Manipal University

About: Manipal University is a education organization based out in Manipal, Karnataka, India. It is known for research contribution in the topics: Population & Health care. The organization has 9525 authors who have published 11207 publications receiving 110687 citations.

Identifying novel targets of oncogenic EGF receptor signaling in lung cancer through global phosphoproteomics.

Abstract: Mutations in the epidermal growth factor receptor (EGFR) kinase domain occur in 10-30% of lung adenocarcinoma and are associated with tyrosine kinase inhibitor (TKI) sensitivity. We sought to identify the immediate direct and indirect phosphorylation targets of mutant EGFRs in lung adenocarcinoma. We undertook SILAC strategy, phosphopeptide enrichment, and quantitative MS to identify dynamic changes of phosphorylation downstream of mutant EGFRs in lung adenocarcinoma cells harboring EGFR(L858R) and EGFR(L858R/T790M) , the TKI-sensitive, and TKI-resistant mutations, respectively. Top canonical pathways that were inhibited upon erlotinib treatment in sensitive cells, but not in the resistant cells include EGFR, insulin receptor, hepatocyte growth factor, mitogen-activated protein kinase, mechanistic target of rapamycin, ribosomal protein S6 kinase beta 1, and Janus kinase/signal transducer and activator of transcription signaling. We identified phosphosites in proteins of the autophagy network, such as ULK1 (S623) that is constitutively phosphorylated in these lung adenocarcinoma cells; phosphorylation is inhibited upon erlotinib treatment in sensitive cells, but not in resistant cells. Finally, kinase-substrate prediction analysis from our data indicated that substrates of basophilic kinases from, AGC and Calcium and calmodulin-dependent kinase groups, as well as STE group kinases were significantly enriched and those of proline-directed kinases from, CMGC and Casein kinase groups were significantly depleted among substrates that exhibited increased phosphorylation upon EGF stimulation and reduced phosphorylation upon TKI inhibition. This is the first study to date to examine global phosphorylation changes upon erlotinib treatment of lung adenocarcinoma cells and results from this study provide new insights into signaling downstream of mutant EGFRs in lung adenocarcinoma. All MS data have been deposited in the ProteomeXchange with identifier PXD001101 (http://proteomecentral.proteomexchange.org/dataset/PXD001101).

A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma.

Abstract: Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade Targeted therapies have emerged as one of the most promising approaches to treat several malignancies Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 975% (39/40) of HNSCC tissues analyzed Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC

A new algorithm for automatic assessment of the degree of TB-infection using images of ZN-stained sputum smear

Abstract: This paper describes a new algorithm for automatic assessment of the degree of TB-infection, by counting the number of Mycobacteria i.e., acid fast bacilli (AFB) in the color images of ZN-stained sputum smear. This algorithm consists of two stages. The first (“pre-processing”) stage involves exploiting color information to segment the candidate AFB in the image from the background, based on classification of pixels in the HSI color-space using Mahalanobis distance. In this context, we introduce a novel “divide and conquer” strategy to improve the robustness of color-classification. The pre-processing stage is followed by connected component labeling, size-thresholding to remove noisy objects, proximity-grouping by using a novel proximity-test algorithm, and area-based classification. Our algorithm identifies and counts the number of AFB irrespective of their shapes, can handle bacilli with beaded structure (which are important and are specific to TB) and has shown reasonable success in isolating clumps. A total of 205 images of ZN-stained sputum smears taken from more than 12 patients were considered in our experiments. Results on 169 images, based on HSI clusters built from 36 other images, are encouraging. Some of the images used in building the data-base and also in validation, include those sent by the RNTCP (Govt. of India) for training-purposes.

Simultaneous Estimation of Esomeprazole and Domperidone by UV Spectrophotometric Method.

Abstract: A novel, simple, sensitive and rapid spectrophotometric method has been developed for simultaneous estimation of esomeprazole and domperidone. The method involved solving simultaneous equations based on measurement of absorbance at two wavelengths, 301 nm and 284 nm, lambda max of esomeprazole and domperidone respectively. Beer's law was obeyed in the concentration range of 5-20 mug/ml and 8-30 mug/ml for esomeprazole and domperidone respectively. The method was found to be precise, accurate, and specific. The proposed method was successfully applied to estimation of esomeprazole and domperidone in combined solid dosage form.