Biomedical subjects

G Sersa

Publications and source records attributed to G Sersa.

46 records · Page 3Linked to original sources

PubMed1989

Adoptive immunotherapy as an adjunctive treatment to thoracic irradiation for pulmonary tumor deposits in mice.

The study was performed to determine whether local thoracic irradiation (LTI) causes accumulation of adoptively transferred peritoneal exudate (PE) cells in the lung and whether such treatment improves the response of tumor deposits in the lung to LTI. Tumors in the lung were generated by sarcoma SA-NH cells injected i.v. into syngeneic (C3Hf/Kam mice. Exposure of mice to a single dose of gamma-rays ranging from 2 to 10 Gy caused a dose-dependent decrease in the number of alveolar exudate cells. Also, LTI caused a dose-dependent reduction in the number of lung tumor nodules in mice that were treated with tumor cells 4 days before irradiation. Adoptive i.v. transfer of syngeneic PE cells several hours or 2 days after LTI not only restored the radiation-depleted alveolar exudate cells to their normal levels but also led to an accumulation of transferred cells in the irradiated lung to a several-fold excess of the normal value. Maleic anhydride-divinyl ether-2-activated PE cells accumulated in the irradiated lung much more than normal PE cells and exerted antitumor activity in normal mice and in mice exposed to LTI. Their antitumor action, however, was much more pronounced in the latter, resulting in the augmentation of radioresponse of tumor nodules by a factor of 1.23. The better antitumor action of activated PE cells in mice given LTI can be ascribed to accumulation of these cells in the irradiated lung. Thus, these results show that the irradiation of the lung predisposes this tissue to accumulation of lymphoid cells, which can be beneficial in the therapy of malignant tumors by combinations of radiotherapy and adoptive immunotherapy.

Animals↗

PubMed1988

Anti-tumor effects of tumor necrosis factor alone or combined with radiotherapy.

Recombinant human tumor necrosis factor (rHuTNF) was investigated for its ability to increase the response of murine tumors to ionizing radiation. Both multiple i.v. administrations of rHuTNF and local tumor irradiation caused a significant delay in tumor growth. The effect of treatment with both agents combined was greater than the additive effect of the individual treatments. Furthermore, rHuTNF significantly increased tumor radiocurability, as assessed by the TCD50 assay. rHuTNF was not cytotoxic to tumor cells, nor did it affect their radiosensitivity. The in vivo anti-tumor effect of rHuTNF and its augmentation of tumor radioresponse were mediated through indirect mechanisms, either immunological or non-immunological. rHuTNF was also effective in reducing the damaging effect of ionizing radiation on bone-marrow progenitor cells, which could increase the therapeutic advantage of the rHuTNF-radiotherapy combination. These experiments suggest that rHuTNF is potentially beneficial in combination with radiotherapy.

Animals↗

PubMed1986

In vitro monocyte maturation in patients with malignant melanoma and colorectal cancer--clinical significance.

In vitro monocyte maturation was studied in 52 malignant melanoma patients, 15 patients with colorectal cancer and 44 healthy donors. Index of maturation (IM) was in malignant melanoma patients 6.3 +/- 5.1%, in colorectal cancer 12.7 +/- 9.6%, and in healthy donors 40.4 +/- 18.0%. The difference between mean values in malignant melanoma patients and patients with colorectal cancer was significant when compared with healthy donors (p less than 0.001). The values in malignant melanoma patients decreased in accordance with stage of the disease and the difference between Stage I and Stage IV was significant (8.2 +/- 4.0% vs. 2.8 +/- 2.0%, p less than 0.01). In patients with colorectal cancer significant difference was established between operated patients and inoperable cases (21.4 +/- 10.0 vs. 5.1 +/- 1.9%, p less than 0.01). Monocyte maturation was influenced by the success of treatment. In patients with complete response the values were significantly higher than in patients with progression (11.7 +/- 6.7% vs. 2.2 +/- 1.5%, p less than 0.001). Autologous serum seems to inhibit the maturation process in vitro in cancer patients, while it apparently has no influence in healthy donors. When a response to treatment was achieved the previously low values of IM increased, while at progression a decrease was noted. The correlation between in vitro monocyte maturation and clinical factors leads to conclusion that the in vitro maturation reflects the in vivo process and may prove useful as a marker of tumor load or spread and may be a sensitive monitor of the treatment effect.

Adenocarcinoma↗

PubMedDate not supplied

Electrochemotherapy with bleomycin in the treatment of hypernephroma metastasis: case report and literature review.

A metastasis of hypernephroma was treated by electrochemotherapy with bleomycin. Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumor in order to increase drug delivery to the cells. In the course of a four-week treatment period, the subcutaneous metastasis of the hypernephroma was treated with three sessions of electrochemotherapy, each consisting of 9-10 runs of 8 electric pulses, 10 min after intravenous injection of bleomycin. This treatment resulted in stabilization of the tumor volume for 12 months, whereas the subcutaneous metastasis next to the electrochemotherapy-treated one that did not receive electric pulses progressed immediately.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Tumor blood flow modifying effect of electrochemotherapy with bleomycin.

BACKGROUND: Electrochemotherapy combines administration of the chemotherapeutic drug, followed by application of electric pulses in order to increase drug delivery into the cells. The aim of this study was to determine the tumor blood flow modifying effect of electrochemotherapy with bleomycin and correlate it with its antitumor effectiveness and extent of tumor necrosis. MATERIALS AND METHODS: Electrochemotherapy of SA-1 subcutaneous tumors in A/J mice was performed by application of electric pulses to the tumors, following administration of bleomycin, and antitumor effectiveness determined by tumor growth delay and tumor cures as well as extent of tumor necrosis. Tumor blood modifying effect of therapy was evaluated by Patent blue staining technique and 86RbCl extraction technique. RESULTS: A good correlation of the two methods evaluating tumor blood flow, Patent blue staining and the established 86RbCl extraction technique was found (r = 0.944). Electrochemotherapy resulted in complete and permanent shut down of tumor blood flow within 12 hours, which lasted for at least 5 days. The results on tumor blood flow reduction correlated well with the good antitumor effectiveness of electrochemotherapy and with the extent of the necrosis in the tumors. CONCLUSIONS: The results indicate that Patent blue staining technique is a simple and reliable method for estimation of tumor blood flow and that antitumor effectiveness of electrochemotherapy with bleomycin could be partly attributed to its tumor blood modifying and anti-vascular effect.

Animals↗

PubMedDate not supplied

Cytotoxicity of bioreductive drug tirapazamine is increased by application of electric pulses in SA-1 tumours in mice.

The application of electrical pulses (electroporation) is a local tumour treatment resulting in the facilitated accumulation of non-permeant chemotherapeutic drugs (electrochemotherapy), as well as in the transient reduction of tumour blood flow. The aim of our study was to determine whether the application of electric pulses to the tumour increased the antitumour effectiveness of the bioreductive drug tirapazamine (TPZ). The survival of SA-1 fibrosarcoma cells was 150-fold lower after the exposure of cells for 1 h to TPZ under anoxic compared with normoxic conditions. The exposure of cells to electric pulses did not increase the cytotoxicity of TPZ. However, the in vivo treatment of subcutaneous tumours with a combination of TPZ (i.p. 25 mg/kg) injected 20 min before the application of electrical pulses significantly enhanced tumour response. Treatment with TPZ and electric pulses, repeated three times at 24-hour intervals resulted in tumour growth delay of 7.2 days. The results of our study showed that the observed antitumour effectiveness is unlikely to be due to increased cellular accumulation of TPZ by application of electric pulses, as indicated from in vitro experiments. The effect is more likely to be attributed to increased tumour hypoxia as a consequence of reduced tumour blood flow induced by application of electric pulses.

Animals↗

PubMedDate not supplied

Effect of hydralazine on interstitial fluid pressure in experimental tumours and in normal tissue.

Interstitial fluid pressure (IFP) has been recognised as the most important obstacle in macromolecular drug delivery to solid tumours. The aim of our study was to measure the IFP simultaneously in tumour and in muscle or in subcutis and to determine whether injection of hydralazine reduces differentially tumour IFP with respect to IFP in surrounding and normal tissues. In addition, it was of interest whether the decrease in IFP due to hydralazine depends on tumour volume and/or on initial IFP. Measurements of IFP were performed by means of the wick-in-needle technique and they were obtained on tumours of different size. In both tumour models, hydralazine significantly reduced the pretreatment IFP level. On average IFP decreased by 31% and 14% from the initial value in SAF and LPB tumours, respectively. On the contrary, hydralazine did not decrease IFP in normal tissue. Injection of NaCl solution instead of hydralazine had no effect on IFP either in tumours or in subcutis/muscle. The results of our study on the effect of hydralazine on IFP in SAF and LPB tumour model are in accordance to previously reported studies. The initial IFP in tumour is positively-correlated with the tumour size, while the decrease in the tumour IFP is independent of the initial IFP value. In addition, the decrease in tumour IFP is not correlated to tumour volume.

Animals↗

PubMedDate not supplied

Electrochemotherapy: potentiation of local antitumour effectiveness of cisplatin in dogs and cats.

The aim of this study was to introduce electrochemotherapy with cisplatin into veterinary medicine, where there is a need for inexpensive and effective treatment of cutaneous and subcutaneous tumours of various histological types. The response to treatment was assessed on tumour nodules in 3 cats with mammary adenocarcinoma and fibrosarcoma, and in 7 dogs with mammary adenocarcinoma, cutaneous mast cell tumour, hemangioma, hemangiosarcoma, adenocarcinoma glandulae paranalis and neurofibroma. Twenty-four tumour nodules of different size were treated; 5 with cisplatin injected intratumourally and 19 with electrochemotherapy, i.e. intratumoural administration of cisplatin followed by delivery of electric pulses to the tumour nodule. Electrochemotherapy with cisplatin had a good antitumour effect on all tumours treated. Their average size 4 weeks after treatment was also greatly reduced (0.01 cm3) compared to those treated by intratumoural cisplatin injection alone (3.0 cm3). Altogether, electrochemotherapy- treated tumours responded with 84% objective responses, whereas only one tumourpartially responded to cisplatin treatment alone. Evaluated by contingency table, the response to treatment with electrochemotherapy was significantly better than that of the cisplatin treated group (p=0.014). Furthermore, there was a significant prolongation of the duration of response in electrochemotherapy treated tumours (p = 0.046). This study showed that electrochemotherapy with cisplatin is an effective, safe and simple local treatment of different histological types of cutaneous and subcutaneous tumours in cats and dogs.

Adenocarcinoma↗

PubMedDate not supplied

Antitumor effectiveness of bolus versus split dose vinblastine treatment in EAT tumors in mice.

Vinblastine (VELBE) is one of the first chemotherapeutic agents used in the treatment of malignancies. To explore the effectiveness of various treatment regimens, bolus versus 24-hour continuous VELBE treatment was tested on an EAT tumor model in mice. Continuous VELBE infusion was simulated by splitting the bolus VELBE dose into 4 fractions, injected at 8-hour intervals. A comparison of antitumor effectiveness between bolus and split dose VELBE treatment was determined by three assays: cell survival, tumor growth delay and animal survival. The cell survival curves of both bolus and split dose VELBE treatments indicated a biphasic response with an initial fast reduction in cell survival followed by a plateau. However, split dose treatment was significantly more effective than bolus treatment at all doses tested (p < 0.001). Tumor growth delay of the split dose VELBE treatment was 6.9 days and of the bolus VELBE treatment 3.0 days, indicating that the split dose treatment is approximately 2-times more effective (p < 0.001). Median survival time of mice treated with split VELBE dose (24.0 days) was significantly longer compared to that of mice treated with bolus VELBE dose (16.5 days) (p < 0.001). The median survival time of control untreated mice (16.0 days) and bolus treated mice did not differ (p = 0.24). Our study shows that at the same VELBE dose the split dose VELBE treatment is more effective than VELBE administered in bolus.

Animals↗

PubMedDate not supplied

Electrochemotherapy with cisplatin in the treatment of tumor cells resistant to cisplatin.

The aim of our study was to investigate the role of electroporation in the treatment of cisplatin resistant tumor cells in vitro. For this purpose we used well characterized human ovarian carcinoma IGROV I cells and their resistant subclone IGROV 1/DDP. The cells were either continuously exposed to cisplatin or treated with electrochemotherapy (exposure time: 5 minutes). After chronic exposure of cells to cisplatin, IGROV 1/DDP cells exhibited 8-fold resistance to cisplatin. Cisplatin cytotoxicity was greatly potentiated by treatment with electric pulses in both cell lines. However, the IGROV 1/DDP cells still exhibited a 50-fold resistance. Our results demonstrate that electroporation treatment potentiates cytotoxicity in both human ovarian carcinoma IGROV 1 cells as well as in their resistant subclone IGROV 1/DDP.

Cell Membrane Permeability↗