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Introduction/Background:Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67.Material and Methods:n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers.Results:Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis.Conclusion:Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.

ABSTRACT:OBJECTIVE: Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignant neoplasm in south Asia and a major public health problem in Pakistan due to its high morbidity and poor survival rates. The objective of the study was to describe the clinical pattern of oral squamous cell carcinoma in tertiary care hospitals of Lahore. METHODOLOGY:A cross sectional study was done at tertiary care hospitals of Lahore where demographic and clinical data of eighty nine histologically diagnosed cases of OSCC was studied. RESULTS:Mean age of the patients was 53.13 ±14.82 years and male to female ratio was 1.4:1 with 58.4%males and 41.6% females. Tongue was the most frequently affected site 37.1%followed by buccal mucosa 30.3%. The most common presenting complaint was non healing ulcer 50.6%.Mean duration of lesions at presentation was 5 ± 3.68 months. 66.3% cases reported with history of smoking, chewing tobacco/snuff and betel quid. Smoking was the most prevalent etiological agent accounting for 22.5% cases and was found to be significantly higher in the male population (p<0.001). CONCLUSIONS:Most cases of oral squamous cell carcinoma (OSCC) in major hospitals of Lahore, Pakistan are reported in 5th to 6 th decade of life, with male preponderance. Ulceration is the most common clinical manifestation in OSCC patients with about two-third cases reporting within 6 months of onset of lesions. Tongue is the most commonly affected site and smoking tobacco and betel quid chewing are the main risk factors implicated in OSCC.

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Nimbolide is an active constituent of Azadirachta indica and is known for its anti‐inflammatory, anti‐oxidant, immune‐modulatory, and anti‐cancer effects. Few studies suggest that nimbolide treatment influences the responses to rheumatoid arthritis, but the underlying molecular mechanisms involved are not yet well established. Therefore, the present study was designed to determine the effect of nimbolide on expression regulation of toll‐like receptors to attenuate rheumatoid arthritis. The rheumatoid arthritis model was established by injecting complete Freund's adjuvant (CFA) intra‐dermally into the sub‐plantar region of the left hind paw of rats. Nimbolide (20 mg/kg) and piroxicam (10 mg/kg) were given to arthritic rats. Rats treated with nimbolide showed a significant reduction in inflammatory cells, rheumatoid factor, ESR, and improved the body weight. The results indicated that nimbolide possesses the capacity to attenuate rheumatoid arthritis by downregulating toll‐like receptors, IL‐17, IL‐23, HSP70, and IFN‐γ expression levels. Nimbolide treatment showed significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to piroxicam, which is a standard non‐steroidal anti‐inflammatory drug used for the treatment of rheumatoid arthritis. It can be concluded that nimbolide can be considered as a potential candidate for therapeutic targeting of the toll‐like receptors pathway in rheumatoid arthritis.