Reduced or absent cyclin H expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma

Bavi, Prashant; Abubaker, Jehad; Hussain, Azhar R.; Sultana, Mehar; Al‐Dayel, Fouad; Uddin, Shahab; Al‐Kuraya, Khawla S.

doi:10.1016/j.humpath.2007.10.014

Cited by 23 publications

(24 citation statements)

References 31 publications

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“…TMAs were constructed from formalin-fixed, paraffin-embedded ovarian cancer specimens as described previously. 21 Tumor regions were mapped by a pathologist for scoring. The TMA was constructed with 0.6 mm diameter cores spaced 0.8 mm apart using a modified Tissue Microarrayer (Beecher Instruments, Sun Prairie, WI, USA).…”

Section: Materials and Methods Patient Selection And Tma Constructionmentioning

confidence: 99%

HGF/c-Met pathway has a prominent role in mediating antiapoptotic signals through AKT in epithelial ovarian carcinoma

Uddin

Bavi

et al. 2011

Laboratory Investigation

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The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a variety of human malignancies. However, its role in epithelial ovarian carcinoma (EOC) has not been clearly elucidated. Therefore, we investigated the role of HGF/c-Met signaling pathway in a large series (156) of Saudi EOC patient samples, a panel of cell lines, and xenografts in a NUDE mouse model. Using immunohistochemistry, c-Met overexpression was found in 27.2% Middle Eastern EOC samples and was associated with an advanced tumor stage (P ¼ 0.0187). c-Met overexpression was also associated with antiapoptotic markers X-chromosome-linked inhibitors of apoptosis (XIAP) (P ¼ 0.0008) and Bcl-XL (P ¼ 0.0493) expression. Treatment of EOC cell lines with PHA665752 causes a dose-dependent inhibition of cell viability and induction of apoptosis. Furthermore, PHA665752 treatment causes dephosphorylation of AKT and downregulation of antiapoptotic proteins XIAP and Bcl-XL. In addition, PHA665752-induced apoptosis occurs through activation of Bax-mediated release of cytochrome c and activation of caspases. Finally, co-treatment of EOC with PHA665752 and cisplatin causes augmented effect on apoptosis of EOC cells and resulted in synergistic inhibition of EOC xenograft tumor growth in NUDE mice. These results indicate that c-Met/HGF pathway may be a potential target for therapeutic intervention for treatment of EOC.

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Section: Materials and Methods Patient Selection And Tma Constructionmentioning

confidence: 99%

HGF/c-Met pathway has a prominent role in mediating antiapoptotic signals through AKT in epithelial ovarian carcinoma

Uddin

Bavi

et al. 2011

Laboratory Investigation

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“…89 Elevated cyclin H is associated with very high-risk gastrointestinal stromal tumors, and reduced or absent cyclin H expression correlates with lower proliferation in B-cell lymphoma. 90,91 The transcriptional regulation elicited by the CAK complex (cyclin H-CDK7-Mat1) impacts embryonic stem (ES) cell differentiation. The complex activates CDK1, CDK2, CDK4, and CDK6 through phosphorylation of the T-loop.…”

Section: Cyclins In the Regulation Of Stem Cellsmentioning

confidence: 99%

Cyclins and Cell Cycle Control in Cancer and Disease

Casimiro¹,

Crosariol²,

Loro³

et al. 2012

Genes & Cancer

197

134

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Cyclin D1 overexpression is found in more than 50% of human breast cancers and causes mammary cancer in transgenic mice. Dysregulation of cyclin D1 gene expression or function contributes to the loss of normal cell cycle control during tumorigenesis. Recent studies have demonstrated that cyclin D1 conducts additional specific functions to regulate gene expression in the context of local chromatin, promote cellular migration, and promote chromosomal instability. It is anticipated that these additional functions contribute to the pathology associated with dysregulated cyclin D1 abundance. This article discusses evidence that examines the functional roles that cyclin D1 may play in cancer with an emphasis on other cyclin family members that also may contribute to cancer and disease in a similar fashion.

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“…The IHC protocol was followed as described. 32 Primary antibodies used, their dilutions, and cut-off levels for evaluation are listed in the Online Supplementary Table S1. Immunohistochemical detection of FoxM1 was performed using antibody from Santa Cruz Bio Technology (SCBT, USA, clone K-19) which has been used previously and extensively validated.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…9 X-tile plots were constructed for assessment of biomarker and optimization of cut-off points based on outcome as has been described earlier. 32,34,35 The expression of CD10, BCL6 and MUM1 was used to classify tumors as germinal center B-cell (GC), like DLBCL and activated B cell (ABC), applying the decision tree described earlier. 36 …”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma

Uddin¹,

Hussain²,

Ahmed³

et al. 2012

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundFoxM1 has been shown to play a critical role in the pathogenesis of various epithelial malignancies. However, its role in lymphoid malignancies has not been fully clarified. We, therefore, investigated the role of FoxM1 expression in a large cohort of diffuse large B-cell lymphoma samples and panel of cell lines. Design and MethodsFoxM1 expression was investigated in a large series of diffuse large B-cell lymphoma tissues in a tissue microarray format by immunohistochemistry. Apoptosis was measured by flow cytometry and protein expression was detected by immunoblotting using diffuse large B-cell lymphoma cell lines following treatment with either pharmacological inhibitor of FoxM1 or small interference RNA knockdown strategy. Invasion/migration and soft agar colony assays were also performed following treatment with FoxM1 inhibitor. ResultsFoxM1 expression was detected in 84.6% of diffuse large B-cell lymphoma tumors and found to be significantly associated with proliferative tumor marker Ki67 (P<0.0001), matrix metalloproteinases-2 (P=0.0008), matrix metalloproteinases-9 (P=0.0002), S-phase kinase associated protein-2 (P<0.0001) and inversely associated with p27 expression (P=0.0215). Expression of small interference RNA targeted against FoxM1 or treatment of diffuse large B-cell lymphoma cells with thiostrepton caused its downregulation accompanied by decreased expression of matrix metalloproteinases-2 and matrix metalloproteinases-9. Inhibition of FoxM1 in diffuse large B-cell lymphoma cells also decreased invasive and migratory capability, and induced caspase dependent apoptosis via activation of the mitochondrial apoptotic pathway. Finally, combined thiostrepton and bortezomib at sub-toxic doses led to efficient apoptosis in diffuse large B-cell lymphoma cells. ConclusionsAltogether, these results suggest that FoxM1 is over-expressed in the majority of diffuse large Bcell lymphoma samples. These data also indicate that targeting FoxM1 signaling can serve as a potential therapeutic modality in the management of diffuse large B-cell lymphoma.Key words: diffuse large B-cell lymphoma, FoxM1, apoptosis, NHL therapy. B-cell lymphoma. Haematologica 2012;97(7):1092-1100. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Uddin S, Hussain AR, Ahmed M, Siddiqui K, Al-Dayel F, Bavi P, and Al-Kuraya KS. Overexpression of FoxM1 offers a promising therapeutic target in diffuse large Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma

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Reduced or absent cyclin H expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma

Cited by 23 publications

References 31 publications

HGF/c-Met pathway has a prominent role in mediating antiapoptotic signals through AKT in epithelial ovarian carcinoma

HGF/c-Met pathway has a prominent role in mediating antiapoptotic signals through AKT in epithelial ovarian carcinoma

Cyclins and Cell Cycle Control in Cancer and Disease

Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma

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