scholarly journals Vochysia tucanorum Mart. butanol fraction presents antitumoral activity in vivo and prevents the installation of cachexia in solid Ehrlich tumor model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Henrique Jorge Novaes Morgan ◽  
Aislan Quintiliano Delgado ◽  
Luiz Leonardo Saldanha ◽  
Nathalia Aparecida De Paula Camaforte ◽  
Anne Lígia Dokkedal ◽  
...  
Keyword(s):  
Body Weight ◽  
Cancer Cachexia ◽  
Tumor Volume ◽  
Biological Activities ◽  
Ehrlich Carcinoma ◽  
Antitumoral Activity ◽  
Ehrlich Tumor ◽  
Mortality And Morbidity ◽  
Solid Ehrlich Carcinoma

Abstract Background Cancer is a multifactorial disease caused by uncontrolled proliferation of cells. About 50–80% of cancer patients develop cachexia, a complex metabolic syndrome associated with an increase of mortality and morbidity. However, there are no effective therapies in medical clinic for cancer cachexia. Vochysia tucanorum Mart. is a common three of the Brazilian “Cerrado”. The butanolic fraction of V. tucanorum (Fr-BuVt), very rich in triterpenes with various biological activities, might be interesting in being tested in cancer cachexia syndrome. Hence, the present study was undertaken to investigate the antitumoral activity of Fr-BuVt and its potential against cachexia development. Methods Ehrlich tumor was used as model of cancer cachexia. Ascitic Ehrlich tumor cells were collected, processed and inoculated subcutaneously in saline solution (1 × 107/100 μl; ≥95% viability) for the obtention of solid Ehrlich carcinoma. After inoculation, solid Ehrlich carcinoma-bearing mice were treated by 14 consecutive days by gavage with Fr-BuVt (200 mg/kg). Body weight and tumor volume were measure during the treatment period. Tumors were removed, weighed and properly processed to measure the content and phosphorylation levels of key-proteins involved to apoptotic and proliferation process by Western Blot. Muscles and adipose tissues were removed for weighed. Serum was collected to cytokines levels and energetic blood markers measurements. Results The treatment with the Fr-BuVt (200 mg/kg, 14 days) decreased the solid Ehrlich tumor volume and weight besides increased the expression of the pro-apoptotic proteins caspase-3 and BAX, but also decreased the expression of the proteins involved in proliferation NFκB, mTOR and ERK. In addition, our data shows that the administration of Fr-BuVt was able to prevent the installation of cancer cachexia in Ehrlich carcinoma-bearing mice, since prevented the loss of body weight, as well as the loss of muscle and adipose tissue. Moreover, an improvement in some blood parameters such as decrease in cytokines TNF-α and IL-6 levels is observed. Conclusions The study revealed that Fr-BuVt has antitumoral activity and prevent installation of cancer cachexia in Ehrlich model. Therefore, Fr-BuVt may represent an alternative treatment for cancer cachexia.

Hyperthermic Potentiation of Cisplatin Cytotoxicity on Solid Ehrlich Carcinoma

1993 ◽  
Vol 79 (4) ◽  
pp. 268-272 ◽  
Author(s):  
Abd El-Moneim Mahmoud Osman ◽  
Mohamed Mohamed Sayed Ahmed ◽  
Mohamed Taky El-Din Khayyal ◽  
Mahmoud Mohamed El-Merzabani
Keyword(s):  
Acid Phosphatase ◽  
Tumor Cells ◽  
Tumor Volume ◽  
Membrane Damage ◽  
Ehrlich Carcinoma ◽  
Total Lipids ◽  
Continuous Increase ◽  
Tumor Tissues ◽  
Nuclear Damage ◽  
Solid Ehrlich Carcinoma

Background Hyperthermia produces marked effects on many biochemical parameters of tumor cells and has been reported to potentiate the effect of many drugs. We therefore evaluated the possible synergistic effect between hyperthermia and cisplatin against solid Ehrlich carcinoma. The study was based on the measurement of some biologic characteristics in tumor tissues, namely: DNA, RNA, and protein content and their rate of synthesis as parameters for nuclear damage; total lipids and cholesterol as parameters for membrane damage; acid-phosphatase and acid-ribonuclease as parameters for lysosomal damage; and tumor volume as a direct parameter for tumor growth. Methods Treatment of solid Ehrlich carcinoma by hyperthermia at 43 °C for 30 min for 3 successive days produced a 41.5 % decrease in tumor volume, as well as a significant decrease in nucleic acids, protein contents and their rate of synthesis, in total lipids and cholesterol, and in acid-phosphatase and acid-ribonuclease. Chemotherapeutic management of the tumor by 5 mg/kg × 3 of cisplatin alone showed a continuous increase in tumor volume but at a lower rate than that of the untreated control. However, when cisplatin was given 1 h prior to hyperthermia, the tumor volume was significantly decreased by 82.6 %. Results The effects observed on all the investigated parameters were intensified when cisplatin was combined with hyperthermia. The results obtained suggest that hyperthermia may enhance the penetration of cisplatin to its target site inside the tumor cells due to a membrane-damaging effect. The enhanced lethality of cisplatin on tumor cells may also be due to the inhibition of DNA repair processes by hyperthermia.

MODIFICATING ACTION OF DICLOFENAC ON EFFECTS OF PHOTODYNAMIC THERAPY – IN VIVO STUDY

2019 ◽  
Vol 65 (3) ◽  
pp. 447-453
Author(s):  
Galina Kireeva ◽  
Stepan Kruglov ◽  
A. Tarasov ◽  
Ye. Plakhov ◽  
Yekaterina Gubareva ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Model ◽  
Significant Inhibition ◽  
Ehrlich Carcinoma ◽  
Control Group ◽  
Ehrlich Tumor ◽  
Antitumor Effects ◽  
Modifying Effect ◽  
Effective Treatment Regimen

Introduction. Non-steroidal anti-inflammatory drugs and, in particular, diclofenac, are considered as drugs with a potentially anticarcinogenic effect and can be used to enhance the effects of antitumor therapy. Aim. To evaluate the effectiveness of diclofenac as a potential modifier of photodynamic therapy (PDT) in vivo in Ehrlich tumor model in mice. Materials and methods. The study was conducted on male mice of BALB/C strain with intradermally grafted Ehrlich carcinoma. Experimental procedures were performed on day 7 after tumor inoculation. The control group did not receive treatment, in one group only diclofenac was administered, photosensitizer was administered in three groups (photoditazin, 5 mg / kg, intravenously once), tumor was irradiated with a laser (ALOD, 662 nm) or PDT was performed, respectively, and in three groups the procedures indicated above in each case were combined with the administration of diclofenac. 2 series of experiments were conducted to assess the reproducibility of the results. The size of the tumor was recorded after exposure. Results. In the first series of the experiment, in all groups with the administration of diclofenac (45 mg/kg/day), a high animal mortality was unexpectedly observed, associated with the toxic effect of diclofenac, which required a change in its administration regime and dose (15 mg/kg) in the second series of the experiment. The administration of diclofenac did not significantly affect the efficacy of PDT, and also did not have a modifying effect in other groups (with the introduction of a photosensitizer or laser irradiation) compared with similar groups without diclofenac. PDT with photoditazine turned out to be the most effective treatment regimen: in 8 out of 10 mice in the group from the 21th day after procedure the tumors were not recorded, the animals were alive until the end of the observation for 60 days. The introduction of a photosensitizer and radiation without a photosensitizer did not lead to a significant inhibition of tumor growth. Conclusion. In vivo on a model of intradermally grafted Ehrlich tumor in mice, diclofenac does not have a modifying effect on the antitumor effects of PDT.

scholarly journals Design and Synthesis of a New Soluble Natural β-Carboline Derivative for Preclinical Study by Intravenous Injection

2019 ◽  
Vol 20 (6) ◽  
pp. 1491 ◽  
Author(s):  
Sébastien Marx ◽  
Laurie Bodart ◽  
Nikolay Tumanov ◽  
Johan Wouters
Keyword(s):  
Cell Lines ◽  
Intravenous Injection ◽  
Biological Activities ◽  
Preclinical Study ◽  
Antitumoral Activity ◽  
Significant Activity ◽  
Physiological Conditions ◽  
Design And Synthesis ◽  
Poorly Soluble

Harmine is a natural β-carboline compound showing several biological activities, including antiproliferative properties, but this soluble natural molecule lacks selectivity. Harmine derivatives were reported to overcome this problem, but they are usually poorly soluble. Here, we designed and synthesized a new 2, 7, 9-trisubstituted molecule (1-methyl-7-(3-methylbutoxy)-9-propyl-2-[(pyridin-2-yl)methyl]-9H-pyrido[3,4-b]indol-2-ium bromide) with a solubility of 1.87 ± 0.07 mg/mL in a simulated injection vehicle. This compound is stable for at least 72 h in acidic and physiological conditions (pH 1.1 and 7.4) as well as in a simulated injection vehicle (physiological liquid + 0.1% Tween80®). Solubility in those media is 1.06 ± 0.08 mg/mL and 1.62 ± 0.13 mg/mL at pH 7.4 and 1. The synthesized molecule displays a significant activity on five different cancer cell lines (IC50 range from 0.2 to 2 µM on A549, MDA-MB-231, PANC-1, T98G and Hs683 cell lines). This compound is also more active on cancer cells (MDA-MB-231) than on normal cells (MCF-10a) at IC50 concentrations. Due to its high activity at low concentration, such solubility values should be sufficient for further in vivo antitumoral activity evaluation via intravenous injection.

scholarly journals Antitumor and Radiosensitizing Effects of Zinc Oxide-Caffeic Acid Nanoparticles against Solid Ehrlich Carcinoma in Female Mice

2021 ◽  
Vol 20 ◽  
pp. 153473542110219
Author(s):  
Hayam M. Sayed ◽  
Mahmoud M. Said ◽  
Nadia Y. S. Morcos ◽  
Mona A. El Gawish ◽  
Amel F. M. Ismail
Keyword(s):  
Zinc Oxide ◽  
Caffeic Acid ◽  
Combined Treatment ◽  
B Cell Lymphoma ◽  
Ehrlich Carcinoma ◽  
Gene Expressions ◽  
Γ Irradiation ◽  
Solid Ehrlich Carcinoma

This study aimed to evaluate the anticancer and radio-sensitizing efficacy of Zinc Oxide-Caffeic Acid Nanoparticles (ZnO-CA NPs). ZnO-CA NPs were formulated by the conjugation of Zinc Oxide nanoparticles (ZnO NPs) with caffeic acid (CA) that were characterized by Fourier Transform Infrared Spectra (FT-IR), X-ray Diffractometer (XRD), and Transmission Electron Microscopy (TEM). In vitro anticancer potential of ZnO-CA NPs was evaluated by assessing cell viability in the human breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines. In vivo anticancer and radio-sensitizing effects of ZnO-CA NPs in solid Ehrlich carcinoma-bearing mice (EC mice) were also assessed. Treatment of EC mice with ZnO-CA NPs resulted in a considerable decline in tumor size and weight, down-regulation of B-cell lymphoma 2 (BCL2) and nuclear factor kappa B (NF-κB) gene expressions, decreased vascular cell adhesion molecule 1 (VCAM-1) level, downregulation of phosphorylated-extracellular-regulated kinase 1 and 2 (p-ERK1/2) protein expression, DNA fragmentation and a recognizable peak at sub-G0/G1 indicating dead cells’ population in cancer tissues. Combined treatment of ZnO-CA NPs with γ-irradiation improved these effects. In conclusion: ZnO-CA NPs exhibit in-vitro as well as in-vivo antitumor activity, which is augmented by exposure of mice to γ-irradiation. Further explorations are warranted previous to clinical application of ZnO-CA NPs.

scholarly journals The Possible Chemosensitizing Effect of Different Doses of Indol-3-Carbinol on Transplantable Tumor Model Treated with Doxorubicin

2016 ◽  
Vol 4 ◽  
pp. 61-72
Author(s):  
Almokhtar A. Adwas ◽  
Abeer A. Elkhoely ◽  
Ahmed M. Kabel ◽  
Mohamed Nabih Abdel-Rahman ◽  
Amany A. Eissa
Keyword(s):  
Survival Rate ◽  
Tumor Volume ◽  
Tumor Model ◽  
Ehrlich Carcinoma ◽  
Dependent Manner ◽  
Transplantable Tumor ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Different Doses ◽  
Solid Ehrlich Carcinoma

Background: Ehrlich carcinoma is a transplantable tumor model used frequently in cancer studies. Doxorubicin (DOX) is one of the anthracyclines that is frequently used in treatment of various types of malignancies including breast, prostate and lung cancer. Indole-3-carbinol (I3C) is a phytochemical that was suggested to have potent anti-tumor and chemosensitizing effects. Objective: To detect the possible chemosensitizing effects of different doses of I3C on solid Ehrlich carcinoma (SEC) treated with DOX in mice. Materials and methods: One hundred and forty mice were divided into seven equal groups as follows: Control untreated group, solid Ehrlich carcinoma (SEC), SEC + DOX, SEC + I3C 1000 ppm, SEC + I3C 2000 ppm, SEC + DOX + I3C 1000 ppm and SEC + DOX + I3C 2000 ppm. Tumor volume, survival rate, tissue glutathione reductase (GR), tissue glutathione peroxidase (GPx), tissue tumor necrosis factor alpha (TNF-α) and tissue interleukin-6 (IL-6) were determined. Parts of the tumor were subjected to histopathological and immunohistochemical examination. Results: DOX and/or I3C produced significant increase in the survival rate, tissue GPx and tissue GR with significant decrease in tumor volume, tissue TNF-α and tissue IL-6 compared to SEC group. Moreover, they improved the histopathological changes with significant increase in tissue caspase-3 activity and p53 compared to SEC group. These effects were significant in DOX/I3C combination groups compared to the use of each of these drugs alone. Conclusion: I3C-in a dose dependent manner - had a chemosensitizing effect against transplantable tumor model treated with DOX in mice and this might represent an adjuvant to the traditional drugs used in cancer chemotherapy.

scholarly journals Solid Ehrlich carcinoma reproduces functional and biological characteristics of cancer cachexia

Life Sciences ◽  
2016 ◽  
Vol 162 ◽  
pp. 47-53 ◽  
Author(s):  
Fernando Tadeu Trevisan Frajacomo ◽  
Camila de Souza Padilha ◽  
Poliana Camila Marinello ◽  
Flávia Alessandra Guarnier ◽  
Rubens Cecchini ◽  
...  
Keyword(s):  
Cancer Cachexia ◽  
Biological Characteristics ◽  
Ehrlich Carcinoma ◽  
Solid Ehrlich Carcinoma

Sensitization of neuroendocrine prostate cancer by RRx-001.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 280-280
Author(s):  
Donna Peehl ◽  
Honguan Zhao ◽  
Shoucheng Ning
Keyword(s):  
Prostate Cancer ◽  
Body Weight ◽  
Tumor Volume ◽  
Metabolic Response ◽  
Clinical Activity ◽  
Preclinical Model ◽  
Neuroendocrine Prostate Cancer ◽  
Pre Treatment

280 Background: RRx-001 is a first-in-class dinitroazetidine nontoxic anticancer agent. Its actions include upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis, epigenetic modulation and induction of viral mimicry. In a phase II clinical study (NCT02489903), RRx-001 reversed resistance to reintroduced platinum doublets in small cell lung cancer (SCLC) and other tumor types. RRx001 demonstrated clinical activity with a complete metabolic response of metastatic castration-resistant neuroendocrine prostate cancer (NEPC) after treatment with RRx-001 and reintroduced platinum doublets. Here, we used a preclinical model to further investigate RRx-001 sensitization of NEPC to platinum therapy. Methods: NCI-H660 spheroids were pre-treated with 1 mM RRx-001 or vehicle prior to treatment with carboplatin or docetaxel and cell proliferation was assessed. Cells were also pre-treated with both 1 mM RRx-001 and 10 mM N-acetyl cysteine (NAC) or 1 mM Buthionine-S,R-sulfoximine (BSO) to investigate the role of reactive oxygen species (ROS) in RRx-001 activity. NCI-H660 xenografts were pre-treated with RRx-001 (mimicking clinical activity) or vehicle prior to treatment with carboplatin, and tumor volume and body weight were monitored. Results: RRx-001 pre-treatment significantly decreased the IC50 of carboplatin from ~86 mM to 36 mM in vitro, whereas no significant effect was observed on the IC50 of docetaxel. The ROS inhibitor NAC reversed > 70% of RRx-001 sensitization to carboplatin, while co-pre-treatment with the ROS generator BSO significantly enhanced RRx-001 activity. In vivo, pre-treatment with RRx-001 prior to carboplatin significantly decreased tumor volume compared to vehicle, with ~50% greater reduction in mean tumor volume at 30 days. Body weight was not affected by RRx-001. Conclusions: This preclinical study supports the concept that “priming” with RRx-001 may be an effective therapeutic strategy to resensitize NEPC to initially highly effective platinum doublets. A phase 3 trial is planned, and studies with additional preclinical NEPC models will identify the mechanism of action of RRx-001.

Overtraining of aerobic physical exercise reduce rats (Rattus norvegicus) memory

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Ni Made Ridla Parwata
Keyword(s):  
Body Weight ◽  
Physical Exercise ◽  
Rattus Norvegicus ◽  
Research Method ◽  
Male Rat ◽  
Control Group ◽  
Adult Male Rat ◽  
The Subject ◽  
Heavy Training

Overtraining syndrome is a decrease in physical capacity, emotions and immunity due to training that is too often without adequate periods of rest. Overtraining is often experienced by athletes who daily undergo heavy training with short break periods. This research aims to look at the effect of overtraining aerobic physical exercise on memory in mice. The research method was experimental in vivo with the subject of adult male rat (Rattus Norvegicus) Winstar strain aged 8-10 weeks, body weight 200-250 gr. Divided into three groups, namely the control group, aerobic group and overtraining group. The results of memory tests with water E Maze showed an increase in the duration of travel time and the number of animal errors made by the overtraining group (p = 0.003). This study concludes that overtraining aerobic physical exercise can reduce memory in rat hippocampus.

Репрограммированые in vitro на М3 фенотип макрофаги останавливают рост солидной карциномы in vivo

2018 ◽  
pp. 41-46
Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Antitumor Effect ◽  
Tumor Development ◽  
Significant Inhibition ◽  
The Body ◽  
Ehrlich Carcinoma ◽  
Solid Carcinoma ◽  
Ec Cells

Цель исследования. Доказательство гипотезы, что репрограммированные in vitro на М3 фенотип макрофаги при введении в организм будут существенно ограничивать развитие солидной карциномы in vivo . Методика. Рост солидной опухоли инициировали у мышей in vivo путем подкожной инъекции клеток карциномы Эрлиха (КЭ). Инъекцию макрофагов с нативным М0 фенотипом и с репрограммированным M3 фенотипом проводили в область формирования солидной КЭ. Репрограммирование проводили с помощью низких доз сыворотки, блокаторов факторов транскрипции STAT3/6 и SMAD3 и липополисахарида. Использовали две схемы введения макрофагов: раннее и позднее. При раннем введении макрофаги вводили на 1-е, 5-е, 10-е и 15-е сут. после инъекции клеток КЭ путем обкалывания макрофагами с четырех сторон область развития опухоли. При позднем введении, макрофаги вводили на 10-е, 15-е, 20-е и 25-е сут. Через 15 и 30 сут. после введения клеток КЭ солидную опухоль иссекали и измеряли ее объем. Эффект введения макрофагов оценивали качественно по визуальной и пальпаторной характеристикам солидной опухоли и количественно по изменению ее объема по сравнению с группой без введения макрофагов (контроль). Результаты. Установлено, что M3 макрофаги при раннем введении от начала развития опухоли оказывают выраженный антиопухолевый эффект in vivo , который был существенно более выражен, чем при позднем введении макрофагов. Заключение. Установлено, что введение репрограммированных макрофагов M3 ограничивает развитие солидной карциномы в экспериментах in vivo . Противоопухолевый эффект более выражен при раннем введении М3 макрофагов. Обнаруженные в работе факты делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли, путем предварительного программирования антиопухолевого врожденного иммунного ответа «в пробирке». Aim. To verify a hypothesis that macrophages reprogrammed in vitro to the M3 phenotype and injected into the body substantially restrict the development of solid carcinoma in vivo . Methods. Growth of a solid tumor was initiated in mice in vivo with a subcutaneous injection of Ehrlich carcinoma (EC) cells. Macrophages with a native M0 phenotype or reprogrammed towards the M3 phenotype were injected into the region of developing solid EC. Reprogramming was performed using low doses of serum, STAT3/6 and SMAD3 transcription factor blockers, and lipopolysaccharide. Two schemes of macrophage administration were used: early and late. With the early administration, macrophages were injected on days 1, 5, 10, and 15 following the injection of EC cells at four sides of the tumor development area. With the late administration, macrophages were injected on days 10, 15, 20, and 25. At 15 and 30 days after the EC cell injection, the solid tumor was excised and its volume was measured. The effect of macrophage administration was assessed both qualitatively by visual and palpation characteristics of solid tumor and quantitatively by changes in the tumor volume compared with the group without the macrophage treatment. Results. M3 macrophages administered early after the onset of tumor development exerted a pronounced antitumor effect in vivo , which was significantly greater than the antitumor effect of the late administration of M3 macrophages. Conclusion. The observed significant inhibition of in vivo growth of solid carcinoma by M3 macrophages makes promising the development of a clinical version of the biotechnology for restriction of tumor growth by in vitro pre-programming of the antitumor, innate immune response.

Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

2017 ◽  
pp. 4-9
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
И.Ю. Малышев
Keyword(s):  
Tumor Growth ◽  
Culture Medium ◽  
Ehrlich Carcinoma ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ec Cells ◽  
Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

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