tumor and patient clinical characteristics was analyzed. There was a significant difference between the genotype frequencies of IL17A G197A of control subjects (GG 68.34 % and GA + AA 31.65 %) and patients with colorectal cancer (GG 47.05 % and GA + AA 52.94 %) (p = 0.001 with odds ratio (OR) 2.45 (1.43-4.11)). IL17A G197A polymorphism is particularly associated with colon cancer. Indeed, the IL17A GG genotype could be considered as a protective factor against colon cancer (p = 0.00001) with OR 3.77 (2.04-6.99). We have noted a significant association of IL17A G197A polymorphism not only with tumor localization (p = 0.003) but also with tumor differentiation (p = 0.0005) in CRC patients. We have also showed a significant association of G197A variant with an increased risk of advanced stage (p = 0.005). Our result suggests that the A allele of IL17A gene is involved in susceptibility to colorectal cancer and is associated with clinical features as tumor location, tumor differentiation, and TNM stage. IL17A polymorphism may serve as biomarker of disease location and progression.

TP53 mutations in colorectal cancer from Tunisia: relationships with site of tumor origin, microsatellite instability and KRAS mutations.

Loss of TP53 function through gene mutation is a critical event in the development and progression of colorectal cancer (CRC). Here we examined 51 primary CRC tumors from Tunisia for mutations in TP53 exons 4-9 using PCR-direct sequencing. TP53 status and mutation site/type were than correlated with nuclear protein accumulation, familial and clinicopathologic variables and data on KRAS mutations and microsatellite instability (MSI-H). The TP53 mutation analysis was possible in the tumor of 47 patients and a deleterious somatic mutation has been detected in 59.6% of the patients (28/47) including 20 (71.4%) missense mutations, 7 nonsense mutations (25%) and 1 (3.6%) frameshift mutation. 89.3% (25/28) of the detected mutations were in exons 5-8, whereas 10.7% (3/28) were in exon 4. Among the 27 non frameshift mutations, 89% (24/27) were transitions and 11% (3/27) were transversions. 64.3% (18/27) of the altered amino acids corresponded to arginine. 74% (20/27) were G>C to A>T transitions, and more than half (14/27) occur at hotspots codons with CpG sites. TP53 mutations correlated closely with TP53 accumulation (p = 0.0090) and inversely with MSI phenotype (p = 0.0658). A KRAS somatic mutation was identified in 25% (7/28) of the TP53 mutated tumors. All these mutations were G>A transitions in codon 12 and all the tumors with combined alterations but one were distally located and MSS. In conclusion, frequency and types of TP53 mutations and correlations with TP53 protein accumulation, and MSI were as reported for non-Tunisian patients. However, no significant associations have been detected between TP53 mutations and clinicopathological data in Tunisian patients as previously reported.

[Immunohistochemical analysis of mismatch repair proteins in colorectal adenomas]. / Analyse immunohistochimique des protéins de réparation de I'ADN dans les adénomes colorectaux.

BACKGROUND: The deficiency of mismatch repair system is one of the main pathways in colorectal cancer. This system consists mainly of four proteins: MLH1, MSH2, MSH6 and PMS2. Colorectal cancer develops in the majority of cases from precancerous lesions called adenomas. Only few studies have reported on the deficiencies of these proteins in adenomas. AIM: In this study we used immunohistochemistry staining in colorectal adenomas to assay functional status of MLH1, MSH2, MSH6, and PMS2 proteins. METHODS: 102 adenomas from 93 patients were collected in our institution during six years (2007-2012). The immunohistochemical technique was performed with 4 antibodies: MLH1, MSH2, MSH6 and PMS2. The loss of expression was retained if adenomatous cells were not stained with positive internal control. Staining was considered as abnormal if nucleus of adenomatous cells showed low nuclear staining and / or heterogeneous one, while positive internal control had normal staining. RESULTS: Loss of expression of MSH2 and MSH6 in adenomatous cells was found in only 1 case which was a tubular adenoma 3mm high-grade dysplasia. Abnormal staining of the adenomatous cells was noted in 23 cases (22.5%) for MSH2 and in 8 cases (7.8%) for MSH6. No cases showed loss of expression of MLH1 and PMS2. Abnormal expression of MSH2 and MSH6 was not correlated with sex of patients, the location of the adenoma, its grade of dysplasia and its histological type. CONCLUSIONS: Loss of Mismatch repair proteins expression is a rare event in adenomas. However, the abnormal expression levels are higher in our study compared to those reported in the literature. This could reflect a higher rate of microsatellite instability in our patients. Multicenter and larger studies with molecular biology techniques are needed.

KRAS mutations in colorectal cancer from Tunisia: relationships with clinicopathologic variables and data on TP53 mutations and microsatellite instability.

Mutations in KRAS gene are among the critical transforming alterations occurring during CRC tumorigenesis. Here we screened 51 primary CRC tumors from Tunisia for mutations in KRAS (codons 12 and 13) using PCR-direct sequencing. Our aim was to analyze tumor mutation frequencies and spectra in Tunisian patients with CRC. KRAS status and mutation site/type were than correlated with familial and clinicopathologic variables and data on TP53 mutations and nuclear protein accumulation and microsatellite instability (MSI). A KRAS somatic mutation has been detected in the CRC tumor of 31.5 % (16/51) of the patients. 81.2 % had a single mutation at codon 12 and 23 % had a single mutation at codon 13. The most common single mutation (50 %) was a G>A transition in codon 12 (c.35G>A; p.Gly12Asp). 81.25 % of the KRAS mutations were transitions and 23 % were transversions. All the mutations in codon 13 were a c.38G>A transition, whereas both G>A transitions and G>T and G>C transversions were found in codon 12. The mutation spectrum was different between MSS and MSI-H tumors and more varied mutations have been detected in MSS tumors. Some amino acid changes were detected only in MSS tumors, i.e. p.Gly12Ser, p.Gly12Cys and p.Gly12Ala. Whereas, the KRAS mutation p.Gly13Asp have been detected only in MSI-H. 43.75 % of the patients harboured combined mutations in KRAS and TP53 genes and the tumor of 71.42 % of them showed TP53 overexpression. In conclusion, the frequency and types of KRAS mutations were as reported for non-Tunisian patients. However, no significant associations have been detected between KRAS mutations and clinicopathologic variables and MSI in Tunisian patients as previously reported.

Prognostic value of tumor-associated macrophages count in human non-muscle-invasive bladder cancer treated by BCG immunotherapy.

PURPOSE: Tumor-associated macrophages can regulate the growth of various cancers positively or negatively. Intravesical bacillus Calmette-Guerin instillation is now the gold standard treatment for bladder carcinoma in situ. The authors investigated the correlation between tumor-associated macrophages infiltrating bladder carcinoma in situ and the response to intravesical bacillus Calmette-Guerin therapy. MATERIALS AND METHODS: The authors examined paraffin-embedded tissues from 41 patients with bladder carcinoma in situ who received intravesical bacillus Calmette-Guerin therapy. Tumor-associated macrophages were immunohistochemically stained by anti-CD68 monoclonal antibody. RESULTS: The median number of tumor-associated macrophages infiltrating among cancer cells and the number in the lamina propria were 4 and 24, respectively. Recurrent carcinoma in situ was found in 4.8% of cases with a lower cancer cell tumor-associated macrophage count but in 47.6% of those with a higher cancer cell tumor-associated macrophage count (less than 4 vs. 4 or greater). Recurrence was found in 31.8% of patients with a lower lamina propria tumor-associated macrophage count but in 21.1% of those with a higher lamina propria tumor-associated macrophage count (less than 25 vs. 25 or greater). The median ratio of tumor-associated macrophages among cancer cells vs. in the lamina propria was 0.2. Recurrence-free survival was significantly better in patients with a lower cancer cell tumor-associated macrophage count (p = .0002). Those with a lower cancer cell-to-lamina propria tumor-associated macrophage ratio had a higher recurrence-free rate (p < .0001). Multivariate analysis revealed that the cancer cell tumor-associated macrophage count and the cancer cell-to-lamina propria tumor-associated macrophage ratio can be prognostic factors for bladder carcinoma in situ. CONCLUSIONS: The count of tumor-associated macrophages infiltrating the cancer area is useful for predicting the response of bladder carcinoma in situ to intravesical bacillus Calmette-Guerin instillation before treatment initiation. Although on univariate analysis TAMs are associated with other poor prognosticators, on multivariate analysis, TAMs appear only to be associated with MI and VI. TAMs may play a significant role in the biology of tumor progression of endometrial adenocarcinoma, but do not appear to be independent prognostic indicators of patient's survival.

Impact of smoking intensity on outcomes of patients with non muscle invasive bladder cancer treated by BCG immunotherapy.

BACKGROUND: Cigarette smoking is a well-known risk factor of bladder carcinogenesis. The clinical impact of smoking on bladder cancer recurrence and response to BCG immunotherapy remains unclear. We sought to investigate the effect of smoking intensity on bladder cancer response to BCG therapy, and the interactions between smoking and clinicopathological factors on bladder cancer recurrence. METHODS: Clinical information was obtained from 81 smokers patients (smokers at diagnosis) with NMIBC treated with transurethral resection of the bladder tumor followed by BCG immunotherapy. The distribution of smoking intensity on patient age (≥60 years or <60 years), gender, tumor grade, tumor stage, carcinoma in situ, multiplicity and tumor size was assessed. The effect of cigarette smoking on cancer recurrence was estimated using Cox proportional hazard models and Kaplan-Meier analysis. RESULTS: The results showed that smoking intensity was significantly associated with response to BCG immunotherapy (p = 0.010). Univariate Cox regression analysis of clinicopathologic characteristics showed that PT1 stage, tumor size more than 3 cm and smoking intensity significantly increased the risk of recurrence (respectively, p = 0.006; p = 0.008 and p = 0.012). These results were confirmed by Kaplan-Meier survival curves. In addition, multivariate analysis using Cox regression selected the model involving stage, tumor size and smoking intensity as the quasi-independent predictor of recurrence. CONCLUSION: These findings suggest that cigarette smoking is an independent predictor for patients with NMIBC. Although the current evidence supports a positive link between smoking intensity and the risk of recurrence on NMIBC treated by BCG immunotherapy, additional studies, are needed before definitive conclusions can be drawn.

Prognostic value of Pheochromocytoma of the Adrenal Gland Scaled Score (Pass score) tests to separate benign from malignant neoplasms.

BACKGROUND: Differentiating malignant from benign pheochromocytoma has been challenging when based on histologic features. This is due to the definition of malignant pheochromocytoma which are defined by the presence of metastases. A PASS score was developed and according to many authors, a PASS score> =4 identified potentially malignant tumors. AIM: To assess the prognostic value of PASS score in differentiating benign pheochromocytomas from malignant ones. METHODS: The records of 11 patients with tumors diagnosed as "pheochromocytoma" were identified from 1970 to 2010 in the files of the pathology, intern medicine and biochemistry departments of the Charles Nicolle hospital and Pasteur Institute. Receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic performance of PASS. The logistic model was developed using the 11 predictive variables. Its performance was evaluated by calculating the area under the ROC curve and comparing it with that of the PASS. RESULTS: In benign tumors, The PASS score was <4 in 3 cases and >=4 in 6 cases. In malignant tumors, the PASS score was >=4 in both cases. According to the ROC curve analysis, a PASS equal or superior to 4 identifies malignant pheochromocytoma with a sensitivity of 50% and a specificity of 45%. CONCLUSION: I think that PASS score, despite its low sensitivity, may help to reserve the more aggressive treatment and narrow follow up for potentially malignant tumors. Widespread of this called score with complete clinical data will help to validate these findings and to add other prognostic factors of value that could be a part of this scaled score such as immunohistochemical findings.

Impaired control of effector T cells by regulatory T cells: a clue to loss of oral tolerance and autoimmunity in celiac disease?

OBJECTIVES: Regulatory T cells (Tregs) are instrumental for tolerance to self-antigens and dietary proteins. We have previously shown that interleukin (IL)-15, a cytokine overexpressed in the intestine of patients with celiac disease (CD), does not impair the generation of functional Tregs but renders human T cells resistant to Treg suppression. Treg numbers and responses of intestinal and peripheral T lymphocytes to suppression by Tregs were therefore compared in CD patients and controls. METHODS: Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) were isolated from duodenal biopsy specimens of CD patients and controls. Concomitantly, CD4+CD25+ T lymphocytes (Tregs) were purified from blood. Responses of IELs and of LPLs, and peripheral lymphocytes (PBLs) to suppression by Tregs were tested by analyzing anti-CD3-induced proliferation and interferon (IFN)-γ production in the presence or absence of peripheral Tregs. Lamina propria and peripheral CD4+CD25+FOXP3+ T cells were assessed by flow cytometry. RESULTS: Although percentages of CD4+CD25+FOXP3+ LPLs were significantly increased in patients with active CD, proliferation and IFN-γ production of intestinal T lymphocytes were significantly less inhibited by autologous or heterologous Tregs in CD patients than in controls (P < 0.01). In all tested CD patients, IEL were unable to respond to Tregs. Resistance of LPLs and PBLs to Treg suppression was observed in patients with villous atrophy who had significantly enhanced serum levels of IL-15 compared with patients without villous atrophy and controls. CONCLUSIONS: Our results indicate that effector T lymphocytes from active CD become resistant to suppression by Tregs. This resistance might cause loss of tolerance to gluten, but also to self-antigens.

Prognostic value of Bcl-2 and Bax tumor cell expression in patients with non muscle-invasive bladder cancer receiving bacillus Calmette-Guerin immunotherapy.

Apoptosis is the distinctive form of programmed cell death that complements cell proliferation in maintaining normal tissue homeostasis. The significance of constitutive apoptosis in the recurrence of Non Muscle Invasive Bladder Cancer has yet to be investigated. The aim of this study is to investigate the prognostic significance of Bax and Bcl-2 in terms of recurrence after BCG immunotherapy. Immunohistochemical analysis was performed on frozen biopsies to evaluate bcl-2 and Bax proteins expression in 28 cases of NMIBC. All patients with confirmed NMIBC were treated with intravesical BCG-immunotherapy. The follow up was performed for 26 months. The correlation between clinicopathological, immunohistochemical data and the response to BCG therapy was performed. Univariate analysis showed that, PT1 stage, High grade and Bax expression increased significantly the risk of recurrence (P = 0.015, P = 0.015 and P= 0.034 respectively). In addition, multivariate analysis selected the model involving stage, age, Bax and Bcl-2 expression as the best independent variables of recurrence. In conclusion, the expression of Bcl-2 and Bax in NMIBC could have a prognostic value in assessing the risk of recurrence after BCG immunotherapy. These findings require further investigations on larger cohort in order to ascertain new molecular markers of the response to BCG immunotherapy.

[Is there a link between the occurrence of Kidney cancer and hypertension in Tunisian population?]. / l'hypertendion artérielle facteur de prédisposition au cancer de rein dans la population tunisienne.

BACKGROUND: Kidney cancer is generally asymptomatic and discovered incidentally at a late stage, which is a negative diagnosis because in most cases the disease is incurable at this stage. Some predisposing factors have been revealed by studies such high blood pressure, which is a frequent among the Tunisian population. AIM: A study among the Tunisian population to determine if there is a link between the occurrence of kidney cancer and the hypertension. METHODS: Our work was conducted on 91 patients with confirmed renal cell carcinoma and 91 healthy subjects who consulted the Urology Department at the Charles Nicolle Hospital in Tunis. The study of clinical records has identified the clinical, pathological and therapeutic features of the 182 patients. RESULTS: 59% of individuals with hypertension have developed kidney cancer with a significant p-value equal to 0.03. The more the value of blood pressure increases the more the risk is (p = 0.03). Smoking in combination with hypertension is a factor favoring the occurrence of cancer with a value of p equal to 0.05. CONCLUSION: In the Tunisian population hypertension is a risk factor for developing kidney cancer, a factor compounded by the high incidence of this disease. What prompts us to make explorations of kidney lodges of hypertensive patients.

Lynch syndrome in Tunisia: first description of clinical features and germline mutations.

PURPOSE: High rates of early colorectal cancers (CRC) are observed in Tunisia suggesting genetic susceptibility. Nevertheless, up to now, no molecular study has been performed in the Tunisian population. In our research, we evaluated the clinical characteristics of Tunisian families suspected of Lynch syndrome and the contribution of DNA mismatch repair (MMR) genes. METHODS: Thirty-one unrelated families suspected of Lynch syndrome were studied. Probands were tested for the presence of germline mutations in the MMR genes MLH1, MSH2, MSH6 and in MUTYH. Available tumours were analysed for microsatellite instability and expression of MMR proteins. Detailed family and medical histories were collected. RESULTS: A total of 134 cancers were noted in the 31 families, the most frequent type of cancer corresponding to CRC (69%), followed by uterine cancer (7.5%). Germline mutations were identified in 11 (35.5%) families (six MSH2, five MLH1, including seven novel mutations), seven of which fulfilled the Amsterdam criteria (sensitivity, 63.6%; positive predictive value, 58.3%). Noteworthy, germline mutations were detected in 52.6% of male patients tested, but in only 8.3% of females (p = 0.02). Moreover, CRC were essentially left sided in families without detected mutation (p = 0.017). Ages of onset of cancers and tumour spectrum were very similar in families with or without MMR germline mutation, contrasting with previous studies performed in other populations. CONCLUSIONS: MMR genes contribute significantly to CRC susceptibility in the Tunisian population. However, the cause of early CRC susceptibility remains unknown in most cases, especially in women and in patients with early left colon or rectal cancer.

Giant trichoblastoma of the scalp.

BACKGROUND: Trichoblastoma is a rare and benign adnexial tumor with characteristic histological features. It occurs on any hair folliclebearing location, and usually presents as a solitary lesion most often less than 2 cm in size. Giant trichoblastoma has been rarely reported in the literature. AIM: To report a new case of giant trichoblastoma, misleading for malignancy. CASE REPORT: A 57-year-old woman presented with a 5 cm-solitary asymptomatic nodular lesion of the scalp, of 28 years. It had been previously excised with recurrence and progressive regrowth. On examination, it was a dome-shaped, erythematous, firm, papillomatous, non infiltrated nodule. Full body work up revealed no metastases. Cutaneous biopsy concluded to trichoblastoma but failed to eliminate malignancy. After excision with secondary skin graft, histological examination confirmed the benignity with clear margins. There was no evidence of recurrence after a 5 year-follow-up period. CONCLUSION: This case illustrates a rare clinical variant of trichoblastoma with an unusual important size. This can be misleading for malignancy, but the slowly progressive course of the tumour in our patient, together with histological benignity led to the correct diagnosis. This tumour is considered as a distinct entity by some authors.