Oral carcinogenesis and non-invasive biomarkers for the diagnosis of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most prevalent cancer in Pakistani population because of consumption of different tobacco-containing products whether smoked or chewed. These patients commonly report at a late stage of the disease. The patient's survival only depends upon early-stage diagnosis. Literature has reported that there is an increased tendency of transformation of oral potentially malignant disorder (OPMD) into OSCC. Biopsy is the gold standard measure for diagnosis but for OPMD cases biopsy was not recommended and most of the times the patients were also not willing to have a biopsy done. So, along with the biopsy there is a need for non-invasive protein biomarker that might aid in the early detection of oral cancer as well as highlight the high-risk individuals. This short communication focuses on the role of early diagnostic biomarkers present in literature, such as synuclein-γ (SNCG), Squamous cell carcinoma antigen (SCCAg), p53, MMPs-12, and IL-6. Furthermore, application of these biomarkers in multi-centre longitudinal studies is needed to establish their role as a non-invasive diagnostic biomarker for OSCC.

Phytochemical, enzymatic and biological studies of root extracts of Farsetia hamiltonii Royle.

Farsetia hamiltonii Royle is a medicinal plant of Cholistan desert, Pakistan, traditionally used for treating diabetes, oxidative stress, arthritis, fever, gastrointestinal and respiratory diseases. This study represents unprecedented phytochemical, enzymatic and biological properties of F. hamiltonii root extracts to prove floric uses. Evaluation of Phytochemical constituents was done by screening, total flavonoid, phenolic contents and gas chromatography-mass spectrometry. The phytochemical screening revealed the presence of glycosides, bounded anthraquinones, flavonoids, saponins, steroids, coumarins and diterpenes in root extracts. Eight compounds were identified in dichloromethane extract, whereas one compound was identified in methanol extract of root part of F. hamiltonii. The dichloromethane extract possesses significant lipoxygenase, chymotripsin and cholinesterase enzyme inhibition activities, whereas methanol extract possess lipoxygenase, alpha glucosidase, chymotrypsin and acetylcholinesterase enzyme inhibition activities. The antibacterial activity of methanol extract was significant against selected five microbial strains. Nine compounds were reported in root part of F. hamiltonii first time. The enzyme inhibition assays on anti-cholinesterase, anti-alpha glucosidase, antilipoxygenase, antichymotripsin and antibacterial activities were found significant for the extracts of root parts of F. hamiltonii. Therefore, results of this study justify folkloric therapeutic potential of F. hamiltonii root in treating diabetes, inflammations and infectious diseases.

Genetic profiles of different ethnicities living in Karachi as regards to tobacco-metabolising enzyme systems and the risk of oral cancer.

OBJECTIVE: To detect polymorphisms of CYP1A1, GSTM1 and GSTT1 gene loci among various tobacco-consuming ethnicities in an urban centre, and to relate these with susceptibility to oral cancer. METHODS: The cross-sectional, case-control study was conducted at Ziauddin University, Karachi, and the Dow University of Health Sciences, Karachi, from 2011 to 2016, and comprised patients having oral squamous cell carcinoma in group A, with oral precancerous lesions in group B, and tobacco habit-matched controls in group C. Routine histopathology was followed by molecular analysis through polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism techniques. Data was analysed using SPSS 20. RESULTS: Of the 358 subjects, 150(42%) were in group A, 100(28%) in group B, and 108(30%) in group C. There were 190(53.1%) Urdu-speaking subjects, 42(11.7%) Memoni-speaking, 37(10.3%) Sindhi-speaking, 34(9.5%) Balochi-speaking, 25(7%) Pashto-speaking, 15(4.2%) Punjabi-speaking, and 15(4.2) of other ethnicities. Among the Urdu-speaking ethnicity, CYP1A1 MspI heterozygous variant was the most prevalent genotype ingroup A 50(66.7%), group B 37(62.7%) and group C 36(64.3%). The homozygous variant was equally distributed in group A 8(13.5%) and group B 10(13.3%), while it remained quite low in group C 4(7.1%). Homozygous genotype was most common in Pashto-speaking subjects in group A 4(57.1%). In Urdu-speaking subjects, GSTM1-null genotype was mostly found in group B 19(32.2%), while GSTT1-null genotype was most common in group A 12(16%). Other than Urdu-speaking, GSTM1-null variant was most frequent in Sindhi-speaking subjects in group B 8(80%). CONCLUSIONS: Intra-ethnic distribution of tobacco-metabolising enzyme genes can be considered an important contributor to oral cancer risk in the population of Karachi.

Ploxomer and ß-cyclodextrin; promising tools to improve solubility of dapoxetine through binary and ternary solid dispersion techniques.

Present study was aimed to formulate solid dispersions (SD) of Dapoxetine (DAPO), a drug with low water solubility with the help of PVP-30, Ploxomer-180 (P-180) and ß-cyclodextrin (CD) by physical mixing to enhance the water solubility and dissolution of drug. Binary and Ternary solid dispersions were prepared with different ratios of drug and polymer and were further evaluated the effects of polymer at individual level as well as when used in combination. The solid dispersions were whitish in color, irregular in shape and have some rough surface when illustrated under SEM. Percentage yield of SDs ranged from 81-95% described the method was structured and significant. Solubility studies were carried out in 0.1N Hcl solution and was observed a remarkable increase in solubility of BSD 8, BSD 12 and TSD 6. Furthermore, the formulations were characterized by FTIR and PXRD. P-180 found an exceptional solubility promoter when used alone and in combination with CD as well. A remarkable enhance in Solubility and dissolution of DAPO was investigated in formulation prepared with ternary SD of Pol-180 and CD.

Gene-gene and gene-environment interaction: An important predictor of oral cancer among smokeless tobacco users in Karachi.

OBJECTIVE: To determine the risk for oral cancer caused by simultaneous occurrence of more than one of the tested cytochrome P450 CYP1A1 MspI, glutathione S-transferase M1 null gnd Glutathione S-transferases T1 null gene polymorphisms. METHODS: The cross-sectional case-control study was conducted from December 2011 to October 2016 at the Ziauddin University, Karachi, in collaboration with Dow University of Health Sciences, Karachi, and comprised oral squamous cell carcinoma cases in group A and healthy tobacco habit-matched controls in group B. All investigations were done using standardised laboratory protocols. The outcomes were determined in terms of association of various combinations of cytochrome P450 1A1MspI, glutathione S-transferasesM1 null and glutathione S-transferases T1 null polymorphisms with oral cancer. Data was analysed using SPSS 20. RESULTS: Of the 238 subjects, 140(58.8%) were in group A and 98(41.2%) were in group B. Mean ages in group A and B were 47.1±12.22 and 41.6±14.58 years, respectively. Male/Female ratio in group A was 1.88:1 while 83.4% were using tobacco. When cytochrome P450 1A1MspI homozygous (m2/m2) and glutathione S-transferases M1 null variants occured simultaneously in an individual, an odds ratio of 12.8 (95% confidence interval: 1.20-135.5; p=0.03) among overall tobacco chewers was observed. For glutathione S-transferases M1 not null and glutathione S-transferases T1 null variant combination among overall tobacco users, the conferred odds ratio was 4.58 (95% confidence interval: 0.99-21.2; p=0.05). The other studied gene combinations did not reveal significant associations (p>0.05). CONCLUSIONS: A higher risk of oral squamous cell carcinoma was found to be associated with combined-gene polymorphisms of phase I and phase II enzymes than that attributed to a single-gene polymorphism.

Mutational Frequencies in Mycobacterial rpoB gene using GeneXpert/MTB Rif Assay in Rifampicin Resistant patients at a tertiary care setting in Urban Sindh, Pakistan: Analysis from a Five-Year Period.

OBJECTIVES: To assess the mutational frequencies in Mycobacterial rpoB gene using GeneXpert/MTB Rif Assay in rifampicin resistant patients during 2013-2017 at a tertiary care setting in Urban Sindh, Pakistan. METHODS: This Retrospective Descriptive Cross-Sectional Study was conducted at the TB laboratories, Ojha Institute of Chest Diseases, Dow University of Health Sciences. The record of 713 positive cases of Rifampicin Resistant Tuberculosis from January 2013 to December 2017 were analysed. These were diagnosed using GeneXpert® that detects mutations in the 81 base pair region of rpoB gene with the help of five molecular probes A, B, C, D and E. All invalid and extra pulmonary samples were excluded. RESULTS: In total, 713 cases were found to be rifampicin resistant during the five-year period, among which 374 (52.45%) were males while 339 (47.55%) were females. Among the five standard probes A, B, C, D and E, 97.48% of the cases had a single mutation. Among these, mutations in Probe E (66.48%) were the most common, followed by Probe B (14.3%) and Probe D (11.08%). Only 13 cases (1.82%) of double mutations and five cases (0.7%) of triple mutations were detected. CONCLUSION: The rpoB gene Probe E region 529-533 appears the most potent site for a mutation and development of rifampicin resistance in the rpoB gene in Mycobacterium tuberculosis, that encodes the ß-subunit of RNA polymerase. The most affected age-group in both males and females is 19-45 Years.

Life-time tobacco consumption and oral cancer among citizens of a high incidence metropolis.

OBJECTIVE: To analyse dose-response relationship between the common risk factor of tobacco consumption and oral lesions like squamous cell carcinoma and pre-cancerous lesions. METHODS: The cross-sectional case-control study was conducted at Ziauddin University, Karachi from 2011 to 2016, and comprised histologically-confirmed cases of oral squamous cell carcinoma in group A, clinically-diagnosed oral pre-cancerous lesions in group B, and habit-matched controls in group C. The subjects were enrolled from 2011 to 2016. Life-time tobacco exposure was calculated using chewing index and smoking index for comparison between cases and controls. Data was analysed using SPSS 20. RESULTS: Of the 358 subjects, 150(42%) were in group A with a mean age of 47.1±12.22 years, 100(28%) were in group B with a mean age of 34.17±13.78 years, and 108(30%) were in group C with a mean age of 41.6±14.58 years. Of all the group A patients, 125(83.33%) and 96(96%) in group B had a positive history of tobacco use, with tobacco-chewers being the most in numbers 172(68.8%). Exclusive smoking was seen in 11(4.4%) cases, 38(15.2%) patients were both tobacco-chewers and smokers, and 29(11.6%) were tobacco-free. Group A and B patients had life-time tobacco exposures either equal or lower compared to group C controls (p>0.05). CONCLUSION: Life-time tobacco exposure indices were either comparable or lower in patients compared to the controls.

Synthesis of TiO2 modified self-assembled honeycomb ZnO/SnO2 nanocomposites for exceptional photocatalytic degradation of 2,4-dichlorophenol and bisphenol A.

In this study, we have successfully synthesized honeycomb-like self-assembled structure of TiO2 modified ZnO/SnO2 nanostructure via co-precipitation method with exceptional high degradation activities for 2,4-dichlorophenol (2,4-DCP) and bisphenol A (BPA) pollutants. The as-prepared samples were calcined in tube furnace at high elevated temperature (700, 800 and 900 °C) for 1 h. Among the TiO2 modified samples, ZST10-700 showed higher charge separation as demonstrated from surface photovoltage spectroscopy, photoluminance and electrochemical curve. Surface morphology, crystallinity, optical property and different functional groups in the samples were determined with SEM, EDX, XRD, UV-Vis DRS and FTIR, respectively. Interestingly, 72% and 58% photocatalytic degradation efficiencies were achieved with optimized ZST10-700 for 2,4-DCP and BPA, respectively. In comparison, the pure ZS-700 only showed 36% and 29% photocatalytic degradation efficiencies, respectively. The improved photocatalytic degradation efficiencies of the optimized ZST10-700 are mainly due to improved charge separation and prolonged charge lifetime. It was further verified that by increasing calcination temperature, the photocatalytic activity decreased, and this is attributed to the formation of photo-inactive phases like Zn2SnO4 and ZnTiO3. We believe that this work will provide an effective strategy to construct ternary heterojunction for the elimination of pollutants.

Conventional clinical and prognostic variables in 150 oral squamous cell carcinoma cases from the indigenous population of Karachi.

OBJECTIVE: To analyze clinical and prognostic variables of Oral Squamous Cell Carcinoma (OSCC) cases from the indigenous population of Karachi and to correlate with the common risk factor of tobacco habit. METHODS: The study was conducted at Ziauddin University, Karachi. One hundred fifty OSCC cases were collected from the Oncology Department of Ziauddin University Hospital, North Nazimabad, Karachi and Otolaryngology ward of Civil Hospital, Karachi, during 2011 and 2015. The reporting included demographic details and variables like intra-oral subsites, clinical stage and histological grade. Recurrence of tumor after initial resection was also documented. RESULTS: The patient's population comprised of 98 males and 52 females. The mean age was 47.1± 12.22 (range:20-78 years). Maximum numbers were seen in the 41-50 years age group. Urdu-speaking community was the most affected ethnic group (n=75). Clinico-pathological analysis revealed that majority of cases were moderately differentiated (59%) and were either clinical stage II (35%) or IV (29%) tumors. The most common intra-oral subsite came out to be buccal mucosa of cheeks (56%) followed by lateral borders of tongue (21%), lips (13%), alveolar (6%), palate (2.6%) floor of mouth (1.3%), etc. Recurrence was observed in 08 out of 150 cases. All patients underwent primary resection±neck dissection and reconstruction where possible. CONCLUSIONS: Overall experience with oral squamous cell carcinoma shows that it has a high tendency for local invasion as well as dissemination to regional lymph nodes, i.e. cervical lymph nodes, both are associated with a poor prognosis. Preventable risk factor of tobacco chewing has been observed in majority of these cases.

Gender difference in components of metabolic syndrome among patients of type 2 diabetes.

BACKGROUND AND OBJECTIVES: Diabetes mellitus, hypertension, obesity and dyslipidemia are the integral components that constitute metabolic syndrome. It has emerged as cause of substantial mortality with gender difference. To compare the gender characteristics of metabolic syndrome in subjects of type 2 diabetes mellitus. METHODS: This observational comparative prospective study was conducted in medical ward of BVH Bahawalpur over period of 6 month from January 2014 to June 2014. Sample size of 100 diagnosed cases of type 2 diabetics (comprising equal number of males and females) were collected. As defined by WHO and IDF, variables of metabolic syndrome studied were BMI, hypertension, hyperglycemia and hyperlipidemia. The lipid values were interpreted in normal or high risk category by applying NCEP ATPIII criterion. Fasting sample were collected for sugar and lipid profile. Anthropometric, demographic and biochemical data was tabulated. Continuous and categorical variables were displayed as mean ± standard deviation and percentage respectively. Student 't' test was use to assess the difference for the lipid profile at 5% significance level. RESULTS: Female patients were found to be overweight, hypertensive and had uncontrolled hyperglycemia as compared to male subjects. Their systolic blood pressure was 150±25.75 and diastolic was 90±17mm/hg. The mean blood glucose concentration was 246.64±105mg/dl. In age group 35-44 years, the mean triglycerides and cholesterol levels in females were 184.54±42.05 and 192.5±34mg/dl respectively. HDL-C was 33.2±5.19mg/dl. In females with age group of 45-54 years, the mean concentration of triglycerides, total cholesterol and HDL-C were 217.75±77.6mg/dl, 190.95±14.4mg/dl and 31.75±3.8mg/dl respectively, and all were in high risk category when compared to cut off values determined by NCEP/ADA. While in females of age group 55-64 years, the values of TGs, total cholesterol and HDL-C were 204±154.11mg/dl, 200.09± 47.8 mg/dl and 33.4±4.6mg/dl respectively and again all these values were significantly raised. CONCLUSION: Female genders were affected in all respects. They had higher BMI, hypertension, hyperglycemia and hyperlipidemia as compared to male counterparts.