2034 Background: KRN951 inhibits VEGF induced phosphorylation of VEGF receptors (VEGFR)2 and 1 (IC50 of 0.16 and 0.21 nM) and phosphorylation of c-Kit and Platelet Derived Growth Factor Receptor (PDGFR), (IC50 of 1.63 and 1.72 nM). Methods: The principal objectives of this study were (1) to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of KRN951 administered once daily (OD) for 28 days followed by 14 days off treatment, (2) to characterize safety and tolerability, (3) to characterize single and multiple dose pharmacokinetics, (4) to explore inhibitory effects on tumor blood flow, and (5) to look for evidence of antitumor activity. Results: 10 male and 5 female patients, median age 57 yrs (28–72) have been enrolled at dose levels of 1 mg (n=6), 2 mg (n=8), and 1.5 mg (n=1). The total number of courses given is 63 (1–15 per patient) At 2 mg DLT consisting of grade 3 asymptomatic proteinuria, grade 3 ataxia and grade 4 intracranial hemorrhage was seen in three patients. In the next-lower dose level of 1 mg one DLT (grade 3 fatigue) was seen. An intermediate dose of 1.5 mg is currently studied. Hypertension occurred in 14/15 patients but could be medically controlled. Pharmacokinetic analysis revealed dose dependent drug exposure and peak plasma concentrations. Plasma levels of sVEGFR2 decreased following exposure to KRN951. Exploratory analysis by means of Dynamic Contrast Enhanced MRI analysis indicated a decrease in tumorperfusion in selected patients. One confirmed partial response lasting more than 80 weeks in a patient with renal cell carcinoma was seen, and stable disease lasting more than 2 courses of treatment was seen in 6 patients. Conclusion: Once daily KRN951 can be administered safely when given for 28 days followed by 14 days off treatment. The recommended phase II dosing is currently being defined. No significant financial relationships to disclose.

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Objectives: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma(MEC) are the commonest salivary gland malignancies in Pakistan constituting almost 75%of all malignant salivary gland tumours. The objective of this study was explore the clinical &morphological spectrum of these tumours in local population and to grade them w.r.t. moderngrading criteria. Study Design: Descriptive study. Setting: Department of Morbid Anatomy andHistopathology/ Oral Pathology, University of Health Sciences Lahore, Pakistan. Period: Jan.2014 to Sep. 2015. Method: Paraffin embedded blocks and detailed clinical data of 20 caseseach of adenoid cystic carcinoma and mucoepidermoid carcinoma reported at local tertiarycare hospitals. The histologic diagnosis was made on Hematoxylin and Eosin staining. Thetumours were graded into grades I, II & III according to the most recent grading criteria. AdCCwas studied with respect to its morphological patterns (tubular, cribriform and solid) while MECwas studied with special concern to the cell types seen in it (mucous, intermediate, squamousand clear cells). Results: The most frequently observed age group for the patients of AdCCwas the 5th (45%) decade with mean age of 41.50±12.224 years and a female predilection of1.5:1. Minor salivary glands were the commonest site involved (80%) of which palate was mostfrequently affected (37.5%) followed by maxilla (25%). Grade I (75%) was most frequently notedgrade in AdCC. Cribriform pattern (60%) was the most frequently encountered predominanthistological pattern followed by equal distribution of tubular and solid Patterns (20% each).MEC affected most patients in 3rd (30%) decade with mean age of and 32.35±13.674 yearsand male predilection (60%). Parotid gland (70%) was the commonest site involved followedby maxilla (10%). Histologically, grade III (40%) was most frequently noted followed by gradeI (35%) and grade II (25%). Squamous cells (65%) were the predominant cell type in mostcases followed by mucous cells in (35%) cases. Conclusion: Adenoid cystic carcinoma andmucoepidermoid carcinoma both affect a younger age group in our population with a female(1.5:1) and male (1:1.5) predilection respectively. The most favoured site for AdCC and MEC ispalate and parotid gland respectively. Grade I AdCC and cribriform pattern are the commonestgrade and pattern encountered in this study. On the other hand, high grade (Grade III) MECis the most regularly encountered grade in MEC. So, proper grading and staging along withmeticulous surgical approach is needed to improve the life expectancy in these patients.

Background: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the commonest salivary gland malignancies in Pakistan constituting almost 75% of all malignant salivary gland tumours. Objective: The objective of this study was to determine the expression of galectin-3 (Gal-3) in AdCC and MEC of salivary glands and to see its relationship with histological differentiation in these tumours. Method: This descriptive study was conducted at the Department of Morbid Anatomy and Histopathology/ Oral Pathology, University of Health Sciences Lahore, Pakistan. Biopsies and detailed clinical data of 20 cases each of adenoid cystic carcinoma and mucoepidermoid carcinoma reported at local tertiary care hospitals from Jan. 2014 to Sep. 2015 were retrieved. The histologic diagnosis was made on Hematoxylin and Eosin staining. The tumours were graded into grades I, II & III according to the most recent grading criteria. AdCC was studied with respect to its morphological patterns (tubular, cribriform and solid) while MEC was studied with special concern to the cell types seen in it (mucous, intermediate, squamous and clear cells). Immunohistochemical expression of galectin-3 was determined in these tumours with respect to histological grades, patterns and cell types seen. Results: Moderate positivity (55%) for anti-galectin-3 antibody was the most frequently observed score for galectin-3 in both MEC and AdCC. Moderate positive (55%) staining reaction was followed by weak positive (30%) staining reaction in AdCC. Total score for antigalectin-3 antibody, positive stromal reaction (intensity) and location of cellular signals for anti-galectin-3 antibody were all found to be significantly associated with grades of AdCC. Also, histological pattern of AdCC (tubular, cribriform and solid) were significantly associated with type of anti-galectin-3 staining pattern of cells (p<0.001). In MEC, moderate positive (55%) staining for anti-galectin-3 antibody was followed by strong positive reaction (30%). The total score for anti-galectin-3 antibody was significantly associated with grades of the tumour and lymph node status. Also, the type of staining reaction in cells was significantly associated with cell type (mucous, squamous and intermediate cells). Conclusion: It can be concluded from the current study that expression of Gal-3 decreases with decreasing differentiation in parenchyma of malignant tumours while its expression in tumour extracellular environment increases with increasing grade of the tumour.Also, it can be concluded that nuclear expression of Gal-3 is associated tumour differentiation and cytoplasmic expression with tumour cell proliferation.