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1

Antiangiogenic gene therapy in inhibition of metastasis.

100%

Szala S., Szary J., Cichoń T., Sochanik A.

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2002

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vol. 49

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issue 2

313-321

EN

This short review attempts to demonstrate the usefulness of antiangiogenic gene therapy in achieving inhibition of growth in experimentally-induced metastases. Certain normal tissues (for example skeletal muscle) may be used in vivo, after genetic modification, as a "bioreactor", able to produce and secrete into the bloodstream proteins known to exert antiangiogenic effects. By inhibiting neoangiogenesis these proteins would thus prevent the development of metastases. The review discusses also the perspectives of antimetastatic therapy based on certain types of allogenic cells (for example myoblasts and fibroblasts) that had been genetically modified and then microencapsulated. The strategy of encapsulation is aimed at protecting the modified cells secreting antiangiogenic factors from being eliminated by the immune system. Secretion of antiangiogenic proteins by these microencapsulated cells can be controlled with inducible promoters. Antiangiogenic genes remaining under the transcriptional control of such promoters may be switched on and off using antibiotics, such as tetracycline derivatives, or steroid hormones.

2

Various cationic carriers for in vitro transfection of tumor and endothelial cell lines.

100%

Zemlińska B., Sochanik A., Missol-Kolka E., Szala S.

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2002

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vol. 49

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issue 1

285-290

EN

We compared the efficiency of in vitro DNA transfer into selected tumor and endothelial cell lines using complexes of plasmid DNA and cationic carriers: DDAB/DOPE, DC-Chol/DOPE, Arg-Chol/DOPE, Gly-Chol/DOPE, Arg-Gly-Chol/DOPE, BGTC/DOPE, and PEI. The best carriers for transfecting the majority of tested cells lines at optimized carrier-to-DNA weight ratios were PEI and BGTC/DOPE.

3

Combination of combretastatin A4 phosphate and doxorubicin-containing liposomes affects growth of B16-F10 tumors

100%

Mitrus I., Sochanik A., Cichoń T., Szala S.

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issue 1

161-165

EN

The study aimed to check the effectiveness of anticancer therapy combining a vascular-disruptive drug (combretastatin phosphate, CA4P) and a liposomal formulation of a chemotherapeutic (doxorubicin). CA4P was synthesized in our laboratory according to a previously described procedure. The antivascular drug and long-circulating doxorubicin-loaded liposomes were used to treat B16-F10 murine melanoma experimental tumors. Seventy-four hours after drug administration, a decrease in the number of tumor blood vessels was apparent and necrotic areas within tumors were visible. Combination therapy consisting of alternate administrations of CA4P and liposomal doxorubicin yielded greater inhibition of tumor growth than monotherapies alone. The best therapeutic results were obtained with the antivascular drug administered intratumorally every second day at 50 mg/kg body mass. In the case of combined therapy, the best results were obtained when the vascular-disruptive agent (CA4P) and the antineoplastic agent (liposomal doxorubicin) were administered in alternation.

4

Combination of vasostatin and cyclophosphamide in the therapy of murine melanoma tumors

88%

Jazowiecka-Rakus J., Jarosz M., Kozłowska D., Sochanik A., Szala S.

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2007

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vol. 54

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issue 1

125-133

EN

Growth of tumors is strongly dependent upon supply of nutrients and oxygen by de novo formed blood vessels. Inhibiting angiogenesis suppresses growth of primary tumors as well and affects development of metastases. We demonstrate that recombinant MBP/vasostatin fusion protein inhibits proliferation of endothelial cells in vitro. The therapeutic usefulness of such intratumorally delivered recombinant protein was then assessed by investigating its ability to inhibit growth of experimental murine melanomas. In the model of B16-F10 melanoma the MBP/vasostatin construct significantly delayed tumor growth and prolonged survival of treated mice. A combination therapy involving MBP/vasostatin construct and cyclophosphamide was even more effective and led to further inhibition of the tumor growth and extended survival. We show that such combination might be useful in the clinical setting, especially to treat tumors which have already formed microvessel networks.

5

Properties of B16-F10 murine melanoma cells subjected to metabolic stress conditions

76%

Mitrus I., Bryndza E., Kazura M., Smagur A., Sochanik A., Cichon T., Szala S.

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2012

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vol. 59

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issue 3

363-366

EN

Neoplastic cells which co-form tumors are usually subjected to various stress factors, mainly hypoxia and shortage of nutrient factors. Such cells employ different strategies that permit their survival under such conditions. Experiments in vitro are usually carried out in the presence of 21% oxygen and medium supplemented with 10% FBS. Altering these parameters can approximate the in vivo conditions found within tumor mass. The present paper reports certain properties (especially ability to metastasize) of B16-F10 cells able to grow upon exposure to altered growth conditions (medium supplemented with 0.06% FBS or presence of 1% oxygen for 24 or 72 hours). These properties were compared with those of control cells cultured in the presence of 21% oxygen and in medium supplemented with 10% FBS. Some properties of the cells exposed to medium supplemented with 0.06% FBS differ from those of cells cultured under low oxygenation conditions (ability to form metastases, to migrate, or to express various proteins). Only the partial deprivation of oxygen did increase both the number of migrating cells and the number of metastases formed. Serum deficiency enhanced only the cell ability to metastasize, but not to migrate. It appears that cultured B16-F10 cells employ different adaptation strategies under conditions of oxygen shortage and those of serum deficiency. Under oxygen deprivation, such cells most likely undergo an epithelial-mesenchymal transition, whereas serum deficiency ("starvation"), while increasing the tumorigenicity of B16-F10 cells, does not induce the epithelial-mesenchymal transition.

6

Antitumor effect of RGD-4C-GG-D(KLAKLAK)2 peptide in mouse B16(F10) melanoma model

76%

Smolarczyk R., Cichoń T., Graja K., Hucz J., Sochanik A., Szala S.

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2006

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vol. 53

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issue 4

801-805

EN

Vasculature targeting agents have been tested as cancer therapeutics for the past few years. Such therapy could be accomplished using, for example, bifunctional (two-domain) peptides. RGD-4C-GG-D(KLAKLAK)2, a peptide designed by Ellerby and coworkers (1999) (full sequence: ACDCRGDCFCGGKLAKLAKKLAKLAK), binds selectively to αVβ3 integrin receptors expressed in tumor neovasculature and, after internalization, effectively induces apoptosis of endothelial cells. The aim of this study was to examine if RGD-4C-GG-D(KLAKLAK)2 would efficiently target cells, among them B16(F10), that overexpress αVβ3 receptors, and whether it would be suitable for therapeutic treatment of primary B16(F10) murine melanoma tumors. Thus, the peptide would target two distinct tumor compartments: that formed by endothelium of blood vessels and that made up of neoplastic cells. The therapeutic peptide was recognized and did induce apoptosis in B16(F10) cell line. Tumor growth inhibition was observed following direct intratumoral administration. However, cessation of peptide administration led to rapid tumor growth and death of the animals.

7

In vivo gene transfer using cetylated polyethylenimine.

76%

Sochanik A., Cichoń T., Makselon M., Stróżyk M., Smolarczyk R., Jazowiecka-Rakus J., Szala S.

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vol. 51

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issue 3

693-702

EN

This report describes gene transfer in vitro as well as in vivo using cetylated low-molecular mass (600 Da) polyethylenimine (28% of amine groups substituted with cetyl moieties), termed CT-PEI. This compound is hydrophobic and has to be incorporated into liposomes in order to be suitable for gene transfer studies. Serum-induced plasmid DNA degradation assay demonstrated that CT-PEI-containing liposomal carriers could protect complexed DNA (probably via condensation). In vitro luciferase gene expression achieved using medium supplemented with 10% serum was comparable to that achieved in serum-reduced medium and was highest for CT-PEI/cholesterol liposomes, followed by CT-PEI/dioleoylphosphatidylcholine liposomes and PEI 600 Da (uncetylated) carrier. In vivo systemic transfer into mice was most efficient when liposome formulations contained CT-PEI and cholesterol. Higher luciferase expression was then observed in lungs than in liver. In conclusion: liposomes containing cetylated polyethylenimine and cholesterol are a suitable vehicle for investigating systemic plasmid DNA transfer into lungs.

8

On the strategy of using nonviral carriers in cancer gene therapy

74%

Sochanik A., Szala S.

Acta Biochimica Polonica

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1996

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vol. 43

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issue 2

293-300

9

Vasostatin increases oxygenation of B16-F10 melanoma tumors and raises therapeutic efficacy of cyclophosphamide

64%

Cichoń T., Jarosz M., Smolarczyk R., Ogórek B., Matuszczak S., Wagner M., Mitrus I., Sochanik A., Jazowiecka-Rakus J., Szala S.

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2012

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vol. 59

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issue 3

377-381

EN

One of the preconditions of effective anticancer therapy is efficient transfer of the therapeutic agent (chemotherapeutic) to tumor cells. Fundamental barriers making drug delivery and action difficult include underoxygenation, elevated interstitial pressure, poor and abnormal tumor blood vascular network and acidic tumor milieu. In this study we aimed at developing an optimized scheme of administering a combination of an angiogenesis-inhibiting drug (vasostatin) and a chemotherapeutic (cyclophosphamide) in the therapeutic treatment of mice bearing experimental B16-F10 melanoma tumors. We report that the strongest tumor growth inhibition was observed in mice that received two, three or four vasostatin doses in combination with one injection of cyclophosphamide (i.e., V2 + CTX, V3 + CTX or V4 + CTX schemes). Double administration of vasostatin increases oxygenation of B16-F10 tumors. On the other hand, its five-fold administration lowers tumor oxygenation, breaks down tumor vascular network (increasing hypoxia) and leads in consequence to death of cancer cells and appearance of necrotic areas in the tumor. A decreased cyclophosphamide dose in combination with two doses of vasostatin (V2 + CTX scheme) inhibits tumor growth similarly to a larger dose of cyclophosphamide alone.

Refine search results

Antiangiogenic gene therapy in inhibition of metastasis.

Various cationic carriers for in vitro transfection of tumor and endothelial cell lines.

Combination of combretastatin A4 phosphate and doxorubicin-containing liposomes affects growth of B16-F10 tumors

Combination of vasostatin and cyclophosphamide in the therapy of murine melanoma tumors

Properties of B16-F10 murine melanoma cells subjected to metabolic stress conditions

Antitumor effect of RGD-4C-GG-D(KLAKLAK)2 peptide in mouse B16(F10) melanoma model

In vivo gene transfer using cetylated polyethylenimine.

On the strategy of using nonviral carriers in cancer gene therapy

Vasostatin increases oxygenation of B16-F10 melanoma tumors and raises therapeutic efficacy of cyclophosphamide