Effect of shock waves combined with cytostatics on the growths of tumors in vivo.

Based on their field of application, the physical parameters of shock waves differ. Experiments referred to in this article used tandem shock waves generated on the surface of a composite anode. There, individual pores of the anode produce multichannel discharges. The composite anode may have a variety of shapes, which, consequently, influence the arrangement of the entire apparatus and the area of their application. Experiments referred to in this article utilise an anode divided into two parts that generated tandem shock waves. The previously conducted experiments have clearly shown that the effect of a tandem shock wave can be very well localized in the focal area, causing necrosis and apoptosis of the tumor cells, and enhancing the effect of cytostatics. This study investigated the effect of tandem shock waves with concomitantly administered cytostatics. We conducted our experiments on Lewis rats. The rats were injected with syngeneic sarcoma tumor cells intradermally and caudally on both the right and left sides. The highest rate of tumor growth inhibition was observed in the cisplatin-treated group that was subsequently treated with shock waves. The effect of shock waves on cell membranes is well described as they increase their permeability due to sonodynamic effect induced by cavitation. The results of experiments referred to in this article conducted in vivo in experimental animals enable us to note that the shock wave increases the effect of chemotherapy administered.

Survivin, a novel target of the Hedgehog/GLI signaling pathway in human tumor cells.

Survivin, an important antiapoptotic protein, is expressed in tumors, whereas in normal tissues the expression of this protein is extremely low, defining a role for survivin as a cancer gene. Survivin exhibits multifunctional activity in tumor cells. However, why survivin expression is sharply and invariably restricted to tumor tissue remains unclear. Here, we identified 11 putative consensus binding sites for GLI transcription factors in the survivin promoter and characterized the promoter activity. Inhibitors of the Hedgehog/GLI pathway, cyclopamine and GANT61, decreased the promoter activity in reporter assays. ΔNGLI2 (which lacks the repressor domain) was the most potent vector in activating the survivin promoter-reporter. Moreover, GANT61, a GLI1/2 inhibitor, repressed endogenous survivin protein and mRNA expression in most cells across a large panel of tumor cell lines. Chromatin immunoprecipitation showed GLI2 binding to the survivin promoter. The ectopic GLI2-evoked expression of endogenous survivin was observed in normal human fibroblasts. GANT61 decreased survivin level in nude mice tumors, mimicking the activity of GANT61 in cultured cells. The immunohistochemistry and double immunofluorescence of human tumors revealed a correlation between the tissue regions showing high GLI2 and survivin positivity. Thus, these results demonstrated that survivin is a classical transcriptional target of GLI2, a Hedgehog pathway signaling effector. This potentially reflects the high expression of survivin in human tumor cells. As the Hedgehog pathway is upregulated in virtually all types of cancer cells, these findings substantially contribute to the explanation of uniform survivin expression in tumors as a potential target for the development of a more effective treatment of cancers through the inhibition of GLI2 to restrain survivin activity.

Biological effects of tandem shock waves demonstrated on magnetic resonance.

OBJECTIVES: The shock wave is used for the treatment of kidney stones, eventually of gall stones, for more than 20 years. It is a pressure wave, which breaks through soft tissues easily and it is possible to focus it into a small volume. The excellent results of the treatment of concrements led to considerations about another usage of the shock wave. The research is now concentrated on the possibility of the damage to tumour tissues. METHODS: In contrast to concrements tumour tissues are not different from healthy tissues as for their acoustic attributes. That is why a new source of shock waves was used in this work. The source allows generating two successive shock waves focused into a common focus, so-called tandem shock waves. The biological effects of the tandem shock waves generated by the new source on rats hepatic tissue and rabbit femoral muscle in vivo were studied in this work. The damage is demonstrated by magnetic resonance imaging. RESULTS: MR images showed tissue damage in focus. There was damage of the liver tissue, muscle and also stomach wall. CONCLUSIONS: We found that the tandem shock waves are able to damage the acoustically homogeneous soft tissue in the focus, i.e. in the depth. In tissues in front of the focus, there is, however, no damage (Fig. 10, Ref. 15).

PAR2 knock-out C57Bl6 mice as a model for evaluating metastases of cancer cells: pilot in vivo study of the metastatic potential of B16 melanoma in knock-out (PAR2-/-) animals.

Proteinase-activated receptor 2 (PAR-2) is a ubiquitous surface molecule. It belongs to the family of G protein-coupled receptors activated by site-specific proteolysis by trypsin. Altered function of PAR-2 has been described in different malignant tumours, both in vivo and in vitro. In the present study, we investigated differences of metastatic spread of B16 melanoma in knock-out animals compared with C57Bl6 mice. Knock-out mice B6.Cg-F2rl1(tm1Mslb)/J (PAR2-/-) and C57Bl6 controls were subcutaneously inoculated with the B16 melanoma tissue cell line. Fourteen days after inoculation, all primary tumours were removed and histopathologically analysed. After one month, animals in both group started to die. Autopsy showed metastatic spread of the melanoma to various organs in both groups. Our experiment confirmed growth and metastatic spread in both groups of mice. Excised tumours differed in volume and weight; average weight (0.62 g in PAR2-/- and 0.4 g in control animals). Metastatic spread was observed in both groups and reached 80 % in PAR2-/- and 50 % in control animals. While in control mice only lung metastases were observed, local tumour recurrence, renal and lung metastases were observed in PAR2-/- mice. The absence of functional PAR-2 could be an important factor influencing the growth and spread of melanoma in vivo, probably associated with tumour cell migration, invasiveness and metastasis formation.

Effects of tandem shock waves combined with photosan and cytostatics on the growth of tumours.

Shock waves, pressure waves manifested as a sharp increase in positive pressure followed by a decrease and the negative part of the wave, are not only used to treat concrements in medicine. Recently, research has been focused on the possibility of their use for damaging the tumour tissue. In contrast to concrements, which are different from the surrounding tissue by their acoustic impedance, the tumour tissue has the same acoustic impedance as the surrounding soft tissue. Therefore, we have developed a new source of shock waves, which is based on the principle of multichannel discharge. This new source generates two successive shock waves (tandem shock waves). The first shock creates acoustic non-homogeneity and cavitations in the tissue, and the second shock is damped in it. In this work we demonstrated the effect of tandem shock waves on the muscle tissue in depth. The damage is shown on the images from the magnetic resonance imaging and histological sections. In the further part of the experiment, we investigated the in vivo effects of tandem shock waves in combination with Photosan and cisplatin on the tumour tissue. The application of tandem shock waves resulted in the inhibition of tumour growth, compared with controls, in both parts of the experiment. The largest inhibition effect was observed in the groups of tandem shock waves combined with Photosan and in the second part with cisplatin.

Polymer-conjugated bovine pancreatic and seminal ribonucleases inhibit growth of human tumors in nude mice.

The hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for RNase A or BS-RNase modification to prevent their degradation in bloodstream or fast elimination. Two PHPMA chains (classic and star-like) were synthesized and their conjugates with both enzymes were tested on the CD-1 nude mice bearing various human tumors. These RNase conjugates injected intravenously or intraperitoneally into the mice bearing melanoma, neuroblastoma or ovarian tumor caused significant reduction of transplanted tumors following ten daily doses of 2.5 and/or 1 mg/kg, respectively, while free RNase A or BS-RNase injected in doses of 10 mg/kg exerted only negligible antitumor activity. Histological examination confirmed potent cytotoxic effect of RNase A conjugates in ovarian tumor. Despite the antitumor activity observed in vivo, the in vitro cytotoxic activity of RNase A conjugates was not pronounced and did not differ from that caused by the free RNase A. The in vitro experiments with 125I-labeled preparations demonstrated that polymer conjugates were internalized by tumor cells very poorly in contrast to the dose-dependent internalization of the wild enzyme preparation. Surprisingly, mice injected with EL-4 leukemic cells, which were preincubated for 4 h with BS-RNase conjugates, exerted significantly prolonged survival compared with the control non-treated mice. It may be supposed that both BS-RNase and RNase A conjugates with PHPMA act after administration in vivo by a mechanism different from that or those occurring under in vitro conditions because in vivo they exert an antitumor action, whereas in vitro, they are ineffective. The experiments proved that RNase A, when conjugated to PHPMA, produced identical aspermatogenic and antitumor effects as BS-RNase conjugated to this polymer and that this preparation may be regarded as a potential anticancer drug.

Poly[N-(2-hydroxypropyl)methacrylamide] conjugates of bovine pancreatic ribonuclease (RNase A) inhibit growth of human melanoma in nude mice.

Recently hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for BS-RNase modification to prevent its degradation in bloodstream or fast elimination. Polymer-conjugated BS-RNase preparations proved to be cytotoxic after intravenous or intraperitoneal application, whereas native BS-RNase was ineffective. Here RNase A unimer was conjugated with two HPMA polymers (classic and star) and their antitumor effects both in vitro and in vivo were compared with those of BS-RNase polymers. Surprisingly, the antitumor effect of RNase A conjugates was also pronounced. The RNase A conjugates (classic and star) injected intravenously to mice bearing melanoma tumor caused a significant reduction in tumor volume following ten doses of 5 and 1 mg/kg, respectively. Despite the antitumor activity observed in vivo, the in vitro tested cytotoxic activity of RNase A did not differ from that caused by native RNase A while native BS-RNase (50 microg/ml) totally inhibited DNA synthesis in treated cells. The experiments with 125I-labeled preparations demonstrated concentration-dependent internalization of native BS-RNase by tumor cells within an hour, whereas the polymer conjugate (S-BS) was not internalized. On the contrary, the in vivo experiments showed that whereas 40% of S-BS conjugate persisted in bloodstream for 24h after administration, 98% of the native BS-RNase was already eliminated. Improved antitumor activities of PHPMA-modified RNases in vivo might be ascribed to their prolonged retention in bloodstream, better proteolytic stability and resistance to the action of the ribonuclease inhibitor.

Proteinase-activated receptor-2 expression on cerebral neurones after radiation damage: immunohistochemical observation in Wistar rats.

Radiation damage results in blood-brain barrier damage followed by blood plasma transfer into the neuropil. The transferred liquid contains high amounts of biologically active substances/proteinases including factor Xa and a free pool of serum trypsin, which is not bound to antiproteases (alpha1 AT, alpha2-macroglobulin). The aim of this study was to follow up expression of proteinase-activated receptor-2 (PAR-2) in the brains of Wistar rats after single exposure to radiation at 26 Gy (60Co, 23 min, 15 sec). After irradiation, the animals were sacrificed on days 10, 20, 30 and 40. Control rat brains served as negative control. Coronal sections of caudal diencephalons were investigated using histology and immunohistochemistry. Polyclonal goat specified antibody against the NH-end of murine and rat PAR-2. Significant PAR-2 membrane positivity of scattered swollen neurons in deeper cortical layers was found in irradiated animals compared with controls. Although this membrane positivity was noticed in all irradiated animals, the most prominent occurred on day 30. Diffuse cytoplasmic positivity was also demonstrated on shrunken neurons in the cortex and hippocampus. Increased cytoplasmic and polarized membrane positivity was also noticed on the neurons of hypothalamic nuclei The causal relationship between blood-brain barrier damage, PAR-2 activation and neurodegeneration has not yet been verified. However, the present findings indicate that PAR-2 mediates a certain cellular response. It remains to be demonstrated whether this is a response to higher concentrations of factor Xa, a free pool of trypsin or other unknown possible proteinases in brain tissue; whether changes in PAR-2 expression are consequences of direct radiation damage to neuronal cells; whether this reaction is protective; and whether primary PAR-2 activation results in neuronal damage.

Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C57Bl6 mice with syngeneic melanoma B16.

PURPOSE: The aim of the present study was to investigate the effect of a mixture of proteolytic enzymes (comprising trypsin, chymotrypsin and papain) on the metastatic model of syngeneic melanoma B16. METHODS: 140 C57B16 mice were divided into two control and two "treated" groups. Control groups received saline rectally, twice a day starting 24 h after intracutaneous transplantation (C1) or from the time point of the primary B16 melanoma extirpation (C2), respectively. "Treated" groups were rectally administered a mixture of 0.2 mg trypsin, 0.5 mg papain, and 0.2 mg chymotrypsin twice daily starting 24 h after transplantation (E1) or after extirpation of the tumor (E2), respectively. Survival of mice and B16 melanoma generalization were observed for a period of 100 days. Immunological evaluation of B16 melanoma cells in the ascites was accomplished. CD44, CD54 and CD106 cells were measured by flow cytometry. RESULTS: Administration of proteolytic enzymes to mice inhibited the growth of primary tumors, and tumor recurrences were less numerous. Importantly, metastasis was considerably curtailed both in the vicinity of the primary tumor and at distant locales. These findings correlated with a decreased expression of CD44 and CD54 molecules in tumors exposed to proteolytic enzymes in vivo. CONCLUSIONS: Our data suggest that serine and cysteine proteinases suppress B16 melanoma, and restrict its metastatic dissemination in C57B16 mice.

Polymer conjugated bovine seminal ribonuclease inhibits growth of solid tumors and development of metastases in mice.

Bovine seminal ribonuclease (BS-RNase) exerts a potent cytotoxic activity when administered intratumorally (i.t.) to the nude mice bearing human tumors. The ineffective treatment with intravenous (i.v.) or intraperitoneal (i.p.) administration led us to the synthesis of polymeric conjugates with BS-RNase to prevent it from degradation in the blood vessel. Hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for BS-RNase modification and a PHPMA-BS-RNase conjugates were prepared. Classic conjugate (P-BS) with BS-RNase bound to the polymer by its oligopeptide site chains was prepared by aminolytic reaction of the polymer precursor bearing reactive ester groups situated in the side chains of polymer, while star-like conjugate (S-BS) was synthesized by the reaction of PHPMA containing end-chain reactive group with BS-RNase in aqueous buffer solution at pH 8. In contrast to the total ineffectiveness of free BS-RNase administered i.v. at a daily dose 10 mg/kg, application of P-BS and S-BS conjugates at doses 2 mg/kg and 0.5 mg/kg caused significant inhibition of the growth of human melanoma in nude mice. On the base of these results the effect of i.v. administered S-BS on the metastatic process and the survival of C57Bl/6 inbred mice inoculated with B16 melanoma cells was investigated. Sixty per cent of mice treated with S-BS (0.5 mg/kg/day) survived 100 days without metastatic foci when the experiment terminated. The average survival time of the treated groups was 75.5 days compared to 32.7 days in the control group. BS-RNase conjugated to water soluble polymers appears to be the first BS RNase preparation which exerts anticancer and antimetastatic activity following its intravenous administration.

Production of TGF-beta1 in lungs after low-dose whole-body radiation exposure in fibrosing (C57BL/6) and non-fibrosing (C3H/J) mouse strain.

The aim of the presented study was to observe acute and subacute discrete TGF-beta1 production after a low-dose whole-body radiation stimulus, known to induce thrombocytopenia. TGF-beta1 mRNA production and the number of thrombocytes was followed up in two mouse strains with different tendencies to the origination of fibroses. Mice of the C57BL/6 and C3H/J strains were exposed to a whole-body dose of 7 Gy. Non-irradiated mice of both strains were used as negative controls. The relative number of thrombocytes recorded in lung capillaries was significantly lower in both strains on day 9 after irradiation in comparison with controls. This finding was in accordance with a decrease in the number of thrombocytes in the peripheral blood in irradiated animals of both strains. On day 56 relative platelet counts reached physiological numbers in comparison to controls. On the other hand, TGF-beta1 mRNA production was higher in the C57BL/6 strain (on day 9) contrary to minimal production in the C3H/J strain (on day 9) or no production in both groups on day 56 and in controls. Thus, TGF-beta1 production without increased thrombocyte trapping in lung vessels in acute stage suggests that an additional mechanism is involved in low-dose radiation-induced cytokine synthesis in lung tissue besides the release of growth factors from thrombocytes.

Expression of proteinase-activated receptor 2 during taurocholate-induced acute pancreatic lesion development in Wistar rats.

BACKGROUND: Proteinase-activated receptor 2 (PAR-2) is a G-protein coupled transmembrane receptor activated by trypsin by site-specific cleavage. Its presence on pancreatic structures was demonstrated in the past. PAR-2 physiologically involves in duct/acinary cells secretion, arterial tonus regulation or capillary liquid turnover. During development of acute pancreatitis/acute pancreatic lesion (APL) these mentioned structures are influenced by very high concentration of trypsin due to its increased basolateral secretion into the interstitium. The aim of our study as presented was to investigate whether PAR-2 is also involved in APL following changes of PAR-2 expression. METHODS: APL was investigated in Wistar rats after injection of 0.1 mL taurocholate into the ductus choledochus. Anatomy, histology, reverse transcriptase polymerase chain reaction (RT PCR) as well as immunohistochemistry and Western-blot analysis of pancreatic tissue were performed using antibody mapping of the new NH2 terminal of PAR-2 after trypsin cleavage. Results from control rats and d 1 or d 4 rats after taurocholate injection were compared. RESULTS: Much higher positivity on acinary/duct cells was observed in APL induced animals than in controls. Similar findings were noticed on arterial smooth muscle cells. Surprisingly, parallel to the exocrine pancreas and vessel findings, enhanced Langerhans' islet cell positivity was observed in experimental animals. CONCLUSIONS: Based on these results, we have demonstrated that during APL development PAR-2 expression increases. This effect is caused by conformational changes after PAR-2 activation, and the new NH2 terminal of activated receptor presentation. We suggest that PAR-2 physiological functions are enhanced during APL development.

Butylaminiperindopril decreases transforming growth factor-beta 1 messenger RNA production in lungs of C57Bl6 mice after low-dose whole-body irradiation.

Transforming growth factor (TGF)-beta is believed to play a key role in the development of many autoimmune and malignant diseases, such as radiation and drug-induced organ disease. The aim of the present study was to determine messenger RNA (mRNA) production of TGF-beta 1 in the lungs of C57Bl6 mice after low-dose whole-body irradiation. Control (irradiated) and irradiated angiotensin-converting enzyme (ACE) inhibitor-treated animals were simultaneously examined. The ACE inhibitor group received butylaminiperindopril for 9 days after irradiation (7 Gy) at a daily dose of 0.1 mg/kg per rectum. On day 9 all mice were sacrificed and the production of mRNA TGF-beta 1 in lung tissue was determined semiquantitatively using reverse transcriptase polymerase chain reaction. In butylaminiperindopril-treated mice, a decrease in transcript of TGF-beta 1 (to 59% in comparison with controls) was observed.

Antitumor action of bovine seminal ribonuclease.

Unlike the bovine pancreatic ribonuclease (RNAase A), bovine seminal ribonuclease (BS RNAase) displays various biological activities including antitumor cytotoxicity. To learn more about its antitumor activity, we investigated BS RNAase effect on athymic nude mice bearing various tumors. BS RNAase (250 micrograms per mouse per day) was administered to the mice with prostate carcinoma for three weeks by three different routes (intraperitoneally--i.p., subcutaneously--s.c., and intratumorally-i.t.). Administration i.p. was ineffective, while s.c. administration reduced significantly size of tumors and i.t. administration abolished half of the tumors in treated mice. The i.t. administration of BS RNase to nude mice bearing melanoma showed even better results. Eighty % of mice were without tumors and in the other mice the tumors were significantly diminished. The best antitumor effect was obtained in case of seminoma. All mice bearing this tumor were cured after ten doses of BS RNAase.

Proteinases reduce metastatic dissemination and increase survival time in C57Bl6 mice with the Lewis lung carcinoma.

The effect of combined proteolytic enzymes, administered by the rectal route, on the metastatic process and the time of survival in C57Bl6 mice with the Lewis lung carcinoma inoculated subcutaneously was investigated. In the control group, which received no enzyme treatment, 90% of animals died of the metastatic spread of cancer by day 18 after primary tumor extirpation. In Group A, which received the multi-enzyme solution from the time of primary tumor extirpation, 30% of mice died of disseminated cancer by day 25. In Group B, which was treated with the enzymes from 6 days before primary tumor extirpation, only 10% of animals showed the metastatic process by day 15. In Group C, which received the enzymes from 24 hours after intracutaneous tumor inoculation, no metastatic dissemination was discernible. In these three groups, the enzyme treatment was carried out throughout the study. None of the control animals survived for 100 days when the study was ended. The treated groups A, B and C showed survival rate 60%, 90% and 100% of animals, respectively, by 100 days.

Antitumor action of bovine seminal ribonuclease. Cytostatic effect on human melanoma and mouse seminoma.

This paper reports on the antitumor activity of BS RNase on human melanoma and mouse seminoma. Human melanoma cells established in culture were extremely susceptible to BS RNase, administered in concentrations ranging from 1-100 microg/ml. Concentrations of BS RNase over 10 microg/ml caused complete inhibition of cell growth. Bovine pancreatic ribonuclease (RNase A), a prototype of the ribonuclease superfamily, did not exert any effect under these conditions. Based on our previous results, athymic mice bearing human melanoma or mouse seminoma were treated with intratumoral administration of BS RNase (12.5 mg/kg b.w.). This dose was injected for five consecutive days excluding weekends. The intratumoral administration of BS RNase to nude mice bearing human melanoma showed a significant antitumor effect. There were no tumors seen in eighty percent of mice treated for three weeks, and tumors in the other mice diminished significantly. After some delay the tumors started to regrow. Prolonging of the treatment to five weeks had a similar effect. The effect of BS RNase on mouse seminoma was well pronounced. Five to seven doses of BS RNase were sufficient to eliminate tumors in all treated mice. However, as in the previous experiment, the growth of tumor tissue later reappeared.

Polyenzyme preparation Wobe-Mugos inhibits growth of solid tumors and development of experimental metastases in mice.

Long-term rectal administration of enzyme mixture containing papain, trypsin and chymotrypsin in the same ratio as the preparation Wobe-Mugos E (Mucos Pharma, Germany) was evaluated for their antitumor effects in C57Bl6 inbred mice inoculated with Bl6 melanoma cells. 30% of animals in the test group (3 pcs) have been cured of cancer. In the rest of animals (70%) the survival time was prolonged by 58.3% compared to the control group (from average survival time of 24 days in control group to 38 days in the test group). Based on histological and immunohistochemical evaluation a faster process of metastasizing was found in control group than in the group treated with the polyenzyme preparation. In the case of melanoma Bl6 an antimetastatic effect of the preparation was thus proved.

Antitumor action of bovine seminal ribonuclease.

Unlike the bovine pancreatic ribonuclease (RNaseA), bovine seminal ribonuclease (BS RNase) displays various biological activities, including antitumor activity, immunosuppressivity, spermatogenicity and embryotoxicity. To learn more about its antitumor effect we tested BS RNase on the growth of 16 cell lines derived from patients with various hematological malignancies. The cells of lymphoid origin were generally more susceptible to BS RNase, administered in the range of concentrations from 2 to 100 micrograms/ml, than the myeloid ones. RNaseA used at the same concentrations did not exert any inhibitory effect. The inhibitory effect of BS RNase persisted in cultured cells after three times wash in complete medium and cell recultivation in fresh medium free of BS RNase. Four cell lines were very little sensitive (KG-1 and U-937) or resistant (JOK and NAMALWA) to BS RNase regardless of their origin. The in vivo antitumor effect of BS RNase was tested on human prostate carcinoma transplanted to athymic nude mice. The daily dose of BS RNase (0.25 mg/20 g) was administered for three weeks except weekends (15 doses) by three different ways (intraperitoneally-i.p., subcutaneously-s.c. and intratumorally-i.t.). Whereas i.p. administration was ineffective, s.c. administration significantly reduced size of the tumors and i.t. administration abolished half of the tumors in treated mice. The average weight of treated mice decreased during the experiment by 10-15%.

Meso-tetra-(4-sulfonatophenyl)-porphine of low neurotoxicity.

The acute toxicity of specially purified meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4) was measured in mice DBA/2 and Wistar rats after i.v. administration of the dye dissolved in saline solution. LD50 of our preparation was 352.5 mg/kg for mice and 574.9 mg/kg for rats. Motor nerve conduction velocity was measured in rats and rabbits in ether anesthesia N. ischiadicus and n. tibialis were stimulated by surface electrodes and M response was registered. No signs of neurotoxicity were found, even after application of 150 mg/kg b.w. of our TPPS4. Histologic evaluation was performed by routine method and standard electron microscopic procedure. Only minimal and sporadic axonal changes were found. The clinical application of low toxic TPPS4 was reconsidered.

[Photodynamic therapy of human tumor xenotransplants in athymic nu/nu mice]. / Fotodynamická terapie lidských nádoru xenotransplantovaných na athymické nu/nu mysi.

The effect of phototherapy on the growth of two human tumors, i.e. carcinoma of the rectum I and III, was studied. The tumors were xenotransplated into athymic nu/nu mice. Meso-tetra-(para-sulfophenyl)-porphin, TPPS4, was used as photosensitizer. Incorporation studies showed the optimal dose for phototherapy to be 10 mg/kg TPPS4 and the time interval 72 hours. Under these experimental conditions (helium-neon laser, 632, 8, 300 J/cm2) one of six tumors was cured in the group with carcinoma of the rectum I, and that both after IV and IT administration of the photosensitizer. The other five experimental animals exhibited only partial responses to phototherapy. In the group with carcinoma of the rectum III, five out of six tumors were cured by IT administration of TPPS4 under the same experimental conditions. In one mouse there was only partial response to phototherapy. After IV administration of TPPS4, however, not a single tumor was cured and the response to phototherapy was only partial in all the six experimental animals.