Biomedical subjects

G Sersa

Publications and source records attributed to G Sersa.

At least 19 recordsLinked to original sources

PubMed2006

Electrically-assisted nucleic acids delivery to tissues in vivo: where do we stand?

Electropulsation (electroporation) is a physical method for delivery of various molecules into the cells in vitro and in vivo. It is an expanding field due to its applicability in cancer therapy, where combined application of electric pulses and chemotherapeutic drugs is used for treatment of cutaneous and subcutaneous nodules of different malignancies. Another application of electropulsation in vivo is electrogene therapy, where after injection of naked plasmid DNA and delivery of electric pulses directly to the tissue the expression of gene of interest can be obtained. However, the transfection efficiency of this methodology in vivo is still lower than with viral vectors. Nevertheless, due to the lack of immunogenicity of the method, easiness of the preparation of large quantities of endotoxin free plasmid DNA, control and reproducibility of the method and the development of electropulsators approved for the clinical use, electrically-assisted nucleic-acid delivery holds a great potential for the clinical application. This aim of this minireview is to critically discuss the main limitations and obstacles associated with electrogene therapy and the failures and problems as well as the successes. Topics on electric field distribution in the tissue, electrode geometries, construction of plasmid, modulation of extracellular space, tissue damage, pro-inflammatory and immune response as well as blood flow modification associated with application of electric pulses and injection of naked DNA are presented with possible directions how to overcome these limitations. Furthermore, for successful electrogene therapy in clinical setting it is of utmost importance to elucidate the mechanisms of DNA transfer into the cells of tissues in vivo. This will enable appropriate selection of electric pulse parameters and plasmid DNA constructs for each particular intended use. In the long run, this review should encourage other scientists to consider electrically assisted gene delivery for gene therapy as it matures.

Age Factors↗

PubMed2002

Reduced blood flow and oxygenation in SA-1 tumours after electrochemotherapy with cisplatin.

Electrochemotherapy is an antitumour treatment that utilises locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. Besides increased drug delivery, application of electric pulses affects tumour blood flow. The aim of this study was to determine tumour blood flow modifying effects of electrochemotherapy with cisplatin, its effects on tumour oxygenation and to determine their relation to antitumour effectiveness. Electrochemotherapy of SA-1 subcutaneous tumours was performed by application of electric pulses to the tumours, following administration of cisplatin. Tumour blood flow modifying effects of electrochemotherapy were determined by measurement of tumour perfusion using the Patent blue staining technique, determination of tumour blood volume, and microvascular permeability using contrast enhanced magnetic resonance imaging, and tumour oxygenation using electron paramagnetic resonance oximetry. Antitumour effectiveness was determined by tumour growth delay and the extent of tumour necrosis and apoptosis. Tumour treatment by electrochemotherapy induced 9.4 days tumour growth delay. Tumour blood flow was reduced instantaneously and persisted for several days. This reduction in tumour blood flow was reflected in reduced tumour oxygenation. The maximal reduction in partial oxygen pressure (pO2) levels was observed at 2 h after the treatment, with steady recovery to the pretreatment level within 48 h. The reduced tumour blood flow and oxygenation correlated well with the extent of tumour necrosis and tumour cells apoptosis induced by electrochemotherapy with cisplatin. Therefore, the data indicate that antitumour effectiveness of electrochemotherapy is not only due to increased cytotoxicity of cisplatin due to electroporation of tumour cells, but also due to anti-vascular effect of electrochemotherapy, which resulted in reduced tumour blood flow and oxygenation.

Animals↗

PubMed2001

Reduced tumor oxygenation by treatment with vinblastine.

Vinblastine (VLB) previously has been shown to perturb tumor blood flow, but the effect of these perturbations on tissue oxygenation is not known. The recent development of electron paramagnetic resonance (EPR) oximetry now has made it feasible to measure the effects of changes of perfusion on the pO(2) in tumors and normal tissues as a function of time and dose. We measured changes in tumor perfusion by Patent blue staining, tumor blood volume and microvascular permeability by contrast-enhanced magnetic resonance imaging, and tumor oxygenation by EPR in s.c. SA-1 murine tumors. We found that treatment with VLB induced dose-dependent reduction in tumor perfusion. One hour after i.p. treatment of mice with 2.5 mg/kg VLB, tumor perfusion was reduced to 20% of the pretreatment value and returned to close to original values within 48 h. A transient tumor blood flow-modifying effect of VLB was demonstrated also by contrast-enhanced magnetic resonance imaging; reduction of tumor blood volume and microvascular permeability was found. Reduced tumor oxygenation was found as measured by EPR oximetry, with the same time course of changes in tumor blood flow. Tumor oxygenation was reduced to 50% of pretreatment value 1 h after the treatment with 2.5 mg/kg VLB and returned to pretreatment levels within 24 h after the treatment. Although the directions of the changes in perfusion and oxygenation were similar, they were quantitatively different. Reduction in oxygenation of normal tissues, muscle, and subcutis also occurred but was smaller and returned to pretreatment values more quickly compared to the changes induced in the tumors. In conclusion, the present study demonstrates that VLB causes a profound reduction in tumor blood flow and oxygenation, which may have implications in controlling side effects of therapy and the planning of combined treatment with VLB, either with other chemotherapeutic drugs or with radiotherapy.

Animals↗

PubMed2001

Electrochemotherapy of tumours resistant to cisplatin: a study in a murine tumour model.

The aim of the study was to determine whether electrochemotherapy with cisplatin could be implemented in treatment of cisplatin-resistant solid tumours. For this purpose, we used cisplatin-sensitive TBL.Cl2 cells and their cisplatin-resistant subclone TBL.Cl2 Pt, which can be grown as in vitro cell cultures and as solid subcutaneous tumours in C57Bl/6 mice. Cytotoxicity of cisplatin alone and combined with electroporation was determined by colony forming assay. Treatment effects of electrochemotherapy in vivo were assessed by tumour growth delay and tumour curability. Platinum content in the cells and tumours was determined by atomic absorption spectroscopy. In vitro, TBL.Cl2 Pt cells were equally sensitive to electrochemotherapy as their cisplatin-sensitive counterparts. In vivo, electrochemotherapy was effective on both tumour types, resulting in a prolonged tumour growth delay and tumour cures. However, electrochemotherapy was more effective on parental than cisplatin-resistant tumours, in which platinum content was significantly lower compared with parental tumours. In conclusion, electrochemotherapy is an effective treatment of cisplatin-resistant solid tumours and may prove useful in clinical chemotherapy for the treatment of tumours with intrinsic or acquired resistance to cisplatin.

Animals↗

PubMed2001

Electroporation of human microvascular endothelial cells: evidence for an anti-vascular mechanism of electrochemotherapy.

Recent studies have indicated that the antitumour effectiveness of electrochemotherapy, a combination of chemotherapeutic drugs with application of high voltage electric pulses applied to the tumour nodule (electroporation), result in a significant reduction in tumour blood flow and may therefore be mediated by an anti-vascular mechanism. The aim of this study was to evaluate the cytotoxicity of electroporation with bleomycin or cisplatin on cultured human microvascular endothelial cells (HMEC-1). The sensitivity of HMEC-1 cells to a 5 min treatment by electroporation with bleomycin or cisplatin (8 electric pulses, pulse duration 100 micros, frequency 1 Hz, electric field intensity 1400 V x cm(-1)) was compared to the sensitivity of cells treated continuously for 3 days with drugs alone. HMEC-1 cells were moderately sensitive to continuous exposure to cisplatin, but showed greater sensitivity to bleomycin. Combination of a 5 min drug exposure with electric pulses increased cytotoxicity approximately 10-fold for cisplatin and approximately 5000-fold for bleomycin. The electroporation of HMEC-1 cells with bleomycin for a 5 min exposure was approximately 250-fold better than a continuous exposure to the drug alone. The results of this study indicate that the anti-tumour action of electrochemotherapy is likely to be due, in part, to the highly sensitive response of vascular endothelial cells. Further studies are necessary to identify the determinants of endothelial response and its relationship to the anti-vascular action of electrochemotherapy in vivo.

Antineoplastic Agents↗

PubMed2000

Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors.

PURPOSE: To evaluate whether a local drug delivery method, i.e., electroporation of tumors, increases the radiosensitizing effect of cisplatin. METHODS AND MATERIALS: Subcutaneous Ehrlich-Lettre ascites (EAT) tumors in CBA mice were treated either by cisplatin, electric pulses, or ionizing radiation. In electrochemotherapy protocol, electric pulses were given to the tumor 3 min after intravenous injection of cisplatin. The interval between electrochemotherapy and irradiation was 20 min. Treatment effectiveness was evaluated by tumor growth delay and local tumor curability. RESULTS: Electrochemotherapy of EAT tumors proved to be effective treatment, resulting in 12% tumor cures, whereas treatment with cisplatin or electric pulses alone did not yield any tumor cures. As expected, injection of cisplatin 20 min prior to irradiation, increased radioresponse of tumors from 27% to 73% tumor cures. Electroporation of tumors also increased radiation response of tumors to 54% tumor cures. Electrochemotherapy given prior to irradiation increased radioresponsiveness of tumors, resulting in 92% tumor cures. CONCLUSIONS: This study shows that delivery of cisplatin into the cells by electroporation of tumors increases the radiosensitizing effect of cisplatin. However, some effect may also be ascribed to application of electric pulses to the tumors that in our study also predisposed tumor cells to radiation damage.

Animals↗

PubMed2000

Electrochemotherapy with cisplatin: the systemic antitumour effectiveness of cisplatin can be potentiated locally by the application of electric pulses in the treatment of malignant melanoma skin metastases.

The application of electric pulses to skin tumour nodules enhances the antitumour effectiveness of cisplatin. This treatment approach, known as electrochemotherapy, was employed in the treatment of skin metastases and lymph node metastases in malignant melanoma patients. Electric pulses were applied to tumour nodules in order to potentiate locally the antitumour effectiveness of systemic cisplatin-based chemoimmunotherapy. The study included nine malignant melanoma patients with skin metastases and metastases in lymph nodes not amenable to surgery, undergoing cisplatin-based chemoimmunotherapy. The antitumour effectiveness of the chemoimmunotherapy was compared with the antitumour effectiveness of electrochemotherapy, i.e. application of electric pulses to tumour nodules together with cisplatin-based chemoimmunotherapy. Application of electric pulses to the 27 skin tumour nodules potentiated locally the antitumour effectiveness of cisplatin. Four weeks after the treatment, 48% of the tumour nodules had an objective response (OR), compared with 22% of the 18 tumour nodules treated with cisplatin-based chemoimmunotherapy alone. Furthermore, the median time to progression was longer in the electrochemotherapy-treated nodules (21 weeks) than in the chemoimmunotherapy-treated nodules (4 weeks). This study shows that application of electric pulses to malignant melanoma tumour nodules can potentiate the antitumour effectiveness of cisplatin in patients undergoing systemic cisplatin-based chemoimmunotherapy. Therefore, electrochemotherapy may be used as an adjunct to systemic ongoing cisplatin treatment, predominantly in patients in whom antitumour effectiveness needs to be potentiated locally.

Antineoplastic Agents↗

PubMed2000

Changed delivery of boron to tumours using electroporation for boron neutron capture therapy with BSH.

For effective boron neutron capture therapy (BNCT) it is important that a sufficient concentration of boron (10B) is present in the tumour during irradiation. This requirement represents a specific problem. The aim of this study was to test whether electroporation can be used as a non-specific drug delivery system to increase the delivery of sodium borocaptate-10B (BSH) into MCF7 (breast carcinoma) and B16F1 (melanoma) tumour cells in vitro and in B16F1 tumours in vivo. For the in vitro determination of 10B uptake, the cells were incubated in medium containing BSH and exposed to electric pulses. Boron levels were determined by inductively coupled plasma atomic emission spectrometry. In vivo, tumours were exposed to electric pulses 3 min after intravenous BSH injection. At different times after exposure the 10B concentration was determined in tumours and in blood. A difference in the 10B accumulation in the two cell lines was observed after continuous incubation of cells with BSH. No accumulation of 10B was observed in MCF7 cells, whereas in B16F1 cells, 10B accumulated well and reached a plateau within 30 min. Electroporation of these cells resulted in an accumulation of 10B into MCF7 cells up to the level of 10B in B16F1 cells. In vivo, the application of electric pulses increased and prolonged the entrapment of 10B (BSH) in the B16F1 melanoma tumours. A sufficient concentration of 10B was present in the tumour exposed to electric pulses for up to 24 h. Boron was quickly washed out from the blood and the level was below the concentrations in the tumours exposed to electric pulses at 2 h. The results of this study show that electroporation may provide a tool to increase boron concentration in the cells that have impaired transport of BSH through the plasma membrane. Furthermore, prolonged entrapment of BSH in tumours in vivo may, in addition to electroporation, be caused by the modifying effect of electric pulses on blood flow.

Animals↗

PubMed2000

Electrochemotherapy with cisplatin: clinical experience in malignant melanoma patients.

Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumor to increase drug delivery into the cells. The aim of this Phase II clinical study was to evaluate the antitumor effectiveness of electrochemotherapy using intratumoral cisplatin administration on cutaneous tumor nodules in malignant melanoma patients. In 10 patients, 133 tumor nodules of different sizes were treated: (a) 82 tumor nodules were treated with electrochemotherapy; (b) 27 tumor nodules were treated with cisplatin; (c) 2 tumor nodules were treated with electric pulses; and (d) 22 tumor nodules were untreated. Four weeks after therapy, 78% objective responses were obtained in the electrochemotherapy group, and 38% objective responses were obtained in the cisplatin group. Exposure of tumor nodules to electric pulses without cisplatin treatment had no effect on tumor growth. Electrochemotherapy was well tolerated by all patients, and a good cosmetic effect was obtained, with only minimal scarring and a slight depigmentation of the skin. At 124 weeks of follow-up, a 77% control rate of the tumor nodules treated by electrochemotherapy was observed, compared to 19% for those that were treated with cisplatin only (P < 0.0001). Our results clearly demonstrate that electrochemotherapy with cisplatin is a highly effective approach for treatment of cutaneous malignant melanoma nodules. The advantages of this therapy include its simplicity, the short duration of treatment sessions, low cisplatin doses, and insignificant side effects, as well as the fact that it can be done on an outpatient basis.

Adult↗

PubMed1999

Blood perfusion of subcutaneous tumours in mice following the application of low-level direct electric current.

Electrotherapy with low-level direct electric current has been proved to be an effective local treatment of solid tumours. In the presented study an attempt was made to evaluate the effect of a single treatment with electrotherapy on blood perfusion of solid subcutaneous fibrosarcoma Sa-1 tumours in A/J mice. The tissue-staining method with Patent blue-violet dye, the rubidium extraction technique, and the noninvasive near-infrared spectroscopy method were used for this purpose. Results of all methods indicate that perfusion and subsequently oxygenation of tumours were reduced due to application of electrotherapy.

Animals↗

PubMed1999

Tumour blood flow changes induced by application of electric pulses.

The effect of electric pulses on tumour blood flow was investigated in the murine fibrosarcoma SA-1. After the application of short intense electric pulses, relative tumour perfusion was measured using an 86RbC1 extraction technique. A significant reduction of tumour perfusion (approximately 30% of control) was observed within 1 h following the application of eight electric pulses to the tumour. Thereafter, tumour blood flow slowly recovered, almost reaching the pretreatment level by 24 h. No change in perfusion was induced in the untreated contralateral normal leg muscle. A similar pattern of blood flow reduction was induced when a second set of electric pulses was applied to the tumour following a 24 h interval. The degree of tumour blood flow reduction was dependent upon the number of electric pulses applied, at 1040 V, and less effect was observed if less than eight pulses were applied. A modification of the amplitude of the electric pulses resulted in changes in the direction of tumour blood flow response. Tumour blood flow increased following pulses in the range between 80 and 560 V and decreased at amplitudes higher than 640 V. These results demonstrate that the local application of electric pulses to solid tumours can modify tumour blood flow. Pulses of increased amplitude resulted in the progressive reduction of tumour blood flow with a corresponding increase in tumour cytotoxicity as measured by growth delay. Tumour blood flow reduction by electric pulses could have potential in exploiting modalities mediated by tumour hypoxia, e.g. activation of bioreductive agents.

Animals↗

PubMed1999

Increased platinum accumulation in SA-1 tumour cells after in vivo electrochemotherapy with cisplatin.

Electrochemotherapy is an anti-tumour treatment that utilizes locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. The aim of our study was to determine whether anti-tumour effectiveness of electrochemotherapy with cisplatin is a consequence of increased plasma membrane permeability caused by electroporation that enables cisplatin binding to DNA. For this purpose, anti-tumour effectiveness of electrochemotherapy was evaluated on SA-1 tumours treated with electric pulses 3 min after intravenous injection of cisplatin (4 mg kg(-1)). Anti-tumour effectiveness was correlated with platinum accumulation in tumours and the amount of platinum bound to DNA, as determined by atomic absorption spectrometry. In tumours treated with electrochemotherapy, cell kill was increased by a factor of 20 compared with treatment with cisplatin only, as determined from tumour growth curves. The amount of platinum bound to DNA and platinum content in the tumours treated by electrochemotherapy was approximately two times higher than in cisplatin-treated tumours. Based on our results, we conclude that in vivo application of electric pulses potentiates anti-tumour effectiveness of cisplatin by electroporation that consequently results in cisplatin increased delivery into the cells. In addition, besides electroporation, immune system and tumour blood flow changes could be involved in the observed anti-tumour effectiveness of electrochemotherapy.

Animals↗

PubMed1998

Effect of vinblastine on cell membrane fluidity in vinblastine-sensitive and -resistant HeLa cells.

The electron paramagnetic resonance method (EPR) was used to study the effects of vinblastine (VLB) on cell membrane fluidity in wild-type HeLa cells (HeLa K) and its subclone, which is resistant to several drugs (HeLa CA). HeLa CA cells, obtained by treatment of HeLa K with CDDP, were found to be more resistant to VLB than to CDDP. The experimentally observed EPR spectra were correlated with the calculated spectra obtained by computer simulation. The results indicate that the cell membrane of HeLa K and HeLa CA cells is heterogeneous and can be described with at least three types of coexisting domains with different fluidity characteristics. The two more fluid domains of HeLa CA cells were found to be more fluid than in HeLa K cells. The fluidity of the less fluid domain remained unchanged but its portion in the membrane was increased. VLB treatment did not affect the membrane fluidity of HeLa CA cells significantly. On the other hand, 1 h of treatment of HeLa K cells with 1 ng/ml VLB did not change the fluidity characteristics of membrane domains but decreased the portion of the less fluid domains. This was also reflected in an average increase of the entire membrane fluidity. The observed changes were detected at VLB concentrations which were far below the cytotoxic level.

Antineoplastic Agents, Phytogenic↗

PubMed1998

The importance of electric field distribution for effective in vivo electroporation of tissues.

Cells exposed to short and intense electric pulses become permeable to a number of various ionic molecules. This phenomenon was termed electroporation or electropermeabilization and is widely used for in vitro drug delivery into the cells and gene transfection. Tissues can also be permeabilized. These new approaches based on electroporation are used for cancer treatment, i.e., electrochemotherapy, and in vivo gene transfection. In vivo electroporation is thus gaining even wider interest. However, electrode geometry and distribution were not yet adequately addressed. Most of the electrodes used so far were determined empirically. In our study we 1) designed two electrode sets that produce notably different distribution of electric field in tumor, 2) qualitatively evaluated current density distribution for both electrode sets by means of magnetic resonance current density imaging, 3) used three-dimensional finite element model to calculate values of electric field for both electrode sets, and 4) demonstrated the difference in electrochemotherapy effectiveness in mouse tumor model between the two electrode sets. The results of our study clearly demonstrate that numerical model is reliable and can be very useful in the additional search for electrodes that would make electrochemotherapy and in vivo electroporation in general more efficient. Our study also shows that better coverage of tumors with sufficiently high electric field is necessary for improved effectiveness of electrochemotherapy.

Animals↗

PubMed1998

Electrochemotherapy with cisplatin: potentiation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients.

This study was aimed at assessing the response to electrochemotherapy with cisplatin of cutaneous tumour nodules in patients with malignant melanoma, squamous cell carcinoma and basal cell carcinoma. In 4 patients, 30 tumour nodules of different sizes were treated; five without treatment, one with electric pulses, five with cisplatin injected intratumorally and 19 with electrochemotherapy, i.e. intratumoral administration of cisplatin followed by delivery of electric pulses to the tumour nodule. After 4 weeks, a complete response (CR) in all 19 electrochemotherapy treated nodules was obtained. All electrochemotherapy treated nodules remained in CR (range 7-11 months), regardless of histological type, except for the metastasis of a squamous cell carcinoma that progressed after 9 months. CR was also obtained in two of five tumour nodules treated with cisplatin intratumorally, but the other three nodules progressed within 3-7 months. Exposure of the tumour nodule to electric pulses without cisplatin treatment had no effect on tumour growth. Electrochemotherapy was well tolerated by all patients and a good cosmetic effect was obtained, with only minimal scarring and a slight depigmentation of the skin. Electrochemotherapy with cisplatin has proved to be effective in patients with cutaneous tumour nodules. Furthermore, electrochemotherapy is easy to perform and can be carried out on an out-patient basis.

Antineoplastic Agents↗

PubMed1998

Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy.

Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate.

Adenocarcinoma↗

PubMed1998

Intratumoral cisplatin administration in electrochemotherapy: antitumor effectiveness, sequence dependence and platinum content.

Electrochemotherapy using intratumoral cisplatin administration was tested on EAT tumors in mice. Mice were treated with eight electric pulses (100 micros, 1 Hz, 1040 V) and/or cisplatin (1, 2, 4 and 8 mg/kg). Cisplatin treatment resulted in up to 20 days of tumor growth delay. Electrochemotherapy resulted in tumor cures; local tumor control reached a plateau at 4 mg/kg in 67% of tumor cures. The maximal effect of electrochemotherapy was achieved when cisplatin was injected 5 min before or simultaneously with electric pulses application. Approximately two times more platinum was bound to DNA in electrochemotherapy than in cisplatin treated tumors at all time points tested. Our study shows that electrochemotherapy with intratumoral cisplatin administration is a very effective local treatment of EAT tumors with high curability rate.

Animals↗

PubMed1998

Intrinsic sensitivity of tumor cells to bleomycin as an indicator of tumor response to electrochemotherapy.

Electrochemotherapy (ECT) involves the use of locally applied electric pulses to increase delivery of chemotherapeutic drugs into cells in tissues. ECT with bleomycin (BLM) is a very effective local treatment, but different tumors have different response rates to ECT. The aim of our study was to compare the responsiveness of SA-1 and EAT tumors to BLM and ECT in vitro and in vivo, in order to find possible reasons for the observed difference in response rate. The difference in sensitivity to ECT in vitro between the SA-1 and EAT cells was 10-fold and was the same as the difference in sensitivity to chronic BLM exposure, as measured by tetrazolium-based colorimetric (MTT) assay. This difference in sensitivity between SA-1 and EAT to ECT was also reflected in tumor cure rate. A six-times lower dose of BLM was needed to obtain local tumor control in SA-1 than in EAT tumors. Therefore, we suggest that the difference in sensitivity to BLM and ECT predominantly reflects the difference in intrinsic sensitivity of the cells to BLM.

Animals↗