Chemotherapy of human malignant glioma

Weller, Michael; Schmidt, Christine; Roth, Wilfried; Dichgans, J.

doi:10.1212/wnl.48.6.1704

Cited by 82 publications

(48 citation statements)

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“…The general procedure has been described, 51 including the preparation of cytoplasmic lysates for the detection of Cyt c from mitochondria. 49 The following antibodies were used: anti-XIAP, anti-RIAP-1, -2 and -3, 52,53 …”

Section: Immunoblot Analysismentioning

confidence: 99%

Adenoviral expression of XIAP antisense RNA induces apoptosis in glioma cells and suppresses the growth of xenografts in nude mice

et al. 2006

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The expression of inhibitor of apoptosis (IAP) family members contributes to the resistance of human cancers to apoptosis induced by radiotherapy and chemotherapy. We report that the infection of malignant glioma cells and several other tumor cell lines with adenoviruses encoding antisense RNA to X-linked IAP (XIAP) depletes endogenous XIAP levels and promotes global caspase activation and apoptosis. In contrast, non-neoplastic SV-FHAS human astrocytes and other non-neoplastic cells express XIAP at very low levels and resist these effects of adenovirusexpressing XIAP antisense RNA (Ad-XIAP-as). Caspase inhibitors such as z-Val-Ala-DL-Asp(OMe)-fluoromethylketone (zVAD-fmk) delay caspase processing and XIAP depletion, suggesting that XIAP depletion results both from antisense-mediated interference with protein synthesis and proteolytic cleavage by activated caspases. However, zVADfmk neither prevents nor delays cell death, indicating a caspase-independent pathway to cell death triggered by IAP depletion. Similarly, B-cell lymphoma-X L (BCL-X L ) inhibits caspase activity, but fails to rescue from apoptosis. Loss of p65/nuclear factor-kB (NF-kB) protein and NF-kB activity is an early event triggered by Ad-XIAP-as and probably involved in Ad-XIAP-as-induced apoptosis. Finally, Ad-XIAPas gene therapy induces cell death in intracranial glioma xenografts, prolongs survival in nude mice and may reduce tumorigenicity in synergy with Apo2L/TNF-related apoptosisinducing ligand (TRAIL) in vivo. Altogether, these data define a powerful survival function for XIAP and reinforce its possible role as a therapeutic target in human glioma cells.

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Section: Immunoblot Analysismentioning

confidence: 99%

Adenoviral expression of XIAP antisense RNA induces apoptosis in glioma cells and suppresses the growth of xenografts in nude mice

et al. 2006

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“…19 Several years ago, it was shown that the use of steroids influences vascular response to radiation 20 and directly inhibits apoptosis in human malignant glioma cells. 21 However, in spite of strong efforts, an adequate replacement medication for dexamethasone has not been found yet. Boswellic acids could be the basis for a new kind of anti-inflammatory and thus antiedema medication with decreased adverse effects, the additional induction of apoptosis, and no modulation of drug (and radiation) sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

Kirste

Treier

Wehrle

et al. 2011

Cancer

114

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BACKGROUND:Patients irradiated for brain tumors often suffer from cerebral edema and are usually treated with dexamethasone, which has various side effects. To investigate the activity of Boswellia serrata (BS) in radiotherapyrelated edema, we conducted a prospective, randomized, placebo-controlled, double-blind, pilot trial. METHODS: Forty-four patients with primary or secondary malignant cerebral tumors were randomly assigned to radiotherapy plus either BS 4200 mg/day or placebo. The volume of cerebral edema in the T2-weighted magnetic resonance imaging (MRI) sequence was analyzed as a primary endpoint. Secondary endpoints were toxicity, cognitive function, quality of life, and the need for antiedematous (dexamethasone) medication. Blood samples were taken to analyze the serum concentration of boswellic acids (AKBA and KBA). RESULTS: Compared with baseline and if measured immediately after the end of radiotherapy and BS/placebo treatment, a reduction of cerebral edema of >75% was found in 60% of patients receiving BS and in 26% of patients receiving placebo (P ¼ .023). These findings may be based on an additional antitumor effect. There were no severe adverse events in either group. In the BS group, 6 patients reported minor gastrointestinal discomfort. BS did not have a significant impact on quality of life or cognitive function. The dexamethasone dose during radiotherapy in both groups was not statistically different. Boswellic acids could be detected in patients' serum. CONCLUSIONS: BS significantly reduced cerebral edema measured by MRI in the study population. BS could potentially be steroid-sparing for patients receiving brain irradiation. Our findings will need to be further validated in larger studies. Cancer 2011;117:3788-

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“…Recently, more and more data from preclinical studies, and to some extent from clinical studies, have strongly recommended a GC-conferred resistance to cancer therapy in the majority of malignant solid tumors -irrespective of tumor origin and the nature of specific anticancer drugs (Wolff et al 1996, Weller et al 1997, Webster et al 2002, Herr et al 2003, Wu et al 2004, Gassler et al 2005, Runnebaum & Brüning 2005, Sui et al 2006, Zhang et al 2006a,b,c,d,e, 2007. In this study, we have demonstrated that Dex could protect human ovarian IgG (10 µg/ml) Anti-β1 (µg/ml) Figure 4 Dex-enhanced cell attachment and cell survival are partially reversed by integrin b1-blocking antibody.…”

Section: Discussionmentioning

confidence: 99%

“…More recent data indicate that GCs can inhibit apoptosis induced by chemotherapy not only in established cancer cell lines and tumor xenografts, but also in the freshly isolated cells from surgical resections from tumors of various origins, including ovary, breast, prostate, pancreas, liver, colon, brain, cervix, bone, skin, and nervous system (Herr et al 2003, Sui et al 2006, Zhang et al 2006a. In addition, the anti-chemotherapeutic effect of GCs can be seen in several anticancer drugs including cisplatin (Wolff et al 1996, Gassler et al 2005, Zhang et al 2006a,b,d, 2007, paclitaxel (Wu et al 2004, Sui et al 2006, 5-fluorouracil (Zhang et al 2006a(Zhang et al , 2007, adriamycin (Weller et al 1997), actinomycin D (Wolff et al 1996), doxorubicin (Wu et al 2004), and gemcitabine (Gassler et al 2005, Zhang et al 2007). The GC-induced pro-survival effects should be of important clinical relevance when they interfere with the effect of chemotherapeutics.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone enhances cell resistance to chemotherapy by increasing adhesion to extracellular matrix in human ovarian cancer cells

Chen¹,

Wang²,

Fu³

et al. 2010

Endocrine-Related Cancer

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Glucocorticoids (GCs) are widely used as co-medication in the therapy of solid malignant tumors to relieve some of the side effects of chemotherapeutic drugs. However, recent studies have shown that GCs could render cancer cells more resistant to cytotoxic drug-induced apoptosis, but the mechanism is largely unknown. In the present study, we found that the treatment of human ovarian cancer cell lines HO-8910 and SKOV3 with synthetic GCs dexamethasone (Dex) significantly increased their adhesion to extracellular matrix (ECM) and their resistance to apoptosis induced by cytotoxic drugs cisplatin and paclitaxel. Dex also increased the protein levels of adhesion molecules integrins b1, a4, and a5 in HO-8910 cells. The neutralizing antibody against integrin b1 prevented Dex-induced adhesion and significantly abrogated the protective effect of Dex toward cytotoxic agents. We further found that transforming growth factor-b1 (TGF-b1) alone not only increased cell adhesion and cell survival of HO-8910 cells in the presence of cisplatin, but also had synergistic pro-adhesion and pro-survival effects with Dex. Moreover, TGF-b1-neutralizing antibody that could block TGF-b1-induced cell adhesion and apoptosis resistance markedly abrogated the synergistic pro-adhesion and pro-survival effects of Dex and TGF-b1. Finally, we further demonstrated that Dex could up-regulate the expression of TGF-b receptor type II and enhance the responsiveness of cells to TGF-b1. In conclusion, our results indicate that increased adhesion to ECM through the enhancement of integrin b1 signaling and TGF-b1 signaling plays an important role in chemoresistance induced by GCs in ovarian cancer cells.

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Chemotherapy of human malignant glioma

Cited by 82 publications

References 0 publications

Adenoviral expression of XIAP antisense RNA induces apoptosis in glioma cells and suppresses the growth of xenografts in nude mice

Adenoviral expression of XIAP antisense RNA induces apoptosis in glioma cells and suppresses the growth of xenografts in nude mice

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

Dexamethasone enhances cell resistance to chemotherapy by increasing adhesion to extracellular matrix in human ovarian cancer cells

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