Ehrlich Tumor Research Articles

Activity of protegrin-1 against mouse Ehrlich ascites carcinoma <i>in vitro</i> and <i>in vivo</i>

BACKGROUND: The problem of multidrug resistance in cancer treatment creates an urgent demand for developing new effective antitumor agents. Due to the unusual mechanism of recognizing and damaging tumor cells, antimicrobial peptides are considered as possible prototypes for designing such therapeutics. AIM: This work was aimed to compare the antitumor potential of the promising membranolytic antimicrobial peptide protegrin-1 in vitro and in vivo in Ehrlich ascites carcinoma mice model. MATERIALS AND METHODS: We used two variants of the model by inducing a tumor in solid or ascites form. In the first case, the mice were injected with the peptide twice a week for three weeks, and in the second injections were provided every other day for six days. The activity of antimicrobial peptides against isolated Ehrlich ascites carcinoma cells in vitro was analyzed using MTT-test. RESULTS: Protegrin-1 demonstrated high activity against Ehrlich ascites carcinoma cells in vitro, but had no significant effect on the lifespan of mice bearing solid or ascites form of Ehrlich tumor at the dosing and administration regimens we used. However, treatment with protegrin-1 caused a decrease in the ascites volume and in the number of cells in the ascites fluid. CONCLUSIONS: Protegrin-1 retains its antitumor properties in vivo, but it may be presumed, that to effectively suppress tumor growth it requires a more frequent and prolonged administration compared with conventional antitumor antibiotics, of which we adopted the administration regimen for protegrin-1 in this study.

Apoptosis and genotoxicity effects of Zygophyllum album and Suaeda palaestina extracts on Ehrlich solid carcinoma in mice

BackgroundVarious medicinal plants and their bioactive compounds exhibited promising anticancer activities by inducing apoptosis, inhibiting angiogenesis, and modulating several signaling pathways in cancer cells. This study aims to assess whether two medicinal plant extracts have anticancer properties, Suaeda Palaestina and Zygophyllum album.MethodsThis study used Ehrlich solid tumor mice as its in vivo model. We divided male mice into five groups (n = 5 per group). Group I was used as a control for Ehrlich ascites carcinoma (EAC). Groups 2 and 3 were given Z. album extract 180 mg/kg and 360 mg/kg body weight intraperitoneally. Groups 4 and 5 were given the same dose of S. palaestina and treated three times a week for 2 weeks, starting on day 10 after EAC implantation. After 3 weeks, we collected blood samples and thigh skeletal muscle, homogenized them, and processed them for analysis. The results showed that Ehrlich solid rats (EST) treated with low-dose dichloromethane extracts from Z. album and S. palaestina had significantly smaller tumor sizes than the control group. Protein expression levels of p53, caspase 3, and Bcl-2 were quantified by western blotting.ResultsThe extracts from both plants induced the hunger mechanism, leading to increased expression of p53 and caspase 3 and decreased expression of Bcl-2 at the protein level in EST mice treated with Z. album and S. palaestina. In addition, the comet assay indicated that these plants have a genotoxic potential for solid tumor cells. The T3 and T4 levels in EST blood samples revealed that both plants had significantly reduced the concentration of T3 and significantly increased T4 compared to the EST mice untreated group. Furthermore, these results showed that Z. album and S. palaestina had antiproliferative effects in EST mice through apoptosis-mediated genotoxicity.ConclusionsThese findings indicated that S. palaestina and Z. album could be considered potential natural sources of anticancer agents.

Aluminum phthalocyanine tetrasulfonate conjugated to surface-modified Iron oxide nanoparticles as a magnetic targeting platform for photodynamic therapy of Ehrlich tumor-bearing mice

BackgroundPhotodynamic therapy (PDT) is a targeted treatment option for cancers that are non-responding to ordinary anticancer therapies. It involves activating a photosensitizer with a light source of a specific wavelength to destroy targeted cells and their surrounding vasculature. Aluminum phthalocyanine tetra sulfonate (AlPcS4) has gained attention as a second-generation photosensitizer for its strong absorption in the red-light region. AlPcS4 can be conjugated to magnetic iron oxide nanoparticles (IONs) to provide targeted drug delivery to the tumor cells while reducing its undesired effect on healthy tissues in other body parts. MethodsMagnetic glutamine functionalized iron oxide nanocomposites loaded with AlPcS4 (IONs-NH2-AlPcS4) were synthesized via the co-precipitation method. The conjugate (IONs-NH2-AlPcS4) was characterized by TEM, Zeta potential, DLS, FTIR, and UV–VIS absorption spectroscopy. Furthermore, its photodynamic activity was investigated using albino mice with induced Ehrlich solid tumors. ResultsAlPcS4 was successfully conjugated to IONs-NH2 with a high loading efficiency of 54±2%. The synthesized conjugate exhibited a spherical shape, with 7 ± 2 nm particle size. The In vivo experiment revealed that the albino mice with induced Ehrlich solid tumor that were treated by combined PDT and magnetic targeting conjugate exhibited significant tumor regression and notably higher levels of necrotic tissue compared to the animals in other groups. ConclusionPDT mediated by magnetic targeting significantly inhibited tumor growth with minimal adverse effects, indicating its great potential as a promising strategy for solid cancer treatment.

Turkish coffee has an antitumor effect on breast cancer cells in vitro and in vivo

BackgroundBreast cancer is the most diagnosed cancer in women. Its pathogenesis includes several pathways in cancer proliferation, apoptosis, and metastasis. Some clinical data have indicated the association between coffee consumption and decreased cancer risk. However, little data is available on the effect of coffee on breast cancer cells in vitro and in vivo.MethodsIn our study, we assessed the effect of Turkish coffee and Fridamycin-H on different pathways in breast cancer, including apoptosis, proliferation, and oxidative stress. A human breast cancer cell line (MCF-7) was treated for 48 h with either coffee extract (5% or 10 v/v) or Fridamycin-H (10 ng/ml). Ehrlich solid tumors were induced in mice for in vivo modeling of breast cancer. Mice with Ehrlich solid tumors were treated orally with coffee extract in drinking water at a final concentration (v/v) of either 3%, 5%, or 10% daily for 21 days. Protein expression levels of Caspase-8 were determined in both in vitro and in vivo models using ELISA assay. Moreover, P-glycoprotein and peroxisome proliferator-activated receptor gamma (PPAR-γ) protein expression levels were analyzed in the in vitro model. β-catenin protein expression was analyzed in tumor sections using immunohistochemical analysis. In addition, malondialdehyde (MDA) serum levels were analyzed using colorimetry.ResultsBoth coffee extract and Fridamycin-H significantly increased Caspase-8, P-glycoprotein, and PPAR-γ protein levels in MCF-7 cells. Consistently, all doses of in vivo coffee treatment induced a significant increase in Caspase-8 and necrotic zones and a significant decrease in β- catenin, MDA, tumor volume, tumor weight, and viable tumor cell density.ConclusionThese findings suggest that coffee extract and Fridamycin-H warrant further exploration as potential therapies for breast cancer.

Therapeutic Effect of Essential Oils (Citrus sinensis) against Ehrlich Ascites Model Induced Renal Toxicity in Female Mice

Background: Cancer is one of the most dangerous diseases of the twentieth century and the speed of its spread is horrific. It is characterized by cellular growth and invades all tissues of the body. In recent years, all countries of the world have turned to cancer research in order to identify new drugs to treat cancer from various sources , Cancer is the most common disease that causes death in the world and this is attributed to many pathological factors, such as reactive oxygen species, which contribute to the initiation, spread and development of cancer. Methods: Our current research aims to investigate the therapeutic role of essential oils (C.S.) against Ehrlich Tumor renal damage in Mice. The mice were divided into four group (Gp1, control group, Gp2, Essential oils (C.S) group, Gp3, EAC group, Gp4, EAC with Essential oils (C.S). Result: Results showed the Essential oils (C.S) in pretreated (G4) lead to an improvement in urea, creatinine levels when compared to the EAC group. Through our results, it was shown that treatment with essential oils (C.S.) improved the levels of urea and creatinine comparing to the Gp3. It was noted that treatment with essential oils (C.S.) improved kidney tissue and VEGF protein expression the Gp4 compared to the Gp3 Groups. It could be concluded that essential oils (C.S) has a possible benefit to the kidneys against EAC induce kidney Toxicity.

Acetylsalicylic Acid with Ascorbate: A Promising Combination Therapy for Solid Tumors.

Cancer is a deadly disease with high mortality rates in developing countries. A recent preclinical study found promising results in treating hepatocellular carcinoma (HCC) by combining acetylsalicylic acid (ASA) and ascorbate (AS), which might offer a safer alternative to expensive clinical chemotherapeutics; however, the impact of this combination on other tumors remains unexplored. Therefore, this study aims to investigate the effectiveness of combining ASA and AS in treating Ehrlich solid tumors. Eighty female Swiss albino mice were divided into eight groups (10 mice/group): four healthy groups (healthy, AS, ASA, and AS+ASA) and four groups with carcinoma (Ehrlich ascites carcinoma [EAC], EAC+AS, EAC+ASA, and EAC+AS+ASA). AS was injected intraperitoneally (4g/kg) daily for 10 days, whereas ASA was ingested orally at 60 mg/kg/day for 10 days. Carcinoma was induced by subcutaneous injection of 1×106 EAC cells/mouse once. Treatment of carcinoma started after 10 days of tumor inoculation. Blood, livers, and tumors were obtained, and tumor weights, volumes, and levels of hemoglobin, aminotransferases, albumin, bilirubin, urea, creatinine, lipid profile, malondialdehyde, nitric oxide, glutathione, catalase, total antioxidant capacity, lactate dehydrogenase, and creatine kinase were estimated. The percentage increase in lifespan was also assessed. Tumor treatment alleviated tumor burden. Tumor size was reduced, lifespan increased, organs (liver, kidney, and heart) functions adjusted, hemoglobin, lipid profile improved, and oxidative stress decreased. Combining ASA with AS showed more effective antitumor effects than only ASA or AS alone. After more validation research, combining ASA with AS may provide benefit in cancer treatment.

Design and Optimization of Sesamol Nanosuspensions to Potentiate the Anti-Tumor Activity of Epirubicin against Ehrlich Solid Carcinoma-Bearing Mice.

There is a growing interest in discovering natural sources of anti-cancer drugs. Sesamol (SES) is a phenolic compound with antitumor effects. The present study aimed to investigate the anticancer properties of SES and its nano-suspensions (SES-NS) combined with Epirubicin (EPI) in breast cancer (BC) using mice bearing a solid Ehrlich tumor. The study involved 35 female albino mice and investigated the effects of SES and EPI on tumor growth, proliferation, apoptosis, autophagy, angiogenesis, and oxidative stress. Methods including ELISA, qRT-PCR, and immunohistochemistry were utilized. The findings revealed reductions in tumor growth and proliferation using SES either alone or combined and evidenced by decreased AKT (AKT Serine/Threonine kinase1) levels, angiogenesis indicated by lower levels of VEGFR (vascular endothelial growth factor), and apoptosis demonstrated by elevated caspase3 and BAX levels. Furthermore, autophagy increased and was indicated by increased levels of beclin1 and lc3, along with decreased oxidative stress as evidenced by elevated TAC (total antioxidant capacity) and reduced MDA (malondialdehyde) levels. Interestingly, SES-NS demonstrated more significant effects at lower doses. In summary, this study underscores the potential of SES as a promising agent for BC treatment. Moreover, SES-NS potentiated the beneficial effects of EPI while mitigating its adverse effects.

Preclinical Effects Of Melatonin On The Development Of Ehrlich's Tumor: A Biochemical, Cognitive, And Molecular Approach.

It has already been shown that melatonin is an antitumoral molecule that affects malignant cells via some mechanisms. The benefit played by this hormone on cancer is due to its antioxidant effects. This study aimed to evaluate the preclinical effects of melatonin in mice with the Ehrlich ascites tumor. Twenty Balb/ c male mice with Ehrlich tumor were treated with different melatonin doses. Their inflammatory and oxidative stress were accessed by gene expression. Hepatotoxicity and hematological parameters were also evaluated through biochemical analyses. Animal welfare was analysed weekly from the categories guided by the NC3Rs. Gene expression analyses have shown that only Tnfα and Sod1 were expressed in all groups studied. Only the M-3 group showed increased Tnfα expression compared to the control. All groups treated with melatonin showed decreased Sod1 expression compared to the control. No signs of hepatotoxicity were caused by any of the melatonin doses used in the treatment. In animals with Ehrlich´s tumor treated with melatonin, a decrease in oxidative stress, an amelioration in welfare and in cognitive tasks could be observed, even if the treatment has not reduced the size of the tumor itself. In parallel with the already patented use of melatonin in the treatment of sleep disorders or chronic kidney disease, our results propose its use to improve the general well-being of breast cancer patients.

The Nociceptive and Inflammatory Responses Induced by the Ehrlich Solid Tumor Are Changed in Mice Healed of Plasmodium berghei Strain ANKA Infection after Chloroquine Treatment.

Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive and inflammatory responses through similar pathophysiological mechanisms. However, it is unclear whether malaria and antimalarial treatment can change the inflammatory and nociceptive responses induced by solid cancer. Therefore, the present study experimentally evaluated the effect of infection by Plasmodium berghei strain ANKA and chloroquine treatment on the nociceptive and inflammatory responses induced by the solid Ehrlich tumor in male BALB/c mice. On the 1st experimental day, mice were infected with Plasmodium berghei and injected with tumor cells in the left hind paw. From the 7th to the 9th experimental day, mice were treated daily with chloroquine. The parasitemia was evaluated on the 7th and 10th days after infection. On the 11th experimental day, mice were evaluated on the von Frey filament test, the hot plate test, and the paw volume test. At the end of the experimental tests on the 11th day, the peripheral blood of all mice was collected for dosing of IL-1β and TNF-α. The blood parasitemia significantly increased from the 7th to the 10th day. The chloroquine treatment significantly decreased the parasitemia on the 10th day. The presence of the tumor did not significantly change the parasitemia on the 7th and 10th days in mice treated and nontreated with chloroquine. On the 11th day, the mechanical and thermal nociceptive responses significantly increased in mice with tumors. The treatment with antimalarial significantly reduced the mechanical nociceptive response induced by tumors. The hyperalgesia induced by tumors did not change with malaria. The mechanical and thermal hyperalgesia induced by the tumor was significantly reduced in mice treated and healed from malaria. On the 11th day, the volume of the paw injected by the tumor was significantly increased. The mice treated with chloroquine, infected with malaria, or healed of malaria showed reduced paw edema induced by the tumor. Mice with tumors did not show a change in IL-β and TNF-α serum levels. Mice with tumors showed a significant increase in serum levels of IL-1β but not TNF-α when treated with chloroquine, infected with malaria, or healed of malaria. In conclusion, the results show that malaria infection and chloroquine treatment can influence, in synergic form, the nociceptive and inflammatory responses induced by the solid tumor. Moreover, the mechanical antinociception, the thermal hyperalgesia, and the antiedema effect observed in mice treated with chloroquine and healed from malaria can be related to the increase in the serum level of IL-1β.

Selenium suppressed growth of Ehrlich solid tumor and improved health of tumor-bearing mice.

Selenium (Se) is an important micronutritional biomolecule in cancer therapy. The current work evaluated the anticancer effect of Se and its ability to improve health of mice with solid Ehrlich carcinoma implanted subcutaneously. Four groups of five female BALB/c mice each were assembled. Ehrlich tumor cells were engrafted into two of them, either with or without Se therapy. The other groups served as control groups, either with or without Se treatment. Se treatment resulted in a notable decrease in both tumor volume and animal body mass in tumor-bearing mice. Treatment with Se markedly increased oxidative stress in tumor while ameliorating oxidative stress in sera of tumors-bearing mice. Similarly, treatment with Se resulted in downregulation of inflammatory cytokines (TNF-α and IL-6) while increasing IL-10 in serum of tumor-bearing mice. Conversely, selenium increased TNF- α and IL-6 and decreased IL-10 in tumor suggesting disruption of tumor immunity. The increased oxidative stress and inflammation in tumor tissue dysregulated cell cycle phases with increase apoptotic tumor cells population in G0/G1 phase. This is supported by the increased levels apoptotic regulating proteins (Bax and caspase-3 and P-53) while decreasing Bcl-2 in the tumor tissue. Treatment with Se also resulted in increased comet parameters indicating DNA damage of tumor cells. Histopathological examination revealed a significant decrease in a number of neoplastic cells within tumor of mice that treated with Se. In conclusion, these findings suggest that Se therapy significantly suppressed solid tumor proliferation and growth while mitigating the health status of tumor-bearing mice.

Chitosan-loaded piperlongumine nanoparticles and kaempferol enhance the anti-cancer action of doxorubicin in targeting of Ehrlich solid adenocarcinoma: in vivo and in silico modeling study

Doxorubicin is a chemotherapeutic drug that generates free radical-induced toxicities. Natural agents are used to potentiate or ameliorate the toxicity of chemotherapy. None of the studies investigating whether antioxidants or prooxidants should be used with chemotherapy have addressed their efficacy in the same study. Therefore, the aim of this study was to investigate the potential synergy between doxorubicin and two natural rarely in vivo studied anticancer agents; the antioxidant “Kaempferol” and prooxidant “Piperlongumine” in Ehrlich tumor mice model. 77 albino mice were divided into 11 groups; Ehrlich ascites carcinoma cells were injected intramuscularly to develop solid tumors. After 14 days, intratumoral injections of single or combinations of free or Chitosan nanoparticles loaded with doxorubicin, Piperlongumine, and Kaempferol were performed. Tumor Characterization of nanoparticles was measured, tumors were histopathologically examined and evaluation of expression for cancer-related genes by real-time PCR. In silico molecular docking was performed to uncover potential novel targets for Piperlongumine and Kaempferol. Despite receiving half of the overall dose compared to the free drugs, the combined doxorubicin/ piperlongumine-chitosan nanoparticles treatment was the most efficient in reducing tumor volume; down-regulating Cyclin D1, and BCL2; as well as the Beclin-1, and Cyclophilin A genes modulating growth, apoptosis, autophagy, and metastasis, respectively; up-regulating the Glutathione peroxidase expression as a defense mechanism protecting from oxidative damage. When combined with doxorubicin, Kaempferol and Piperlongumine were effective against Ehrlich solid tumors. However, the combination with the Piperlongumine-loaded chitosan nanoparticles significantly enhanced its anticancer effect compared to the Kaempferol or the same free compounds.

2-Aminoethyl Dihydrogen Phosphate (2-AEH2P) Associated with Cell Metabolism-Modulating Drugs Presents a Synergistic and Pro-Apoptotic Effect in an In Vitro Model of the Ascitic Ehrlich Tumor.

The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.

Ocimum basilicum L. (basil) presents pro-apoptotic activity in an Ehrlich's experimental tumor murine model.

This study aimed to evaluate the therapeutic effect of an ethanol extract of Ocimum basilicum L. (EEOb) aerial parts against Ehrlich's experimental tumor (EET) in mice. Swiss mice were divided into two groups (control and treated; n = 6). On day 21, all mice were inoculated subcutaneously with 2 × 106 (0.05 mL) EET cells in the left paw for solid tumor development. This study lasted 28 days. Treatment began 24 hours after inoculation with EET. Measurements of dorsoplantar thickness were used to assess tumor growth. The paw pad was collected for histopathological analysis and stained using the argyrophilic nucleolar organizing regions (AgNOR) technique and immunohistochemistry for proliferating cell nuclear antigen, Bcl-2 and Bax. The treatment of animals with EEOb at 100 mg/kg intraperitoneally was able to reduce the growth (Control = 3.7 ± 0.1 mm vs. EEOb = 5.7 ± 0.2 mm) and the number of AgNORs of solid Ehrlich tumor. The antitumor effect of EEOb was associated with the induction of apoptosis of tumoral cell, as suggested by the reduction of the content of Bcl-2 induced by extract. The study demonstrated that daily administration of EEOb is able to reduce the growth of EET by induce apoptosis of tumoral cells.

Pigmented Microbial Extract (PMB) from Exiguobacterium Species MB2 Strain (PMB1) and Bacillus subtilis Strain MB1 (PMB2) Inhibited Breast Cancer Cells Growth In Vivo and In Vitro.

Breast cancer (BC) continues to be one of the major causes of cancer deaths in women. Progress has been made in targeting hormone and growth factor receptor-positive BCs with clinical efficacy and success. However, little progress has been made to develop a clinically viable treatment for the triple-negative BC cases (TNBCs). The current study aims to identify potent agents that can target TNBCs. Extracts from microbial sources have been reported to contain pharmacological agents that can selectively inhibit cancer cell growth. We have screened and identified pigmented microbial extracts (PMBs) that can inhibit BC cell proliferation by targeting legumain (LGMN). LGMN is an oncogenic protein expressed not only in malignant cells but also in tumor microenvironment cells, including tumor-associated macrophages. An LGMN inhibition assay was performed, and microbial extracts were evaluated for in vitro anticancer activity in BC cell lines, angiogenesis assay with chick chorioallantoic membrane (CAM), and tumor xenograft models in Swiss albino mice. We have identified that PMB from the Exiguobacterium (PMB1), inhibits BC growth more potently than PMB2, from the Bacillus subtilis strain. The analysis of PMB1 by GC-MS showed the presence of a variety of fatty acids and fatty-acid derivatives, small molecule phenolics, and aldehydes. PMB1 inhibited the activity of oncogenic legumain in BC cells and induced cell cycle arrest and apoptosis. PMB1 reduced the angiogenesis and inhibited BC cell migration. In mice, intraperitoneal administration of PMB1 retarded the growth of xenografted Ehrlich ascites mammary tumors and mitigated the proliferation of tumor cells in the peritoneal cavity in vivo. In summary, our findings demonstrate the high antitumor potential of PMB1.

Physico-chemical properties of curcumin nanoparticles and its efficacy against Ehrlich ascites carcinoma

Curcumin is a bioactive component with anticancer characteristics; nevertheless, it has poor solubility and fast metabolism, resulting in low bioavailability and so restricting its application. Curcumin loaded in nano emulsions (Cur-NE) was developed to improve water solubility and eliminate all the limitations of curcumin. Size distribution, zeta potential, transmission electron microscopy (TEM) measurements, UV–Visible spectra, IR spectra and thermogravimetric analysis (TGA), were used to characterize the prepared Cur-NE. Cancer therapeutic efficacy was assessed by oxidative stress (superoxide dismutase (SOD), Glutathione–S–Transferase (GST), malondialdehyde (MDA) and nitric oxide (NO), DNA damage, apoptotic proteins (caspase-3 and 9), besides investigating tumor histology and monitoring tumor growth. Additionally, the cytotoxicity and genotoxicity of the liver, kidney, heart, and spleen tissues were examined to gauge the adverse effects of the treatment method’s toxicity. The results showed that Cur-NE is more effective than free curcumin at slowing the growth of Ehrlich tumors while significantly increasing the levels of apoptotic proteins. On the other hand, Cur-NE-treated mice showed some damage in other organs when compared to mice treated with free curcumin. Cur-NE has a higher efficacy in treating Ehrlich tumor.

Features and applications of Ehrlich tumor model in cancer studies: a literature review.

Breast cancer is the most prevalent cancer worldwide, responsible for a large number of deaths, especially among women. Therapeutic options for breast cancer include surgery, radiotherapy, chemotherapy, hormone therapy, and immunotherapy, but further studies of the pathogenesis of this disease and new treatments are still needed. In vitro and in vivo cancer models are important research tools. Murine Ehrlich tumors are one of these models, especially for hormone-positive breast cancer. The present narrative review discusses characteristics of the Ehrlich tumor model, laboratory manipulations of Ehrlich cells (ECs), and applications in pharmacological, pathological, and translational studies. This review was based on scientific articles, books, and theses on Ehrlich tumors. We searched the PubMed, SciELO, Google Scholar, Google, and Clarivate databases. Hormone-positive ECs produce solid Ehrlich carcinoma (SEC) and ascitic Ehrlich carcinoma (AEC), with different features and applications. The presence of SEC or AEC induces systemic and immunological alterations that are similar to cancer in humans, what makes this model applicable to different studies in the cancer field. Ehrlich tumors are a relevant tool for improving our understanding of the pathogenesis of breast cancer and investigating the tumor microenvironment, side effects of therapies, and new treatment options. Despite some limitations, such as the absence of an invasive phenotype to produce metastasis, both SEC and AEC are relevant in preclinical and translational studies of breast cancer.

Efficacy of iron-silver bimetallic nanoparticles to enhance radiotherapy

Radiotherapy (RT) is one of the primary cancer treatment methods. Radiosensitizers are used to enhance RT and protect healthy tissue. Heavy metals have been studied as radiosensitizers. Thus, iron oxide and iron oxide/silver nanoparticles have been the main subjects of this investigation. A simple honey-based synthesis of iron (IONPs) and iron-silver bimetallic nanoparticles (IO@AgNPs) were prepared followed by characterization with transmission electron microscope (TEM), absorption spectra, vibrating sample magnetometer (VSM), and X-ray diffraction (XRD). Additionally, Ehrlich carcinoma was induced in 30 adult BALB/c mice and divided into 6 groups. Mice of group G1 were not treated with nanoparticles or exposed to irradiation (control group), and group G2 and G3 were treated with IONPs and IO@AgNPs respectively. Mice of group G4 were exposed to a high dose of gamma radiation (HRD) (12 Gy). Groups G5 and G6 were treated with IONPs and IO@AgNPs followed by exposure to a low dose of gamma radiation (LRD) (6 Gy) respectively. The impact of NP on the treatment protocol was evaluated by checking tumor growth, DNA damage, and level of oxidative stress in addition to investigating tumor histopathology. Additional research on the toxicity of this protocol was also evaluated by looking at the liver’s cytotoxicity. When compared to HRD therapy, combination therapy (bimetallic NPs and LRD) significantly increased DNA damage by about 75% while having a stronger efficacy in slowing Ehrlich tumor growth (at the end of treatment protocol) by about 45%. Regarding the biosafety concern, mice treated with combination therapy showed lower alanine aminotransferase (ALT) levels in their liver tissues by about half the value of HRD. IO@AgNPs enhanced the therapeutic effect of low-dose radiation and increased the efficacy of treating Ehrlich tumors with the least amount of harm to normal tissues as compared to high radiation dosage therapy.

Morphometric parameters of pelvic lymph nodes in experimental metastatic prostate cancer

The study purpose. Identification of structural and functional changes in pelvic lymph nodes in experimental metastatic prostate cancer. Materials and methods. The study included 30 male mice aged 3 months. All animals ( n = 30) were divided into 2 groups. The first group (the main one, n = 20) included mice that had a model of metastatic prostate cancer created by transplanting an Ehrlich tumor into the prostate parenchyma. These animals were further divided into two equal subgroups: 1a ( n = 10) – mice were withdrawn from the experiment on day 7; 1b ( n = 10) – mice were withdrawn from the experiment on day 18. The second group ( n = 10) included mice that were not manipulated, they made up the control group. After the end of the experiment, morphological analysis of the prostate gland and regional (pelvic) lymph nodes in mice of both groups was performed using light microscopy. Statistical processing of the results was carried out using the Statistica 8.0 software package. The differences were considered statistically significant at p < 0.05. Results. When compared to the control group the mice of groups 1a and 1b, the prostate parenchyma was almost completely replaced by atypical cells, which demonstrates the presence of neoplastic processes in the prostate gland. In group 1a mice, the number of pelvic lymph nodes was 1.9 times as large, and in group 1b animals, this indicator was 2.7 times higher compared to the second group ( p < 0.01). In animals of the first group, the proportion of mast cells in the pelvic lymph nodes increased by 121 % compared to the control group ( p < 0.01). At the same time, we revealed a direct relationship of mast cells with the number of tumor cells and immunoblasts in the medullar sinuses, which indicates the participation of tissue basophils in tumor metastasis. We also recorded a significant increase in the area of the medullar sinuses of regional lymph nodes in animals of groups 1a by 12.4 % ( p < 0.05) and 1b by 20.2 % ( p < 0.01) against the background of an increase in the number of mast cells in this zone compared to the control group, which indicates the possible participation of mast cells in lymphangiogenesis. Conclusion. Mast cells can potentially play a role in the development of malignant neoplasms of the prostate gland. The number of mast cells increases in pelvic lymph nodes in animals with a created model of metastatic prostate cancer. The obtained direct dependence of the increase in the number of mast cells and the increase in the number of tumor cells with immunoblasts suggests the participation of tissue basophils in the spread of metastases. It can be assumed that infiltration of lymph nodes by mast cells may correlate with a poor prognosis of prostate cancer, since these granulocytes contribute to tumor metastasis.

Evaluation of Euphorbia tirucalli L. Immunomodulatory and Antitumor Activity

Euphorbia tirucalli L. is commonly used to treat various pathologies, including cancer. The objective of this study was to evaluate the effect of a crude extract of E. tirucalli on the development of Ehrlich solid tumors and immune function. We prepared an extract by macerating the aerial parts of the plant with 80% ethanol (1:10 g/v) for 15 days. Its effects on tumor development were assessed in male Swiss mice (n=10). The mice were injected subcutaneously with 10⁶ tumor cells and then treated by gavage daily with the extract (33.33, 67, and 133.34 mg kg-1) or saline (0.5% ethanol) for 30 days. The treatment had no toxic effect and did not reduce tumor growth. However, the weight of tumor mass was lowest in the mice treated with extract at 67 mg kg-1. Immunomodulatory activity was evaluated in mice (n=8), with and without tumors, treated with the extract (67 mg kg-1), under the same conditions as described above for 7 and 14 days. Lymphoproliferation, NK activity and IL-12, TNF-a, IFN-y, and IL-10 levels did not differ significantly between the groups. However, IL-4 levels were reduced in the E. tirucalli treated groups at 7 and 14 days when compared to the controls. We concluded that the extract is not toxic and cannot inhibit Ehrlich solid tumor development. Its immunomodulatory activity involves its ability to modulate IL-4 levels.

Antitumor Effect of Açaí (Euterpe oleracea Mart.) Seed Extract in LNCaP Cells and in the Solid Ehrlich Carcinoma Model.

Euterpe oleracea (açaí) fruit has approximately 15% pulp, which is partly edible and commercialized, and 85% seeds. Although açaí seeds are rich in catechins-polyphenolic compounds with antioxidant, anti-inflammatory, and antitumor effects-almost 935,000 tons/year of seeds are discarded as industrial waste. This work evaluated the antitumor properties of E. oleracea in vitro and in vivo in a solid Ehrlich tumor in mice. The seed extract presented 86.26 ± 0.189 mg of catechin/g of extract. The palm and pulp extracts did not exhibit in vitro antitumor activity, while the fruit and seed extracts showed cytotoxic effects on the LNCaP prostate cancer cell line, inducing mitochondrial and nuclear alterations. Oral treatments were performed daily at 100, 200, and 400 mg/kg of E. oleracea seed extract. The tumor development and histology were evaluated, along with immunological and toxicological parameters. Treatment at 400 mg/kg reduced the tumor size, nuclear pleomorphism, and mitosis figures, increasing tumor necrosis. Treated groups showed cellularity of lymphoid organs comparable to the untreated group, suggesting less infiltration in the lymph node and spleen and preservation of the bone marrow. The highest doses reduced IL-6 and induced IFN-γ, suggesting antitumor and immunomodulatory effects. Thus, açaí seeds can be an important source of compounds with antitumor and immunoprotective properties.