Clinical and prognostic significance of apoptotic profile in patients with newly diagnosed nodal diffuse large B-cell lymphoma (DLBCL)

Marković, Olivera; Marisavljević, Dragomir; Čemerikić, Vesna; Peruničić, Maja; Savić, Saša; Filipović, Branka; Mihaljević, Biljana

doi:10.1111/j.1600-0609.2010.01567.x

Cited by 23 publications

(15 citation statements)

References 42 publications

(66 reference statements)

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“…However, we have found no correlation between caspase-3 expression and expression of survivin. This is in the agreement with results of other studies conducted on human lymphomas (Martinez et al 2004, Markovic et al 2011. Moreover, our findings show that expression of caspase-3 was very low in all examined lymphomas.…”

Section: Discussionsupporting

confidence: 93%

“…In the papers of Zuo et al (2006Zuo et al ( , 2007 apoptotic index correlated positively with expression of survivin, whereas Li et al (2006) found a negative correlation between survivin expression and either AI or expression of caspase-3. No correlation between survivin expression and caspase-3 expression was found in Markovic et al (2011) and Martinez et al (2004).…”

Section: Discussionmentioning

confidence: 83%

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Survivin expression in correlation with apoptotic activity in canine lymphomas

Sokołowska¹,

Urbańska²

2017

Polish Journal of Veterinary Sciences

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Survivin regulates cell cycle and mitosis and has antiapoptotic properties. Because of its dual function survivin has been the subject of much research focusing on its role in tumorigenesis and the relationship between survivin expression and apoptotic and/or proliferative activity in many types of human tumor including non-Hodgkin's Lymphomas. Such studies have not been conducted in canine lymphomas. The aim of this study was to evaluate the expression of survivin in canine lymphomas of low (5/25) and high (20/25) grades in relation to apoptotic markers (apoptotic index and index of caspase-3). Survivin was found in all examined lymphomas. Most tumors (18/25) showed survivin expression in 10%-25% of positive cells. Only in single cases was lower (0-10% positive cells, 1/25) or higher (25%-50% and >50% positive cells, 5/25 and 1/25, respectively) survivin expression. No significant differences between mean values of either index of survivin or apoptotic index was found between low and high grade lymphomas. However, such a difference among lymphoma grades was shown regarding the caspase-3 index. No correlation between the survivin index and either the apoptotic index or caspase-3 index was found, irrespective of the method of quantification: in whole specimens or in areas of low and high survivin expression. Positive correlation was consistently noted only between both apoptotic markers. The results indicate that survivin is commonly expressed in canine lymphomas. It seems that survivin does not exhibit anti-apoptotic activity in canine lymphomas. Lack of correlation between survivin expression and apoptotic markers could indicate its potential role in cell cycle activation in lymphoma cells.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 83%

Survivin expression in correlation with apoptotic activity in canine lymphomas

Sokołowska¹,

Urbańska²

2017

Polish Journal of Veterinary Sciences

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“…Its overexpression has been associated with chemoresistance and a poor clinical outcome in patients with cancer, including DLBCL (15)(16)(17). As well, survivin inhibition has been demonstrated to sensitize tumors to cytotoxic drugs, including taxanes, etoposide, mitomycin C, and cisplatin in vitro and in vivo (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Combination of YM155, a Survivin Suppressant, with Bendamustine and Rituximab: A New Combination Therapy to Treat Relapsed/Refractory Diffuse Large B-cell Lymphoma

Kaneko

Mitsuoka

Amino

et al. 2014

Clinical Cancer Research

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Purpose: There remains an unmet therapeutic need for patients with relapsed/refractory diffuse large Bcell lymphoma (DLBCL). The purpose of this study was to evaluate the therapeutic potential of sepantronium bromide (YM155), a survivin suppressant, in combination with either bendamustine or both bendamustine and rituximab using DLBCL models.Experimental Design: Human DLBCL cell lines, DB, SU-DHL-8, and WSU-DLCL2, were treated with YM155 in combination with bendamustine. Cell viability, apoptosis induction, protein expression, and cellcycle distribution were evaluated. Furthermore, antitumor activities of YM155, in combination with bendamustine or both bendamustine and rituximab, were evaluated in mice bearing human DLBCL xenografts.Results: The combination of YM155 with bendamustine showed greater cell growth inhibition and sub-G 1 population than either agent alone. YM155 inhibited bendamustine-induced activation of the ATM pathway and accumulation of survivin at G 2 -M phase, with greater DNA damage and apoptosis than either single agent alone. In a DLBCL DB murine xenograft model, YM155 enhanced the antitumor activity of bendamustine, resulting in complete tumor regression without affecting body weight. Furthermore, YM155 combined with bendamustine and rituximab, decreased FLT-PET signals in lymph nodes and prolonged overall survival of mice bearing disseminated SU-DHL-8, an activated B-cell-like (ABC)-DLBCL xenografts when compared with the combination of either rituximab and bendamustine or YM155 with rituximab.Conclusions: These results support a clinical trial of the combination of YM155 with bendamustine and rituximab in relapsed/refractory DLBCL.

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“…3 The cause of most DLBCL remains unknown; however, dysregulation of apoptosis or defective repair plays a role in its pathogenesis. 4,5 Forkhead box protein M1 (FoxM1) is a member of the FoxM family that consists of more than 50 proteins that are characterized by a conserved 100 amino acid DNA binding domain. 6,7 Deregulation of FoxM1 has been implicated in the pathogenesis of many cancers because of its ability to drive cell cycle progression and prevention of growth arrest.…”

Section: Introductionmentioning

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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Clinical and prognostic significance of apoptotic profile in patients with newly diagnosed nodal diffuse large B-cell lymphoma (DLBCL)

Cited by 23 publications

References 42 publications

Survivin expression in correlation with apoptotic activity in canine lymphomas

Survivin expression in correlation with apoptotic activity in canine lymphomas

Combination of YM155, a Survivin Suppressant, with Bendamustine and Rituximab: A New Combination Therapy to Treat Relapsed/Refractory Diffuse Large B-cell Lymphoma

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

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