Ehrlich Tumor Research Articles

Antitumor and radiosensitizing synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice.

Considerable attention has been paid to the introduction of novel naturally occurring plant-derived radiosensitizer compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally (i.p.) injected into non-irradiated or γ-irradiated (6.5 Gy whole-body γ-irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days. Investigations included molecular targets involved in proliferation, inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich carcinoma tumors and demonstrated a synergistic radiosensitizing efficacy together with γ-irradiation. These effects were achieved through downregulating the expression of angiogenic and lymphangiogenic regulators, including signal transducer and activator of transcription 3, vascular endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix metalloproteinase-2 and -9 activities, which play a key role in tumor invasion and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors verified the recorded data. In conclusion, a synergistic radiosensitizing efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich carcinoma in the current in vivo murine model, representing therefore a potential therapeutic strategy for increasing the radiation response of solid tumors.

Cis-[RuCl(BzCN)(bipy)(dppe)]PF6 induces anti-angiogenesis and apoptosis by a mechanism of caspase-dependent involving DNA damage, PARP activation, and Tp53 induction in Ehrlich tumor cells

Antimetastatic activities, low toxicity to normal cells and high selectivity for tumor cells make of the ruthenium complexes promising candidates in the search for develop new chemotherapeutic agents for the treatment of cancer. This study aimed to determine the cytotoxic, genotoxic and to elucidate the signaling pathway involved in the death cell process induced by cis-[RuCl(BzCN)(bipy)(dppb)]PF6(1) and cis-[RuCl(BzCN)(bipy)(dppe)]PF6(2) in Ehrlich ascites carcinoma (EAC) in vitro. Moreover, we report for the first time the anti-angiogenic potential on chick embryo chorioallantoic membrane (CAM) model. Peripheral blood mononuclear cells (PBMC) were isolated from healthy controls with an age range of 20–30 years and used to calculate the selectivity index (SI). The complex 2 (IC50 = 8.5 ± 0.4/SI = 6.3) showed high cytotoxic and selectivity index against EAC cells than complex 1 (IC50 = 14.9 ± 0.2/SI = 0.2) using the MTT assay. Complex 2 induced DNA damage on Ehrlich tumor cells at concentrations and time periods evalueted. In consequence, it was observed an increase of Tp53 gene expression, G0/G1-arrest cells, and increased levels of cleaved PARP protein. Beside that, the treatment of EAC with complex 2 led to an increase in Annexin V-positive cells and apoptosis induction by Caspase-7. Additionally, the complex 2 inhibited the angiogenesis caused by Ehrlich tumor cells in CAM model. This complex is active and selective for Ehrlich tumor cells, inducing DNA damage, cell cycle arrest and cell death by caspase-dependent apoptosis involving PARP activation (PARP1), and Tp53 induction.

Development and characterization of hyaluronic acid modified PLGA based nanoparticles for improved efficacy of cisplatin in solid tumor

Cisplatin is a potent and widely used chemotherapeutic agent to treat a variety of tumors. However, its clinical use is associated with undesirable side effects and acquired resistance to cisplatin. In this study, cisplatin loaded hyaluronic acid (HA) functionalized poly (lactic-co-glycolic acid)–poly (ethylene glycol) nanoparticles (CP-HA-PLGA-PEG-NPs) were fabricated using double emulsion solvent evaporation method to target CD44 receptor expressed on cancerous cells. The developed nanoconstructs were characterized for various in vitro parameters, including size distribution, zeta potential, morphology, drug loading and in vitro release. The HA content on the HA-PLGA-PEG-NPs was quantified by a turbidimetric method. The in vitro anticancer study in human ovarian cancer (SKOV-3) cells showed significantly (p<0.05) higher cytotoxicity of CP-HA-PLGA-PEG NPs as compared to free cisplatin and non-targeted nanoparticles (CP-PLGA-PEG NPs). Further, laser scanning confocal microscopy revealed that there was enhanced cellular uptake of HA-PLGA-PEG NPs in CD44-over expressing ovarian cancer cell line (SKOV-3). The in vivo antitumor activity of CP-HA-PLGA-PEG-NPs was significantly (p<0.05) higher than free cisplatin and CP-PLGA-PEG-NPs in Ehrlich tumor (solid) bearing mice. The results demonstrated the potential of target specific nanoconstruct of cisplatin in the improved cancer chemotherapy.

The effects of β-caryophyllene oxide and trans-nerolidol on the efficacy of doxorubicin in breast cancer cells and breast tumor-bearing mice

BackgroundOne approach to improve effect of chemotherapy is combination of classical cytostatic drugs with natural compounds, e. g. sesquiterpenes. In our previous study, sesquiterpenes β-caryophyllene oxide (CAO) and trans-nerolidol (NER) improved the anti-proliferative effect of doxorubicin (DOX) in intestinal cancer cell lines. PurposeThe present study was designed to evaluate the effect of CAO and NER on DOX efficacy, focusing on cell proliferation, migration, apoptosis and DOX accumulation in breast cancer cells MDA-MB-231 and MCF7 in vitro and in mice bearing solid Ehrlich tumors (EST) in vivo. MethodsThe impact of cytotoxic effect was assessed by the neutral red uptake test. The ability to migrate was tested using real-time measurement in x-CELLigence system. Expressions of molecules were examined using western blot analysis. The accumulation of DOX inside the cells using time lapse microscopy was observed. The mice with inoculated EST cells were treated repeatedly with DOX and DOX+CAO or DOX+NER and the growth of tumors were monitored. DOX concentrations in plasma and tumor were assayed using HPLC. ResultsIn MDA-MB-231, combination of DOX with CAO enhanced anti-proliferative effect and acted strongly synergistic. NER increased accumulation of DOX inside the cells; moreover combination DOX with NER suppressed migration ability in vitro. In vivo, apoptosis was activated especially in group treated with DOX and CAO. However, none of tested sesquiterpenes was able to improve DOX accumulation in tumors and DOX-mediated inhibition of tumor growth. ConclusionIn conclusion, sesquiterpenes CAO and NER increased the efficacy of DOX in breast cancer cells in vitro, but did not improve its effect in vivo, in Ehrlich solid tumor bearing mice.

Development and evaluation of long-circulating nanoparticles loaded with betulinic acid for improved anti-tumor efficacy

The clinical application of betulinic acid (BA), a natural pentacyclic triterpenoid with promising antitumor activity, is hampered due to its extremely poor water solubility and relatively short half-life in the systemic circulation. In order to address these issues, herein, we developed betulinic acid loaded polylactide-co-glycolide- monomethoxy polyethylene glycol nanoparticles (PLGA-mPEG NPs). The PLGA-mPEG co-polymer was synthesized and characterized using NMR and FT-IR. BA loaded PLGA-mPEG NPs were prepared by an emulsion solvent evaporation method. The developed nanoparticles had a desirable particle size (∼147nm) and exhibited uniform spherical shape under transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The PLGA-mPEG NPs were able to decrease the uptake by macrophages (i.e. J774A.1 and Raw 264.7 cells) as compared to PLGA nanoparticles. In vitro cytotoxicity in MCF7 and PANC-1 cells demonstrated enhanced cytotoxicity of BA loaded PLGA-mPEG NPs as compared to free BA. The cellular uptake study in both the cell lines demonstrated time dependent uptake behavior. The enhanced cytotoxicity of BA NPs was also supported by increased cellular apoptosis, mitochondrial membrane potential loss, generation of high reactive oxygen species (ROS) and cell cycle arrest. Further, intravenous pharmacokinetics study revealed that BA loaded PLGA-mPEG NPs could prolong the circulation of BA and remarkably enhance half-life by ∼7.21 folds. Consequently, in vivo studies in Ehrlich tumor (solid) model following intravenous administration demonstrated superior antitumor efficacy of BA NPs as compared to native BA. Moreover, BA NPs treated Ehrlich tumor mice demonstrated no biochemical, hematological and histological toxicities. These findings collectively indicated that the BA loaded PLGA-mPEG NPs might serve as a promising nanocarrier for improved therapeutic efficacy of betulinic acid.

Beta-Adrenergic Blockade Decreases the Neuroimmune Changes in Mice Induced by Cohabitation with an Ehrlich Tumor-Bearing Cage Mate

Objectives: Cohabitation with Ehrlich tumor-bearing (ETB) mice induced behavioral, neurochemical, hormonal, and immune effects in the conspecifics as a consequence of stress-induced activation of the sympathetic nervous system (SNS) with catecholamine release. In the current study, the nonspecific β-AR blocker d,l-propranolol and the specific β₂-AR blocker ICI-118.551 were employed as pharmacological tools to assess the extent to which catecholamines participated in the effects induced by cohabitation with ETB mice. Methods: Two experiments were performed, 1 with d,l-propranolol treatment and the other with ICI-118.551. One mouse in the experimental group was called the “companion of the sick partner” (CSP) since it was forced to live in the same cage with 2 (experiment 1) or 1 (experiment 2) cage mate that had been i.p. injected with 5 × 10⁶ Ehrlich tumor cells. Results: The d,l-propranolol treatment, but not the ICI-118.551 treatment, attenuated the effects of cohabitation with 2 ETB mice on both open-field behavior and the hypothalamic levels and turnover rate of norepinephrine. The 2 β-AR blockers were unable to change the serum corticosterone levels and adrenal weights of the CSP mice; however, these drugs abrogated the effects of cohabitation on neutrophil oxidative burst and phagocytosis. Finally, an increase in the 5-HT turnover rate was observed in the olfactory bulb of CSP mice compared to their respective controls, an effect that was not modified by β-AR blockade. Conclusion: These results confirm and strengthen our hypothesis that the SNS is involved in the effects induced by cohabitation with ETB mice and point towards β₂-AR participation in the immune effects analyzed.

The Effect Infrared and Ultraviolet Radiation in the Development of the Cells in the Porous Permeable Titanium Nickel Based Alloy Scaffold

The respond of the cells to electromagnetic radiation depends on many factors, including microenvironment. Different cells exhibit different behavior when exposed to low-intensity radiation employed in the research. The effect of infrared (IR) and ultraviolet (UV) radiation leads to the reliable change in the number of viable cells. Viable cells of Ehrlich tumor, spleen and bone marrow of C57BL/6 mice placed in a porous permeable TiNi-based alloy scaffold were studied. The level of the radiation effect was determined for different types of cells. A comparative analysis of the viable cells cultured in the porous permeable TiNi scaffold was performed.

English

High levels of cyclooxygenase (COX) enzymes and its metabolites, especially prostaglandin E2 (PGE2) are generated in inflammatory conditions and, eventually, can contribute to neoplasms growth, justifying, in certain malignancies. COX occurs in two major isoforms, physiologically as isoform COX-1 and during inflammation as COX-2. In certain neoplasms, benefits are reported with the use of the selective COX-2 inhibitor drug, meloxicam. This study aimed to evaluate the effect of meloxicam on the development of solid Ehrlich tumor. Fourteen male Swiss mice, 30-45 days old, 35-45 g of weight, were inoculated with 107 of the tumor cells, and divided in two groups according to the treatment: Phys) 0.1 mL intraperitoneal injection (IP) of sterile 0.9% saline solution, and Mel) treated with meloxicam, 2 mg/kg, 0.1 mL, IP, both once a day. After 21 days, all the animals were euthanized and the tumor removed, weighed and prepared for histomorphometric and immunohistochemical evaluation for COX-2. Mel group presented significantly reduction of the tumor weight and COX-2 production, as well as an increase in stromal component, but did not interfere in tumor growth, in comparison to Phys group. From these results it was concluded that meloxicam did not restrain tumor growth in this experimental model. Reduction in tumor weight alone cannot be taken as a reliable criterion for evaluation of tumor progression. &nbsp; Key words: Ehrlich solid tumor, arachidonic acid, inflammation, Meloxicam.

Effects of Methylene Blue Mediated Photodynamic Therapy on SolidEhrlich Tumor and Second Ehrlich Tumor Implant in Mice

<span style=font-family: times= new= roman,serif;mso-fareast-font-family:times= roman;color:black=>1. Abstract PhotoDynamic Therapy (PDT) uses interaction of light, photosensitizing agent and production of reactive oxygen species, leading to cell death. Methylene Blue (MB) is sued for PDT due to its photochemical properties. Here we investigated the effects of Methylene Blue Mediated Photodynamic Therapy ( MB-PDT) on the solidEhrlich tumor and second Ehrlich tumor implant in mice. For MB-PDT, MB at 1%and diode laser were used. Swiss male mice received dorsal inoculation of Ehrlichtumor cells and, 9 days after, mice were separated into 3 groups: MB-PDT ( Group1 ) surgically removed (Group 2 ), or untreated ( Group 3 ). One day after treatment,all groups received a second Ehrlich tumor implant on the left footpad, measured for17 days. Spleen, lymph nodes and tumor mass were weighed upon necropsy andprocessed for histopathology. Group 1 Ehrlich tumors showed significant sizereduction after MB-PDT. Morphometry of second Ehrlich tumor in Group 1 miceshowed significantly lower volume fraction of tumor cells, higher inflammatoryinfiltrate and necrosis. Relative spleen weight was higher in Group 1 mice, withwhite pulp hyperplasia. Per these results, MB-PDT reduced primary Ehrlich tumorgrowth and impacted the growth of a second tumor. These results point towardspossible biotechnological applications of MB-PDT. 2. Keywords: Photodynamic Therapy, Methylene Blue, Ehrlich Tumor, CancerTreatment.

Effects of Methylene Blue Mediated Photodynamic Therapy on SolidEhrlich Tumor and Second Ehrlich Tumor Implant in Mice

Effects of Methylene Blue Mediated Photodynamic Therapy on SolidEhrlich Tumor and Second Ehrlich Tumor Implant in Mice

Qa-2 expression levels is related with tumor-infiltrating lymphocytes profile during solid Ehrlich tumor development

The Qa-2 has been described as Human Leucocyte Antigen G (HLA-G) murine homolog. This homology is well accepted to gene and protein structure, in different pathology process and embryos implantation. However, in some neoplasm, this homology is questioned, where Qa-2 has been proposed as an immunogenic molecule, associated to tumor rejection. In this way, the aim of this study was to describe the pattern of Qa-2 expression and its relationship with the profile of tumor-infiltrating lymphocytes in solid Ehrlich tumor. The Ehrlich tumor growth was evaluated in Balb/c female mice in different tumor stages. The inflammatory infiltration features were determined by histopathology and, both lymphocyte type and tissue Qa-2 expression by immunohistochemistry. ELISA kit was used to determine soluble Qa-2 in the serum from the animals. We observed that Qa-2 in neoplastic cells increases in intermediate tumor development stages, while, serum Qa-2 increases in the late stage. Qa-2 increasing is correlated with CD3+ increase. Our results suggest that Qa-2 has a role opposite to HLA-G in Ehrlich solid carcinoma, and may be modulating the immune response by attracting the inflammatory infiltrate, especially T CD8+ Lymphocytes.

EFFECT OF ε-AMINOCAPROIC ACID ON THE GROWTH OF AN INOCULATED ASCITIC AND SOLID EHRLICH TUMOR OF MICE

The antitumor activity of the antifibrinolytic drug ε-aminocaproic acid (ACC) in the therapeutic form (5% ACC solution in physiological solution instead of drinking water) was studied in the ascitic and solid Ehrlich tumor. ACC did not affect the growth of ascitic, as well as a solid Ehrlich tumor, when the drug was administered 72 hours after the tumor inoculation. At the same time, when it was administered 7 days after tumor inoculation, the drug had a statistically significant antitumor effect on the tumor nodes formed (8-10 mm in diameter). ACC antitumor effect allows to assume that it influences tumor stroma rather than the parenchyma. This effect is not fully understood and needs further study.

Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations

Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models.

Nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex can inhibit Ehrlich solid tumor growth in mice: A potential new antitumor drug

The chief chemotherapeutic drug, cisplatin had common bad effects such as nephrotoxicity, ototoxicity and bone marrow depression. This led us to develop a new potential anticancer drug based on nickel metal ion that may be less toxic. Nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex cytoprotective effect, superoxide dismutase (SOD)-like activity and anticancer activities were studied. In vitro, the complex showed SOD-like activity of 86.62%. It was capable to kill 90.2% of Ehrlich ascites carcinoma (EAC) cells and to protect 92.48% of human RBCs. In vivo, the complex lowered the tumor burden markedly in a concentration-dependent manner. Noticeably, solid tumor growth was suppressed; tumor volume and weight were reduced and mice life span was lengthened. The hematological indices were improved, catalase activity was re-elevated and malondialdehyde (MDA) level was reversed towards normal. Nucleic acids, cholesterol, triglycerides, liver enzymes, urea and creatinine contents were reduced to near normal ranges. Glutathione (GSH), SOD, albumin and total protein levels were increased. In conclusion, our results revealed that the complex has the ability to suppress Ehrlich solid tumor growth in mice with minimal side effects. This may possibly via its redox activity. Surprisingly, nickel complex antitumor activities were more potent than those of cisplatin.

Antitumoral activity of sesquiterpene lactone diacethylpiptocarphol in mice

Ethnopharmacological relevanceSesquiterpene lactones are organic compounds derived from plants that exhibit anti-inflammatory and antitumor activities being one of the locking mechanisms of action of NF-kB pathway and synthesis of cytokines such as IL-1 and TNF- α. Aim of the studyThe overall objective of the present study was to evaluate the antitumor activity of the sesquiterpene lactone diacethylpiptocarphol (DPC) from Vernonia scorpioides (Lam.) Pers. in animal models Ehrlich tumors that has shown antitumor activity. Materials and methodsThe antitumor effects of Intraperitonial administration of DPC (5mg/kg/day) were evaluated in Balb/c mice on Ehrlich tumors, and further the body weight, the ascitic cells volume measurement, solid tumor measured and TNF-α level was determinate. ResultsBalb/c mice bearing Ehrlich tumors were treated daily with 5mg/kg/day of the DPC for one week and showed no tumor in the peritoneum after treatment, besides presenting a reduction of TNF-α cytokine. Also the solid tumor reduced size after one week of treatment with DPC. ConclusionsSesquiterpene lactone DPC, isolated from Vernonia scorpioides showed antitumor activity because it decreased the size of the solid tumor and abolished the ascitic tumor development, and also did not affect the mice body weight, however the treatment reduced the TNF-α level in mice.

Combination of bacteriolytic therapy with magnetic field for Ehrlich tumour treatment.

Referable to the limited response of the current available cancer treatment modalities, new effective cancer fighting treatments are needed. This work investigates the efficiency of intratumoural injection of Pseudomonas aeruginosa bacteria combined with a local tumour exposure to extremely low frequency square pulsed magnetic field (ELF SPMF) in the mouse Ehrlich tumour. 64 Ehrlich ascites tumour-implanted female albino BALB/C mice were equally split up into 4 groups. Group 1 (GP1) was the positive control group. Group 2 (GP2) received a single intratumoural injection of P. aeruginosa bacteria. Group 3 (GP3) was exposed to ELF SPMF for tumour local exposure. Group 4 (GP4) was treated with P. aeruginosa intratumoural injection followed by local exposure of the tumour to ELF SPMF. Treatment monitoring was evaluated using ultrastructural examination, flow cytometry analysis in addition to the measurement of tumour dielectric properties. Tumour cell apoptosis was obvious in GP2 and GP4, but, with higher severity and percentages in GP2. Tumour biophysical properties revealed a significant increase in static conductivity σS of GP2, and decreases in dielectric increment Δɛ´of both GP2 and GP4 compared to the GP1. Unfortunately, GP2 mice showed severe signs of toxicity. We advocate the utilization of the combination of P. aeruginosa and SPMF to yield the most effective antitumour agent with less bacteria-related toxicity.

Nicotinic acid inducing G0/G1 cell cycle arrest and apoptosis in Ehrlich ascites carcinoma cells in vivo

Niacin, nicotinic acid; (NA), is a water-soluble vitamin (vitamin B3) which serves as a precursor of nicotinamide adenine dinucleotide and is one of the premier lipid lowering agents for treatment of cardiovascular diseases. Aims: the aim of the present study was to evaluate whether treatment with nicotinic acid has antitumor effect on the Ehrlich ascites carcinoma (EAC) cells. Methods: Female Swiss albino mice were transplanted with EAC cells and treated one day later with nicotinic acid at 50mg/mouse, orally (NA-50), nicotinic acid at 100mg/mouse, orally (NA-100) and cisplatin at 40 µg/mouse, i.p. (CIS-40) as a reference drug, all groups were treated for six consecutive days. At day 7, mice were euthanized and EAC cells were harvested, counted and the gene expression levels of the NA receptor GPR109A were analyzed in the EAC cells by RT-PCR Results: Mice treated with NA-100 showed significant reduction in the EAC cell number as compared to treatment with NA-50. This anti-tumor effect of 100mg NA was still lower than treatment with 40 µg CIS which induced killing of most EAC cells. Although the EAC cell number in NA-100 treated group lower than those induced by CIS, the NA-100 induced antitumor effect was mediated by arresting the G1 phase of EAC cell cycle as measured by flow cytometry. As demonstrated by higher percentage of cells in the sub-G1 phase in that group. GPR109A expression level was higher in NA-100 treated group than in CIS treated group. Conclusion: NA has antitumor and anti-proliferative effects on Ehrlich tumor in ascitic form as demonstrated by arresting the cell cycle of EAC-cells through increasing the expression GPR109A.

Preclinical Validation of the Located Hyperthermia Using Gold Macro-Rods and Ultrasound as an Effective Treatment for Solid Tumors.

Hyperthermia, the procedure of raising the temperature of a part of or the whole body above normal for a defined period of time, is applied alone or as an adjunctive with various established cancer treatment modalities such as radiotherapy and chemotherapy. In this study used a method for inducing hyperthermia in solid tumors with a combination of gold macro rod (GR) and ultrasound, the feasibility of this technique was described only with computational models and in vitro. The Ehrlich tumor, derived from a mouse adenocarcinoma, has been used to investigate the bio-heat transfer and the effect of gold rods irradiated with ultrasound. The in vivo measurements demonstrated that the technique inhibited more 80% of the tumor growth in both experimental models tested. These results not only confirm the bio heat transfer to tissue as predicted by analytical calculation and in vitro measurements, but are also proved to be a potential alternative to kill cancer cells.

GROWTH FACTORS AND COX2 IN WOUND HEALING: AN EXPERIMENTAL STUDY WITH EHRLICH TUMORS.

ABSTRACTBackground: Healing is an innate biological phenomenon, and carcinogenesis acquired, but with common humoral and cellular elements. Carcinogenesis interferes negatively in healing. Aim: To evaluate the histological changes in laparotomy scars of healthy Balb/c mice and with an Ehrlich tumor in its various forms of presentation. Methods: Fifty-four mice were divided into three groups of 18 animals. First group was the control; the second had Ehrlich tumor with ascites; and the third had the subcutaneous form of this tumor. Seven days after tumor inoculation, all 54 mice were submitted to laparotomy. All of the animals in the experiment were operated on again on 7th day after surgery, with resection of the scar and subsequent euthanasia of the animal. The scars were sent for histological assessment using immunohistochemical techniques to evaluate Cox-2 (cyclooxygenase 2), VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor). Semi-quantitatively analysis was done in the laparotomy scars and in the abdominal walls far away from the site of the operation. Results: Assessing the weight of the animals, the correct inoculation of the tumor and weight gain in the group with tumoral ascites was observed. The histological studies showed that groups with the tumor showed a statistically significant higher presence of Cox-2 compared to the control. In the Cox-2 analysis of the abdominal wall, the ascites group showed the most significant difference. VEGF did not present any significant differences between the three groups, regardless of the site. The FGF showed a significant increase in animals with the tumor. Conclusion: Histological findings in both laparotomy scar and the abdominal wall showed that with Ehrlich's neoplasia there was an exacerbated inflammatory response, translated by more intense expression of Cox-2 and greater fibroblast proliferation, translated by more intense expression of FGF, that is, it stimulated both the immediate inflammatory reactions, observed with Cox-2 reactions, and late scarring by fibroblasts and FGF.

Anticancer activity and tissue distribution of platinum (II) complex with lignin-derived polymer of benzene-poly-carboxylic acids

Platinum-containing antineoplastic agents with physiologically active ligands seem to be a promising direction in anticancer drug design. PDBA is a novel promising antineoplastic agent, containing polymer ligand of natural origin (international patent WO2013/143549 A1). Polymer ligand of PDBA has a highly functionalised polyphenolic backbone, which exerts its own pharmacological effect via immune modulation and regulation of gene expression. PDBA is a cis-diammineplatinum(II) complex, containing mono-deprotonated benzene-poly-carboxylic acids, derived from lignin, and hydroxyl group as O-donor ligands (approximate bulk formula C83H70N2O27Pt). The agent is being evaluated in Phase II controlled clinical trials in metastatic breast cancer patients. In the present study, tissue distribution and tumour growth inhibition effects of PDBA, cisplatin and carboplatin were compared in SHR female mice, bearing inoculated solid Ehrlich carcinoma. The agents were administered subcutaneously every second day for the period of 10days (5 injections) at 62.5mg/kg, 3.0mg/kg and 18.5mg/kg for PDBA, cisplatin and carboplatin, respectively. Experimental animals were sacrificed on the Days 11, 16 and 23 after the inoculation of the tumour. The doses of all studied drugs were selected to obtain similar antitumour efficacy with ca. 50% growth inhibition of the Ehrlich tumour at the end of the study. The efficacy of a single platinum reactive moiety [cis-diammineplatinum(II)] was shown to be the highest for cisplatin, followed by PDBA and finally carboplatin. However, the toxicity of PDBA was considerably lower than that of carboplatin and especially cisplatin. The drugs were mainly distributed in lungs, kidneys, liver, spleen and tumour tissue. PDBA showed quite high accumulation in the tumour tissue, possibly, owing to the effect of the lignin-derived ligand.