scholarly journals The role of interfering RNA in immune response proliferative processes regulation in experimental model of endometrial cancer associated with thyroid disease

2013 ◽  
Vol 94 (3) ◽  
pp. 340-343
Author(s):  
V M Zaporozhan ◽  
G S Maryniuk ◽  
O L Kholodkova ◽  
D U Andronov

Aim. To assess the proliferation and dendritic cells markers expression degree at short interference RNA (siRNA) transfection in endometrial cancer associated with experimental thyroid disease. Methods. Experiments were performed on female rats distributed to five groups: I - control group; IIA and IIIА - animals with simulated hypo-and hyperthyroidism and transplanted Guérin’s carcinoma, IIВ and IIIB - animals with simulated hypo- and hyperthyroidism and transplanted Guérin’s carcinoma in combination with siRNA transfection. Orthogonal tumor dimensions were measured starting from the 7-th day after tumor suspension inoculation. Proliferation and dendritic cells markers expression were assessed in tumor samples by immunohistochemistry after the exclusion of animals from the experiment. Results. siRNA inhibitory effect was more marked in animals with hypothyroidism, indicating an important role of thyroid hormones in regulating cell cycle controlling genes expression. Transfection of siRNA increased mature dendritic cells (CD83) expression in tumor tissue in animals with hypothyroidism and increased immature dendritic cells (CD1a) expression in tumor tissue in animals with hyperthyroidism. Conclusion. siRNA transfection inhibits the tumor cells proliferation mainly at hypothyroidism compared to hyperthyroidism.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1497-1497
Author(s):  
Zonghong Shao ◽  
Chunyan Liu ◽  
Mengying Zheng ◽  
Huaquan Wang ◽  
Rong Fu

Abstract Severe aplastic anemia (SAA) is a hematologic disease characterized by severe bone marrow failure. The abnormal activation of myeloid dendritic cells (mDCs) in SAA might accelerate the polarization of Th0 cells to Th1 cells ,thus causing the over-function of T lymphocytes and apoptosis of hematopoietic cells. Hence, mDCs played an important role in the primary stage of the immune response. Here, we analyze the protein components of mDC from SAA as well as normal control to explore the possible reason that activate mDC. The protein components of mDCs was detected by proteomics technology. Furtherly we applied both realtime PCR and western blot from a perspective of mRNA and protein to validate our discovery. Results revealed that expression of pyruvate kinase M2(PKM2) were enhanced in mDCs from SAA patients at an early stage of the onset. Concurrently, the level of PKM2 in mDCs of SAA patients was conspicuously higher than that in normal control not only at a protein level but also at the gene level. To clarify the role of PKM2 in the activation of mDCs, we investigate the effect of targeted PKM2 siRNA -knockout in mDCs at the cellular level. We measured the levels of costimulatory molecules CD80 and CD86 on mDCs by flow cytometry and identified significantly higher expression of CD86 in the control group relative to the transfected group. To quantify antigen uptake and processing capacities of mDCs, cells were treated with carboxylate-modified yellow-green (YG) microspheres and then analyzed by flow cytometry. The percentage of phagocytosis (PP) was determined by the following formula: PP = M1 + M2 + M3 + M4, where M1, M2, M3, and M4 correspond to the number of cells with one, two, three and four microspheres. Phagocytosis index(PI)=(intracellular cpms/ intracellular + extracellular cpms)x100%.After PKM2 siRNA transfection, we observed lower phagocytic ability of mDCs. Additionally, the level of PP of mDCs from control group was higher than that of PKM2 siRNA -knockout group. Through scanning electron microscopy (SEM), mDCs before siRNA transfection from SAA patients presented longer and more branched protrusions than those seen in PKM2 siRNA transfected mDCs. Next, the effects of PKM2 on cytotoxic T cells(CTL) activation by mDCs from SAA patients were also determined. mDCs before and after PKM2 siRNA transfection were co cultured with CTL cells for 72 hours. After cell co culture, the mRNA expressions of perforin were identified significantly higher in the control group relative to the transfected group. Culture supernatant were collected for quantification of IFN-γ and IL-4 by commercial ELISA kits. The levels of IFN-γ and IL-4 in contral group were much higher than that of transfected group .Additionally, flow cytometry experiments assessing annexin V/propidium iodide staining showed that high PKM2 expression in mDCs was significantly associated with reduced apoptosis rate of CTLs. Therefore, the enhanced function of mDCs from SAA could activate the downstream CTL function and then enhance the killing effect to target cells. Our findings demonstrated that elevated levels of PKM2 in mDCs play an important role in the activation of mDCs and thereby affecting the immune status of SAA by enhancing the function of mDCs and downstream CTLs. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;


Antibodies ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 44
Author(s):  
Lamin B. Cham ◽  
Tom Adomati ◽  
Fanghui Li ◽  
Murtaza Ali ◽  
Karl S. Lang

The integrin associated protein (CD47) is a widely and moderately expressed glycoprotein in all healthy cells. Cancer cells are known to induce increased CD47 expression. Similar to cancer cells, all immune cells can upregulate their CD47 surface expression during infection. The CD47-SIRPa interaction induces an inhibitory effect on macrophages and dendritic cells (dendritic cells) while CD47-thrombospondin-signaling inhibits T cells. Therefore, the disruption of the CD47 interaction can mediate several biologic functions. Upon the blockade and knockout of CD47 reveals an immunosuppressive effect of CD47 during LCMV, influenza virus, HIV-1, mycobacterium tuberculosis, plasmodium and other bacterial pneumonia infections. In our recent study we shows that the blockade of CD47 using the anti-CD47 antibody increases the activation and effector function of macrophages, dendritic cells and T cells during viral infection. By enhancing both innate and adaptive immunity, CD47 blocking antibody promotes antiviral effect. Due to its broad mode of action, the immune-stimulatory effect derived from this antibody could be applicable in nonresolving and (re)emerging infections. The anti-CD47 antibody is currently under clinical trial for the treatment of cancer and could also have amenable therapeutic potential against infectious diseases. This review highlights the immunotherapeutic targeted role of CD47 in the infectious disease realm.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 213-213 ◽  
Author(s):  
Margaret V. Ragni ◽  
Wenhu Wu ◽  
Xiaoyan Liang ◽  
Lina Lu

Abstract Inhibitor formation is a severe complication of hemophilia, occurring in up to 25% and associated with poor response to factor replacement, uncontrolled bleeding, and high morbidity. Preventing inhibitor formation is, thus, a major goal of hemophilia management. The role of dendritic cells (DC) in regulating immune response has been increasingly recognized: immature DC (imDC) induce T regulatory cells in vitro and promote Ag-specific tolerance in vivo. We, therefore, studied the role of imDC propagated from bone marrow with GM-CSF + TGFβ to prevent inhibitor formation in the hemophilia A murine model. Following tail vein injection of recombinant F.VIII (Advate, Baxter) 2.5 U (0.2 μg) on days 0, 2, and 4 in hemophilia A exon 16 KO C57Bl/6 mice, anti-VIII antibodies were detected by semi-quantitative APTT (scored 1-4), peaking on day 6. On rechallenge with F.VIII 2.5 U on days 12, 14, and 16, anti-VIII was detected, peaking on day 17. Anti-VIII production was associated with high level splenic T cell proliferation in response to F.VIII stimulation in vitro, measured by 3H-thymidine incorporation in mixed lymphocyte reaction (MLR). By contrast, there was no antibody formation in F.VIII-treated Wt C57Bl/6 mice: the latter was associated with low T cell response to F.VIII in vitro. Functionally immature DC (imDC) were propagated from the bone marrow of hemophilia A mice with GM-CSF (4ng/ml) and TGFβ (0.2ng/ml). For comparison, functionally mature dendritic cells (mDC) were propagated with GM-CSF (4ng/ml) and IL-4 (1000U/ml).The former (imDC) demonstrated deficient NF-kB binding activity in nuclear protein as detected by gel shifting assay and expressed low level of costimulatory molecules CD80, CD86; by contrast, the latter (mDC) demonstrated enhanced NF-kB binding activity and high levels of co-stimulatory molecules. Administration of 2x106 F.VIII-pulsed imDC (20U/ml x 24h) 7 days before F.VIII dosing on days 0, 2, and 4, led to reduction in inhibitor formation on day 6 (score 1.6 vs. 2.3 in control group) which was further reduced on day 8 (score 1.0 vs. 2.0 in control group). The inhibitor could not be detected on day 8 in 2 of 4 mice pretreated with F.VIII-pulsed imDC. By contrast, high levels of inhibitor were detected in mice pretreated with F.VIII-pulsed mDC (score 3.3). Rechallenge with F.VIII on day 10 in imDC-treated mice resulted in no increase in the reduced or absent anti-VIII effect on day 12. Splenic T cells (CD3+) from the imDC-pretreated mice showed lower proliferative capacity when restimulated in vitro with F.VIII, suggesting that imDC induced F.VIII unresponsiveness. These studies show that FVIII-pulsed imDC reduce the intensity of inhibitor formation, and suggest the potential role of modified DC in preventing or reducing F.VIII inhibitor formation.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Li ◽  
Yang Li ◽  
Ying Zhang ◽  
Dan Hu ◽  
Yonghong Gao ◽  
...  

Objectives. We investigated the role of cardiomyocyte autophagy and its regulatory mechanisms by WenxinKeli (WXKL) in cells subjected to hypertrophy. Methods. H9C2 cardiomyocytes were divided into 8 groups. Cytoskeletal proteins as well as endogenously expressed autophagy marker proteins were studied by confocal imaging. Western blotting was used to assess the levels of light chain-3 (LC3) and mechanistic target of rapamycin (mTOR). The cell viability assay was used to detect the content of ATP. Flow cytometry was used to detect apoptotic cardiomyocytes. Results. (1) Compared with the control group, the length and width of cells in the Angiotensin II (AngII) group were significantly increased, while those in the 3-methyladenine (3-MA) and the WXKL groups were decreased. (2) Compared with AngII group, the expression of LC3 II/I protein in the 3-MA and WXKL groups was downregulated, while the expression of mTOR protein was upregulated. (3) Compared with the AngII group, the cardiomyocytes in the WXKL group showed increased ATP and decreased apoptosis rate and number of autophagosome. Conclusions. We propose a novel role of WXKL as a likely inhibitor of cardiac hypertrophy by regulation of pathological autophagy.


2021 ◽  
Vol 2 (1) ◽  
pp. 29-34
Author(s):  
Hassanein Fadel Mohammed ◽  
Sarah Hassan Jaber

This study for the diagnosis of thyroid using pcsk9.The current study was conducted on seventy women patients suffering from thyroid disease attending in Center for diabetes and Endocrinology Unit in each of Al-Sadder Teaching Hospital and AL FURAT AL AWSAT Hospital in Al-Najaf province/ Iraq, and during the period from September until December 2017. The sample patients were divided into four study groups: premenopausal hypothyroidism patients group (20), postmenopausal hypothyroidism (15), premenopausal hyperthyroidism patients groups (17), and postmenopausal hyperthyroidism (18). The control group composed of 18 healthy women, also divided into premenopausal control and postmenopausal control.  The results indicated a significant increase (p<0.05) in pcsk9 in hypothyroidism patients compared with the control group, while a significant decrease (p<0.05) in pcsk9 in hyperthyroidism patients compared with the control group.  The results indicated a significant decrease (p<0.05) in pcsk9 in premenopausal hyperthyroidism patients compared with the control group, and a significant decrease (p<0.05) in pcsk9 in postmenopausal hyperthyroidism patients compared with the control group. The results indicated a significant increase (p<0.05) in pcsk9 in premenopausal hypothyroidism patients compared with the control group, and a significant increase (p<0.05) in pcsk9 in the postmenopausal hypothyroidism patients compared with the control group, also a significant increase in pcsk9 in postmenopausal than premenopausal.


Author(s):  
Abeer Ali Al-Balawi ◽  
Yousri Mohamed Ahmed ◽  
Ashwag Albukhari ◽  
Shareefa A. ALGhamdi ◽  
Mustafa A. Zeyadi ◽  
...  

Backgound: The generation of oxidative stress can be referred to Aluminium toxic effect in animals and humans. This study aimed to evaluate the role of broccoli (Br) and beetroot (Be) extarcts as antioxidant that prevents oxidative stress that associated with aluminum toxicity. Materials and Methods: Fifty Wister female rats were grouped into five groups (each 10 rats): Group 1: control group, administered drinking water only. Group 2: (Neurogenerative) which were induced by oral administration of aluminum chloride (20 mg/kg b.w) daily for one month. Group 3: Rats given aluminum chloride were treated with Rivastigmine (Ri) (1 mg/kg b.w) as a reference drug daily for five weeks. Group 4: Rats given aluminum chloride were treated with beet root extract (50 mg/kg b.w) daily for six weeks. Group 5. Rats given aluminum chloride were treated with broccoli extract (50 mg/kg b.w) daily for five weeks. Results: (AlCl3) group showed a significant increase in Ach level (P<0.05) and a non-significant change in DOP and NE levels compared to control. (AlCl3+Be) was non-significant (P˂0.05) change in Ach, DOP and NE levels compared to (AlCl3) group and showed a significant (P<0.05) increase in Ach level compared to control. (AlCl3+Br) showed a significant (P<0.05) increase in NE level and non-significant (P˂0.05) change in Ach and DOP levels compared to (AlCl3) group. (AlCl3+Ri) showed a significant (P<0.05) increase in Ach, DOP and NE levels compared to (AlCl3) group. Also, showed a significant (P<0.05) increase in Ach and NE compared to control. Conclusion: Neuroprotective role of broccoli in the present study which may result from its antioxidant properties due to its bioactive content such as glucosinolate, isothiocyanate, Sulforaphane, and flavonoids. Therefore, Broccoli can have a favorable effect on neurotoxicity due to their antioxidant and anti-inflammatory properties.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
B A Barta ◽  
M Ruppert ◽  
K E Froehlich ◽  
M J Cosenza-Contreras ◽  
A Olah ◽  
...  

Abstract Introduction Women benefit from higher levels of protection from cardiovascular diseases until menopause, after which they gradually lose their privileged status. Pivotal role of sex hormones, primarily estrogens were the focus of interest in explaining this clinical observation. Estradiol (E2) was a prime target of these investigations showing promising results. Nonetheless the potential influence of other estrogens and numerous estrogen metabolites have so far been neglected. Purpose The aim of our study was to investigate the influence of circulating steroid hormones on early functional and proteomic changes following repeated ischemic periods in female rats by applying the highly unbiased methods of in vivo pressure-volume analysis and mass spectrometry based proteomics. Methods Diffuse subendocardial ischemia was induced in female (F-Isch) Wistar rats with sc. injection of isoproterenol (ISO, 85mg/kg) daily for two consecutive days, while the control group (F-Co) received an equivalent volume of sc. saline solution. 48 hours after the first injection pressure-volume analysis (P-V) was carried out to assess left ventricular function. FFPE tissue slides were scanned and analyzed digitally, while peptides from the snap frozen left ventricular myocardium were measured by liquid chromatography-tandem mass spectrometry using isobaric labeling (TMT11plex). Serum and plasma samples were taken to measure circulating steroid hormone levels with mass spectrometry. Results Two day induction of ischemia resulted in 17% mortality in F-Isch. ISO treatment resulted in significant myocardial tissue damage compared to controls as assessed by histology. Ischemia led to a prominent impairment of diastolic aspects (active relaxation and myocardial stiffness) of left ventricular function (Tau: 11.1±0.7 vs. 16.1±1.1 F-Co vs. F-Isch; EDPVR: 0.05±0.005 vs. 0.131±0.016 F-Co vs. F-Isch.). Unsupervised hierarchical clustering performed on P-V parameters identified two distinct subgroups of F-Isch with severe or mild functional impairment. Supervised PLS-DA analysis of P-V and hormone datasets found three estrogens that might play a role in determining functional outcomes (2-Hydroxyestrone: 2-OHE1, 4-Hydroxyestrone: 4-OHE1, 4-Methoxyestrone: 4-MeE2). PLS analysis followed by gene ontology enrichment associated E2 and 2-OHE1 concentrations with mitochondrial protein expressions, while 4-OHE1 seemed to influence the reassembly of contractile structures after ischemia. Conclusions Our study has highlighted 2-OHE1 and 4-OHE1 as well as E2 as potentially influential estrogens on early post-ischemic recovery both on functional and on proteomic level. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): New National Excellence Program of the Ministry of Human Capacities of Hungary (ÚNKP-20-3-I-SE-1 to BA. B.) National Research, Development and Innovation Office (NKFIH) of Hungary (K134939 to T. R.)


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuman Wang ◽  
Aihua Wang ◽  
Yu Zhang ◽  
Kejing Zhu ◽  
Xiong Wang ◽  
...  

Abstract Background Prolactinoma is a functional pituitary adenoma that secretes excessive prolactin. Dopamine agonists (DAs) such as bromocriptine (BRC) are the first-line treatment for prolactinomas, but the resistance rate is increasing year by year, creating a clinical challenge. Therefore, it is urgent to explore the molecular mechanism of bromocriptine resistance in prolactinomas. Activation of the P38 MAPK pathway affects multidrug resistance in tumours. Our previous studies have demonstrated that inhibiting MAPK14 can suppress the occurrence of prolactinoma, but the role of MAPK11/12/13/14 (p38 MAPK) signalling in dopamine agonist-resistant prolactinomas is still unclear. Methods A prolactinoma rat model was established to determine the effect of bromocriptine on MAPK11/12/13/14 signalling. DA-resistant GH3 cells and DA-sensitive MMQ cells were used, and the role of MAPK11/12/13/14 in bromocriptine-resistant prolactinomas was preliminarily verified by western blot, RT-qPCR, ELISA, flow cytometry and CCK-8 experiments. The effects of MAPK11 or MAPK14 on bromocriptine-resistant prolactinomas were further verified by siRNA transfection experiments. Results Bromocriptine was used to treat rat prolactinoma by upregulating DRD2 expression and downregulating the expression level of MAPK11/12/13/14 in vivo experiments. The in vitro experiments showed that GH3 cells are resistant to bromocriptine and that MMQ cells are sensitive to bromocriptine. Bromocriptine could significantly reduce the expression of MAPK12 and MAPK13 in GH3 cells and MMQ cells. Bromocriptine could significantly reduce the expression of MAPK11, MAPK14, NF-κB p65 and Bcl2 in MMQ but had no effect on MAPK11, MAPK14, NF-κB p65 and Bcl2 in GH3 cells. In addition, knockdown of MAPK11 and MAPK14 in GH3 cells by siRNA transfection reversed the resistance of GH3 cells to bromocriptine, and haloperidol (HAL) blocked the inhibitory effect of bromocriptine on MAPK14, MAPK11, and PRL in MMQ cells. Our findings show that MAPK11 and MAPK14 proteins are involved in bromocriptine resistance in prolactinomas. Conclusion Bromocriptine reduces the expression of MAPK11/12/13/14 in prolactinomas, and MAPK11 and MAPK14 are involved in bromocriptine resistance in prolactinomas by regulating apoptosis. Reducing the expression of MAPK11 or MAPK14 can reverse bromocriptine resistance in prolactinomas.


Author(s):  
E.M. Frantsiyants ◽  
V.A. Bandovkina ◽  
I.V. Kaplieva ◽  
E.I. Surikova ◽  
I.V. Neskubina ◽  
...  

Diabetes mellitus is an independent risk factor for a number of malignant diseases. It is associated with increased mortality from cancer. The role of growth factors in the pathophysiology of diabetes mellitus and malignant tumors is dual and not fully defined. The aim of the study was to examine the level of some growth factors and their receptors in the tissue of Guerin carcinoma and its perifocal zone growing in rats of both sexes with diabetes mellitus. Materials and Methods. The authors determined the content of VEGF-A, VEGF-C their receptors sVEGF-R1 and sVEGF-R3, EGF and sEGF-R, TGFβ1 and sTGFβ1-R2, TNFα and sTNFα-R1, FGF21 in the samples of the tumor and the perifocal zone of Guerin carcinoma in nonlinear white rats of both sexes with diabetes mellitus (main group). ELISA test was used for this purpose. The control group consisted of animals with Guerin carcinoma without comorbid pathology. Results. Tumors in female rats (main group) had a higher content of VEGF-C, EGF, TNFα and FGF21, VEGF-C/VEGF-R3, but a lower TGFβ1 level. In the perifocal zone these indicators, except TNFα, were lower than in the control group. In males (main group), TNFα and VEGF-A/VEGF-R1 levels in the tumor were higher. The content of VEGF-C, EGF, EGF-R and TGFβ1 was lower than in the control. At the same time, all the studied parameters were lower in the perifocal zone, except FGF21 and EGF-R. Conclusion. Diabetes mellitus as a concomitant disease decreased the life expectancy of animals of both sexes with Guerin carcinoma. At the same time, high ratios of VEGF-A/VEGF-R1 in males, and VEGF-C/VEGF-R3, EGF/sEGF-R, and FGF21 in females in tumor samples were accompanied by the tumor growth in males and activation of metastatic processes in females. Key words: Guerin carcinoma, diabetes mellitus, rats, growth factors, receptors. Сахарный диабет является самостоятельным фактором риска возникновения ряда злокачественных заболеваний и связан с повышенной смертностью от рака. Роль факторов роста в патофизиологии сахарного диабета и злокачественных опухолей двойственна и до конца не определена. Целью настоящего исследования явилось изучение уровня некоторых факторов роста и их рецепторов в ткани карциномы Герена, растущей на фоне сахарного диабета, и ее перифокальной зоне у крыс обоего пола. Материалы и методы. У нелинейных белых крыс обоего пола в образцах опухоли и перифокальной зоны карциномы Герена, растущей на фоне сахарного диабета (основная группа), методом ИФА определяли содержание VEGF-A, VEGF-C и их рецепторов sVEGF-R1 и sVEGF-R3, EGF и sEGF-R, TGFβ1 и sTGFβ1-R2, TNFα и sTNFα-R1, FGF21. В качестве контрольной группы выступали животные с карциномой Герена без коморбидной патологии. Результаты. У самок крыс основной группы в опухоли было выше содержание VEGF-C, EGF, TNFα и FGF21, VEGF-С/VEGF-R3, но ниже уровень TGFβ1, в перифокальной зоне эти показатели, за исключением TNFα, были ниже, чем в группе контроля. У самцов основной группы в опухоли был выше уровень TNFα и VEGF-A/VEGF-R1, содержание VEGF-C, EGF, EGF-R и TGFβ1 оказалось ниже, чем в контроле. При этом в перифокальной зоне все исследованные показатели были ниже, за исключением FGF21 и EGF-R. Выводы. Сахарный диабет как сопутствующее злокачественному росту заболевание способствовал снижению продолжительности жизни животных обоего пола с карциномой Герена. При этом высокие в образцах опухоли соотношения VEGF-A/VEGF-R1 у самцов, VEGF-С/VEGF-R3, EGF/sEGF-R и FGF21 у самок сопровождались ростом объемов опухоли у самцов и активацией метастатических процессов у самок. Ключевые слова: карцинома Герена, сахарный диабет, крысы, факторы роста, рецепторы.


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