Clinical Evaluation of Proline, Glutamic acid, and Leucine-Rich Protein 1 Expression in Astrocytomas and Correlations with the Proliferation Marker Ki-67.

Malignant astrocytomas presenting in humans of any age group are a challenge to diagnose and treat. Hence, there is a quest for new markers to ascertain their grades and predict disease outcomes. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a nuclear receptor co-regulator, is an oncogene found in various cancers. We postulate that by screening for PELP1, its correlation with survival outcomes of patients across various grades can indicate a plausible novel diagnostic marker and a potential therapeutic target in gliomas. Immunostaining of 100 cases of astrocytomas for PELP1 was performed on paraffin-embedded sections. Results showed that PELP1 expression increases with higher grades; the mean H-score of PELP1 in grade-I astrocytomas was determined to be 112.3, whereas in grade-IV it was 235.1 (P value = 0.0001). Survival analysis of patients with H-score of 200-300 was only 8.8% and 68.8% in patients with scores of 0-100. PELP1 expression in high-grade astrocytomas is an important factor in determining the outcomes. Graphical abstract Evaluation of molecular expression of PELP1 along with Ki-67 LI signifies a linear increase in its expression pattern among different grades of astrocytomas from low- to high-grade tumors, which can serve as a potential prognostic molecular marker in differentiating various types of astrocytomas in humans.

Herbal formulation, DIA-2 and Rosiglitazone ameliorates hyperglycemia and hepatic steatosis in type 2 diabetic rats.

DIA-2 is a herbal mixture containing standardized extract of Allium sativum and Lagerstroemia speciosa. Recently we have reported the anti-diabetic effect of DIA-2 in high fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic (T2D) rats. The purpose of this study was to investigate and compare the effects of DIA-2 with Rosiglitazone (RG) on plasma biomarkers of hepatocellular injury, liver carbohydrate metabolizing enzymes, glycogen content, oxidant/antioxidant status and histopathological changes in T2D rats. ALT and ALP levels were significantly decreased after DIA-2 and RG treatment compared to T2D rats. Total protein and albumin remained unaltered in all the groups. Significant decrease in AST levels were observed after DIA-2 (125 mg/kg) and RG treatment. Hepatic hexokinase activity was significantly increased after RG and DIA-2 treatment and fructose-1, 6-bisphosphatase activity were inversely correlated with hexokinase activity. Hepatic gucose-6-phosphatase activity was significantly (p < 0.05) reduced after DIA-2 (62.5 mg/kg) and RG treatment. Lipid peroxides levels was significantly decreased in the liver of DIA-2 (62.5; p < 0.01 & 125 mg/kg; p < 0.05) treated animals. Hepatic glycogen content (p < 0.05) and antioxidant enzymes [SOD (p < 0.01; 62.5 mg/kg); GPx and GSH (125 mg/kg; p < 0.01)] were significantly increased after DIA-2 treatment. RG treatment on hepatic glycogen, GPx (p < 0.01) and SOD, GSH (p < 0.05) levels were significant when compared to T2D rats. These biochemical parameters were also correlated with histopathological evaluation. The above findings revealed that administration of DIA-2 could ameliorate the biochemical and histopathological changes in liver of T2D rats indicating the protective role of DIA-2 against HFD/STZ induced diabetes. In addition, DIA-2 and RG treatment resulted in amelioration of hepatic steatosis in T2D rats.

DIA-2, a polyherbal formulation ameliorates hyperglycemia and protein-oxidation without increasing the body weight in type II diabetic rats.

BACKGROUND: The dried bulbs of Allium sativum (Garlic) and leaves of Lagerstroemia speciosa (Banaba) are used as medicinal food for the treatment of diabetes and other ailments. AIM: The present study was undertaken to ascertain whether the combination of both garlic and banaba extract produces synergistic therapeutic effect in diabetic state. METHODS: In the in vitro studies, the effect of standardized aqueous extract of Allium sativum (ASE), methanolic extract of Lagerstroemia speciosa (LSE) and their mixture (1:1 ratio), DIA-2 on insulin stimulated glucose uptake in 3T3-L1 cells, erythrocyte sorbitol accumulation and protein glycation were evaluated. Impetus from the in vitro findings triggered to screen the anti-diabetic potential of DIA-2 in rat model of type II diabetes and associated oxidative stress. In the in vivo studies, acute oral toxicity of DIA-2 was determined following OECD-423 guidelines in female rats. Anti-diabetic activity of DIA-2 was investigated in high fat diet/low dose streptozotocin induced type II diabetes at four dose levels (62.5, 125, 250 and 500 mg/kg b.w) in rats. RESULTS: Combination of ASE and LSE produced synergistic and a dose dependent increase in glucose uptake in 3T3 adipocyte cell lines when compared to the individual extracts. A similar effect was observed in the inhibition of sorbitol accumulation and protein glycation tests. DIA-2 restored the glucose and lipid level near to normal level without gain in body weight which is the most commonly encountered side effect with the use of conventional antidiabetic agents, particularly insulin, insulin secretagogues, sulfonylureas and thiazolidinediones. DIA-2 also decreased hepatic protein carbonyl content levels significantly in the diabetic rats. CONCLUSIONS: The study concluded that DIA-2 posses potent anti-diabetic activity and anti-oxidant effects.  

In vitro cytotoxic, antioxidative and alpha-glucosidase inhibitory potential of a herbal mixture comprised of Allium sativum and Lagerstroemia speciosa.

BACKGROUND: Hyperglycemia induced over production of free radicals in the mitochondrial electron transport chain is now considered as one of the central mechanisms in the pathogenesis of diabetic complications. Allium sativum and Lagerstroemia speciosa contains active principles possessing anti-diabetic and antioxidant properties. This study is aimed at evaluating the evidence that supports this traditional claim and investigates the possible synergistic effect on these herbs when given as a herbal mixture in vitro. AIM: The present study investigates the cytotoxic, antioxidant and a-glucosidase inhibitory potential of Allium sativum (ASE), Lagerstroemia speciosa (LSE) and their combinations using in vitro methods. MATERIALS AND METHODS: The total phenol, total flavonoid and total tannin content were determined in ASE and LSE. The cytotoxic effects of ASE, LSE and their combination in the ratio of 1:2, 1:1 w/w were evaluated using 3T3 L1 preadipocyte cells. Effect of ASE, LSE and its mixture on intracellular reactive oxygen species (ROS) production were determined by 2', 7'dichlorfluorescein diacetate (DCF DA) staining technique in 3T3-L1 adipocytes. The ability of the herbal extracts and their combination to scavenge super oxide radicals and to inhibit alpha-glucosidase enzyme (a carbohydrate metabolising enzyme) were measured using in vitro methods. RESULTS: The total phenols and tannins were expressed as microgram (microg) of gallic acid equivalents/mg of extract (GAE/mg), flavonoids as microg of quercetin equivalents/mg of extract (QE/mg). LSE had significant higher total phenol (300.11 +/- 1.99), flavonoid (53.12 +/- 0.48) and tannin content (118.90 +/- 0.15) compared to ASE which possessed total phenol (159.93 +/- 0.87); flavonoid (9.37 +/- 0.73) and tannin content (80.5 +/- 0.19). The IC50 value, the concentration of the extracts that cause 50% inhibition or cell death was measured as an index of cytotoxicity. The IC50 value was found to be in the following decreasing order: 1:2 mixture (98 microg/ml) > ASE (323.6 microg/ml) > 1:1 mixture (428.1 microg/ml) > LSE (2154 microg/ml). The 1:1 mixture was comparatively less cytotoxic under the tested concentration range (1 x 10(0) pg - 1 x 10(8) pg) than 1:2 combinations. The results observed with lactate dehydrogenase (LDH) release were similar to that of cell viability assay. The 1:1 mixture (DIA-2 hereafter) was considered for further investigations. DIA-2 inhibited the ROS levels, which is evidenced by the decreased DCF fluorescence. DIA-2 could also efficiently scavenge the super oxide radical generated from PMS/NADH-NBT system showing an IC50 value 69.99 microg/ml, the IC50 value of ASE (157.7 microg/ml), LSE (20.43 microg/ml), and ascorbic acid (49.64 microg/ml) used as positive control. The results of in vitro a-glucosidase inhibitory assay showed highest IC50 value with LSE (0.3 microg/ml) and DIA-2 (0.7 microg/ml) than ASE (136.3 microg/ml) and positive control miglitol (651.8 microg/ml). CONCLUSIONS: DIA-2 exerts synergistic effect in scavenging the ROS and inhibiting the enzyme alpha-glucosidase in vitro compared to its individual extracts. The possible synergistic therapeutic effects may be due the presence of the antioxidant rich flavonoids, phenols and tannins present in LSE and ASE.

Pediatric oral leiomyosarcoma: rare case report.

Soft tissue sarcomas comprise a group of histologically diverse malignant neoplasms arising from mesenchymal cell lines. Among these, leiomyosarcomas are sarcomas exhibiting smooth muscle differentiation. Occurrence of this neoplasm in the oral cavity is exceedingly rare and its presentation is unusual in children. We present a case report of leiomyosarcoma of the oral cavity in an eight-year old child. Primary oral leiomyosarcoma, being a rare entity in children, this case report emphasizes the prompt recognition of this tumor to institute appropriate multimodality treatment.

Granular cell tumor in inguinal region: A case of mistaken identity on cytology.

A 63-year-old male presented with sudden increase in size of a right inguinal swelling which was present for the past 10 years. Clinical diagnosis of inguinal soft tissue mass/lymph node enlargement was made and patient was investigated further for a conclusive diagnosis. Ultrasound examination suggested it to be a lymph node and guided fine needle aspiration cytology was performed. Cytology was suggestive of a reactive lymph node. Subsequently, an excision biopsy was performed that revealed a granular cell tumor with many lymphoid aggregates. On reviewing the cytosmears, we realised that the granular neoplastic cells were mistaken for histiocytes; and the lymphoid background and bare nuclei mislead us to consider it a reactive lymph node. Since granular cell tumor can occur almost anywhere, a careful examination of cytosmears and knowledge of its distinctive cyto-morphological features would be helpful in providing an accurate diagnosis on cytology.

Dietary chlorophyllin inhibits the canonical NF-κB signaling pathway and induces intrinsic apoptosis in a hamster model of oral oncogenesis.

Chlorophyllin, a water-soluble, semi-synthetic derivative of the ubiquitous green pigment chlorophyll is shown to exert potent anticarcinogenic effects. In the present study, we investigated the chemopreventive effects of chlorophyllin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by analyzing the expression of NF-κB family members and markers of intrinsic apoptosis. Dietary administration of chlorophyllin (4 mg/kg bw) suppressed the development of HBP carcinomas by inhibiting the canonical NF-κB signaling pathway by downregulating IKKß, preventing the phosphorylation of IκB-α, and reducing the expression of nuclear NF-κB. Inactivation of NF-κB signaling by chlorophyllin was associated with the induction of intrinsic apoptosis as evidenced by modulation of Bcl-2 family proteins, enforced nuclear localization of survivin, upregulation of apoptogenic molecules, activation of caspases, and cleavage of PARP. The results of the present study demonstrate that chlorophyllin inhibits the development of DMBA-induced HBP carcinogenesis by targeting NF-κB and the intrinsic apoptotic pathway. Thus, dietary agents such as chlorophyllin that simultaneously target divergent pathways of cell survival and cell death are novel candidates for cancer chemoprevention.

Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG.

The modulation of intracellular nuclear factor-kappaB (NF-κB) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is known to possess attractive remedial features. In the present study, we investigated the modulatory effects of eugenol on NF-κB signaling in a rat model of gastric carcinogenesis induced by N-methyl-N(')-nitro-N-nitrosoguanidine (MNNG) by analysing the expression of nuclear factor-kappaB (NF-κB) family members ((NF-κB (p50 and p65), inhibitor of kappaB alpha (IκBα), phosphorylated IκBα (p-IκBα), IκB kinase ß (IKKß)) and the NF-κB target genes that promote (e.g., cyclin D1, cyclin B and PCNA) or inhibit (e.g., p53, p21, and Gadd45) cell proliferation and cell survival. MNNG-induced gastric tumours were characterized by NF-κB activation that correlated with upregulation of IKKß, and phosphorylation and degradation of IκBα. Furthermore, upregulation of cyclins and PCNA with downregulation of p21, p53, and Gadd45 suggested that the proliferative advantage in gastric carcinomas is dependent on elevated constitutive NF-κB activity. Administration of eugenol significantly reduced the incidence of MNNG-induced gastric tumours by suppressing NF-κB activation and modulating the expression of NF-κB target genes that regulate cell proliferation and cell survival. The targeting of NF-κB signaling pathway by eugenol may have a significant impact on chemopreventive and therapeutic approaches for cancer.

Papillary lesions of breast - An introspect of cytomorphological features.

BACKGROUND: True papillary lesions of the breast have a significantly high error rate on fine needle aspiration cytology (FNAC), as many other nonpapillary breast lesions exhibit overlapping features on cytosmears. AIM: To evaluate the utility of individual morphological features in offering a more precise cytodiagnosis in papillary lesions of the breast. MATERIALS AND METHODS: Cytology smears reported as papillary lesions on nipple discharge / FNAC and histopathology over a period of two years were studied and correlated. A subjective assessment of morphological features, namely, the cellular yield, presence of three-dimensional papillary clusters, stromal bare nuclei, presence of cyst macrophages and cellular atypia was carried out on cytosmears. RESULTS: Fourteen cases of papillary lesions were identified. Thirty-six per cent of the cases were found to be true positive, 43% false negative and 21% false positive with a sensitivity of 42% for papillary lesions. Eight of nine papillary lesions showed cyst macrophages. Stromal bare nuclei were seen in three of four malignant papillary lesions. However, the number of stromal bare nuclei was less compared to benign lesions. None of the malignant nonpapillary lesions showed stromal bare nuclei. CONCLUSIONS: Cytomorphological features alone are inadequate for the precise diagnosis of papillary lesions of the breast.

Solid variant of papillary carcinoma of nipple: an under recognized entity.

Papillary lesions of the breast represent a heterogeneous group with differing biological behavior. Solid papillary carcinomas are uncommon tumors composed of circumscribed large cellular nodules separated by bands of fibrosis. Correct diagnosis is crucial but may be difficult, as many other benign and malignant lesions have similar histological appearances. Immunohistochemistry plays a useful role in their differentiation. We describe one such case of a solid variant of papillary carcinoma of the left nipple in a 75-year-old woman, who had no other palpable mass in rest of the breast tissue. The case is documented for the rarity of its occurrence and significance of recognition of this lesion.

Coronary atherosclerosis in sudden cardiac death: an autopsy study.

BACKGROUND: The incidence of ischemic heart disease (IHD) has markedly increased in India over the past few years. Considering the variations in racial, dietary and lifestyle patterns in our population, it is essential to study the biology of coronary atherosclerosis in our patients. Vulnerable plaques have a large number of foam cells, extracellular lipid, thin fibrous caps and clusters of inflammatory cells and are more prone to rupture. These plaques are nourished by the microvessels arising from the vasa vasorum of the blood vessels and by lumen-derived microvessels through the fibrous cap. This autopsy study was designed to analyse the coronary arterial tree in cases of sudden cardiac death, classify coronary atherosclerotic plaques and to assess the factors contributing to vulnerability of the plaques including inflammation, calcification and microvascular density. MATERIALS AND METHODS: Seven cases of sudden cardiac death were included in the study. The hearts were perfusion-fixed and the coronary arteries along with their main branches were dissected and studied. The location of the plaques, type of plaques, presence of inflammation and calcification were assessed. The cap thickness and microvessel density per 1000 um 2 were assessed. The statistical significance was estimated. RESULTS AND CONCLUSIONS: Extensive high-grade coronary atherosclerotic disease was seen in all sudden cardiac death cases. Majority of the plaques were vulnerable. High-grade inflammation was seen in most of the vulnerable and ruptured plaques. All the ruptured plaques were uncalcified indicating that calcification probably stabilizes the plaques and protects against rupture. Increased microvessel density was noted in ruptured plaques compared to vulnerable plaques. However, it was not statistically significant.

Characterization of morphologically benign biologically aggressive meningiomas.

BACKGROUND: Meningiomas are presently categorized into three grades by World Health Organization (WHO). Grade I, in general, is expected to behave in a benign fashion. However, a borderline group of grade I meningioma also exists, which may behave aggressively. AIMS AND OBJECTIVE: To evaluate the proliferation index and p53 antigen expression of meningiomas and correlate with histological grade and clinical course. MATERIALS AND METHODS: All 123 cases of meningiomas, diagnosed between January 2000 and August 2007, were regraded according to WHO 2000 criteria. Immunostaining for Ki-67 antigen and p53 protein were performed on 68 cases selected for the study. RESULTS: Six of the 68 cases presented with recurrence. Mean Ki-67 labeling index (Ki-67 LI) was 3.8%, 13.7%, 19.4% for grade I, II, and III cases, respectively. Multivariate analysis of mean Ki-67 LI showed statistically significant difference between subgroups. Mean p53 expression was found to be 15.5%, 57%, 60.8%, and 62.5% for grade I, II, III, and recurrent cases, respectively. Multivariate analysis of mean p53 expression showed no statistically significant difference between higher grades. All recurrent cases were histologically WHO grade I, and showed a high Ki-67 LI and p53 expression with mean Ki-67 LI and p53 expression of 8.6% and 62.5% respectively. CONCLUSION: Utilization of markers for proliferation and cell cycle regulators in combination with histopathological features helps in the identification of a subset of biologically aggressive morphologically benign meningiomas.

Cytologic features of pulmonary blastoma.

Pulmonary blastomas are rare lung neoplasms constituting 0.5% of all lung tumors. This tumor has an aggressive course and needs to be recognized on cytology. A preoperative diagnosis of pulmonary blastoma is difficult to obtain by cytopathologic methods. A diagnosis of biphasic pulmonary blastoma should be considered when there is a dimorphic population of cells on cytology. A 30-year-old male presented with gradually progressing breathlessness and left-sided chest pain for the past one month. Chest radiograph and computed tomography of thorax revealed an anterior mediastinal mass that was subjected to ultrasound-guided fine-needle aspiration cytology. Aspiration cytology showed a highly cellular lesion with a dimorphic population of tumor cells in a necrotic background. The possibility of a non-small cell carcinoma was suggested. Subsequent histopathology revealed the tumor to be a pulmonary blastoma. The importance of recognizing the dimorphic population of cells in cytology is discussed.

Combinatorial chemopreventive effect of Azadirachta indica and Ocimum sanctum on oxidant-antioxidant status, cell proliferation, apoptosis and angiogenesis in a rat forestomach carcinogenesis model.

INTRODUCTION: We investigated the combinatorial chemopreventive efficacy of Azadirachta indica (AI) and Ocimum sanctum (OS) against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis, based on changes in oxidant-antioxidant status, cell proliferation, apoptosis and angiogenesis. METHODS: Male Wistar rats were assigned to four groups. Rats in groups 1 and 2 received MNNG (150 mg/kg body weight i.g.) three times with a gap of two weeks in between the treatment. Group 2 rats additionally received ethanolic AI (100 mg/kg body weight i.g.) and OS (150 mg/kg body weight i.g.) leaf extract three times per week for 26 weeks. Group 3 animals were given AI and OS leaf extract alone, whereas group 4 served as the control. RESULTS: Lipid and protein oxidation and status of the antioxidants, superoxide dismutases, catalase, reduced glutathione (GSH) and GSH-dependent enzymes together with markers of proliferation (proliferating cell nuclear antigen [PCNA], glutathione S-transferase-Pi [GST-P]), invasion (cytokeratin [CK]), angiogenesis (vascular endothelial growth factor [VEGF]) and apoptosis (Bcl-2, Bax, cytochrome C and caspase-3) were used to biomonitor chemoprevention. Rats administered MNNG developed forestomach carcinomas that displayed low lipid and protein oxidation coupled to enhanced antioxidant activities, and overexpression of PCNA, GST-P, CK, VEGF and Bcl-2 with downregulation of Bax, cytochrome C and caspase-3. Coadministration of AI and OS extract suppressed MNNG-induced gastric carcinomas accompanied by modulation of the oxidant-antioxidant status, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. CONCLUSION: The results of the present study suggest that chemoprevention by AI and OS combination may be mediated by their antioxidant, antiangiogenic, antiproliferative and apoptosis inducing properties.

Autofluorescence: a screening test for mycotic infection in tissues.

Fungal infection is a major health concern as the clinical features are not very distinctive. Lack of rapid diagnostic techniques results in delay in diagnosis, which may even culminate in a fatal outcome. The fact that many pathogenic fungal organisms autofluoresce in hematoxylin and eosin (H and E)-stained sections under ultraviolet illumination led us to evaluate the role of autofluorescence as a rapid screening technique for fungal infections. The aim of the present study was to assess the value of autofluorescence as a screening method for detecting fungi on tissue sections and to compare the results of autofluorescence with conventional histochemical stains for fungi. Hematoxylin and eosin-stained slides of mycotic lesions were examined under fluorescent microscope and the findings were compared with results of Gomori's methenamine silver and periodic acid-Schiff stains. We found fungal autofluorescence in 63 out of 64 cases studied, with a sensitivity of 97.8% and specificity of 100% in comparison with fungal stains. This was statistically significant (P < 0.05). We conclude that autofluorescence can be used as a rapid screening method for identification of fungi in tissue sections as it does not require any other specialized staining procedure.

Histological reclassification, histochemical characterization and c-kit immunoexpression in renal cell carcinoma.

OBJECTIVES: Renal cell carcinoma is the most lethal of all urologic malignancies. Several parameters such as histological subtype, nuclear grade and TNM staging help in determining the prognosis and treatment options. A newer therapeutic modality has been suggested based on expression of c-kit antigen by the tumor cells. This study was designed to evaluate various histological parameters and correlate them with c-kit expression. MATERIALS AND METHODS: The study was done on 40 consecutive cases of renal epithelial tumors. Histological sections were reviewed and reclassified according to WHO (2004) classification and nuclear grade assessed. Hale's colloidal iron stain was done to identify the chromophobe variant. Immunostaining with c-kit was done and its expression was studied. The results were correlated and statistical significance was assessed. RESULTS: The age range was 31-81 years, with a male to female ratio of 2:1. Seventy per cent of the cases were clear cell RCC (ClRCC), 17.5% were chromophobe type, 7.5% were papillary RCCs and 5% cases were oncocytomas. Fuhrman nuclear grading revealed 60.5% cases to be of low grade and 39.5% high grade. Hale's colloidal iron staining was positive in chromophobe RCC and oncocytomas, while it was negative in ClRCC. Immunostaining with c-kit was positive only in oncocytomas. CONCLUSIONS: Clear cell RCC was the most common histological subtype of RCC. Clear cell RCC known to have a poor prognosis, showed a statistically significant higher nuclear grade than chromophobe and papillary RCCs which have a better prognosis. Hale's colloidal iron staining was extremely useful in distinguishing chromophobe RCC and oncocytoma from the granular cell variant of clear RCC. Our study revealed c-kit negativity in all RCC. As Imatinib could be ineffective in such tumors, its clinical activity has to be carefully assessed in such tumors through further studies.

Proliferation, angiogenesis and apoptosis-associated proteins are molecular targets for chemoprevention of MNNG-induced gastric carcinogenesis by ethanolic Ocimum sanctum leaf extract.

INTRODUCTION: This study was designed to evaluate the chemopreventive effects of ethanolic Ocimum sanctum (OS) leaf extract on cell proliferation, apoptosis and angiogenesis during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis. METHODS: The rats were divided into four groups of ten each. Rats in group one were given MNNG (150 mg/kg body weight) by intragastric intubation three times, with a two-week interval between treatments. Rats in group two were administered MNNG as in group one, and in addition, they received intragastric intubation of ethanolic OS extract (300 mg/kg body weight) three times per week, starting on the day following the first exposure to MNNG. The intubation of ethanolic OS extract continued until the end of the experimental period. Rats in group three were given ethanolic OS leaf extract only. Group four served as controls. All the rats were killed after an experimental period of 26 weeks. RESULTS: Intragastric administration of MNNG-induced well-differentiated squamous cell carcinomas that showed increased cell proliferation, and angiogenesis with evasion of apoptosis, as revealed by the upregulation of proliferating cell nuclear antigen (PCNA), glutathione S-transferase-pi (GST-pi), Bcl-2, cytokeratin (CK) and vascular endothelial growth factor (VEGF) and with downregulation of Bax, cytochrome C and caspase 3 protein expression. Administration of ethanolic OS leaf extract reduced the incidence of MNNG-induced gastric carcinomas. This was accompanied by decreased expression of PCNA, GST-pi, Bcl-2, CK and VEGF, and overexpression of Bax, cytochrome C, and caspase 3. CONCLUSION: This study provides evidence that, in MNNG-induced gastric carcinogenesis, the key proteins involved in the proliferation, invasion, angiogenesis and apoptosis, are viable molecular targets for chemoprevention using ethanolic OS leaf extract.

Disseminated malignant fibrous histiocytoma (giant cell rich): a case report.

Giant cell rich malignant fibrous histiocytoma accounts for 3 -15% of all malignant fibrous histiocytomas. Currently, the nomenclature giant cell malignant fibrous histiocytoma is reserved for undifferentiated pleomorphic sarcomas with prominent osteoclastic giant cells. It is considered to be synonymous with malignant giant cell tumor of soft parts. We report a case of disseminated giant cell malignant fibrous histiocytoma involving the scalp, cervical node, lungs, spine, abdominal wall, base of penis, gluteal cleft, paraspinal region and back. The diagnosis was established after staining for a panel of immunohistochemical markers namely cytokeratin, vimentin, S100, desmin, CD68 and smooth muscle actin. CD68 positivity in tumor cells helped in arriving at the final diagnosis. It is essential to recognize this tumor as a giant cell rich distinct entity and differentiate from other giant cell rich pleomorphic sarcomas since therapeutic and prognostic differences are being appreciated currently.

Malignant myoepithelioma of the mastoid region - A case report.

A 23-year-old male patient presented with a post auricular mass and an attico antral type of chronic suppurative otitis media. He underwent excision of the mass and canal wall down mastoidectomy. Histopathological diagnosis of malignant myoepithelioma was made.The patient refused treatment and later he died with systemic metastasis.This case is reported for the rarity of the site, young age of presentation and aggressive behaviour.

Morphological and morphometric analysis of coronary atherosclerosis--an autopsy study.

Coronary atherosclerosis is the most frequent cause of ischemic heart disease. The composition and vulnerability of the atherosclerotic plaque determines the development of acute coronary syndromes. In this study, 224 advanced atherosclerotic plaques were identified from the main coronary arterial branches of 10 autopsy heart specimens. The plaques were classified by American heart association (AHA) and modified American heart association classification. Vulnerability of the plaques and factors influencing vulnerability were assessed. Vulnerable plaques were mostly of Type IV category of AHA classification and of thin cap fibroatheroma type by modified American heart association classification. Inflammation was more frequent and was of a higher grade in vulnerable plaques. Calcification was predominantly of mild grade.