N-myc downstream-regulated gene 1 can promote vasculogenic mimicry and angiogenesis in urothelial carcinoma.

Urothelial carcinoma (UC) of the bladder is a common cause of cancer-related death worldwide. Vasculogenic mimicry (VM) is a process by which the malignant cells can generate vascular-like structures formed of periodic acid-Schiff (PAS) positive/CD31 negative extracellular matrix independent of angiogenesis and thus promotes tumor progression. N-myc downstream-regulated gene 1 (NDRG1) is a protein that can modulate tumor angiogenesis; however, its role in regulating tumor angiogenesis and VM formation has not been previously investigated in UC. This study aims to evaluate the role of intra-tumor microvessel density (MVD) (as a surrogate measure of angiogenesis), VM, and NDRG1 in UC and their correlation with different clinicopathologic features, then assess the correlation between them in UC. Sixty specimens of UC of the bladder were included. PAS-CD31 immunohistochemical double staining method was used to evaluate the intra-tumor MVD and VM. Immunohistochemical expression of NDRG1 was also examined. VM and NDRG1 expression were detected in 41.7% and 83.3% of UC specimens respectively. The mean of intra-tumor MVD, VM area, and NDRG1 was significantly higher in tumors with higher grade, lymphovascular invasion, and higher T stage. NDRG1 expression was positively correlated with MVD and VM. We can suggest that MVD, VM, and NDRG1 may serve as poor prognostic markers for UC. The positive correlation between NDRG1 and both MVD and VM may provide the first evidence that NDRG1 can induce tumor angiogenesis and VM in UC which may offer a novel pathway for further therapeutic strategies.

Adipose tissue-derived mesenchymal stem cells reduce endometriosis cellular proliferation through their anti-inflammatory effects.

OBJECTIVE: Endometriosis is a chronic debilitating inflammatory condition characterized by the presence of endometrial tissues outside the uterine cavity. Pelvic soreness and infertility are the usual association. Due to the poor effectiveness of the hormone therapy and the high incidence of recurrence following surgical excision, there is no single effective option for management of endometriosis. Mesenchymal stem cells (MSCs) are multipotent stromal cells studied for their broad immunoregulatory and anti-inflammatory properties; however, their efficiency in endometriosis cases is still a controversial issue. Our study aim was to evaluate whether adipose tissue-derived MSCs (AD-MSCs) could help with endometriosis through their studied anti-inflammatory role. METHODS: Female Wistar rats weighting 180 to 250 g were randomly divided into two groups: group 1, endometriosis group; established by transplanting autologous uterine tissue into rats' peritoneal cavities and group 2, stem cell treated group; treated with AD-MSCs on the 5th day after induction of endometriosis. The proliferative activity of the endometriosis lesions was evaluated through Ki67 staining. Quantitative estimation of interferon γ, tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, IL-10, and transforming growth factor ß expression, as well as immunohistochemical detection of CD68 positive macrophages, were used to assess the inflammatory status. RESULTS: The size and proliferative activity of endometriosis lesions were significantly reduced in the stem cell treated group. Stem cells efficiently mitigated endometriosis associated chronic inflammatory reactions estimated through reduction of CD68 positive macrophages and the expression of the proinflammatory cytokines. CONCLUSION: Stem cell therapy can be considered a novel remedy in endometriosis possibly through its anti-inflammatory and antiproliferative properties.

Association of Hirschsprung's disease with anorectal malformations: the early alarming signs for diagnosis and comorbidity related to this association.

BACKGROUND AND AIM: The association of Hirschsprung's disease (HD) and anorectal malformation (ARM) is rare. The aim of this study is to highlight the frequency of this rare association and comorbidity that may be related to this association. PATIENTS AND METHODS: Eleven cases out of four hundred forty six cases (2.5%) with ARM found to have HD association presented to Assiut University Children Hospital. All cases were diagnosed by complete clinical, radiological assessment and histopathological examination before correction. The evaluating parameters for those patients were the early warning signs for diagnosis, any unnecessary procedures done and any associated morbidity related to misdiagnosis of this association. RESULTS: Age at presentation of these eleven cases ranged from 2 days to 10 years. The diagnosis started early during neonatal period only in four cases either by change of bowel caliber or nonfunctioning stoma. In the remaining seven cases the diagnosis was delayed because of unsuspected association. Fecal fistula after closure of stoma and wound dehiscence followed by incisional hernia is evident associated comorbidity. CONCLUSIONS: The incidence of HD in ARM population seems to be more common than its incidence in the general pediatric population. Caliber change of the bowel during the first operation or nonfunctioning stoma is early alarming sign for diagnoses of such association and should direct the attention for stomal biopsy.

A Simple Immunohistochemical Panel Could Predict and Correlate to Clinicopathologic and Molecular Subgroups of Urinary Bladder Urothelial Carcinoma.

BACKGROUND: Although gene expression profiling provided a comprehensive molecular characterization of different subtypes of bladder urothelial carcinoma (UC), which are distinct in their biological features and prognosis, such a system is not yet applicable for routine clinical practice. This study aimed to examine the expression of these molecular classes of UC using simple panel of immunohistochemical markers. MATERIALS AND METHODS: Tissue sections from 192 specimens of UC were stained with FGFR3, CK5, CCNB1, HER-2, and P53. The molecular classes identified were correlated with clinicopathologic characteristics and patient survival. RESULTS: The most frequent class in our cohort was urobasal B (UroB) (44.1%), followed by squamous cell carcinoma-like (SCCL) (22%), genomically unstable (GU) (20.3%), and urobasal A (UroA) (13.6%). Patients with SCCL were significantly younger (P < .0001). Both the SCCL and GU types were of significantly higher histopathologic grade (P < .0001). UroA tumors were mainly of the T1 stage (75%), whereas 61.5% of the SCCL and 58.3% of the GU types were of stage T2 (P < .001). Prognosis was significantly different among groups. The SCCL class showed the lowest overall survival (38.5%; P = .030) and metastasis-free survival (69.2%; P = .017). The best prognosis was for UroA, with an overall survival of 75% and no metastatic events. CONCLUSION: The distribution of UC subtypes in our study was uniquely different from other studies. This simple immunohistochemical panel could be suggested as a clinically applicable tool that has the potential to be used routinely in guiding individualized treatment of UC.

Protective effect of the standardized leaf extract of Ginkgo biloba (EGb761) against hypertension-induced renal injury in rats.

BACKGROUND: Ginkgo biloba leaves extract has been widely used worldwide to protect against oxidative stress-induced cell damage and improves blood circulation. METHODS: The potential protective role of the standardized leaf extract of Ginkgo biloba (EGb761) on hypertension-induced renal injury was investigated in rats. Hypertension was induced in rats by L-NAME. RESULT: Repeated treatment with EGb761 produced progressive reductions in the systolic, diastolic and mean arterial blood pressure. Also, EGb761 increased the progressive reductions in blood pressure induced by losartan. Hypertension-induced marked elevation of renal malondialdehyde (MDA) and nitrite levels and reduction of reduced glutathione (GSH) level were inhibited by EGb761. In addition, hypertension-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß)) levels in renal tissues were inhibited by EGb761. Also, treatment with EGb761 inhibited hypertension-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1B in the kidney tissues. EGb761 enhanced losartan effects on renal tissues oxidative stress, nitrite, and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1B. effects. CONCLUSIONS: These results indicate that EGb761 has the ability to protect against hypertension-induced renal injury.

Stem Cell Markers Describe a Transition From Somatic to Pluripotent Cell States in a Rat Model of Endometriosis.

OBJECTIVE: To study Thy1 as a fibroblast marker, SSEA1 as a marker of intermediate pluripotency, and Oct4 as a marker of established pluripotency in rat model of endometriosis. DESIGN: In vivo animal study. MATERIALS AND METHODS: Endometriosis was induced in 20 albino female rats through autologous transplantation of one uterine horn to mesentery of intestine. Other 20 rats had their horn removed without transplantation (controls). Rats were sacrificed 4 weeks after induction surgery. Ectopic, eutopic, and control endometria were harvested from endometriosis and control animals respectively. Quantitative syber green based RT-PCR was used to detect expression of Thy-1 (CD90), FUT4 (SSEA1), and POU5F1 (Oct4) genes in tissues. Relative expression was normalized to that of ß actin. Thy1, SSEA1, and Oct4 protein expression were detected by immunohistochemistry. RESULTS: Ectopic endometrium expressed significantly higher mRNA of Oct4 and SSEA1 as compared to control endometrium. Expression levels of Oct4 and SSEA1 were comparable between ectopic and eutopic endometria and between eutopic and control endometria. Thy1 (CD90) gene expression level was comparable among ectopic, eutopic, and control endometria. Oct4 immunoscore were significantly higher in ectopic (6.6±0.91) than eutopic (2.5±0.78) or control endometrium (3.7±0.1) (P value 0.02). Thy1 and SSEA1 immunoscores were comparable among all three types of endometria. CONCLUSIONS: Using rat model of endometriosis, ectopic endometrium showed significantly higher Oct4, and SSEA1, but similar Thy1 gene expression to that of control endometrium. This indicates increased transition from somatic to pluripotent cell states in ectopic endometrium which may play a role in endometriosis pathogenesis.

A putative Chondroprotective role for IL-1ß and MPO in herbal treatment of experimental osteoarthritis.

BACKGROUND: Herbal treatment may have a chondroprotective and therapeutic effect on Osteoarthritis (OA). We investigated the mechanism of action of ginger and curcumin rhizomes cultivated in Egypt in treatment of OA in rat model. METHODS: Thirty-five albino rats were intra-articularly injected with Monosodium Iodoacetate in the knee joint. Ginger and curcumin was orally administered at doses of 200 and 400 mg/kg (F200 and F400). Serum levels of cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), malondialdehyde (MDA), myeloperoxidase (MPO), Interleukin-1 beta (IL-1ß) and superoxide dismutase activity (SOD) were measured using ELISA. The composition of the herbal formula hydro-ethanolic extract was characterized using UPLC-ESI-MS. Histopathological changes in injected joints was examined using routine histopathology. Statistical analysis was performed using one-way ANOVA. RESULTS: Serum levels of COMP, HA, MPO, MDA, and IL-1ß were significantly decreased in F 200, F 400 and V groups when compared to OA group (P value <0.0001). On the other hand SOD levels were significantly elevated in treated groups compared to OA groups (P value <0.0001). CONCLUSIONS: The ginger/curcumin at 1:1 had chondroprotective effect via anti-inflammatory and antioxidant effect in rat OA model. Further pharmacological and clinical studies are needed to evaluate this effect.

Protective effect of the standardized extract of ginkgo biloba (EGb761) against hypertension with hypercholesterolemia-induced renal injury in rats: Insights in the underlying mechanisms.

The potential protective role of the standardized leaf extract of ginkgo biloba (EGb761) on hypertension with hypercholesterolemia-induced renal injury was investigated in rats. Hypertension was induced by L-N(G)-nitroarginine methyl ester (L-NAME) and hypercholesterolemia was induced by feeding rats with a diet containing 1% cholesterol. In these animals repeated treatment with EGb761 produced a progressive reduction in the systolic, diastolic and mean arterial blood pressure (BP). EGb761 increased the progressive reduction in the systolic, diastolic and mean arterial BP induced by repeated administration of losartan with simvastatin. EGb761 corrected the compromised serum lipid profile and enhanced the effect of losartan with simvastatin on lipid profile. EGb761 protected against hypertension with hypercholesterolemia-induced renal injury as assessed by measurement of serum renal function markers and by histopathological examination. EGb761 enhanced the renoprotective effect of losartan with simvastatin in these rats. Concomitantly, hypertension with hypercholesterolemia-induced elevation of renal tissue malondialdehyde (MDA) and nitrite levels and reduction of intracellular reduced glutathione (GSH) level were inhibited by repeated treatment with EGb761. In addition, hypertension with hypercholesterolemia-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) levels in renal tissues were inhibited by treatment with EGb761. Also, EGb761 inhibited hypertension with hypercholesterolemia-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1ß in the kidney tissues. Losartan with simvastatin produced similar effects on renal tissues oxidative stress, nitrite and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1ß. EGb761 enhanced losartan with simvastatin effects. These results indicate that EGb761 has the ability to protect against hypertension with hypercholesterolemia-induced renal injury. The ability of EGb761 to provide this renoprotective effect may positively correlate, besides its antihypertensive and antihypercholesterolemic effects, to its ability to suppress renal oxidative stress, nitrosative stress and inflammation.

Suppression of transforming growth factor-beta1 expression in keloids after cryosurgery.

The biological mechanism underlying cryosurgical treatment of keloids remains unclear. Transforming growth factor-beta1 (TGF-ß1) has been implicated in the pathogenesis of keloids and was reported to be the target of several therapeutic modalities. However, the effect of cryosurgery on its expression in keloid tissue has not been yet investigated. In this study, 26 consecutive keloid patients were treated with cryosurgery for 2-6 sessions. Keloids were biopsied before starting cryosurgery and after two treatment sessions for the immunohistochemical evaluation of TGF-ß1 expression. The average volume reduction, after two treatment sessions (in 22 patients completing the study) was 68.77 ± 15.82%. Dermal overexpression of TGF-ß1 was demonstrated in all keloid specimens before treatment. Following therapy, significant reduction of that expression was detected in all keloid specimens (P = 0.016). In addition to attesting the clinical efficacy of cryosurgery, our findings indicate that cryosurgery effectively suppressed TGF-ß1 expression, possibly contributing to keloid regression.

IL-10 and TGF-ß: Roles in chondroprotective effects of Glucosamine in experimental Osteoarthritis?

OBJECTIVE: Osteoarthritis (OA) is a complex disease of the whole joint. Glucosamine (GlcN) treatment may have a chondroprotective effect on OA. We investigated the mechanism of action of glucosamine treatment through interleukin-10 (Il-10) and transforming growth factor ß-1 (TGF ß-1). METHODS: Thirty male albino rats were used. A single intraarticular (i.a.) injection of 2mg of Monosodium Iodoacetate (MIA) was injected into the knee joint of anesthetized rats. GlcN (50 or 100mg/kg/day, p.o. for 2 month) was administered orally. Serum levels of Il-10 and TGF-ß1 were determined by ELISA. Histopathological changes in treated and control joints were examined using hematoxylin-eosin (H & E) staining. RESULTS: The mean serum level of IL-10 significantly decreased in the OA group compared to control group (P value<0.0001). On the other hand, mean serum level of IL-10 significantly increased in GlcN treated groups when compared to the OA group (P value<0.0001). Serum level of TGF ß-1 was significantly elevated in OA group compared to control group (P value<0.0001). On the other hand, the mean serum level of TGF ß-1 was significantly decreased in the GlcN treated groups when compared to the OA group (P value<0.0001). Histopathological evaluation of GlcN treated groups showed different grades of healing, according to Osteoarthritis Research Society International (OARSI) grading system. CONCLUSION: Our results showed that IL-10 and TGF-ß1 possibly mediate GlcN chondroprotective effects in OA. Both serum biomarkers can be useful in the follow-up of articular cartilage damage in clinical settings.

Demographic features and prevalence of myocarditis in patients undergoing transarterial endomyocardial biopsy for unexplained cardiomyopathy.

BACKGROUND: The diagnosis of myocarditis is still a challenge. The true incidence of the disease is unknown due to great variation in clinical manifestations. OBJECTIVE: The aim of this study was to identify the demographic features and in-hospital prevalence of myocarditis in patients undergoing transarterial endomyocardial biopsy (EMB) for unexplained cardiomyopathy. PATIENTS AND METHODS: This was a prospective observational study. We recruited all patients with unexplained cardiomyopathy presented at Assiut University Hospital from January 2014 till December 2014. The inclusion criteria were namely acute symptoms of heart failure, worsening of ejection fraction (EF) despite optimized therapy, hemodynamically significant arrhythmias, heart failure with concurrent rash, fever, or peripheral eosinophilia and new-onset cardiomyopathy in the presence of known amyloidosis. We excluded patients with uncontrolled hypertension, diabetes mellitus, ischemic, congenital, rheumatic heart disease, peripartum cardiomyopathy, cardiotoxic exposure, alcoholic and familial cardiomyopathies. All patients were subjected to full examination with ECG, echocardiography and coronary angiography, and then 3 EMB samples via femoral artery were taken from the LV. The histopathological examination of all biopsies was done. RESULTS: Out of the 1100 patients admitted to our department, 15 patients (1.4%), who had unexplained cardiomyopathy were included in our study. Seventy-three percent were males with mean age 37.8 ± 17 y. 87% were from rural areas, and 73.3% presented with dyspnea grade III to IV for a duration period that varied from 2 to 8 weeks. 33% had an EF > 40%. 33 EMB samples from 11 patients were examined. 7 out of 11 patients (63.6%) proved to have myocarditis on pathological examination, 5 of them had active myocarditis, 1 had chronic myocarditis and 1 had borderline myocarditis. Three patients (27.3%) had no pathological evidence of inflammation and one patient (9.1%) had cardiac amyloidosis. Four out of 15 patients (26.7%) did not undergo EMB because of LV thrombus or bleeding tendency. None of our patients had any complication from EMB. CONCLUSION: The in-hospital prevalence of myocarditis is high among patients with unexplained cardiomyopathy. EMB via femoral artery is safe and essential in confirming the diagnosis.

Glypican-3 and Melanoma Antigen Genes 1 and 3 as Tumor Markers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the commonest liver cancer; its incidence and prevalence are continuously increased. Glypican3 (GPC3), melanoma antigen-1, 3 genes (MAGE1 and 3) are tumor markers used in HCC. We evaluated their role in HCC detection and assessed their relation to tumor parameters. Three groups, HCC group, liver cirrhosis group and a control group were studied. AFP, GPC3, and MAGE1 and 3 mRNA were determined in all study subjects. Tissue GPC3 was examined in patients with HCC only. Serum AFP and GPC3 were elevated in HCC group compared to other groups (P < 0.000 and P < 0.001, respectively). AFP at cutoff 44.4ng/ml and GPC3 at cutoff 5.6µg/L resulted in 81% and 90.1% sensitivity, 73.3% and 92.6% specificity, respectively. The combined measurement of both increased the sensitivity and the specificity to 100% and 93.3%, respectively. GPC 3 was detected in tissues of 81.0% of the cases. MAGE-1 and MAGE-3 genes expression were detected in 61.9% and 52.4%, respectively in HCC cases but not in other groups. GPC3, MAGE1and 3 were increased with advanced tumor stage, size, and nodule numbers. We concluded that GPC3 is a promising diagnostic marker for HCC, and MAGE 1 and 3 could be helpful in early detection of extrahepatic metastasis of HCC.

Alterations of mTOR and PTEN protein expression in schistosomal squamous cell carcinoma and urothelial carcinoma.

BACKGROUND: mTOR signaling pathway is commonly activated in cancer. PTEN, a tumor suppressor gene, is a potent inhibitor of this pathway. To date the expression pattern of mTOR and PTEN in schistosomal bladder squamous cell carcinoma and urothelial carcinoma was not investigated. Also, whether alterations of these proteins are associated with pathological parameters was not established. HYPOTHESIS: We hypothesize that "expression of mTOR and/or PTEN will be altered in schistosomal-related urothelial and squamous cell carcinomas". PATIENTS AND METHODS: To test our hypothesis we examined the expression pattern of mTOR and PTEN in normal and hyperplastic urothelium, squamous metaplasia, schistosomal urothelial carcinomas (70 cases) and squamous cell carcinomas (47 cases) using immunohistochemical methods. RESULTS: mTOR protein expression was absent in the normal, hyperplastic urothelium and metaplastic squamous epithelium. mTOR was over-expressed in muscle invasive urothelial and high grade squamous cell carcinomas. In contrast, PTEN protein expression was seen in the normal and hyperplastic urothelium. The expression was reduced (metaplastic squamous epithelium) or lost in muscle invasive urothelial and high grade squamous carcinomas. Alterations of these proteins were associated with some clinicopathological features. mTOR expression was negatively correlated with PTEN expression in urothelial carcinoma only. CONCLUSIONS: We report, for the first time, altered expression of mTOR and PTEN proteins in schistosomal urothelial and squamous cell carcinomas. Alterations of these proteins may contribute to the progression and aggressive behavior of schistosomal bladder carcinoma. Targeting mTOR, may be a promising therapeutic strategy in these tumors.

Evaluation of Non Invasive versus Invasive Methods for Diagnosis of Helicobacter pylori Infection among Patients with Gastroduodenal Disorders.

H. pylori, a spiral gram-negative bacterium, is associated with gastroduodenal diseases. All H. pylori diagnostic assays have limitations. Cytotoxin-associated gene A (cag A), a virulence marker, can be identified by PCR. We evaluated H. pylori diagnostic methods, invasive: rapid urease test (RUT), and histopathological examination (HE), and serology as non-invasive method. Positive cases were studied for presence of cag A gene. Upper endoscopies and gastric biopsies were performed on 67 dyspeptic patients for RUT, HE and PCR. Anti H. pyloriIgG were measured by ELISA. Of 67 dyspeptic patients, 23 (34%) had more than one endoscopic finding, 46 (68.7%) were H.pylori positive by HE, and 21(31.3%) were negative with variable grades of mucosal antral neutrophil infiltration. Of the 46 HE positives, PCR detected CagA in 22 (47.8%). Using HE as the gold standard test, the sensitivity of ELISA and RUT was 93.48% and 86.96%, respectively; and the specificity was 85.71% and 47.62%, respectively. In conclusion, IgG detection by ELISA is a suitable screening test for diagnosis of H. pylori associated gastroduodenal diseases. Histopathology should be performed in ELISA negative cases to exclude infection.

Identification and potential role of telocytes in human uterine leiomyoma.

BACKGROUND: Telocytes are specialized interstitial tissue cell type. Our aim is to characterize telocytes in human uterine leiomyoma (ULM) and its adjacent myometrium (Myo-F) as well as normal myometrium (Myo-N). METHODS: ULMs and Myo-F tissues were taken from hysterectomy specimens done to treat symptomatic uterine fibroids (N = 20). Myo-N is isolated from hysterectomies done on ULM- free uteri for other benign indications (N = 15).Telocytes were detected using immunohistochemistry to detect c-Kit (CD-117), as a surface marker expressed on telocytes, and electron microscopic examination to identify telocytes characteristic ultrastructure. Cellular count and electron microscopic features of telocytes in each of the studied tissues were compared. RESULTS: Telocytes could be detected in ULMs, Myo-F and Myo-N using c-KIT immunostaining. Electron microscopy confirmed the presence of telocytes in the three types of tissues identifying their characteristic features including small triangular or fusiform cell bodies with extensive cellular prolongations. ULM telocytes showed ultrastructural features suggestive of high cellular activities. Cell counts of ULM telocytes (3.35 ± 0.39) were significantly higher (P value = 0.00039) than that of Myo-F (1.39 ± 0.13). Myo-N (2.6 ± 0.36) contained higher telocyte numbers than Myo-F (1.39 ± 0.13), but the difference did not reach statistical significance (P value = 0.19). CONCLUSIONS: Telocytes are detected in higher numbers and activity in ULMs than Myo-F or Myo-N. In ULMs, telocytes can work as a hormonal sensors for stem cells, provide scaffold for newly formed myocytes, or control important downstream signaling pathways.

Expression of survivin in squamous cell carcinoma and transitional cell carcinoma of the urinary bladder: a comparative immunohistochemical study.

PURPOSE: To compare the expression of survivin and its association with clinicopathological criteria in major types of urinary bladder carcinoma, specifically, transitional cell carcinoma with and without squamous differentiation and squamous cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for survivin and Ki67 was performed on paraffin-embedded sections of 104 carcinomas: 52 transitional cell carcinoma, 20 transitional cell carcinoma with squamous differentiation, and 32 squamous cell carcinoma. Expression of survivin in >10% of tumor cells was described as altered survivin status. Ki67 staining in >20% of tumor cells was described as a high proliferation index. RESULTS: Altered survivin expression was detected in 60/104 specimens (58%) and was significantly more frequent in transitional cell carcinoma (78%) than in squamous cell carcinoma (38%) or transitional cell carcinoma with squamous differentiation (40%) (p<0.0001). In transitional cell carcinoma but not in squamous cell carcinoma, altered survivin status was associated with higher tumor grade, higher proliferation index, and recurrence. In the whole specimens, altered survivin expression was significantly associated with advanced stage (p<0.001), recurrence (p=0.005), distant metastasis (p<0.001), and death (p=0.001). In the multivariate analysis, altered survivin was an independent poor prognostic factor for recurrence. CONCLUSIONS: Unlike in transitional cell carcinoma, alteration of survivin expression in squamous cell carcinoma occurs less frequently and is not associated with features of tumor aggression or patient outcome. These findings raise a question: are urinary bladder carcinoma patients with squamous cell carcinoma type suitable candidates for survivin vaccine? This is an important question to be answered before approving the vaccine in management.

Intralesional vs. contact cryosurgery in treatment of keloids: a clinical and immunohistochemical study.

BACKGROUND: Cryosurgery is a safe and effective treatment of keloids. Intralesional cryosurgery has been shown to bring about significant improvement in keloids. The histopathological and immunohistochemical changes in keloids following cryosurgery are not well-assessed. METHODS: Twenty-three patients with 66 keloids were treated with either the contact (cryoprobe) method or intralesional cryosurgery. Keloid specimens were obtained before treatment and after two sessions of treatment for evaluation of keloid pathology and immunohistochemical changes in expression of vascular endothelial growth factor (VEGF) and tenascin C induced by both cryosurgical techniques. RESULTS: A better therapeutic response was detected after intralesional cryosurgery (excellent response [ER], 87%) than contact cryosurgery (ER, 60%; P < 0.05). The intralesional technique achieved higher rates of flattening after the first two sessions (ER in 61.3% and 22.9%, respectively; P < 0.05) and caused fewer side effects compared with the contact method. Both cryosurgical methods resulted in a significant decrease in VEGF and tenascin C expression in keloids. CONCLUSIONS: Intralesional cryosurgery is superior to contact cryosurgery in terms of efficacy and safety. Both techniques may have beneficial effects on keloids, at least partially, through the modulation of VEGF and tenascin C expression.

Cardiac histopathological and immunohistochemical changes due to electric injury in rats.

It has been a puzzling forensic task to determine the cause of death as a result of electric shock in the absence of recognizable skin marks or definite postmortem morphological findings. In forensic pathology, while classical macroscopic and microscopic morphology remain core procedures to investigate deaths, a variety of subsidiary measures has been developed and incorporated to detail that pathology. C-fos, one of a small group of genes called primary response genes and its protein product, fos, are crucial elements of complex signaling mechanisms believed to be responsible for cell response to stimulation. It has been found that c-fos plays a significant role in myocardial lesions, and has close relation to injury repair of the molecule. The aim of this study was to detect the histopathological findings in the myocardium after fatal and non-fatal electrical injury in rats and to investigate the potential role of c-fos expression using immunohistochemistry to distinguish antemortem from postmortem electrocution. Forty adult female rats were implemented and randomly divided into four groups (A, B, C and D). Group (A) rats were subjected to instantaneous antemortem electricity and their hearts were collected either immediately (A1) or after an hour (A2) before being subjected to cervical dislocation. Group (B) rats were electrically injured instantaneously postmortem, hearts were collected immediately (B1) or an hour later (B2) while Group (C) rats were electrified up to death, and their hearts were also gathered either immediately (C1) or after an hour (C2) from electrocution. Lastly, another group of rats served as a control group (Group D). Subgroup (D1): rats were clamped but not electrified, before death and another group of rats were clamped but not electrified, after being killed by cervical dislocation. Sections from the hearts of all groups were fixed in formalin and routinely processed. The c-fos oncogene expression was evaluated in all groups by immunohistochemistry. Significant histopathological findings were detected in groups A and C. Few c-fos oncogene protein positive cardiomyocyte nuclei were seen in rats of groups (A1) and (B1). Additionally, increased expression in rats of groups C1, C2 and A2 were observed. On the other hand, no c-fos protein expression was seen either in the control (groups D1 and D2) or in group B2. Significant differences (p < 0.001) in c-fos expression were observed among rats of groups with antemortem electric injury (A1, A2) and those of postmortem injury (B1 and B2). Thus, in addition to classical histopathological methods, c-fos can be regarded as a target in identifying electrical injury, and can be used as an indicator to distinguish antemortem from postmortem electric shock.

Camellia sinensis (green tea) extract attenuate acrylamide induced testicular damage in albino rats.

UNLABELLED: Acrylamide is a proved toxin for testicular function, found in food when heated for long period of time. Green tea (Camellia sinensis) is a potent antioxidant; the aim of this study was to investigate the protective effect of green tea extract against the toxic effects of acrylamide in rat testes. METHODS: acrylamide was administered orally to rats in different doses and also the extract of green tea was administered orally to different groups of animals in combination with the acrylamide. The weight of animals, testosterone hormone level and histopathological effect upon testicles were evaluated. RESULTS: Testosterone hormone level in serum, and histopathological findings were significantly improved with the co-administration of green tea extract with the acrylamide. Green tea extract reversed all the toxic effects of acrylamide even in high dose for long period (90 days). CONCLUSION: Green tea extract is a potent antioxidant antidote for the acrylamide toxic effects upon testicular function.

Diagnostic utility of deamidated gliadin peptide antibody in celiac disease compared to anti-tissue transglutaminase and IgA- endomysium antibodies.

Deamidated gliadin peptide antibodies have recently been suggested as reliable tools for celiac disease (CD) diagnosis. We compared their utility for diagnosis CD in comparison to the routinely used anti-endomysial, and anti-tissue transglutaminase antibodies. We studied 65 patients (17 men, 48 women; age range, 17- 63 years) who underwent intestinal biopsy because of clinical suspicion of small-bowel disorders. Serum samples were obtained at the time of biopsy for measuring IgA and IgG anti-tissue transglutaminase (tTG), IgA and IgG anti-deamidated gliadin peptide (DOP) by ELISA and IgA anti-endomesial antibody (EmA) by indirect immunoflouresce. Characterization of patients was based on histological criteria (Marsh type II lesion or greater). Biopsy revealed that 14 patients had positive criteria for CD. The remaining 51 negative patients were used as controls. Assay sensitivity and specificity for diagnosing celiac disease were 85.7% and 92.2% for IgA and 92.9 and 100% for IgG antibodies to DGP respectively. Serum IgA and IgG DGP, IgA and IgG -tTG and IgA EmA were significantly higher in CD patients than in control group (P = 0.000). None of the controls was positive for IgG DGP or IgA -EmA, but 4 of 51 (7.8 %) were positive for IgA- DGP, 6 of 51 (11.8 %) were positive for IgA anti-tTG, and 2 of 51 (3.9%) were positive for IgG anti-tTG. IgG-DGP has the best sensitivity (92.9%), specificity (100%), positive predictive value (100%), and negative predictive value (96.2%). In conclusion, the DGP antibodies tests, alone or in combination with the tTG antibodies, are useful tools for screening purposes and with better patient acceptance than intestinal biopsy.