Exploring nature's bounty: identification of Withania somnifera as a promising source of therapeutic agents against COVID-19 by virtual screening and in silico evaluation.

Coronaviruses are etiological agents of extreme human and animal infection resulting in abnormalities primarily in the respiratory tract. Presently, there is no defined COVID-19 intervention and clinical trials of prospective therapeutic agents are still in the nascent stage. Withania somnifera (L.) Dunal (WS), is an important medicinal plant in Ayurveda. The present study aimed to evaluate the antiviral potential of selected WS phytoconstituents against the novel SARS-CoV-2 target proteins and human ACE2 receptor using in silico methods. Most of the phytoconstituents displayed good absorption and transport kinetics and were also found to display no associated mutagenic or adverse effect(s). Molecular docking analyses revealed that most of the WS phytoconstituents exhibited potent binding to human ACE2 receptor, SAR-CoV and SARS-CoV-2 spike glycoproteins as well as the two main SARS-CoV-2 proteases. Most of the phytoconstituents were predicted to undergo Phase-I metabolism prior to excretion. All phytoconstituents had favorable bioactivity scores with respect to various receptor proteins and target enzymes. SAR analysis revealed that the number of oxygen atoms in the withanolide backbone and structural rearrangements were crucial for effective binding. Molecular simulation analyses of SARS-CoV-2 spike protein and papain-like protease with Withanolides A and B, respectively, displayed a stability profile at 300 K and constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In a nutshell, WS phytoconstituents warrant further investigations in vitro and in vivo to unravel their molecular mechanism(s) and modes of action for their future development as novel antiviral agents against COVID-19.

Anticancer Potential of Dietary Natural Products: A Comprehensive Review.

Nature is a rich source of natural drug-like compounds with minimal side effects. Phytochemicals better known as "Natural Products" are found abundantly in a number of plants. Since time immemorial, spices have been widely used in Indian cuisine as flavoring and coloring agents. Most of these spices and condiments are derived from various biodiversity hotspots in India (which contribute 75% of global spice production) and form the crux of India's multidiverse and multicultural cuisine. Apart from their aroma, flavor and taste, these spices and condiments are known to possess several medicinal properties also. Most of these spices are mentioned in the Ayurveda, the indigenous system of medicine. The antimicrobial, antioxidant, antiproliferative, antihypertensive and antidiabetic properties of several of these natural products are well documented in Ayurveda. These phytoconstituemts are known to act as functional immunoboosters, immunomodulators as well as anti-inflammatory agents. As anticancer agents, their mechanistic action involves cancer cell death via induction of apoptosis, necrosis and autophagy. The present review provides a comprehensive and collective update on the potential of 66 commonly used spices as well as their bioactive constituents as anticancer agents. The review also provides an in-depth update of all major in vitro, in vivo, clinical and pharmacological studies done on these spices with special emphasis on the potential of these spices and their bioactive constituents as potential functional foods for prevention, treatment and management of cancer.

Synergic effects of cancer stem cells markers, CD44 and embryonic stem cell transcription factor Nanog, on bladder cancer prognosis.

Background: Therapy that targets cancer stem cells has the potential to eradicate cancer and prevent tumour recurrence. Therefore, we hypothesized the combined prognostic significance of stem cell markers CD44 (prevalent in basal layer of urothelial carcinoma) and Nanog (embryonic stem cell transcription factor) in bladder cancer.Material and Methods: CD44 and Nanog expression were determined by immunohistochemistry in 112 bladder cancer cases of which 79 were non-muscle invasive and 33 muscle invasive.Results: A significant correlation was found between CD44 and Nanog expression (r = 0.41, p < 0.001). The bladder cancer patients with high CD44 and Nanog expression had poor recurrence-free survival and poor overall survival (all p < 0.01). Multivariate Cox regression analysis identified lymph node positivity (hazard ratio; HR 3.81, 95% confidence interval; CI 1.66-8.75), CD44 (HR/95%CI 7.03 [3.04-16.22]) and Nanog (HR/95%CI 2.89 [1.23-6.77]) as independent prognostic biomarkers for recurrence-free survival, whilst a combined index of CD44 and Nanog expression (high expression group; HR/95%CI 25.45 [6.71-96.50] for recurrence-free survival) and lymph node positivity (HR/95%CI 3.68 [1.63-8.33] for recurrence-free survival) were independent prognostic biomarkers for recurrence-free survival and overall survival (all p < 0.001).Conclusions: A combined index of CD44 and Nanog expression is a promising prognostic predictor of recurrence-free survival and overall survival in bladder cancer. It may help identification of patients who will benefit from intensive treatment.

Evaluation of apoptotic activity of Withania coagulans methanolic extract against human breast cancer and Vero cell lines.

BACKGROUND: The genus Withania (Family: Solanaceae) holds an important position in Ayurveda, the Indian traditional system of medicine. Withania somnifera Dunal and Withania coagulans Dunal have been documented in folklore as panaceas for various ailments since time immemorial. W. coagulans (WC), commonly called as Indian cheese maker is used for fermenting milk for cheese production in various parts of India. OBJECTIVES: In the study, in vitro cytotoxicity of methanolic extract of dried fruits (berries) of WC was evaluated in a dose dependent manner using trypan blue dye exclusion method against human breast cancer cell line MDA-MB-231 and normal kidney epithelial cell line Vero in the range 20-200 µg/ml. MATERIAL AND METHODS: The percentage viability of the cell lines was determined by using MTT assay and cytometry. RESULTS: Methanolic extract of WC showed significant anticancer activity against MDA-MB-231 cell line. Cell viability was reduced to about 50% at 40 µg/ml of methanolic extract in 50% DMSO. Cytotoxicity of the extract was lower in 10% and 1% DMSO. On the other hand, methanolic extract of WC did not exhibit any significant in vitro activity against Vero cells at 170 and 200 µg/ml. AGE of isolated DNA from treated cancer cells revealed characteristic ladder like fragmentation, a hallmark of apoptosis. HPLC profiling was carried out for identification of the active components, which demonstrated the presence of Withaferin A in the methanolic extract. CONCLUSION: Methanolic extract of WC possesses apoptotic activity against human breast cancer cells in vitro albeit lower in comparison to W. somnifera and warrants further investigation.

Correlation of Hormone Receptor and Human Epidermal Growth Factor Receptor-2/neu Expression in Breast Cancer with Various Clinicopathologic Factors.

BACKGROUND: A significant development in the breast carcinoma management is the correlation between the presence of hormone receptors in the tumor and response to hormonal therapy and chemotherapy. Human epidermal growth factor receptor-2/neu (Her-2/neu) overexpression also serves as a very useful parameter to predict response to herceptin. AIM OF STUDY: The study was conducted to correlate immunohistochemical expression of markers such as estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu with various clinicopathologic parameters. MATERIALS AND METHODS: The study included 509 cases of breast carcinoma over a period of 5 years (from May 2009 to May 2014). Immunohistochemistry (IHC) for ER, PR, and her-2/neu was performed. RESULTS: ER positivity was observed in 42.8% (218/509) cases, PR positivity in 31.8% (194/509) cases whereas her-2 neu positivity was seen in 40.7% (203/509) cases. Triple marker (ER, PR, and Her-2/neu) negative cases were 23.6% (120/509) cases. ER and PR expression was found to have a statistically significant correlation with tumor grade. Statistically significant correlation was observed between tumor size and tumor grade and her-2/neu expression. Her-2/neu expression showed statistically significant association with tumor stage. As the tumor grade increased, the proportion of triple-negative cases went on increasing, which was statistically significant. CONCLUSION: IHC has an increasingly important prognostic role in determination of factors that affect clinicopathologic features. Nevertheless, the results of this large series showed different patterns of findings with respect to clinicopathologic features.

Circulating Tumor Cells in Breast Cancer: Correlation with Clinicopathological Parameters, Hormone Profile and MicroRNA Polymorphisms.

OBJECTIVE: Circulating tumor cells are isolated tumor cells in the peripheral blood that serve as important prognostic indicators for many kind of tumors. The study was conducted to know the rate of detection of circulating tumor cells among breast cancer patients in comparison with benign breast diseases and control subjects and to know the association between CTC positivity and various clinicopathological parameters, hormonal profile and microRNA polymorphisms. MATERIAL AND METHOD: In the present case control study, we included 182 healthy controls, 108 cases of benign breast disease and 114 breast carcinoma cases. Various clinicopathological details of cases were recorded. Immunohistochemistry was performed for estrogen (ER) and progesterone receptors (PR) and Her-2 neu. Circulating tumor cells were analyzed using flow cytometry (EpCAM, CK, CD45). Genotypic frequency of micro RNA polymorphisms was determined by PCR-RFLP assay. RESULTS: Circulating tumor cell positivity was observed in 11/114 (9.64%) breast cancer cases but absent in benign and control groups, and was significantly associated with tumor size, histologic type, tumor grade, metastasis and skin infiltration (p < 0.05). Circulating tumor cell positivity did not show any correlation with the immunohistochemical profile. No significant associations between pre-miRNA genetic variations miR-196a2 C/T (rs11614913), miR-146a G/C (rs2910164) and miR-499 T > C (rs3746444) polymorphisms and circulating tumor cell positivity were observed. CONCLUSION: The flow cytometry protocol for detection and molecular characterization of circulating tumor cells is a time and cost-effective technique, suitable for routine clinical use. However, more elaborate studies are needed to establish the findings as our study was limited by small sample size.

Role of human papilloma virus in oral leukoplakia.

BACKGROUND: Controversy surrounds regarding the role of human papillomavirus (HPV) in oral precancerous and cancerous lesions in India where smokeless, tobacco consumption is rampant. AIMS: The present study was carried out with an aim to investigate the presence and type of HPV infection in oropharyngeal leukoplakia and to determine the association of HPV positivity with various patient and lesion characteristics. SETTINGS AND DESIGN: Prospective case series. MATERIALS AND METHODS: A total of fifty confirmed cases of oral leukoplakia (OL), aged 18-55 years were enrolled in the study. Specimens were obtained from the site of lesion. All the specimens were subjected to histopathological analysis and HPV-16, 18 detection was done using real-time polymerase chain reaction technique. RESULTS: Mean age of patients was 34.00 ± 8.85. Majority were males (62%), from middle social class (78%) and were educated up to graduation or above (54%). All the patients had one or more adverse habits (betel, chewing tobacco, smoking and alcohol) with mean duration of disease was 3.53 ± 3.05 years. Five patients (10%) had diabetes. Burning sensation (86%) and trismus (36%) were the reported complaints. Maximum were Stage II (50%), sized 2-4 cm2 (60%), homogenous (70%). Floor of mouth and tongue were most commonly involved sites (50%). Majority had mild dysplasia (58%). Acanthosis (66%), hyperplasia (62%), koliocytosis (40%), and keratosis (98%) were quite common. HPV (16/18) could not be detected in any specimen. CONCLUSIONS: The present study highlighted the fact that association of HPV with oral leukoplakia seems to be overestimated and needs to be reexamined with consensus Human papilloma virus (HPV) primers to detect HPV types with more valid empirical relationships.

Evaluation and Comparison of the In Vitro Cytotoxic Activity of Withania somnifera Methanolic and Ethanolic Extracts against MDA-MB-231 and Vero Cell Lines.

Withania somnifera Dunal (WS), commonly known as Ashwagandha in India, belongs to the family Solanaceae. It is extensively used in most of the Indian herbal pharmaceuticals and nutraceuticals. In the current study, the in vitro cytotoxic activity of methanolic, ethanolic, and aqueous extracts of WS stems was evaluated using cytometry and the MTT assay against the MDA-MB-231 human breast cancer cell line. Methanolic and ethanolic extracts of WS showed potent anticancer activity on the MDA-MB-231 human breast cancer cell line, whereas the aqueous extract did not exhibit any significant activity at 100 µg/ml. The percentage viability of the cell lines was determined by using the Trypan blue dye exclusion method. Cell viability was reduced to 21% and 0% at 50 and 100 µg/ml of the methanolic extract, respectively, as compared to 19% and 0% at 50 and 100 µg/ml for the ethanolic extract and 37% at 100 µg/ml in sterile Milli-Q water after 48 hours of treatment. Methanolic and ethanolic extracts of WS were shown to possess IC50 values of 30 and 37 µg/ml, respectively, by the MTT assay and cytometer-based analysis, with the methanolic extract being more active than the other two. On the other hand, methanolic and ethanolic extracts of WS did not exhibit any significant in vitro activity against the normal epithelial cell line Vero at 50 µg/ml. HPLC was carried out for the analysis of its phytochemical profile and demonstrated the presence of the active component Withaferin A in both extracts. The methanolic and ethanolic extracts of Withania should be studied further for the isolation and characterization of the active components to lead optimization studies.

Effect of methyl butyrate aroma on the survival and viability of human breast cancer cells in vitro.

BACKGROUND: Aroma can have far reaching effects on mind, body and soul. Pleasant aromas are known to have a soothing effect on the mind and are known to relieve stress and enhance concentration. Recently, it has been demonstrated that aroma may also have some curative effects as well as benefits and can be used both for prophylaxis and therapy of diseases. Our aim was to test our hypothesis whether aroma can cure or prevent cancer. Methyl butyrate (MB) is the methyl ester of butyric acid having a characteristic sweet and fruity odor like that of apples and pineapples. It occurs in many plant products in minute quantities and in pineapple oil. METHODS: In the present study, the effect of aroma of MB has been evaluated on human breast cancer cell line MDA-MB-231 in vitro. The percentage viability of the cell line was determined by using Trypan blue dye exclusion assay. RESULTS: It was found that MB at a concentration of 0.01M was effective in causing considerable cytotoxicity (40%) in breast cancer cells (without even coming in contact with cells) while at 0.02M, % cytotoxicity was found to be 50%. Mechanism of action of MB on cancer cells was investigated by acridine orange-ethidium bromide assay using fluorescence microscopy and DNA fragmentation assay. MB aroma appeared to induce necrosis in cancer cells exposed to it. CONCLUSION: No study involving the effect of aroma/smell on cancer cells has ever been reported before and warrants further investigation on other cancer and normal cell lines.

A rare case of giant vaginal fibromyoma.

Vaginal fibroids rarely exist as a primary vaginal tumor. Approximately 300 cases have been reported in the literature. Here we are reporting a rare case of giant vaginal fibromyoma. It was diagnosed as cervical fibroid polyp preoperatively but found to be vaginal fibromyoma peroperatively.

Clinico-pathological Profile of Bronchogenic Carcinoma Among Females in North India.

OBJECTIVE: The present study was undertaken to explore the clinico-pathological profile of bronchogenic carcinoma among females. METHODS: One hundred and twenty-four female patients with histopathologically proven bronchogenic carcinoma who were hospitalised in the Department of Pulmonary Medicine, King George's Medical University, Lucknow from July 1985 to February 2007 were retrospectively studied. RESULTS: Their mean age was 61 years; 12.9% of these were less than 40 years of age. Of these, 79% of female patients of lung cancer were first regarded as pulmonary tuberculosis; 76% belonged to rural area. Use of biomass fuel and kerosene oil exposure was the predominant risk factors evident among the 116 non-smoker women. Adenocarcinoma was observed in 43.5%, followed by squamous cell carcinoma in 33.1% and the remaining 23.4% cases were small cell carcinoma. The majority (77.4%) of non-small cell lung cancer (NSCLC) patients had advanced stage disease (I]Ib and IV) and 58% of small cell lung cancer (SCLC) patients had limited disease and 42% of SCLC patients had extensive disease at the time of diagnosis. CONCLUSION: Adenocarcinoma was found to be the most common histopathological type of bronchogenic carcinoma among these females.

Common genetic variants in pre-microRNAs and risk of breast cancer in the North Indian population.

OBJECTIVE: MicroRNAs (miRNAs) are short regulatory RNAs that can modulate gene expression and function as negative regulators. Common genetic variants like single nucleotide polymorphisms (SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences in carcinogenesis. Therefore, we evaluated the genetic variants in pre-miRNAs: hsa-miR-146a G/C (rs2910164), hsa-miR-196a2 C/T (rs11614913), and hsa-miR-499 T>C (rs3746444) for their role in breast cancer susceptibility. STUDY DESIGN: The study comprised 121 breast cancer patients, 115 with benign breast disease, and 164 controls. The genotypic frequency of miRNA polymorphisms was determined by PCR-RFLP assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. In silico analysis was done using various bioinformatics tools (F-SNP, FAST-SNP). RESULTS: The heterozygous variant of miR-146a G/C (rs2910164) is associated with the reduced risk of breast cancer at the genotype level as well as at the allele level (p < 0.05, OR = 0.5) as compared to controls. On the contrary, no significant difference was observed in the distribution of miR-196a2 C/T (rs11614913) and miR-499 T>C (rs3746444) polymorphisms in any groups both at genotype and allele levels. On the other hand, in multivariate analysis, we found that the miR-196a2 (rs11614913) C>T was associated with an increased risk of breast cancer risk in postmenopausal females (p = 0.02, OR = 3.2). We also attempted to find out the risk of malignant breast disease in relation to each of the above SNPs on dividing our data on the basis of benign and malignant status, but no significant difference was observed. In silico analysis using F-SNP showed change in transcriptional regulation by miR-146a G/C (rs2910164), miR-196a2 C/T (rs11614913) and miR-499 T>C (rs3746444) variations; the functional score was 0.100, 0.065 and 0.277, respectively. CONCLUSION: The results of the present study demonstrate that miR-146a G/C (rs2910164) polymorphism is associated with reduced genetic susceptibility to breast cancer. However, multivariate analysis showed as miR-196a2 (rs11614913) C>T to be associated with increased risk of breast cancer risk in postmenopausal females. Further multicentric studies involving a large number of cases need to be carried out to strengthen the present results.

Grading systems in the cytological diagnosis of breast cancer: a review.

In developing countries, diagnosis of breast carcinoma is still made on fine-needle aspiration cytology (FNAC). For the resource-poor settings, FNAC is cheaper, less invasive and can sample different areas of the lesion compared with core needle biopsy. The role of breast FNA is usually limited to just categorize the lesion as benign or malignant. Prognostic information from cytomorphology, conveyed to the clinician depends upon the cytopathologist's way of formatting the report. PubMed-based literature search collated the information from articles describing the architectural and cytological features studied on breast aspiration smears. This review focuses on cytomorphological features and the different grading systems with their strengths, short-comings, and practical applicability. Eight worldwide articles proposing new methods of grading the cytological smears from breast cancers were published between 1980 and 2006. All the grading methods were developed for the most common type of breast cancer, that is, infiltrating duct carcinoma (not otherwise specified) type, and most of the workers used Papanicolaou-stained smears for the purpose of grading. Moreover, if interpreted carefully FNAC smears can convey information on most of the histological features. Hence, in developing countries, the focus should be on extracting the maximum information from cytological smears, so that a more precise "surgical pathology" type diagnosis can be given, instead of merely reporting as benign or malignant. Among all the discussed grading systems, we suggest grading system by Howell would be most appropriate and closest to the accepted histologic grading system as it applies Scarff-Bloom-Richardson histological grading system with modifications on FNA smears. We recommend it to be followed by all cytopathologists, in order to bring uniformity in the reporting of breast FNAs for grading the malignant lesions.

Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast.

BACKGROUND: Aim of this study was to investigate the prognostic significance of CD3+ TILs in infiltrating ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Immuno-histochemistry was done with CD3 antibodies in tissue sections of 127 breast cancer patients, and CD3+ intra-tumoral and stromal TILs were counted in relation to clinico-pathological variables. RESULTS: Intra-tumoral and stromal CD3+ TILs were significantly associated with positive lymph node status (P = 0.006, P = 0.043, respectively) without significant association with age, menopausal status, family history, and hormonal status. The higher CD3 intra-tumoral and stromal counts both showed significant association with good prognosis (P = 0.039, P = 0.044, respectively). The intra-tumoral count was higher than stromal count and was independently associated with disease-free survival in stage I and II cancer (P = 0.021). CONCLUSIONS: CD3+ TILs may serve as independent marker of good prognosis in IDC breast. The findings of this study need further validation on a larger sample size.

Solitary cylindroma with malignant transformation.

A 59-year-old woman presented with a history of rapidly progressive recurrent tumor of 6.5 cm diameter of the scalp. Histopathological examination revealed a case of malignant cylindroma. There has been no recurrence or metastases and the patient is disease free at the end of 15 months postoperatively. Malignant transformation occurs less often in solitary form of cylindroma, but once transformed, tumors behave aggressively with extensive local infiltrative growth or metastases. The case is reported to document a rare case of malignant cylindroma arising in a patient with solitary cylindroma on the parieto-temporal region.

Comparative evaluation of the modified Scarff-Bloom-Richardson grading system on breast carcinoma aspirates and histopathology.

BACKGROUND: Fine needle aspiration (FNA) is a quick, minimally invasive procedure for evaluation of breast tumors. The Scarff-Bloom-Richardson (SBR) grade on histological sections is a well-established tool to guide selection of adjuvant systemic therapy. Grade evaluation is possible on cytology smears to avoid and minimize the morbidity associated with overtreatment of lower grade tumors. AIM: The aim was to test the hypothesis whether breast FNA from the peripheral portion of the lesion is representative of Scarff-Bloom-Richardson grade on histopathology as compared to FNA from the central portion. MATERIALS AND METHODS: Fine-needle aspirates and subsequent tissue specimens from 45 women with ductal carcinoma (not otherwise specified) were studied. FNAs were performed under ultrasound guidance from the central as well as the peripheral third of the lesion for each case avoiding areas of necrosis/calcification. The SBR grading was compared on alcohol fixed aspirates and tissue sections for each case. RESULTS: Comparative analysis of SBR grade on aspirates from the peripheral portion and histopathology by the Pearson chi-square test (χ(2) =78.00) showed that it was statistically significant (P<0.001) with 93% concordance. Lower mitotic score on aspirates from the peripheral portion was observed in only 4 out of 45 (9%) cases. The results of the Pearson chi-square test (χ(2) = 75.824) with statistically significant (P=0.000). CONCLUSION: This prospective study shows that FNA smears from the peripheral portion of the lesion are representative of the grading performed on the corresponding histopathological sections. It is possible to score and grade by SBR system on FNA smears.

Primary hydatid cyst in the soft tissue of the face: an exceptional occurrence.

To emphasize that solitary hydatid cyst can be localized in the soft tissue and present as a soft tissue mass even in an unusual site like face, we report the case of a 42-year-old male patient presenting with a slowly growing mass in right temporal region. Computed tomography (CT) scan showed an encapsulated mass with multiple cysts. Histopathological examination revealed the characteristic findings, which were consistent with soft-tissue hydatid disease. In the absence of visceral organ involvement, this is the first reported case of a primary subcutaneous hydatid cyst in the skin of face in India. In the English literature, only one case of this kind has been reported till date. When imaging methods confirm cystic nature of a swelling, even in unusual sites, one should always keep a possibility of hydatid cyst and manage accordingly during surgery to avoid precipitation of acute anaphylaxis.

A case-control study of bidi smoking and bronchogenic carcinoma.

OBJECTIVE: To evaluate the risks imposed by tobacco smoking, in particular, bidi smoking, in the development of lung cancer. METHODS: Two hundred eighty-four histologically confirmed patients of bronchogenic carcinoma and 852 controls matched for age, sex, and socioeconomic status were interviewed according to a predesigned questionnaire. Effects of individual variables defining the various aspects of tobacco smoking, in particular, bidi smoking, were assessed using logistic regression models. RESULTS: 81.3% cases of bronchogenic carcinoma were ever smokers as compared with 42.2% among controls. The odd ratios for ever smoking, bidi smoking, and cigarette smoking were 5.9 (confidence interval [CI] 4.3, 8.4), 6.1 (CI 4.3, 8.7), and 5.3 (CI 2.7, 10.4), respectively. CONCLUSION: Bidi smoking poses a very high risk for lung cancer even more than that of cigarette smoking.

Nuclear factor kappa-B and histopathology of chronic gastritis.

BACKGROUND: Studies suggest that nuclear factor kappa-B (NFkappaB) activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. MATERIALS AND METHODS: This study examines the expression and activity of NFkappaB in situ in antral biopsies of 42 consecutive patients with immunohistochemical techniques. RESULTS: NFkappaB was highly expressed in the gastric epithelial cells. The number of cells showing activated NFkappaB correlated with the activity of gastritis (P < 0.05), a measure of neutrophil influx, whereas no correlation was found with the chronicity of inflammation, a measure of the presence of mononuclear inflammatory cells. There was also a strong inverse association with the presence and grade of atrophy. CONCLUSION: This correlation is direct evidence of the importance of NFkappaB dependent signal transduction for neutrophil influx in gastritis. The role of NFkappaB appears to be only in the initial stages of gastritis, there is no role for the molecule in the development of chronic inflammation or atrophy.

Lipid peroxidation and antioxidants in different stages of cervical cancer: Prognostic significance.

BACKGROUND: Free radical Injury is associated with cancer, but how the extent of oxidative stress correlates with the FIGO (International Federation of Gynecology and Obstetrics) stage in Carcinoma Cervix (Ca Cx), and its significance as a prognostic marker, is not clear and needs an in-depth study. AIM: To correlate the blood levels of Lipid Peroxidation (LPO), Reduced Glutathione (GSH), Superoxide Dismutase (SOD), and Vitamin A and E levels with the clinical stage in Ca Cx. SETTINGS AND DESIGN: This is a Prospective Case Control Study. MATERIALS AND METHODS: LPO, SOD, reduced GSH were estimated by Bio Chemical Assays and Vitamins by High Performance Liquid Chromatography (HPLC). STATISTICAL ANALYSIS: The cases and controls were compared using One Way ANOVA and different stages over different time periods were individually compared by Repeated Measure Analysis of Variance. RESULTS: The results indicated a statistically significant increase of LPO vis-a-vis the FIGO stage of Ca Cx and control, while the antioxidant status as depicted by GSH and SOD decreased. Vitamin A and E levels were significantly lower in cancer cases as compared to the control. CONCLUSION: Increased LPO and reduced antioxidant levels may be taken as associated predictive markers, thus suggesting that Ca Cx cases should get nutritive supplements to contain the blood LPO level and maintain a positive balance of antioxidants for a better outcome in terms of delayed recurrence and better Quality of Life (QOL).