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

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.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Henrique Jorge Novaes Morgan ◽  
Aislan Quintiliano Delgado ◽  
Luiz Leonardo Saldanha ◽  
Nathalia Aparecida De Paula Camaforte ◽  
Anne Lígia Dokkedal ◽  
...  

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.


Author(s):  
Almokhtar A. Adwas ◽  
Abeer A. Elkhoely ◽  
Ahmed M. Kabel ◽  
Mohamed Nabih Abdel-Rahman ◽  
Amany A. Eissa

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.


2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.


2021 ◽  
Vol 12 (1) ◽  
pp. 150-156
Author(s):  
Soehartati A. Gondhowiardjo ◽  
Handoko ◽  
Marlinda Adham ◽  
Lisnawati Rachmadi ◽  
Henry Kodrat ◽  
...  

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16577-e16577
Author(s):  
Matias Bustos ◽  
Rebecca Gross ◽  
Rebeka Dejenie ◽  
Ryu Suyeon ◽  
Negin Rahimzadeh ◽  
...  

e16577 Background: Renal cell carcinoma (RCC) has shown an increase in incidence based on continued incidental finding of these tumors by imaging. There is a need for reliable biomarkers like MicroRNAs (miRNA) that are released by the tumor cells and can be detected in assays using blood or urine samples. The first aim of the present pilot study is to determine the diagnostic ability of cell-free miRNA (cfmiR) biomarkers released by RCC tumor cells in urine and plasma samples. The secondary aim was to determine cfmiRs utility in monitoring RCC before and after radical or partial nephrectomy. Methods: We profiled tumor tissues (n = 11), pre-operative (pre-P n = 18; pre-U n = 17) and post-operative (post-P n = 18; post-U n = 17) plasma and urine paired samples from 18 RCC patients with a median follow-up of 18.4 months. As a control, we utilized plasma (n = 73) and urine (n = 16) samples taken from normal healthy donors (NHD). All specimens (n = 170) were processed and analyzed using HTG EdgeSeq miRNA whole transcriptome assay. All of the samples were normalized and DESeq2. Only miRNAs with a FC < -1.5 or > 1.5, FDR < 0.05, normalized counts > 30 were considered Results: We assessed urine, plasma, and tissue for 2083 miRNAs. The pre-U profiles from patients with RCC and NHD were compared to find differentially expressed (DE) cfmiRs. We found 182 cfmiRs DE in pre-U RCC, of which 106 were upregulated and 76 were downregulated. Similarly, we found 830 cfmiRs DE in the pre-P from RCC compared to NHD, of which 192 were upregulated and 638 were downregulated. We then searched for the top 100 miRNAs most frequently detected and identified in the tumor and in pre-P and pre-U samples. Forty miRNAs were consistently found and highly detected in all of the specimens. Of those 40 miRNAs, 33 cfmiRs were found DE in pre-P and 9 cfmiRs significantly decreased in post-P samples after surgery to the level values observed in the plasma from NHD. In the pre-P and pre-U samples from RCC patients, let-7a-5p, let-7b-5p, miR-23b-3p, and miR-30d-5p were found to be consistently upregulated compared to their respective controls. By using receiving operating characteristic (ROC) curves we assessed the area under the curve (AUC) of all the four cfmiRs in detecting RCC patients. The values of AUC for the four cfmiRs detected in pre-P ranged from 76.2-81% [sensitivity, 61.1-83.3%; specificity, 74-86.3%] and in pre-U samples ranged from 76.1-82.4% [sensitivity, 64.7-70.6%; specificity, 100%]. We observed that the four cfmiRs significantly decreased in the post-U samples from RCC patients after surgery to the level values observed in urine from NHD. Conclusions: Our results propose a four cfmiR signature as a potential diagnostic/monitoring urine biomarker that is also detectable in the plasma and tumor tissues from RRC. Further studies to validate these cfmiRNAs as biomarkers for RCC in blood and urine are ongoing.


2021 ◽  
Author(s):  
zhengtuan guo ◽  
qiang yv ◽  
chunlin miao ◽  
wenan ge ◽  
peng li

Wilms tumor is the most common type of renal tumor in children. MicroRNAs (miRNA) are small non-coding RNAs that play crucial regulatory roles in tumorigenesis. We aimed to study the expression profile and function of miR-27a-5p in Wilms tumor. MiR-27a-5p expression was downregulated in human Wilms tumor tissues. Functionally, overexpression of miR-27a-5p promoted cell apoptosis of Wilms tumor cells. Furthermore, upregulated miR-27a-5p delayed xenograft Wilms tumor tumorigenesis in vivo. Bioinformatics analysis predicted miR-27-5p directly targeted to the 3’-untranslated region (UTR) of PBOV1 and luciferase reporter assay confirmed the interaction between miR-27a-5p and PBOV1. The function of PBOV1 in Wilms tumor was evaluated in vitro and knockdown of PBOV1 dampened cell migration. In addition, overexpression of PBOV1 antagonized the tumor-suppressive effect of miR-27a-5p in Wilms tumor cells. Collectively, our findings reveal the regulatory axis of miR-27-5p/PBOV1 in Wilms tumor and miR-27a-5p might serve as a novel therapeutic target in Wilms tumor.


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