Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin

Heller, Richard; Jaroszeski, Mark J.; Reintgen, Douglas S.; Puleo, A P A Chris; DeConti, Ronald C.; Gilbert, R. Alton; Glass, L. Frank

doi:10.1002/(sici)1097-0142(19980701)83:1<148::aid-cncr20>3.0.co;2-w

Cited by 262 publications

(207 citation statements)

References 27 publications

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“…36,37 In addition, as oral squamous cell carcinomas frequently occur on the lips, tongue, gingiva, palate, tonsils and buccal mucosa, that type of injection is convenient. In the present study, we found that BLM (20 mg) treatment with sonoporation in the presence of Optison significantly inhibited tumor growth, as compared with the control groups ( Figure 5).…”

Section: Discussionmentioning

confidence: 96%

Local delivery system of cytotoxic agents to tumors by focused sonoporation

Iwanaga¹,

Tominaga²,

Yamamoto³

et al. 2007

Cancer Gene Ther

124

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Recently, ultrasound-targeting microbubble destruction has been employed in molecular gene therapy, and a new potent nonviral gene transfer method known as 'sonoporation' has been developed. We investigated the efficiency of sonoporation toward growth inhibition of human gingival squamous carcinoma cell line, Ca9-22, in vitro and in vivo. The cytotoxicity of bleomycin (BLM) was investigated using flow-cytometric analysis and Hoechst's staining in vitro assay systems. We found that the delivery of BLM by sonoporation induced cytotoxic effect toward Ca9-22 cells in vitro. Our in vivo results showed that tumors nearly disappeared in Ca9-22 cell-implanted nude KSN/slc mice treated with a low dose of BLM followed by sonoporation during the 4-week experimental period. Histological analysis revealed that the cytotoxic effect was mainly apoptosis. We previously reported that the cytolethal distending toxin B (cdtB) from Actinobacillus actinomycetemcomitans, a periodontopathic bacterium, is responsible for cell cycle arrest and apoptosis in vitro. Thus, we used sonoporation to transfect a cdtB-expressing plasmid into Ca9-22 cells and examined cell viability in vitro and in vivo. We found that an administration of cdtB-expressing plasmid followed by sonoporationinduced marked growth inhibition of Ca9-22 cells and apoptotic cells were also observed in vitro and in vivo. These findings suggest that local administration of cytotoxic agents with sonoporation is a useful method for molecular cancer therapy.

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Section: Discussionmentioning

confidence: 96%

Local delivery system of cytotoxic agents to tumors by focused sonoporation

Iwanaga¹,

Tominaga²,

Yamamoto³

et al. 2007

Cancer Gene Ther

124

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“…Several cytostatic agents, including fotemustine (Schallreuter et al, 1991), bleomycin (Glass et al, 1996;Heller et al, 1998), and cisplatin (Burris et al, 1998) have been used intralesionally, with varying results. As immune mechanisms have been shown to play a significant role in the pathogenesis and clinical course of melanoma (reviewed in Curiel- Lewandrowski and Demierre, 2000), a number of reports have addressed the treatment of melanoma metastases with intralesionally injected immunemodulatory cytokines, including interferon- alpha (von Wussow et al, 1988), interferon-beta (Fierlbeck et al, 1992;Umeda et al, 1998;Cornejo et al, 2000), and GM-CSF (Vaquerano et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…The therapeutic value of several intralesionally administered cytostatic agents and cytokines, such as fotemustine (Schallreuter et al, 1991), bleomycin (Glass et al, 1996;Heller et al, 1998), cisplatin (Burris et al, 1998), interferon-alfa (von Wussow et al, 1988), interferon-beta (Fierlbeck et al, 1992;Umeda et al, 1998;Cornejo et al, 2000), and GM-CSF (Vaquerano et al, 1999) has been investigated with varying outcome. However, none of these therapies has yet been shown to be a convincing alternative to conventional therapies.…”

mentioning

confidence: 99%

Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases

et al. 2003

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The objective of the present study was to validate the use of intralesional injection of interleukin-2 (IL-2) in patients with skin and softtissue melanoma metastases. A total of 24 patients with AJCC stage III or IV melanoma and single or multiple skin and soft-tissue metastases were included. Interleukin-2 injections were administered intralesionally into the total number of cutaneous and soft-tissue metastases accessible from the skin, 2 -3 times weekly, over 1 -57 weeks. Single doses varied from 0.6 to 6 Â 10 6 IU, depending on lesion size. The clinical response was monitored by sonography and confirmed by histopathology; response evaluation was confined to the intralesionally treated tumours. Complete response (CR) of the treated metastases was achieved in 15 patients (62.5%), the longest remission lasting 38 months to date. In five patients, partial response (PR) was achieved (21%) and in another three patients, progressive disease was observed (one patient not assessable). A total of 245 metastases were treated with CR in 209 (85%), and PR in 21 (6%). The therapy was generally well tolerated; the observed adverse events were mainly of grade 1 -2 severity. Immunohistochemical studies showed the tumour cells undergoing apoptosis and revealed a mixed character of the inflammatory infiltrate. The unusual high CR rate in metastatic melanoma of 62.5% and the limited toxicity suggest that treatment of skin and softtissue melanoma metastases with intralesional injection of IL-2 may be a safe and effective alternative to conventional therapies. The optimal dosage and duration of this therapy still remain to be defined in larger prospective multicentre trials.

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“…Later in 1998, the same group of investigators published the results of a bigger cohort of patients with a variety of cutaneous and subcutaneous malignant nodules. Twelve of 34 patients had 84 metastatic melanoma nodules with documented OR rates up to 99% (89% complete response (CR) and 10 % partial response (PR)) 76 . That same year, the combined data produced by five institutions in USA, France and Slovenia was published by Mir et al 39 In this study, twenty patients with metastatic melanoma lesions showed responses in 131 (92%) of 142 lesions, with CR of 53% and PR of 39%.…”

Section: Ect Development and Clinical Applications In Melanomamentioning

confidence: 99%