Effect of p27 gene combined with Pientzehuang (characters: see text) on tumor growth in osteosarcoma-bearing nude mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of p27 gene recombinant adenovirus combined with Chinese medicine Pientzehuang ([characters: see text]) on the growth of xenografted human osteosarcoma in nude mice.</p><p><b>METHODS</b>Tissue transplantation was used to construct the orthotopic model of human osteosarcoma Saos-2 cell in nude mice. Thirty tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group: blank control group (model of osteosarcoma), empty vector group (recombinant adeno-associated virus-multiple cloning site), Pientzehuang group, p27 gene group and combined treatment group (p27 gene combined with Pientzehuang). The effect of combined treatment on human osteosarcoma was analyzed through the tumor formation, tumor volume and inhibition rate of tumor growth. The expression of p27 was measured by immunohistochemical staining and Western blot.</p><p><b>RESULTS</b>The orthotopic model of osteosarcoma in nude mice was successfully constructed. The general appearance of tumor-bearing nude mice in Pientzehuang and p27 gene groups was markedly improved compared with the blank control group; and in the combined treatment group it was significantly improved compared with the Pientzehuang and p27 gene groups. The tumor growth in the Pientzehuang and p27 gene groups was significantly inhibited compared with the blank control group P<0.05); while in the combined treatment group it was markedly inhibited compared with the Pientzehuang and p27 gene groups (P<0.05). The rates of tumor growth inhibition were 34.1%, 56.5% and 63.8% in the Pientzehuang, p27 gene and combined treatment groups, respectively. Meanwhile, the protein expression of p27 gene in the p27 gene group was significantly increased compared with the blank control group (P<0.05); and it was significantly increased in the combined treatment group compared with the p27 gene and Pientzehuang groups (P<0.05).</p><p><b>CONCLUSION</b>p27 gene introduced by adenovirus combined with Pientzehuang can inhibit the growth of human osteosarcoma cell Saos-2 in nude mice.</p>

Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>To develop a vaccine-based immunotherapy for sarcoma, we evaluated a mixture of heat shock proteins (mHSPs) as a vaccine for sarcoma treatment in a mouse model. Heat shock protein/peptides (HSP/Ps) are autoimmune factors that can induce both adaptive and innate immune responses; HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.</p><p><b>METHODS</b>In this study, we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity. We extracted mHSP/Ps, including HSP60, HSP70, GP96, and HSP110, from the mouse sarcoma cell lines S180 and MCA207 using chromatography. The immunity induced by mHSP/Ps was assessed using flow cytometry, ELISPOT, lactate dehydrogenase release, and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Of S180 sarcoma-bearing mice immunized with mHSP/Ps isolated from S180 cells, 41.2% showed tumor regression and long-term survival, with a tumor growth inhibition rate of 82.3% at 30 days. Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells, 50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%. All control mice died within 40 days. The proportions of natural killer cells, CD8+, and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.</p><p><b>CONCLUSIONS</b>Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors. This mHSP/P vaccine exerted greater antitumor effects than did HSP70, HSP60, or tumor lysates alone.</p>

Reversión del eclipse inmunológico y vacunación terapéutica contra el cáncer en un modelo experimental / Reversion of the immunological eclipse and therapeutic vaccination against cancer in an experimental model

Aunque existen vacunas para prevenir la aparición de tumores en animales de experimentación, la mayoría de los intentos por aplicar aquellas vacunas con fines terapéuticos contra tumores establecidos no han sido exitosos. Para comprender la naturaleza de esta refractariedad, estudiamos un tumor de ratón fuertemente inmunogénico inducido por el carcinógeno químico metilcolantreno. En nuestro modelo, el inicio de esta refractariedad coincidió con el comienzo de un estado de inmunosupresión conocido como "eclipse inmunológico" caracterizado por una pérdida o bloqueo de la respuesta inmune antitumoral después que el tumor ha superado cierto tamaño crítico. Este eclipse inmunológico fue acompañado por un proceso de inflamación sistémica en el organismo. El tratamiento de los ratones portadores de tumor con una única dosis del corticoide sintético dexametasona (DX) redujo los parámetros de inflamación sistémica e indujo la reversión del eclipse. Esta reversión no fue por sí misma curativa pero permitió que un tratamiento inmunológico basado en células dendríticas estimuladas con antígenos tumorales, que por sí solo era absolutamente ineficaz, pudiera ejercer un significativo efecto inhibidor sobre un tumor en crecimiento. El esquema de dos pasos que comprende, primero, un tratamiento antiinflamatorio para revertir el eclipse y segundo, una estrategia de vacunación basada en células dendríticas destinada a estimular la respuesta inmune antitumoral, podría servir, eventualmente, como un modelo de inmunoterapia contra tumores en animales y seres humanos.

Although animals can be prophylactically immunized against the growth of tumor implants, most of the attempts to use immunotherapy to cause the regression of animal and human tumors once they become established have been unsuccessful. To understand the nature of this refractoriness we have studied a methylcholanthrene-induced and strongly immunogenic murine fibrosarcoma. In our model, the onset of this refractoriness was associated with the beginning of an immunosuppressive state known as "immunological eclipse" characterized by a loss of the antitumor immune response when tumor grows beyond a critical size. This immunological eclipse was accompanied by the emergence of a systemic inflammatory condition. Treatment of tumor-bearing mice with a single dose of a synthetic corticosteroid, dexamethasone (DX), reduced significantly all parameters of systemic inflammation and simultaneously reversed the immunological eclipse. The reversion of the eclipse upon DX treatment was not curative itself, but allowed an immunological therapy based in dendritic cells pulsed with tumor antigens, which was itself absolutely ineffective, to exert a significant inhibitory effect against an established growing tumor. The two-step schedule using an anti-inflammatory treatment to reverse the immunological eclipse plus a dendritic cell-based vaccination strategy aimed to stimulate the anti-tumor immune response, could serve eventually as a model of immunotherapy against animal and human tumors.

Inhibition of chemically induced carcinogenesis by drugs used in homeopathic medicine.

Homeopathy is considered as one modality for cancer therapy. However, there are only very few clinical reports on the activity of the drugs, as well as in experimental animals. Presently we have evaluated the inhibitory effects of potentized homeopathic preparations against N'-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in rats as well as 3-methylcholanthrene-induced sarcomas in mice. We have used Ruta, Hydrastis, Lycopodium and Thuja, which are commonly employed in homeopathy for treating cancer. Administration of NDEA in rats resulted in tumor induction in the liver and elevated marker enzymes such as gamma-glutamyl transpeptidase, glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and alkaline phosphatase in the serum and in liver. Concomitant administration of homeopathic drugs retarded the tumor growth and significantly reduced the elevated marker enzymes level as revealed by morphological, biochemical and histopathological evaluation. Out of the four drugs studied, Ruta 200c showed maximum inhibition of liver tumor development. Ruta 200c and phosphorus 1M were found to reduce the incidence of 3-methylcholanthrene-induced sarcomas and also increase the life span of mice harboring the tumours. These studies demonstrate that homeopathic drugs, at ultra low doses, may be able to decrease tumor induction by carcinogen administration. At present we do not know the mechanisms of action of these drugs useful against carcinogenesis.

In vivo and in vitro anti-tumor effect of Sanjie Kangliu Decoction / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the anti-tumor effect of Sanjie Kangliu (swelling-dispersing) Decoction in vivo and in vitro.</p><p><b>METHODS</b>The mice bearing tumors (established by subcutaneous inoculation of SRS-82 cells) were fed with Sanjie Kangliu Decoction. The tumor was isolated and weighed to calculate the tumor inhibition rate, followed by morphological observation of the tumor cells under electron microscope. The DNA of the tumor cells was then extracted for agarose gel electrophoresis. In the in vitro experiment, cultured SRS-82 cells were treated with the serum of rats fed with Sanjie Kangliu Decoction, and the cell viability and apoptosis was examined by MTT assay and flow cytometry, respectively. Immunocytochemistry was employed to test the expression intensity of Bcl-2 protein of the rat serum-treated cells, and in situ hybridization performed to detect matrix metalloproteinase (MMP)-2 mRNA expression.</p><p><b>RESULTS</b>In the tumor-bearing mouse models, Sanjie Kangliu Decoction administration resulted in significant reduction of the tumor mass and apoptosis of the tumor cells as shown by typical apoptotic changes of the cell morphology and presence of DNA ladder in agarose gel electrophoresis. In comparison with the mice without the decoction treatment, the treated mice showed significantly lower tumor cell viability, higher cell apoptosis rate, and weaker Bcl-2 expression. The expression of MMP-2 mRNA showed no distinct difference between the groups.</p><p><b>CONCLUSION</b>Sanjie Kangliu Decoction has obvious anti-tumor effect both in vivo and in vitro possibly through the mechanism of inducing tumor cell apoptosis by reducing Bcl-2 expression without affecting the expression of MMP-2 mRNA.</p>

Exploração funcional do processo de glicosilação aberrante em tumores: mecanismos envolvidos na atividade pró-migratória de galectina-3 / Exploiting the functional significance of aberrant glycosylation in tumors: mechanisms involved in the activity of galectin-3

Com o objetivo de analisar a expressão dos ligantes de galectina-3 associados à transformação maligna, desenvolvemos uma proteína quimérica, a Gal-3/FA. Observamos que a Gal-3/FA pode ser usada como sonda em ensaios de overlay e de imunoistoquímica. Entre os ligantes de galectina-3 identificamos a 1 integrina, mediador da migração celular. A galectina-3 age como modulador positivo do processo de migração em superfícies de laminina-1. Na presença de galectina-3 observamos diminuição de FAK fosforilado e recrutamento da fosfatase SHP-2 para os complexos focais, levando ao turnover desses complexos / Exploiting the functional significance of aberrant glycosylation in tumors: mechanisms involved in the promigratory activity of galectin-3 / We have generated a novel tool for exploiting the clinical and biological significance of a common hallmark of cancer cells, namely the process of aberrant glycosylation. This tool is a chimeric galectin-3 fused to alkaline phosphatase which allowed for in situ identification of galectin-3 ligands in both human and murine tissues...

Cancare-a herbal formulation inhibits chemically induced tumours in experimental animals.

Cancer chemopreventive potential of Cancare, a multi-herbal formulation on chemically induced tumours was studied by N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in rats and 20-methylcholanthrene (20-MC) induced sarcoma development in mice. Oral administration of Cancare was found to inhibit the liver tumour development induced by N-nitrosodiethylamine. Animals administered with NDEA had visible liver tumours by the end of 30th weeks and the liver weight was raised to 6.1 +/- 1.4 g/ 100 g body wt. None of the animals treated with Cancare (150 mg/ kg) developed any visible liver tumours by this period and the liver weight was 3.0 +/- 0.6 g/ 100 g body wt. Gamma-Glutamyl transpeptidase, a marker of hepatocellularcarcinoma, which was raised to 83.7 +/- 8. 9 U/l in serum of NDEA treated group was reduced to 35.2 +/- 6.1 U/l by simultaneous administration of Cancare. Elevated levels of serum alkaline phosphatase, glutamate pyruvate transaminase, bilirubin, liver glutathione S-transferase, glutathione and gamma-Glutamyl transpeptidase in the NDEA administered group was significantly reduced by Cancare administration. Cancare administration inhibited the sarcoma development and increased the life span of mice administered with 20-MC dose dependently. All animals in the control group developed sarcomas by 150th day and dead by 174th day after 20-MC administration. Cancare administration (30 mg and 150 mg/kg) inhibited the sarcoma development (46.7 and 60%) as well as increased the life span (53.3 and 66.7%) as estimated on 240th day after 20-MC administration. The results are indicative of the chemopreventive potential of Cancare against chemically induced neoplasmas.

Antioxidant and anticarcinogenic activity of Lycovin--an indigenous herbal preparation.

Aqueous extract of Lycovin has been found to be a potent inhibitor of lipid peroxide formation, (IC50 = 500 micrograms/ml) and scavenger of hydroxyl radical (IC50 = 44 micrograms/ml) and superoxide radical (IC50 = 30 micrograms/ml) in vitro. Lycovin syrup 1.5 ml and 7.5 ml/kg body wt administered orally, reduced the development of sarcoma induced by 20 MC by 35% and 70% respectively. Lycovin syrup was also found to inhibit the hepatocarcinogenesis induced by NDEA. The tumour incidence was 100% in the control group, while none of the drug treated animals developed tumour. Liver weight, gamma-glutamyl transpeptidase (GGT), GSH-S-transferase (GST), reduced glutathione, (GSH) and aniline-4-hydroxylase in liver were elevated in NDEA alone treated animals. The serum parameters indicative of liver injury such as bilirubin, lipid peroxides, alkaline phosphatase and glutamate pyruvate transaminase were also elevated by NDEA administration. These elevated parameters were significantly reduced in animals treated with Lycovin syrup along with NDEA in a dose dependent manner. Even though the exact mechanism of action is not known at present, the observed anticarcinogenic activity may be due to the inhibition of P.450 enzyme activity and subsequent inhibition of the production of the ultimate carcinogen as well as scavenging of oxygen free radicals during promotion of the transformed cell.

Role of bio-metal Fe(III) in anticancer effect of dacarbazine.

Physicochemical, Microbial and Pharmacological studies on Fe(III)-Dacarbazine complex have been done in solid and aqueous phase. On the basis of elemental analysis, polarographic studies, amperometric titrations and IR spectral studies the probable formula for the complex has been worked out to be 1:1, Fe(III)-Dacarbazine. The metal ligand interaction has been studied using polarographic method at 25 +/- 1 degrees C and at ionic strength of mu = 1.0 (KCl). Microbial studies on the complex was done against various pathogenic bacteria viz. Pseudomonas mangiferae, Staphylococcus aureus, Salmonella typhi and Vibrio cholarae and fungi i.e. Trichothecium and Chrysosporium sp. using Raper's method. Mouse sarcoma cell line 180 and Balb/C mice were used for the anticancer screening of solid complex in vitro and in vivo respectively. The observed polarographic data, on lingane treatment revealed the formation of single (1:1) (M:L) complex with Fe(III) and dacarbazine ligands. The results of amperometric titrations of Fe(III) with dacarbazine in IM KCl supporting electrolyte pH 7.0 +/- 0.1 supported the above findings the IR data speaks of the complex formation between the metal and the dacarbazine ligand through the two nitrogen one each of primary amide and trizo groups. The results of microbial and pharmacological studies with the M:Drug complex revealed that the anticancer activity of the drug metal complex is nearly doubled as compared to the pure drug. As such Fe(III) dacarbazine complex may be recommended to the therapeutic experts for its possible use as more potent anticancer drug.

Multimodality treatment using AK-2123, hydralazine, radiation & hyperthermia on a transplantable mouse tumour.

The in vivo response of a transplantable mouse tumour, Sarcoma 180 to AK-2123 (AK), local irradiation (RT) and local hyperthermia, as influenced by a vasoactive drug, hydralazine (HDZ), was assessed on the basis of tumour cure (complete response CR), volume doubling time (VDT), regrowth delay (RD) and animal survival up to 120 days. A single ip injection of 200 mg/kg b.wt. AK produced more than 15 per cent CR. Combination of any two agents resulted in a better response than the single agent treatments. AK in combination with 43 degrees C, 30 min (HT) was more effective than HT combination with 10 Gy. The presence of 5 mg/kg HDZ, injected immediately after 5 Gy, in combination with AK increased the therapeutic effect over that produced by AK+10Gy. Combination of all the three agents (AK+10Gy+HT) produced 100 per cent CR and prolonged disease free animal survival. A similar response could be obtained by the presence of HDZ with a lower radiation dose of 5 Gy in combination with AK and HT (AK+5Gy+HDZ+HT). This multimodality treatment offers the possibility of further reduction in the doses of individual agents, and in the possible side effects on normal tissues without compromising the tumour cure effect.

Response of mouse sarcoma-180 to cis-platin in combination with radiation & hyperthermia.

The in vivo response of a transplantable mouse tumour, sarcoma-180, to cis-platin (cDDP, 1.0, 2.5 or 5.0 mg/kg b.wt), local hyperthermia (HT, 42 degrees C, 30' or 60' and 43 degrees C, 30') and irradiation (RT, 10 Gy) was assessed on the basis of tumour cure (complete response, CR), volume doubling time (VDT) and regrowth delay (RD) as well as animal survival up to 120 days. Each agent was given as a single modality or in different combination regimens. A single injection of cDDP produced a dose dependent increase in all the parameters. Of all the single treatments, HT at 43 degrees C, 30' gave the maximum tumour cure. Combination of any of the two treatments resulted in a better response than all the single treatments. The chemosensitizing effect of heat was more pronounced than its radiosensitizing effect. Combination of all the three modalities, cDDP (2.5 mg/kg) + RT + HT (43 degrees C, 30') resulted in 100 per cent CR, without any local recurrence. This treatment also resulted in a significant increase in 120 day tumour free survival compared to all single modality treatments and bimodality treatments, except cDDP + 43 degrees C, 30'. This study indicates a potential advantage of the trimodality approach over single and bimodality treatments in the local control of solid tumours.

Alterations of lipid kinetics and lipoprotein lipase activity in jaundiced tumor bearing rats

Obstructive jaundice is associated with high perioperative morbidity and mortality, and preoperative biliary decompression is still controversial. Profound alterations in intermediary metabolism have been observed with obstructive jaundice. To determine the effect of the common bile duct (CBD) obstruction on lipid metabolism in tumor-bearing animals, free fatty acid (FFA) and very low density lipoprotein-associated triglyceride (VLDL-TG) kinetics were assessed in 20 tumor bearing (subcutaneous MCA sarcoma) Fischer-344 rats, using an obstructive jaundice model. The animals were studied after chronic vascular catheterization, in an unanesthetized, undisturbed state. They were separated into 4 groups: Normal controls (CTL), Tumor-bearing non-jaundiced rats (TBR), Non Tumor Bearing-Jaundiced (NTB-J), Tumor Bearing (tumor burden: 1O per cent body weight)-Jaundiced (TBR-J). All rats were studied 7 days after CBD ligation, or at 1O per cent tumor burden. VLDL-TG and FFA kinetics were assessed by constant infusion of 3H-palmitate-labeled VLDL-TG, and l4C-palmitate bound to albumin, respectively. FFA rate of appearance (FFA-Ra) and clearance (FFA-CI), VLDL-TG rate of appearance (VLDL-TG-Ra) and clearance (VLDL-TG-CI) were determined at steady-states. Tumor burden signiricantly affects FFA-Ra and FFA-CI, as well as VLDL-TG-CI, while CBD ligation selectively affects VLDL-TG-Ra and VLDL-TG-CI. There was significant interaction between tumor burden and jaundice in FFA-Ra. CBD decompression increased significantly VLDL-TG-CI. We conclude that, in jaundiced tumor-bearing rats, tumor burden predominantly affects lipolysis, while CBD obstruction primarily affects triglyceride synthesis and clearance. Lipoprotein lipase (LPL) activity was also markedly decreased by the presence of jaundice and tumor burden, with the associated decrease in the clearance of VLDL-TG.

Inmunidad concomitante contra el sarcoma E 100 comparando dos líneas de ratas / Concomitant immunity against the sarcoma E 100 comparing 2 lineas of rats

El fenómeno de inmunidad concomitante (IC) se define clásicamente como la capacidad que tiene un animal portador de un tumor progresor de inhibir el crecimiento de un segundo inóculo del mismo tumor. En dos líneas de ratas, que tienen distinto comportamiento al desafiarse con Sarcoma E 100 (SE 100), lnea IIMc: 90 por ciento de toma y 100 por ciento de regresión; línea "m": 100 por ciento de toma y muerte), se indujo IC a fin de establecer la participación del huésped en la generación de este fenómeno frente al mismo tumor. Las ratas recibieron el segundo desafío los días 3 ó 14, al igual que los respectivos grupos testigos. Los animales reinoculados el día 7 presentarón menor porcentagen de toma y menores superficies tumorales; además en las ratas IIMc se observó menor desarrollo del primer inóculo. El ensayo de Winn en ratas IIMc confirmó la presencia de células esplénicas (CE) comprometidas contra el SE 100 en los bazos de: ratas inmunes: portadoras de un solo tumor; de primer inóculo en crecimiento y segundo negativo en IC. En línea "m" el porcentagen de toma sólo fue menor en el grupo inoculado conjuntamente con el CE de ratas inmunes. Sólo un 10 por ciento (3/30) de ratas "m" pudieron inmunizarse contra el SE 100. Estos resultados perimitirían atribuir el fenômeno de IC, en ratas IIMc, a mecanismos inmunitários y en ratas "m", de acuerdo a lo postulado por Gorelik, a un factor o factores liberados y/o inducidos por el primer tumor. Se sugiere que prevalecería uno u otro mecanismo según las características biológicas del huésped

In vivo sister chromatid differentiation and baseline sister chromatid exchanges in a mouse ascites tumour model.

Induction of differentially stained sister chromatids at G2/M and determination of baseline sister chromatid exchanges (SCEs) in ascites form of mouse sarcoma 180 cell line have been done by in vivo incorporation of 5-bromodeoxyuridine (BrdU) for two consecutive DNA replication cycles. The baseline SCE frequency is 6.24 at log phase of tumour growth.

Immunologic and survival studies in mice immunised with cryodestroyed ascites fibrosarcoma (AFS) cells.

Adult mice weighing 20 g, divided into 5 groups, were immunised with single and three cycle cryodestroyed ascites fibrosarcoma cells using different modes of immunisation with respect to dose and administration frequency. Survival against subsequent challenge with the same tumour cells and immune response given by leucocyte migration inhibition, were studied in these animals. It appears from the present study that animals with relatively low antigenic load have a significantly (P less than 0.001) high mean survival time and/or survival index compared with controls than those with relatively high antigenic load. Survival in animals immunised with three cycle cryodestroyed tumour cells is significantly (P less than 0.001) higher than that with single cycle even in face of a greater challenging tumour dose with mode of immunisation remaining the same. Preliminary observations on percentage leucocyte migration inhibition showed that there exists no difference in percentage inhibition with either viable or cryodestroyed tumour cell antigens added to migration chamber excepting in animals immunized with three cycle cryodestroyed tumour cells where percentage inhibition was significantly (P less than 0.001) greater with viable than with cryodestroyed tumour cell antigen without altering the percentage inhibition between the two groups. Factors maximising immune response and their modulating effects are discussed.

Herencia de la susceptibilidad a los tumores y a las metástasis en roedores / Inheritance of susceptibility to tumors and metastases in rodents

Se investigaron los factores genéticos que regulan la susceptibilidad al Sarcoma E100 (SE100) y al linfoma TACB (L-TACB) de ratas y la capoacidad metastásica de este tumor. A partir de una línea e endocriada de ratas se obtuvo una sublínea resistente eR y otra susceptible eS al S-E 100. Las frecuencias fenotípicas de resistencia y susceptibilidad en e, eR,, eS, F1 y F2 permitieron elaborar un modelo teórico de dos pares de genes independientes que regularían la susceptibilidad al S-E 100. El comportamiento del L-TACB y las diferentes respuestas inmunes a antígenos del S-E 100 y del L-TACB y a antígenos no relacionados (glóbulos rojos de camero) en eR y eS avalaron la hipótesis de que los genes seleccionados regularían la respuesta inmune antitumoral. L participación del sistema inmunológico no descartó la presencia de factores de crecimeiento tumoral en la respuesta diferencial de eR y eS sugerida por la respuesta a injertos de S-E 100 irradiados debajo de la cápsula renal. Los patrones de herencia de dos linfomas, el L-TACB y el DGE en la rata y en el ratón evidenciaron que la susceptibilidad a estos linfomas está regida por genes dominantes. La capacidad metastática del L-TACB estaría condicionada por genes distintos de los que facilitarían el crescimiento del tumor primario

Chlorophyll derivatives: a new photosensitizer for photodynamic therapy of cancer in mice

The in vivo photosensitizing efficacy of chlorophyll derivatives(CpD), which had been developed as a new photosensitizer, was compared with that of hematoporphyrin derivatives (HpD). A murine tumor model implanted subcutaneously with S-180 cells on the abdomen was used. The CpD or HpD was administered by intratumoral injection, and light of appropriate wavelength was irradiated on the tumor areas for 10 minutes at 1h and 24h or 24h and 48h after the injection of photosensitizer. When CpD was injected, the early irradiation group (1h and 24h) showed a 100% tumor cure rate; however, the late irradiation group (24h and 48h) showed a 60% tumor cure rate (p less than 0.01). This showed that the early irradiation with light after injection of CpD was an important factor for obtaining better results. With HpD, there was no difference in tumor cure rate between early (1h and 24h, 80%) and late irradiation (24h and 48h, 80%) groups. Thus, in early irradiation groups, the tumor cure rate using CpD (100%) was superior to that of HpD (80%) (p less than 0.05). However, in late irradiation groups, the tumor cure rate using CpD (60%) was inferior to that of HpD (80%), but this difference was not statistically significant (p greater than 0.1). Pathologic sections of these tumors were made before treatment and 48h and 3 weeks after treatment. These showed geographic necrosis at 48h after treatment and no viable tumor tissue at 3 weeks after treatment. Our results showed that CpD was as effective as HpD as a photosensitizer for in vivo photodynamic therapy.

Chlorophyll derivatives: a new photosensitizer for photodynamic therapy of cancer in mice

The in vivo photosensitizing efficacy of chlorophyll derivatives(CpD), which had been developed as a new photosensitizer, was compared with that of hematoporphyrin derivatives (HpD). A murine tumor model implanted subcutaneously with S-180 cells on the abdomen was used. The CpD or HpD was administered by intratumoral injection, and light of appropriate wavelength was irradiated on the tumor areas for 10 minutes at 1h and 24h or 24h and 48h after the injection of photosensitizer. When CpD was injected, the early irradiation group (1h and 24h) showed a 100% tumor cure rate; however, the late irradiation group (24h and 48h) showed a 60% tumor cure rate (p less than 0.01). This showed that the early irradiation with light after injection of CpD was an important factor for obtaining better results. With HpD, there was no difference in tumor cure rate between early (1h and 24h, 80%) and late irradiation (24h and 48h, 80%) groups. Thus, in early irradiation groups, the tumor cure rate using CpD (100%) was superior to that of HpD (80%) (p less than 0.05). However, in late irradiation groups, the tumor cure rate using CpD (60%) was inferior to that of HpD (80%), but this difference was not statistically significant (p greater than 0.1). Pathologic sections of these tumors were made before treatment and 48h and 3 weeks after treatment. These showed geographic necrosis at 48h after treatment and no viable tumor tissue at 3 weeks after treatment. Our results showed that CpD was as effective as HpD as a photosensitizer for in vivo photodynamic therapy.

Efecto inhibidor de Staphylococcus aureus sobre el crecimiento de un sarcoma en ratas / Inhibitory effect of Staphylococcus aureus on the growth of rat sarcoma

Se investigó el efecto modulador de la respuesta antitumoral de S. aureus y diversas poblaciones celulares en ratas portadoras de un sarcoma transplantable (S-E 100). Se comprobó en estas experiencias la capacidad inhibitoria del crecimiento del S-E 100 en ratas endocriadas, a través de la inoculación i.p. de células de exudado peritoneal (CEP), células de bazo (C.B.) y células de bazo no-adherenrtes (CBN-A), provenientes de ratas previamente desafiadas con S. aureus. También se inocularon i.p. células de animales normales (CEPN, CBN, CBN-AN). Se midió el tamaño del S-E 100 en los días 4, 7, 14, 21 y 28 después de iniciado el tratamiento. Se determinó que S. aureus, así como las poblaciones celulares provenientes de animales previamente inoculados con el germen (CE, CB, CBN-A), inhibe significativamente el crecimiento del tumor. Las células de animales normales no inciden en tal efecto. Se discute si este fenómeno es producido por la proteína A de S. aureus o a través de la activación de las poblaciones celulares (linfocitos, macrófagos, NK) inoculadas