Oncoprotective Effect Research Articles

Pharmacoinformational, basic and clinical studies of 7-hydroxymatairesinol in the context of searching for effective and safe therapeutic approaches to the treatment of mastopathy

7-hydroxymatairesinol (7(OH)MR) is the main lignan of spruce extracts, characterized by oncoprotective and anti-inflammatory properties. The results of chemoreactome modeling made it possible to formulate the molecular mechanisms of the pharmacological effects of 7(OH)MR for anti-inflammatory (inhibition of 5-lipoxygenase, matrix metalloproteinase MMP2, mitogen-activated kinase p38-alpha, leukotriene b4 receptor, prostacyclin receptor), oncoprotective (antioxidant effect due to inhibition heme oxygenase-2, inhibition of cyclin-dependent kinases 3 and 4, epidermal growth factor, mTOR protein). An assessment of the transcriptomic effects of 7(OH)MR in breast cancer cells showed significant dose-dependent effects on the transcription of 3468 of 12700 genes. The 7(OH)MR molecule, reducing the expression of proliferative genes (401 genes) and chronic inflammation (148 genes), while simultaneously increasing the transcription of oncoprotective immunity genes (100 genes), inhibits the proliferation of tumor cells. Experiments on solid Ehrlich carcinoma showed a significant oncoprotective effect of 7(OH)MR at doses of 60, 120 mg/day, even while taking estrogen (p = 0.007). A clinical study showed that 7(OH)MR (60 mg/day, 1 month) helps normalize estrogen metabolism and improve the clinical symptoms of mastopathy.

Estetrol: a new word in modern hormonal contraception. A review

The concept of the demographic policy of the Russian Federation is to increase the birth rate, preserve citizens' health, and increase life expectancy. One of the priority areas is the reproductive health of women. The pleiotropic effect of the components of combined hormonal drugs is successfully used in clinical practice by obstetricians-gynecologists not only for contraception but also for conditions requiring prophylaxis and drug therapy. Estrogens have a protective effect on the reproductive and extragenital organs; however, evidence of the effect of estrogen-containing drugs on breast tissue and hemostasis remains debatable. We analyzed the data published in the international databases PubMed, Google Scholar, and MEDLINE (search depth – 5 years). Estetrol (E4) is a native fetal estrogen produced by the fetal liver during pregnancy. The key difference from other estrogens is its highly selective and differentiated effect on various tissues and its unique antiproliferative properties. The review presents the results of studies on estrogenic and antiestrogenic effects of E4 and the combination of E4 with progestogen (Esteretta drug product approved in Russia), with particular attention paid to the oncoprotective effect of E4. Research data suggest that E4 may have different effects on breast epithelial cells and breast cancer cells compared to other estrogens. Clinical data indicate that E4 has a more selective pharmacological profile compared to other estrogens, which is reflected in a low estrogenic effect on the liver, including the production of sex hormone binding globulin, hemostasis parameters, and lipid profile.

Oncoprotective effects of chondroprotectors: glucosamine, chondroitin sulfate and undenatured type II collagen

Objective: to systematize fundamental, clinical, and epidemiological data on the oncoprotective effects of chondroprotectors: chondroitin sulfate (CS), glucosamine (including glucosamine sulfate, GS), and undenatured type II collagen (UC-II).Material and methods. A systematic computer analysis of 6176 publications on the relationship between CS/GS/UC-II and tumor diseases found by the query “(glucosamine OR chondroitin OR ((“Collagen Type II” OR “type II collagen”) AND pharmacology)) AND (Cancer OR cancers OR tumor OR tumors OR tumors OR tumour*) NOT tumor necrosis)” in PubMed and Embase databases was performed. All articles of any format from 1900 to the present day with full available abstracts were taken. A topological approach to data analysis was used.Results. Large-scale clinical and epidemiological studies and meta-analyses showed that regular consumption of CS/GS reduced the risk of colorectal cancer and lung cancer, as well as mortality from tumor diseases. The mechanisms of oncoprotective action of CS/GS are through inhibition of the pro-inflammatory cascade of tumor necrosis factor alpha, CD44 receptor and nuclear factor kappa B, and initiation of tumor cell apoptosis. By modulating the CD44 receptor and specific O-glycosylation of intracellular proteins, GS inhibits the pro-inflammatory effects of arachidonic acid cascade, interleukins IL-6, IL-8, the PI3K/Akt proliferative pathway, and cyclin-dependent kinases. The first postgenomic studies of CS/GS oncoprotective effects, including microbiome studies, was performed. Additionally, CS contributes to the inhibition of the effects of vascular endothelial growth factor and matrix metalloproteinases involved in tumor metastasis and invasion. Potentially, CS/GS oncoprotective effects may be enhanced by the anti-inflammatory effect of UC-II: the addition of NC-II substance to CS/GS complex makes it possible to reduce the autoimmune branch of pathogenesis not only in primary, but also in secondary OA and rheumatoid arthritis.Conclusion. The CS and glucosamine (including GS) chondroprotectors exhibit oncoprotective effects. The use of CS and GS together with UС-II standardized pharmaceutical forms can enhance their anti-inflammatory and immunomodulatory effects.

The effect of hormonal contraception on the risk of breast cancer: A review

Hormonal-induced changes in the breast occur due to both endogenous and exogenous sex hormones. For two decades, the safety of hormonal contraceptives (HC) in terms of their effect on breast tissue has been discussed in the literature. The pleiotropic effect of the components in the combined HC, on the one hand, prevents unwanted pregnancy; on the other hand, they help to maintain good health of women of childbearing age due to a wide range of non-contraceptive effects (eliminating hyperandrogenism manifestations, reducing the pain severity during menstruation and the menstrual blood loss, the risk of recurrence of functional ovarian cysts, oncoprotective effect due to reducing the risk of ovarian, endometrial, colorectal, pancreatic, and lung cancer). However, according to epidemiological studies, in addition to the beneficial effects, there are risks that require further study, including the controversial impact of HC on the oncogenesis and progression of breast cancer. In addition, some young women with breast cancer experience induced menopause after antitumor treatment. However, amenorrhea is not a marker for complete disabling of ovarian function, and pregnancy is associated with a risk of disease recurrence or progression. Therefore, in each case, it is necessary to determine the need for an effective and safe method of contraception.

Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance.

Unscheduled increases in ploidy underlie defects in tissue function, premature aging, and malignancy. A concomitant event to polyploidization is the amplification of centrosomes, the main microtubule organization centers in animal cells. Supernumerary centrosomes are frequent in tumors, correlating with higher aggressiveness and poor prognosis. However, extra centrosomes initially also exert an onco-protective effect by activating p53-induced cell cycle arrest. If additional signaling events initiated by centrosomes help prevent pathology is unknown. Here, we report that extra centrosomes, arising during unscheduled polyploidization or aberrant centriole biogenesis, induce activation of NF-κB signaling and sterile inflammation. This signaling requires the NEMO-PIDDosome, a multi-protein complex composed of PIDD1, RIPK1, and NEMO/IKKγ. Remarkably, the presence of supernumerary centrosomes suffices to induce a paracrine chemokine and cytokine profile, able to polarize macrophages into a pro-inflammatory phenotype. Furthermore, extra centrosomes increase the immunogenicity of cancer cells and render them more susceptible to NK-cell attack. Hence, the PIDDosome acts as a dual effector, able to engage not only the p53 network for cell cycle control but also NF-κB signaling to instruct innate immunity.

An Update on Tamoxifen and the Chemo-Preventive Potential of Vitamin E in Breast Cancer Management.

Breast cancer (BC) is the most common female cancer in terms of incidence and mortality worldwide. Tamoxifen (Nolvadex) is a widely prescribed, oral anti-estrogen drug for the hormonal treatment of estrogen-receptor-positive BC, which represents 70% of all BC subtypes. This review assesses the current knowledge on the molecular pharmacology of tamoxifen in terms of its anticancer and chemo-preventive actions. Due to the importance of vitamin E compounds, which are widely taken as a supplementary dietary component, the review focuses only on the potential importance of vitamin E in BC chemo-prevention. The chemo-preventive and onco-protective effects of tamoxifen combined with the potential effects of vitamin E can alter the anticancer actions of tamoxifen. Therefore, methods involving an individually designed, nutritional intervention for patients with BC warrant further consideration. These data are of great importance for tamoxifen chemo-prevention strategies in future epidemiological studies.

Metformin in the prevention of colorectal cancer with diabetes mellitus

The purpose of the review is to present an analysis of current literature data on the prospects of using the oncoprotective effect of metformin in colorectal cancer. Metformin is a drug with a long history, it is a first-line drug for the treatment of type 2 diabetes mellitus (DM2), as well as the most commonly prescribed drug worldwide. Modern researches show that in addition to its role in glucose control, metformin can reduce the risk and mortality from some malignancies and improve the response of patients with DM2 to certain types of cancer treatment. Accumulated data indicate that metformin could be a candidate drug for drug prevention of colorectal cancer.

Revealing the features of the formation of the properties of processed cheese with wild onions

Processed cheeses belong to food products of high nutritional and biological value. Bioflavonoids, which are widespread in higher plants and have a number of unique properties, are practically not found in traditional processed cheese chunks. Quercetin is most commonly found in plant flavonoids. Most studies have confirmed the following basic biological properties of quercetin: immunostimulating effect (increases the activity of phagocytes, T- and B-lymphocytes; increases the production of antibodies, reduces the manifestations of secondary immunodeficiency, the incidence of viral infections); oncoprotective effect due to a decrease in the damaging effect of oxygen radicals on the genetic apparatus; antioxidant protection; positive effect in cardiovascular diseases, etc. The cheapest, most bioavailable and frequently used plant raw materials are onions, which also contain bioflavonoids. The article explores the use of wild onions in the creation of functional processed cheese. In connection with the spread of coronavirus infection, it is necessary to strengthen the body's immunity with the help of nutrition. The experiments carried out have established the quantitative presence of flavonoids, vitamin K in processed cheese with wild onions. Inulin and saponins were found in the composition of wild onions, which also proves the advisability of using wild onions in food. The research results on the development of a technology for a new processed cheese and a method of adding wild onion filler in different variations: fresh and in the form of a powder are presented. It was found that fresh addition of Allium odorum imparts a sharp onion aroma, and when dried it imparts a slightly chalky aroma to the final product. The positive effect of the vegetable filler on the shelf life of processed cheese has been proven.

Anticancer Effects of Propionic Acid Inducing Cell Death in Cervical Cancer Cells.

Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.

Oncoprotective Effect of Short-Term Hypoxic Training in Model of Ehrlich Ascites Carcinoma in Mice

The search for non-drug therapies to enhance antitumor protection is one of the most urgent tasks of pathophysiology and medicine. We evaluated the impact of a course of interval hypobaric hypoxia (0.306 kg/cm2) on the development of Ehrlich ascites carcinoma (EAC) in mice. In the first series of experiments, the mice were subjected to hypoxic training over 10 days, and in the second series the hypoxic training was provided daily for 3 weeks, except for weekends. The tumor volume was analyzed using a caliper on day 16 (the terminal period). The weight of the mice was measured on day 0, and the final net weight was measured on day 22. The rate of cancer development in mice exposed to hypoxic training within the first 10 days decreased by 58%. Exposure to 3 weeks of hypoxic training showed no significant antitumor effect. Upon completion of the hypoxic training, the rate of tumor development increased, and at the end of the study, no significant differences in survival were found. Further research is needed to determine the optimal antitumor effect and duration of the course of interval hypobaric training.
 Keywords: Ehrlich ascites carcinoma (EAC), mice, hypobaric hypoxia, antitumor protection, leukocytes, leukogram

The effectiveness of the transcranial electrical stimulation method in obstetrics and gynecology

The review examines the use of protective (endorphinergic and serotonergic) mechanisms of the brain in obstetrics and gynecology. To review the current state of the problem an analysis of the eLIBRARU, PubMed, Embase, MEDLINE, Cochrane databases was carried out, and works for 2015-2020 were selected. It has been shown that the method of non - invasive non - drug effects on the human body - transcranial electrical stimulation (TES) - activates and accelerates reparative processes, normalizes psychophysiological status, has anti-inflammatory and immune-stimulating effects, has an onco-protective effect, stabilizes the autonomic nervous system, provides drug - free disturbance homeostasis in general. This makes it possible to successfully use TES in obstetrics and gynecology in such pathological conditions as the threat of pregnancy termination at different times, nausea and vomiting of pregnant women, preeclampsia, pathological prelaminar period, menstrual dysfunction, climacteric syndrome, leiomyoma and endometriosis of the uterus, endometrial hyperplastic processes, chronic inflammatory diseases of the pelvic organs with pain syndrome, surgery and obstetrics care. TES is characterized by high efficiency, safety, ease of use, availability and economic profitability. TES reduces the number of prescribed drugs and shortens the recovery time. This method is used both as monotherapy and as a component of a complex action including medication and non-medication. The results of the TES studies presented in the review complement each other and demonstrate the importance of modern alternative methods of treatment, and the authors of these studies are unanimous in their opinion on the fruitfulness of the use of transcranial electrical stimulation as a type of non-drug therapy in various fields of obstetrics and gynecology.

DNA methylation in the upstream CpG island of the GPER locus and its relationship with GPER expression in colon cancer cell lines.

The G-protein coupled estrogen receptor (GPER), a proposed tumor suppressor, relays short-term non-genomic responses in target cells and tissues. It frequently undergoes down-modulation in primary tumors of the breast, ovary, and endometrium. Liu and co-workers recently reported loss of GPER expression in colorectal cancer and attributed it to DNA methylation-dependent silencing. We hypothesized that GPER expression is inversely correlated with methylation in the upstream CpG island (upCpGi) in the GPER locus.Methylation in the upCpGi was analysed by bisulfite sequencing and correlated with GPER expression in a panel of colon cancer cell lines. Eight downstream CpGs of the upCpGi was differentially methylated across the cell lines. Methylation in this differentially methylated region (DMR) correlated inversely with GPER expression. Two cell lines, namely SW620 and COLO-320DM, were compared in terms of their viability in response to varying concentrations of G1, a GPER specific agonist. SW-620 cells, which had the least methylated DMR and the highest level of GPER expression, showed significant loss of viability with 1µM G1. COLO-320DM, which had the most methylated DMR and the lowest level of GPER expression, did not show a significant response to 1µM G1. At 5µM G1, SW620 cells showed a greater reduction in viability than COLO-320DM cells.DNA methylation in the DMR is inversely correlated with GPER expression. DNA methylation-dependent silencing of GPER maybe, at least in part, the underlying reason behind the loss of estrogen's oncoprotective effect via GPER in the colon.

Abstract 6103: Absence of Mitsuokella multacida is associated with early onset of colorectal cancer

Abstract Colorectal cancer (CRC) is a global burden, with an expected 2.2 million annual cases and 1.1 million deaths by 2030. Nearly 90% of CRC cases occur in people over the age of 50. However, early onset (<50 years) of CRC is increasing in Egypt. Prior studies suggest that alteration in microbiome composition (dysbiosis) disturbs the symbiotic relationship between the colorectum and resident micro-organisms and promotes CRC. We hypothesize that, for Egyptians, microbiome dysbiosis is responsible for early-onset of CRC. We further hypothesize that there is cross-talk between the microbiome, tumor molecular features, and the immune microenvironment. Thus, we investigated the molecular profiling of these patients via integrated transcriptional-microbiome analysis. We assessed the colonic microbiota and the expression of specific host response genes in normal colonic mucosal samples from 8 healthy individuals and samples from 20 Egyptian CRC patients. A retrospective convenience sample design was employed. Colonoscopy was performed on these patients at Alexandria University Hospital, Alexandria, Egypt. Microbiota composition was determined by 16S rRNA amplicon sequencing. A panel of 784 genes involved in tumor, microenvironment, and immune response were used to characterize differential expression across patient groups by the Nanostring method. This panel facilitates the estimation of immune cell abundance for 15 tumor-infiltrating immune cell types. Differential abundance and cross-talk between the relative abundance of microbiota and tumor RNA expression were evaluated using negative binomial model fitting and Wald statistics. One third of our CRC patient population was under 50 years old at the time of diagnosis with CRC, and most were female. Healthy controls were even younger than CRC cases, and most were females. There were differences in relative abundances of bacteria between healthy controls and those with CRCs. Analysis showed a low abundance of Mitsuokella multacida, a short-chain fatty acid (SCFA)-producing bacterium, in CRC patients when compared to healthy individuals. In particular, this trend was evident for older CRC patients (≥ 50 years); of note, this bacterium was absent in younger patients (<50 years) (adj. p-value = 0.01). Further, there was a high abundance of Fusobacterium nucleatum in all CRC patients compared to healthy individuals (adj. p-value = 0.04). In cross-talk analysis for healthy controls, elevated abundance of M. multacida was inversely associated with macrophage abundance (global p-value =0.055).For Egyptian patients, the absence of SCFA-producing multacida in younger patients may be a reason for early onset of CRC. These findings suggest that the oncoprotective effect of Mitsuokella multacida should be further investigated. These studies are supported by the US-Egypt STDF grants (NAS 2000007148 and 144/17) and the Impact funds of University of Alabama at Birmingham. Citation Format: Amr Elkholy, Michael Behring, Mohammed Mohsen, Prachi Bajpai, Amira Embaby, Doaa Header, Reham Abo Elwafa, Hesham Saeed, Mona Fouad, Waleed Arafat, Upender Manne. Absence of Mitsuokella multacida is associated with early onset of colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6103.

Incretins today: multiple effects and therapeutic potential

Glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones initially discovered in the 1960s. GIP and GLP-1 have gained great scientific interest due to their properties in increasing insulin secretion and lowering blood glucose levels. The study of these incretin hormones has progressed substantially in recent decades, in that their systemic effects has begun to be actively discussed. In particular, incretins are involved in the pathogenesis of obesity and non-alcoholic fatty liver disease. Moreover, incretins are able to improve cognitive function, suppress the formation of -amyloid plaques and provide an oncoprotective effect. Recent data show promising oncoprotective effect of GLP-1 agonists on prostate and breast cancer.
 This review provides systematisation of recent data on the role and mechanisms of action of incretin hormones on carbohydrate metabolism, as well as effects not related to glucose homeostasis, which contributes to a better understanding of potential vectors for the development of incretinotropic therapy. In addition, this review offers insight into pathogenic prerequisites and highlights the current issues in creating innovative polyagonists for treatment of type 2 diabetes mellitus.

Oncoprotective Effects of Short-Chain Fatty Acids on Uterine Cervical Neoplasia

Short-chain fatty acids (SCFAs) produced by fermentation from prebiotics not only provide energy but also activate cell membrane receptors, thereby contributing to the maintenance of homeostasis in the human body. Recently, free fatty acid receptor 2 (FFAR2), which uses SCFAs as ligands, was found to exert oncoprotective effects on several types of neoplasia. This study examined whether SCFAs have oncoprotective effects on uterine cervical neoplasia. Immunohistochemical analysis revealed that FFAR2 was expressed in atypical cells and cancer cells of cervical neoplasia. Moreover, reverse transcription polymerase chain reaction showed that FFAR2 was expressed in a human cervical cancer cell line, HeLa. We also found that SCFAs inhibited the proliferation of HeLa cells, and a FFAR2 antagonist, GLPG0974, used to suppress the binding of SCFAs significantly restored the cell viability of HeLa cells blocked by acetic acid treatment. These results suggest that ingestion of prebiotics and the resulting production of SCFAs may play an oncoprotective role against uterine cervical neoplasia via FFAR2 expression.

Potential of Phenylbutyrate as Adjuvant Chemotherapy: An Overview of Cellular and Molecular Anticancer Mechanisms.

Despite the advancement in cancer therapy, a high number of patients fail treatment because of drug resistance. Several preclinical in vitro data suggest that phenylbutyrate has antiproliferative, antiangiogenic, antimetastatic, immunomodulatory, and differentiating properties. Moreover, phenylbutyrate administration in vivo provided an oncoprotective effect. However, the results of clinical trials indicate that the antineoplastic potential of phenylbutyrate is hindered by its pharmacokinetic and pharmacodynamic properties. Thus, understanding the exact mechanisms of the anticancer effect of phenylbutyrate could assist in the selection of patients who will best benefit from this drug. The present review discusses the proposed mechanisms of antineoplastic effect of phenylbutyrate and the preclinical and clinical evidence suggesting its potential role as anticancer in different types of cancer.

OC-055 Blood-Based Biomarkers in the Oesophageal Cancer Model – Results from the PigA Mutant Phenotype Study

Introduction Improving our mechanisms of risk stratification of patients with Barrett’s oesophagus (BO) requires easily analysable, cheap and reproducable biomarkers. The PigA phenotype assay is a novel flow cytometric analysis, which can be undertaken using a fingerprick test. The PigA gene codes for GPI-anchors, which tether proteins to the surface of circulating blood cells. Silencing mutations, induced by acid or bile, will therefore result in absence of surface GPI-anchors and negative fluorescence on flow cytometry analysis. Our laboratory has already demonstrated the effects of bile in inducing such mutant events in blood based cell lines. Methods Here, we investigate the baseline background PigA phenotype frequency in patients with GORD, BO, and those with oesophageal adenocarcinoma (OAC). We recruited 120 patients for analysis of baseline frequency in circulating red blood cells. We correlated these findings with symptoms, diet, lifestyle, endoscopic features and radiological stage. We also undertook Western Blotting analysis of endoscopic biopsies to assess GPI-anchor status in retrieved tissue. Results A clear correlation was seen with increased PigA frequency with histological status from healthy patients with GORD to those with OAC, p Older age, smoking status and unhealthy lifestyle (diet measured using the DQS score) all resulted in higher frequencies. Length of Barrett’s and degree of inflammation (LA classification) had no effect, but aspirin use appeared to be protective and resulted in lower frequencies (p Evaluation of patients with cancer (n = 15) found that PigA frequency increased with increasing lymph node involvement and metastasic spread (both p Finally western blotting of crude protein extracted from oesophageal biopsies revealed a reduction in GPI-anchor levels from normal squamous tissue, through to cancer, thus corroborating our results above. Conclusion We have developed a blood-based biomarker assay, which can potentially stratify patients’ underlying genomic instability by indirectly measuring GPI-anchor status on circulating blood cells. We have also demonstrated the potential onco-protective effects of aspirin in these patients. The mechanisms behind these observations remain unclear, but western blot analysis suggests mutation may occur in the distal oesophagus where circulating blood cells are exposured to mutagenic chemicals such as bile and acid. Further evaluation in other cancer models as well as a wider cohort of non-cancer patients (to evaluate lifetyle) will establish how useful the assay may be outside of the Barrett’s model. Disclosure of Interest None Declared

Nucleolar control of p53: a cellular Achilles' heel and a target for cancer therapy.

Nucleoli perform a crucial cell function, ribosome biogenesis, and of critical relevance to the subject of this review, they are also extremely sensitive to cellular stresses, which can cause loss of function and/or associated structural disruption. In recent years, we have learned that cells take advantage of this stress sensitivity of nucleoli, using them as stress sensors. One major protein regulated by this role of nucleoli is the tumor suppressor p53, which is activated in response to diverse cellular injuries in order to exert its onco-protective effects. Here we discuss a model of nucleolar regulation of p53, which proposes that key steps in the promotion of p53 degradation by the ubiquitin ligase MDM2 occur in nucleoli, thus providing an explanation for the observed link between nucleolar disruption and p53 stability. We review current evidence for this compartmentalization in p53 homeostasis and highlight current limitations of the model. Interestingly, a number of current chemotherapeutic agents capable of inducing a p53 response are likely to do so by targeting nucleolar functions and these compounds may serve to inform further improved therapeutic targeting of nucleoli.

Effects of Specific Antibodies and Immunocompetent Cells on Tumor Growth in Passive Transfer Experiment

Experiments with passive transfer of immunocompetent cell and serum demonstrated suppression of tumor growth after transfer of splenocytes from animals immunized with Trypanosoma cruzi. The nonspecific constituent of antitumor effect of immunocompetent cells was detected. The previously reported oncoprotective effect of mucins 2 and 3 was not confirmed.

Mechanism of biological effect of the delta-sleep-inducing peptide includes activation of deoxyribonucleotide synthesis

To find out the mechanism of oncoprotective effects of the delta-sleep-inducing peptide, we have studied the dynamics of ribonucleotide reductase activity, which is a vital enzyme in the DNA biosynthesis, using electron paramagnetic resonance (EPR), and a concentration of low molecular mass iron complexes in the murine spleen after intraperitoneal injection of the peptide and the antitumor preparation methylnitrosourea. The data obtained give evidence on the different effects on the ribonucleotide synthesis system by the substances under study. The peptide induced significant activation of the enzyme as a consequence of activation of processes of protein synthesis. Methylnitrosourea injection leads to a decrease in the concentration of the ribonucleotide reductase active form due to destruction of the enzyme active center. The prospects of the study are discussed.