Do tobacco stimulate the production of nitric oxide by up regulation of inducible nitric oxide synthesis in cancer: Immunohistochemical determination of inducible nitric oxide synthesis in oral squamous cell carcinoma--a comparative study in tobacco habituers and non-habituers.

BACKGROUND: Oral cancer accounts for 6% of all cancers. The most prevalent form of oral cancer is oral squamous cell carcinoma (OSCC), which accounts for 90% of the oral cancer cases. The major risk factor for development of OSCC is the use of tobacco in various forms. NO has been studied widely over the years due to its role in various physiological and pathophysiological processes, including its complex role in carcinogenesis. MATERIALS AND METHODS: A total of 20 cases of OSCC in tobacco habituers and tobacco non-habituers were retrieved respectively from the archival biopsy specimens. Immunohistochemistry was done to assess the inducible nitric oxide synthase (iNOS) protein. RESULTS: This study was performed to assess the correlation between tobacco and nitric oxide in OSCC in order to know the association of these two in the process of carcinogenesis. The results showed the enhanced expression of iNOS in tobacco habituers in comparison with tobacco non-habituers. Though the increased expression of iNOS is found, significant difference is not obtained with scores, but significant difference was found with intensity of staining. CONCLUSIONS: The results of the present study indicate the enhanced expression in OSCC of tobacco habituers when compared to OSCC of tobacco non-habituers indicating the effect of tobacco on nitric oxide. Carcinogenic chemical compounds in Tobacco induce nitric oxide production by iNOS, by its tumor-promoting effects which may enhance the process of carcinogenesis.

Volumetric breast composition analysis: reproducibility of breast percent density and fibroglandular tissue volume measurements in serial mammograms.

BACKGROUND: Volumetric breast composition analysis represents a useful tool for assessing changes in breast composition over time. However, no data exist on the reproducibility of this method in serial mammograms. PURPOSE: To assess the reproducibility of two volumetric breast composition parameters, breast percent density (PD) and fibroglandular tissue volume (FTV), in consecutive mammograms. MATERIAL AND METHODS: Volumetric breast composition analysis to determine PD and FTV was performed in two consecutive unilateral mammograms of 211 patients. All mammograms were obtained on the same digital mammography unit within a maximum interval of 24 months. Volumetric data for analysis for both examinations were available for 174 patients. Thirty-two patients had successful volumetric analysis of additional consecutive examinations on a second digital mammography unit. Inter-examination correlation of measurements and absolute differences were analyzed. Bland-Altman analysis was performed to compare readings from different mammography units. RESULTS: Mean FTV remained constant over the study period. A reduction in PD of 0.5% and a mean increase in breast volume (BV) of 3% were observed. FTV measurements obtained on the same mammography unit were significantly more reproducible than PD measurements (Pearson correlation coefficients of 0.947 and 0.920, respectively; P < 0.05). A 15% difference between mean absolute volume measurements (FTV and BV) obtained on different mammography units was observed (P ≤ 0.001), while mean PD was close to the expected value. CONCLUSION: Volumetric breast composition analysis is highly reproducible in serial mammograms in normal women. FTV is a more reproducible parameter than PD, indicating that absolute quantification of breast parenchyma may be preferable to the measurement of relative parameters such as PD. However, a disadvantage of using FTV is that it is susceptible to systematic differences when measurements are obtained on different imaging platforms.

Clinical and molecular features associated with cystic visceral lesions in von hippel-lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) is an uncommon oncogenic disorder which occurs as a result of genetic mutations on chromosome 3p. Retinal capillary haemangiomas and CNS haemangioblastomas have been well-characterised in genotypic-phenotypic analyses, but cystic visceral lesions are less common and have been less frequently studied. The aim of this study was to perform genotypic and phenotypic analysis of a cohort of VHL patients that developed cystic visceral lesions to determine whether their genotype differs from that seen in other manifestations of VHL and whether the ocular manifestations differ. METHODS: This study reports a prospective case series of twenty-one patients identified from the Hammersmith Hospital Genetics Service database as having VHL mutations. Patients underwent regular ocular and systemic screening as well as genotypic analysis. The main outcome measures were the development of VHL lesions, either ocular or systemic. RESULTS: Cystic visceral lesions were detected in six of the 21 patients from the clinic (29%). These included renal cysts in four patients, pancreatic cysts in three patients, and an epididymal cystadenoma in one patient. Renal cysts were not associated with any specific genotype. Pancreatic cysts appeared to occur in association with VHL gene deletions and all developed CNS haemangioblastomas. Only one patient developed ocular manifestations, which occurred in this patient in the form of two retinal capillary haemangiomas. CONCLUSIONS: VHL gene deletions appeared to be associated with pancreatic cysts and the development of CNS haemangioblastomas. Ocular manifestations are uncommon in this group of patients.

Adenovirus-delivered short hairpin RNA targeting PKCalpha improves contractile function in reconstituted heart tissue.

PKCalpha has been shown to be a negative regulator of contractility and PKCalpha gene deletion in mice protected against heart failure. Small interfering (si)RNAs mediate gene silencing by RNA interference (RNAi) and may be used to knockdown PKCalpha in cardiomyocytes. However, transfection efficiencies of (si)RNAs by lipofection tend to be low in primary cells. To address this limitation, we developed an adenoviral vector (AV) driving short hairpin (sh)RNAs against PKCalpha (Ad-shPKCalpha) and evaluated its potential to silence PKCalpha in neonatal rat cardiac myocytes and in engineered heart tissues (EHTs), which resemble functional myocardium in vitro. A nonsense encoding AV (Ad-shNS) served as control. Quantitative PCR and Western blotting showed 90% lower PKCalpha-mRNA and 50% lower PKCalpha protein in Ad-shPKCalpha-infected cells. EHTs were infected with Ad-shPKCalpha on day 11 and subjected to isometric force measurements in organ baths 4 days later. Mean twitch tension was >50% higher in Ad-shPKCalpha compared to Ad-shNS-infected EHTs, under basal and Ca(2+)- or isoprenaline-stimulated conditions. Twitch tension negatively correlated with PKCalpha mRNA levels. In summary, AV-delivered shRNA mediated highly efficient PKCalpha knockdown in cardiac myocytes and improved contractility in EHTs. The data support a role of PKCalpha as a negative regulator of myocardial contractility and demonstrate that EHTs in conjunction with AV-delivered shRNA are a useful model for target validation.