Chemotherapy in malignant mesothelioma: a review

Krarup-Hansen, Anders; Hansen, Heine H.

doi:10.1007/bf00685684

Cited by 64 publications

(23 citation statements)

References 76 publications

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“…Cisplatin is one of the most effective drugs in MPM and is commonly used in combination regimens. 23,24 Its cytotoxicity is mediated through platinum-DNA adducts, resulting in apoptosis and cell cycle arrest. However, this apoptosis is responsible for the characteristic nephrotoxicity, ototoxicity, and neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the treatment of malignant pleural mesothelioma

Adusumilli¹,

Chan²,

Chun³

et al. 2006

Cancer Biology & Therapy

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Background: NV1066, a replication-competent oncolytic herpes simplex virus type 1 (HSV-1) attenuated by a deletion in the gene γ 1 34.5, preferentially replicates in and kills malignant cells. γ 1 34.5 encodes ICP34.5, a viral protein essential for productive replication, which has homology with mammalian stress response induced GADD34 (growth arrest and DNA damage-inducible protein). We hypothesized that cisplatin upregulates GADD34 expression, which enhances NV1066 replication and oncolysis.Methods: Ten human malignant pleural mesothelioma (MPM) cell lines were infected with NV1066 at multiplicities of infection (MOI; ratio of viral particles per tumor cell) 0.005 to 0.8 in vitro, with and without cisplatin (1 to 4 µM). In the MPM cell line VAMT, viral replication was determined by plaque assay, cell kill by lactate dehydrogenase assay, and GADD34 induction by quantitative RT-PCR and Western blot. Synergistic efficacy was confirmed by the isobologram and combination index methods of Chou-Talalay. GADD34 upregulation by cisplatin was inhibited with GADD34 siRNA to further confirm the synergistic efficacy dependence with GADD34.Results: Combination therapy with NV1066 and cisplatin showed strong synergism in epithelioid (H-2452, H-Meso), sarcomatoid (H-2373, H-28), and biphasic (JMN, Meso-9, MSTO-211H) MPM cell lines, and an additive effect in others. In VAMT cells combination therapy enhanced viral replication 4 to11-fold (p < 0.01) and cell kill 2 to 3-fold (p < 0.01). Significant dose reductions for both agents (2 to 600-fold) were achieved over a wide range of therapeutic-effect levels (LD 50 -LD 99 ) without compromising cell kill. Synergistic cytotoxicity correlated with GADD34 upregulation (2 to 4-fold, p < 0.01) and was eliminated following transfection with GADD34 siRNA.Conclusion: Cisplatin-induced GADD34 expression selectively enhanced the cytotoxicity of the γ 1 34.5-deficient oncolytic virus, NV1066. This provides a cellular basis for combination therapy with cisplatin and NV1066 to treat MPM and achieve synergistic efficacy, while minimizing dosage and toxicity.

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Section: Discussionmentioning

confidence: 99%

Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the treatment of malignant pleural mesothelioma

Adusumilli¹,

Chan²,

Chun³

et al. 2006

Cancer Biology & Therapy

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“…Reports are usually limited to response rates with no survival data presented (7). Response rates have usually been between 15 and 20% including CR and PR (5,7,23).…”

Section: Eschwege Et Al (1 8)mentioning

confidence: 99%

“…There is at present no curative or standard treatment. Radical surgical removal of the tumour is extremely difficult (5,6) and standard chemotherapeutic drugs have generally been inactive (3,4,7).…”

mentioning

confidence: 99%

Altered Fractionation of Hemithorax Irradiation for Pleural Mesothelioma and Failure Patterns After Treatment

et al. 1997

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“…Irradiation of a large field, including organs like the spinal cord, heart, oesophagus and liver, makes it difficult for the radiation oncologist to give an adequate radiation dose without exceeding normal tissue tolerance. Chemotherapy has so far shown to be of only limited use in the primary treatment of malignant mesothelioma (Chahinian et al, 1982(Chahinian et al, , 1993S0rensen et al 1985;Krarup-Hansen and Hansen, 1991;Ruffle, 1993), but the most active compounds (e.g. doxorubicin) might be of use for the treatment of minimal residual tumour.…”

mentioning

confidence: 99%

Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies

Baas

Murrer²,

Zoetmulder³

et al. 1997

Br J Cancer

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Summary Five patients with a pleural malignancy (four malignant mesotheliomas and one localized low grade carcinoid) were treated with maximal surgical resection of the tumour followed by intraoperative adjuvant photodynamic therapy (PDT). The additional photodynamic treatment was performed with light of 652 nm from a high power diode laser, and meta-tetrahydroxy phenylchlorin as the photosensitizer. The light delivery to the thoracic cavity was monitored by in situ isotropic light detectors. The position of the light delivery fibre was adjusted to achieve optimal light distribution, taking account of reflected and scattered light in this hollow cavity. There was no 30-day post-operative mortality and only one patient suffered from a major complication (diaphragmatic rupture and haematopericardium). The operation time was increased by a maximum of 1 h to illuminate the total hemithoracic surface with 10 J cm-2 (incident and scattered light). The effect of the adjuvant PDT was monitored by examination of biopsies taken 24 h after surgery under thoracoscopic guidance. Significant damage, including necrosis, was observed in the marker lesions with remaining malignancy compared with normal tissue samples, which showed only an infiltration with PMN cells and oedema of the striated muscles cells. Of the five patients treated, four are alive with no signs of recurrent tumour with a follow-up of 9-11 months. One patient was diagnosed as having a tumour dissemination in the skin around the thoracoscopy scar and died of abdominal tumour spread. Light delivery to large surfaces for adjuvant PDT is feasible in a relatively short period of time (< 1 h). In situ dosimetry ensures optimal light distribution and allows total doses (incident plus scattered light) to be monitored at different positions within the cavity. This combination of light delivery and dosimetry is well suited for adjuvant treatment with PDT in malignant pleural tumours.

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Chemotherapy in malignant mesothelioma: a review

Cited by 64 publications

References 76 publications

Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the treatment of malignant pleural mesothelioma

Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the treatment of malignant pleural mesothelioma

Altered Fractionation of Hemithorax Irradiation for Pleural Mesothelioma and Failure Patterns After Treatment

Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies

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