Tumor Necrosis Factor-α–Induced Protein 3 As a Putative Regulator of Nuclear Factor-κB–Mediated Resistance to O<sup>6</sup>-Alkylating Agents in Human Glioblastomas

Bredel, Markus; Bredel, Claudia; Juric, Dejan; Durán, George E.; Yu, Ronald; Harsh, Griffith R.; Vogel, Hannes; Recht, Lawrence D.; Scheck, Adrienne C.; Šikić, Branimir I.

doi:10.1200/jco.2005.02.9405

Cited by 131 publications

(116 citation statements)

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“…Moreover, cells with mutated mismatch repair genes were particularly resistant to temozolomide, but not to chloroethylating agents (Gerson, 2002;Liu et al, 1996). In addition to repair mechanisms, also signals regulating cell death and survival pathways were implicated to regulate temozolomide response (Bredel et al, 2006). When comparing alkylating agents with several other chemotherapeutics, an increased response in the recurrence-derived BTL cell lines was also observed in anthracyclines, whereas all cells were persistently unresponsive to VP-16, CDDP, and bleomycin.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

et al. 2007

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Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustine but responded to temozolomide after re-operation to temozolomide. The primary tumour -derived BTL1 cells showed chromosomal imbalances typical of highly aggressive glioblastomas. Interestingly, BTL2 cells established from the first recurrence developed under therapy showed signs of enhanced chromosomal instability. In contrast, BTL3 cells from the second recurrence resembled a less aggressive subclone of the primary tumour. Although BTL2 cells exhibited a highly aggressive phenotype, BTL3 cells were characterised by reduced proliferative and migratory potential. Despite persistent methylation of the O 6 -methylguanine-DNA methyltransferase promoter, BTL3 cells exhibited the highest temozolomide sensitivity. A comparable situation was found in two out of five glioblastoma patients, both characterised by enhanced survival time, who also relapsed after surgery/chemotherapy with less aggressive recurrences. Taken together, our data suggest that pretreated glioblastoma patients may relapse with highly chemosensitive tumours confirming the feasibility of temozolomide treatment even in case of repeated recurrence.

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Section: Discussionmentioning

confidence: 99%

Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

et al. 2007

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“…(30) TNFAIP3 negatively regulates nuclear factor kappa B (NF-jB) activation, and decreased TNFAIP3 expression is involved in the progression of B cell lymphomas and glioblastomas. (31,32) MiR-18a is also involved in interleukin 6/signal transducer and activator of transcription 3 signaling pathway that mediates inflammation in human hepatocytes. (33) In contrast, it is well known that HCC is closely associated with inflammation, such as that induced by viral hepatitis, alcoholic, or nonalcoholic steatohepatitis.…”

Section: Discussionmentioning

confidence: 99%

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

et al. 2016

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There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. First, we performed microarray analyses of samples from a liver with primary HCC, a liver that was noncancerous, and a liver that had recurrence-metastasis from 3 patients with posttransplant recurrence. Then we selected miRNAs with consistently altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous livers was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. MicroRNA-18a (miR-18a) expression was increased, and microRNA-199a-5p (miR-199a-5p) expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha-induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor, and insulin-like growth factor 2. In conclusion, increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT.Liver Transplantation 22 665-676 2016 AASLD.Received August 31, 2015; accepted December 9, 2015.Hepatocellular carcinoma (HCC) is the most frequent cancer of the liver and the third most common cause of cancer deaths worldwide.(1) Curative treatment is limited to hepatic resection and liver transplantation (LT). However, the overall cumulative recurrence rate after hepatic resection is approximately 80% at 5 years.(2) Among various recurrent patterns of HCC, the prognosis of extrahepatic recurrence-metastasis (M) is much poorer than that of intrahepatic metastasis and multicentric recurrence. (3)(4)(5) LT can overcome the problems of intrahepatic metastasis and multicentric recurrence theoretically. However, the recurrence of HCC after LT is a critical problem to be solved because the outcomes of patients with HCC recurrence after LT are extremely poor. (6) Abbreviations: AFP, alpha-fetoprotein; DCP, des-gamma-carboxyprothrombin; DDLT, deceased donor liver transplantation; HBsAg, hepatitis B surface antigen; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HIF1A, hypoxia-inducible factor 1 alpha; IGF1R, insulin-like growth factor 1 receptor; IGF2, insulin-like growth factor 2; LDLT, living donor liver transplantation; LT, liver transplantation; M, recurrence-metastasis; miR-18a, microRNA-18a; miR-199a-5p, microRNA-199a-5p;...

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“…3г). В последние годы МГК находит применение в он-кологии, главным образом для оценки общей или без-рецидивной выживаемости онкологических пациентов в зависимости от экспрессии маркерных генов [15,20,21] или предсказания чувствительности, устойчивости неопластических клеток к химиопрепаратам [8]. J.M.…”

Section: рис 3 диаграмма расположения групп пациентов в пространствunclassified

“…В литературе найдено несколько работ, посвященных оценке чувст-вительности клеток неоплазий к химиопрепаратам с привлечением МГК [8,15]. В указанных работах химиочувствительность опухолевых клеток определя-лась на основании уровня экспрессии генов, связан-ных с прогнозом пациентов.…”

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Research of the intracranial neoplasia cell sensitivity to chemotherapy drugs

Чернов¹,

Яцков²,

Скакун³

2016

Ross. ž. det. gematol. onkol.

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Tumor Necrosis Factor-α–Induced Protein 3 As a Putative Regulator of Nuclear Factor-κB–Mediated Resistance to O⁶-Alkylating Agents in Human Glioblastomas

Abstract: Our results offer strong evidence for TNFAIP3 as a key regulator of the cytoplasmic signaling to activate NF-kappaB en route to O6-alkylating agent resistance in glioblastoma cells. This pathway may be an attractive target for therapeutic modulation of glioblastomas.

Cited by 131 publications

References 55 publications

Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

Research of the intracranial neoplasia cell sensitivity to chemotherapy drugs

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Tumor Necrosis Factor-α–Induced Protein 3 As a Putative Regulator of Nuclear Factor-κB–Mediated Resistance to O6-Alkylating Agents in Human Glioblastomas

Abstract: Our results offer strong evidence for TNFAIP3 as a key regulator of the cytoplasmic signaling to activate NF-kappaB en route to O6-alkylating agent resistance in glioblastoma cells. This pathway may be an attractive target for therapeutic modulation of glioblastomas.

Cited by 131 publications

References 55 publications

Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

Research of the intracranial neoplasia cell sensitivity to chemotherapy drugs

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Tumor Necrosis Factor-α–Induced Protein 3 As a Putative Regulator of Nuclear Factor-κB–Mediated Resistance to O⁶-Alkylating Agents in Human Glioblastomas