Browsing by Author "Barbhuiya, Mustafa A."

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    Calcium calmodulin dependent kinase kinase 2-a novel therapeutic target for gastric adenocarcinoma
    (2015) Subbannayya, Yashwanth; Syed, Nazia; Barbhuiya, Mustafa A.; Roa Strauch, Juan Carlos Enrique; Marimuthu, Arivusudar; Sahasrabuddhe, Nandini; Pinto, Sneha M.; Manda, Srikanth Srinivas; Renuse, Santosh; Manju, HC; Zameer, Mohammed Abdul Lateef; Sharma, Jyoti; Brait, Mariana; Srikumar, Kotteazeth; Raja, Remya; Vijaya Kumar, M.; Kumar, KV Veerendra; Prasad, TS Keshava; Ramaswamy, Girija; Kumar, Rekha Vijay; Pandey, Akhilesh; Gowda, Harsha; Chatterjee, Aditi
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    Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways
    (2015) Wu, Xinyan; Zahari, Muhammad Saddiq; Ma, Binyun; Liu, Ren; Renuse, Santosh; Sahasrabuddhe, Nandini A.; Chen, Lily; Chaerkady, Raghothama; Kim, Min-Sik; Roa Strauch, Juan Carlos Enrique; Zhong, Jun; Jelinek, Christine; Barbhuiya, Mustafa A.; Leal-Rojas, Pamela; Yang, Yi; Kashyap, Manoj Kumar; Marimuthu, Arivusudar; Ling, Min; Fackler, Mary Jo; Merino, Vanessa
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    Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer
    (2015) Subbannayya, Tejaswini.; García Cañete, Patricia; Roa Strauch, Juan Carlos Enrique; Leal Rojas, Pamela.; Barbhuiya, Mustafa A.; Raja, Remya.; Renuse, Santosh.; Sathe, Gajanan.; Pinto, Sneha M.; Syed, Nazia.
    Abstract Background Poor prognosis in gallbladder cancer is due to late presentation of the disease, lack of reliable biomarkers for early diagnosis and limited targeted therapies. Early diagnostic markers and novel therapeutic targets can significantly improve clinical management of gallbladder cancer. Methods Proteomic analysis of four gallbladder cancer cell lines based on the invasive property (non-invasive to highly invasive) was carried out using the isobaric tags for relative and absolute quantitation labeling-based quantitative proteomic approach. The expression of macrophage migration inhibitory factor was analysed in gallbladder adenocarcinoma tissues using immunohistochemistry. In vitro cellular assays were carried out in a panel of gallbladder cancer cell lines using MIF inhibitors, ISO-1 and 4-IPP or its specific siRNA. Results The quantitative proteomic experiment led to the identification of 3,653 proteins, among which 654 were found to be overexpressed and 387 were downregulated in the invasive cell lines (OCUG-1, NOZ and GB-d1) compared to the non-invasive cell line, TGBC24TKB. Among these, macrophage migration inhibitory factor (MIF) was observed to be highly overexpressed in two of the invasive cell lines. MIF is a pleiotropic proinflammatory cytokine that plays a causative role in multiple diseases, including cancer. MIF has been reported to play a central role in tumor cell proliferation and invasion in several cancers. Immunohistochemical labeling of tumor tissue microarrays for MIF expression revealed that it was overexpressed in 21 of 29 gallbladder adenocarcinoma cases. Silencing/inhibition of MIF using siRNA and/or MIF antagonists resulted in a significant decrease in cell viability, colony forming ability and invasive property of the gallbladder cancer cells. Conclusions Our findings support the role of MIF in tumor aggressiveness and suggest its potential application as a therapeutic target for gallbladder cancer.
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    PIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40kDa (PRAS40)
    (2019) Subbannayya, Tejaswini; Leal-Rojas, Pamela; Zhavoronkov, Alex; Ozerov, Ivan, V; Korzinkin, Mikhail; Babu, Niraj; Radhakrishnan, Aneesha; Chavan, Sandip; Raja, Remya; Pinto, Sneha M.; Patil, Arun H.; Barbhuiya, Mustafa A.; Kumar, Prashant; Guerrero-Preston, Rafael; Navani, Sanjay; Tiwari, Pramod K.; Kumar, Rekha Vijay; Prasad, T. S. Keshava; Roa, Juan Carlos; Pandey, Akhilesh; Sidransky, David; Gowda, Harsha; Izumchenko, Evgeny; Chatterjee, Aditi
    Gallbladder cancer (GBC) is a rare malignancy, associated with poor disease prognosis with a 5-year survival of only 20%. This has been attributed to late presentation of the disease, lack of early diagnostic markers and limited efficacy of therapeutic interventions. Elucidation of molecular events in GBC can contribute to better management of the disease by aiding in the identification of therapeutic targets. To identify aberrantly activated signaling events in GBC, tandem mass tag-based quantitative phosphoproteomic analysis of five GBC cell lines was carried out. Proline-rich Akt substrate 40kDa (PRAS40) was one of the proteins found to be hyperphosphorylated in all the invasive GBC cell lines. Tissue microarray-based immunohistochemical labeling of phospho-PRAS40 (T246) revealed moderate to strong staining in 77% of the primary gallbladder adenocarcinoma cases. Regulation of PRAS40 activity by inhibiting its upstream kinase PIM1 resulted in a significant decrease in cell proliferation, colony forming and invasive ability of GBC cells. Our results support the role of PRAS40 phosphorylation in GBC cell survival and aggressiveness. This study also elucidates phospho-PRAS40 as a clinical marker in GBC and the role of PIM1 as a therapeutic target in GBC.
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    Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer
    (2017) Weber, Helga; Valbuena Mora, José Rafael; Barbhuiya, Mustafa A.; Stein, Stefan; Kunkel, Hana; García Muñoz, Patricia; Bizama, Carolina; Riquelme, Ismael; Espinoza, Jaime A.; Kurtz, Stephen E.; Tyner, Jeffrey W.; Calderon, Juan Francisco; Corvalán R., Alejandro; Grez, Manuel; Pandey, Akhilesh; Leal Rojas, Pamela; Roa Strauch, Juan Carlos Enrique