The use of hypomethylating agents in the treatment of hematologic malignancies

Kihslinger, Jane E.; Godley, Lucy A.

doi:10.1080/10428190701493910

Cited by 35 publications

(25 citation statements)

References 55 publications

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“…About epigenetic therapeutic strategy the DNA demethylation agent combined with HDI have been shown to produce synergistic reactivation of anti-tumor effects to yield promising results in clinical studies (Kihslinger et al, 2007). Both quercetin and butyrate themselves exhibited combined effectiveness of demethylation and HDI in anti-human esophageal cancer 9706 cells.…”

Section: Discussionmentioning

confidence: 99%

Aberrant Epigenetic Alteration in Eca9706 Cells Modulated by Nanoliposomal Quercetin Combined with Butyrate Mediated via Epigenetic-NF-κB Signaling

Naigang¹,

Wang²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 15 (11), 4539-4543 IntroductionThere is close relationship between neoplasia and inflammation. Many cancers arise from sites of chronic inflammation or irritation, and an oncogenic change always induces an inflammatory microenvironment to promote development of tumors. Inflammatory conditions in selected organs increase the risk of cancer, and in the tumor microenvironment smoldering inflammation contributes to proliferation and cancer progression. Natural bioactive compounds exhibit anti-inflammatory modulation (Pan et al., 2009;Gupta et al., 2011). The dietary flavonoid quercetin and resveratrol have nonsteroidal anti-inflammatory activity that may have applications for anti-inflammation treatment (Donnelly et al., 2004;Tuñón et al., 2009). Our other experiment indicates that the pro-inflammatory cytokine IP-10 in co-cultured human esophageal cancer 9706 cells can be inhibited by the polyphenol quercetin. Prevention of cancer has to be associated with prevention of inflammation, especially chronic inflammation.Flavonoid quercetin is one kind of yellowish powdered crystalline compound, (C15H10O7 in structure with five OH groups), widespread in vegetables, fruits and some

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Section: Discussionmentioning

confidence: 99%

Aberrant Epigenetic Alteration in Eca9706 Cells Modulated by Nanoliposomal Quercetin Combined with Butyrate Mediated via Epigenetic-NF-κB Signaling

Naigang¹,

Wang²,

Yang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…This highlights the possibility that the mechanistic functions of azacitidine may be multifactorial. [29][30][31] Previous studies have shown the DNA methylation decrease with azacitidine treatment, though one must also entertain the possibility that DNA methylation reduction serves as a pharmacodynamic rather than a therapeutic marker. Up to 90% of azacitidine is incorporated into mRNA, while the deoxyribonucleoside structure in another DNMT inhibitor, 5-aza-2'-deoxycytidine (decitabine), leads to complete DNA incorporation.…”

Section: Discussionmentioning

confidence: 99%

A phase I biological study of azacitidine (Vidaza^TM) to determine the optimal dose to inhibit DNA methylation

Bernstein

Byun²,

Mohrbacher³

et al. 2010

Epigenetics

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“…Classical DNMT inhibitors (DNMTi's), including decitabine and azacitidine, can induce significant clinical responses and even prolong the survival of patients with higher-risk myelodysplastic syndrome 16,17 and are being actively investigated in other myeloid malignances. 18 These studies raise the possibility that DNMTi's might be useful in tumors with active DNA replication, such as DLBCL; however, the optimal dose schedule for these agents remains to be fully clarified.…”

Section: Non-hodgkin Lymphomas Ii: Breakthroughs In Treatment Of Highmentioning

confidence: 99%

Targeting the epigenome and other new strategies in diffuse large B-cell lymphoma: beyond R-CHOP

Cerchietti

Leonard

2013

Hematology

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Diffuse large B-cell lymphoma, the most common lymphoma subtype, is curable in the majority of patients. However, one of the greatest unmet needs in lymphoma treatment remains novel approaches to prevent relapsed or refractory disease. Genomic profiling has provided important prognostic information that is being used in the development of novel therapeutic strategies currently in clinical trials. It is clear, however, that epigenetic alterations provide an additional series of targets that can be pharmacologically modified and offer great potential to improving patient outcomes. Greater understanding of this area is providing important new insights that are now being explored in the clinical setting. Demethylating agents and drugs that disrupt histone modifiers are in early clinical trials with promising results, and other approaches targeting epigenetic pathways are in active preclinical and early clinical development. Selected novel approaches to target the epigenome in diffuse large B-cell lymphomaGenome-wide DNA methylation and histone modification patterning and next-generation sequencing leading to directed functional studies have vastly increased our understanding of epigenetic deregulation in diffuse large B-cell lymphoma (DLBCL). Most importantly, these analyses have revealed rational therapeutic targets for development (Table 1). Epigenetic alterations in lymphoma, in contrast to genetic lesions, are themselves pharmacologically reversible and therefore represent strategies for novel therapeutic approaches. In the clinical setting, epigenetic therapy is currently limited to pharmacologically tilting the balance in favor of histone acetylation and/or DNA hypomethylation to cause antilymphoma effects. Histone acetylation relaxes chromatin, which leads to transcription activation and reexpression of genes that can result in favorable biologic responses, including apoptosis of tumor cells. In addition, DNA demethylation can induce the reactivation of genes that are silenced by hypermethylation, causing similar biological effects that can result in tumor cell death. Several examples of epigenetic therapy approaches for DLBCL are currently being used in the clinical setting or are expected to be explored in patients in the near future. Targeting aberrant DNA methylationDNA methylation patterning contains epigenetic information that encodes transcriptional programming information that leads to the phenotype of normal and malignant cells. 1 Aberrant DNA hypermethylation of tumor suppressor genes can result in their inappropriate transcriptional silencing, which contributes to loss of checkpoints and related functions in cancer. Inactivation of tumor suppressor pathways is therefore an important contributor to resistance to chemotherapy in cancer, 2-4 in part because the activity of most chemotherapy agents largely depends on the same proapoptotic and prodifferentiation pathways that become disabled during carcinogenesis. Inactivation of these pathways by mutations or hypermethylation can therefore affect drug ...

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The use of hypomethylating agents in the treatment of hematologic malignancies

Cited by 35 publications

References 55 publications

Aberrant Epigenetic Alteration in Eca9706 Cells Modulated by Nanoliposomal Quercetin Combined with Butyrate Mediated via Epigenetic-NF-κB Signaling

Aberrant Epigenetic Alteration in Eca9706 Cells Modulated by Nanoliposomal Quercetin Combined with Butyrate Mediated via Epigenetic-NF-κB Signaling

A phase I biological study of azacitidine (Vidaza^TM) to determine the optimal dose to inhibit DNA methylation

Targeting the epigenome and other new strategies in diffuse large B-cell lymphoma: beyond R-CHOP

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The use of hypomethylating agents in the treatment of hematologic malignancies

Cited by 35 publications

References 55 publications

Aberrant Epigenetic Alteration in Eca9706 Cells Modulated by Nanoliposomal Quercetin Combined with Butyrate Mediated via Epigenetic-NF-κB Signaling

Aberrant Epigenetic Alteration in Eca9706 Cells Modulated by Nanoliposomal Quercetin Combined with Butyrate Mediated via Epigenetic-NF-κB Signaling

A phase I biological study of azacitidine (VidazaTM) to determine the optimal dose to inhibit DNA methylation

Targeting the epigenome and other new strategies in diffuse large B-cell lymphoma: beyond R-CHOP

Contact Info

Product

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A phase I biological study of azacitidine (Vidaza^TM) to determine the optimal dose to inhibit DNA methylation