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1.
Medicina (Kaunas) ; 59(8)2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37629735

ABSTRACT

Background and Objectives: The muscles in the upper arm are categorized into two groups: ventral muscles, which include the biceps brachii, coracobrachialis, and brachialis, and dorsal muscles comprising the triceps brachii and anconeus. These muscles are positioned in a way that they contribute to movements at the shoulder and elbow joints. Given the importance of the upper arm muscles for various reasons, they need to be well-known by medical professionals. Ventral upper arm muscles exhibit various topographical and morphological variations. Understanding these variations is critical from both anatomical and clinical standpoints. Therefore, our aim was to conduct an anatomical study focusing on these muscles and potentially identify ventral upper arm muscle variations that could contribute to the broader understanding of this area. For this anatomical study, 32 upper limbs obtained from 16 adult cadavers were dissected. Case report: During our anatomical survey, an accessory coracobrachialis muscle in the left upper extremity of one cadaver was discovered. This additional muscle was located anterior to the classical coracobrachialis muscle and measured 162 mm in length. It originated from the distal anterior surface of the coracoid process and was inserted into the middle third of the humeral shaft. The accessory muscle was supplied by the musculocutaneous nerve. No apparent anatomic variations were observed in the other upper arm muscles in any of the cadavers. Conclusions: Gaining insight into the ventral upper arm muscle variations holds vital significance in both anatomy and clinical practice, as they can influence surgical approaches, rehabilitation strategies, and the interpretation of imaging studies. Based on the morphological characteristics of the accessory coracobrachialis muscle discovered in our case, we hypothesize that it could have caused an atypical palpable mass in the medial brachial area, adjacent to the short head of the biceps brachii.


Subject(s)
Arm , Upper Extremity , Adult , Humans , Muscles , Humerus , Cadaver
2.
Bratisl Lek Listy ; 124(8): 567-571, 2023.
Article in English | MEDLINE | ID: mdl-37218487

ABSTRACT

OBJECTIVES: The aim of the study was to evaluate renal arterial variations in Slovak context. METHODS: Forty cadavers (80 formalin-fixed cadaveric kidneys) were included in the study. The accessory renal arteries (ARAs) were evaluated on the basis of point of origin, termination in the kidney (superior pole, hilum, inferior pole), and symmetry. RESULTS: The incidence of ARAs was detected in 20 % (8/40) of the cadavers. Double renal arteries were observed in 9 (11.25 %, n = 80) of kidneys. Among 8 cadavers with ARAs, the unilateral presence of ARA was found in 7 cadavers and bilateral presence in 1 cadaver. Among 9 ARAs, polar artery was the most common anomaly seen in 7 (78 %) kidneys (inferior polar artery 5, superior polar artery 2) followed by the hilar artery in 2 kidneys. CONCLUSIONS: This is the first cadaveric study on the incidence and morphology of ARAs in Slovakia. The study has shown that the variations in renal arterial anatomy are a frequent finding (20 % of cadavers) while all of the described variants have significant implications for a variety of surgical procedures in the retroperitoneal space. The variations in renal arteries should be considered an integral part of anatomy teaching as they point to the diverse clinical reality of anatomy (Tab. 1, Fig. 1, Ref. 35). Text in PDF www.elis.sk Keywords: renal artery, variation, polar artery, double renal artery, cadaver.


Subject(s)
Kidney , Renal Artery , Humans , Adult , Slovakia/epidemiology , Incidence , Kidney/blood supply , Cadaver
3.
Prague Med Rep ; 123(4): 225-242, 2022.
Article in English | MEDLINE | ID: mdl-36416461

ABSTRACT

Pollution with heavy metal salts is an important environmental problem today, having an adverse effect on public health. The endocrine system maintains homeostasis in the body. The antioxidant protection (GPX-1) of the pineal gland in mature rats was studied. Animals of the experimental group represented a model of microelementosis, achieved by adding a mixture of heavy metal salts for 90 days to drinking water: zinc (ZnSO4×7H2O) - 5 mg/l, copper (CuSO4×5H2O) - 1 mg/l, iron (FeSO4) - 10 mg/l, manganese (MnSO4×5H2O) - 0.1 mg/l, lead (Pb(NO3)2) - 0.1 mg/l, and chromium (K2Cr2O7) - 0.1 mg/l. Morphological, statistical and immunohistochemical (GPX-1) research methods were used. Long-term (90-days) intake of heavy metal salts mixture in the body of experimental animals brought about development of the general adaptation syndrome, the stage of chronic stress "subcompensation" in the pineal gland. Morphological rearrangements were of nonspecific polymorphic nature as severe hemodynamics disorder in the organ, impairment of vascular wall morphology, development of tissue hypoxia and oxidative stress, accompanied by processes of accelerated apoptosis in part of pinealocytes, by a significant decrease in glutathione peroxidase level in the organ and reactive astrogliosis as a response to the damaging agent's action. Along with the negative changes in the pineal gland, a compensatory-adaptive processes with signs of functional stress also occurred. A sufficiently high degree of glutathione peroxidase activity in 39% of pinealocytes located perivascularly, active adaptive glial reaction and activation of synthetic processes in some pinealocytes were also observed.


Subject(s)
Metals, Heavy , Pineal Gland , Rats , Animals , Salts , Glutathione Peroxidase , Metals, Heavy/toxicity
4.
Surg Radiol Anat ; 44(10): 1355-1359, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36175768

ABSTRACT

PURPOSE: An unusual unilateral origin and course of the prevertebral part of the right vertebral artery and anomalous course of the right inferior thyroid artery was observed during dissection of the neck of a cadaver. METHODS: An accidental finding in the cadaver within the anatomical dissection was assessed. RESULTS: The right vertebral artery originated a nonstandard from brachiocephalic trunk and travelled in the anterior cervical region, along the longus colli muscle in front of the transverse processes from C7 to C4, and it entered the transverse foramen of C3. During its course, the position of the right inferior thyroid artery varied: it turned medially and passed posterior to the vertebral vessels and later curved inferomedially to its termination. Additionally, the left vertebral artery of the same cadaver arose directly from the subclavian artery and entered the transverse foramen at C6, and the left inferior thyroid artery passed anterior to the vertebral artery. CONCLUSION: Variation in the vertebral artery and inferior thyroid artery alone have been reported, but a combined variation is rare. The anatomical information from this study will be useful during dissection, angiography, endovascular surgery, thyroidectomy and non-invasive procedures in the cervical region.


Subject(s)
Subclavian Artery , Vertebral Artery , Humans , Vertebral Artery/diagnostic imaging , Vertebral Artery/abnormalities , Subclavian Artery/abnormalities , Brachiocephalic Trunk , Thyroid Gland/blood supply , Cadaver , Cervical Vertebrae
5.
Medicina (Kaunas) ; 58(2)2022 Feb 16.
Article in English | MEDLINE | ID: mdl-35208621

ABSTRACT

Background and Objectives: Nowadays colorectal carcinoma (CRC) is one of the most common causes of death in patients with malignant neoplasms worldwide. Our work aimed to determine the possible involvement of glutathione peroxidases 4 and 8 (GPx4 and GPx8) in this specific tumor process. Materials and Methods: The expression of GPx4 and GPx8 in 58 specimens of human colorectal cancer tissues and normal tissues was detected by the indirect immunohistochemical method under a light microscope. Statistical analysis was done by Chi-squared test. Histological findings were compared with data such as gender, age, tumor grade, histotype and lymph nodes alteration. Results: In all specimens of healthy tissue the presence of both, GPx4 and GPx8, was detected in the cytoplasm of epithelial cells. On the other hand, a positive immunohistochemical reaction against GPx4 only in 41.4% and against GPx8 only in 29.3% of human colorectal adenocarcinoma specimens were observed. Any significant difference between the presence of GPx and the age, the gender of the patient, tumor grade, histotype of cancer and the lesion of regional lymph nodes has not been detected. Conclusions: Our foundation could mean, that GPx4 and GPx8 have no important role in CRC pathogenesis, but the loss of these enzymes probably indicates a serious pathological process ongoing in the large intestine. To our knowledge, this is the first paper describing GPx8 presence in human colorectal carcinoma.


Subject(s)
Antioxidants , Colorectal Neoplasms , Glutathione Peroxidase/metabolism , Humans , Peroxidases/metabolism , Slovakia/epidemiology
6.
J Int Med Res ; 49(10): 3000605211050185, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34648377

ABSTRACT

Ameloblastoma is a benign odontogenic tumor characterized by slow growth causing painless facial swelling. The tumor can behave locally aggressively, and may have direct destructive effects on the surrounding soft and hard tissues. This paper reports the unique case of a female patient with giant ameloblastoma of the mandible. Computed tomography (CT) revealed an enormous swelling of the left side of the face, resorption of the affected hemi-mandible, left maxilla, and tissues of the temporal, infratemporal, and pterygopalatine fossae. Pressure from the tumor resulted in displacement and destruction of the facial skeleton, upper aero-digestive tract structures, and some structures of the neck. The patient was treated by radical hemimandibulectomy with removal of the tumorous mass. Precise knowledge of the anatomical structures, and their locations and topographical relationships is required in the diagnosis and treatment plan for each surgical procedure in cases of giant ameloblastoma. CT imaging can be used to determine the extent and exact location of the lesion, revealing other important details that may help in selecting appropriate treatment.


Subject(s)
Ameloblastoma , Ameloblastoma/diagnostic imaging , Ameloblastoma/surgery , Female , Head , Humans , Mandible , Neck , Tomography, X-Ray Computed
7.
Biology (Basel) ; 10(9)2021 Sep 04.
Article in English | MEDLINE | ID: mdl-34571749

ABSTRACT

The aim of this study was to detect carbonic anhydrase IX (CAIX) and survivin in the colorectal adenocarcinoma cells of the Slovakian population. We used an indirect three-step immunohistochemical method with DAB staining for the localization of the proteins and investigation their expression. We compared their expression with expression in healthy colorectal tissue. In 74 tissues of colorectal adenocarcinomas, 42% showed CAIX positivity and 20% showed survivin positivity. Brown membrane immunostaining was visible in CAIX-positive tumors. Survivin-positive tumors had strong brown cytoplasmic immunostaining. Co-expression of both proteins was present in five specimens (7%). The samples of normal colorectal tissue (without carcinoma) were CAIX-negative and survivin-negative. We also applied the Chi-squared test for evaluation statistically significant association between the expression of proteins and selected clinical and histopathological parameters. We did not find any statistically significant correlations between CAIX or survivin expression and sex of patients, the grade of the tumor, nodal status and presence of metastasis (p > 0.05). The fact that all samples of normal colorectal tissue were CAIX- and survivin-negative could lead to the possibility of using these two proteins as potential tumor diagnostic markers. On the basic of the available publications and data, we suggest that CAIX and survivin could be negative independent prognostic markers of colorectal cancer, which could affect response to therapy.

8.
Int J Mol Sci ; 22(12)2021 Jun 14.
Article in English | MEDLINE | ID: mdl-34198613

ABSTRACT

Breast cancer is the most common cancer in females. The aim of this study was to determine the effect of paclitaxel (PTX) and doxorubicin (DOX) therapy on the ßIII-tubulin, carbonic anhydrase IX (CA IX), and survivin expression in chemically-induced rat mammary tumors. Animals with induced mammary carcinogenesis were randomly divided into treatment groups and an untreated group. The total proportion of tumors, the proportion of carcinoma in situ (CIS), and invasive carcinoma (IC) were evaluated. Protein expression in tumor tissue was determined using IHC. Statistical analysis of the data, evaluated by Fisher-exact test and unpaired t-test. Significantly increased levels of proteins in the tumor cells were confirmed using the IHC method for all studied proteins. The expression of ßIII-tubulin, CA IX, and survivin increased significantly after treatment with both cytostatics (PTX and DOX). Depending on the type of tumor, a significant increase in all proteins was observed in IC samples after PTX treatment, and CA IX expression after DOX treatment. In CIS samples, a significant increase of ßIII-tubulin and survivin expression was observed after a DOX treatment. The results suggest that ßIII-tubulin, survivin, and CA IX may be significant drug resistance markers and the clinical regulation of their activity may be an effective means of reversing this resistance.


Subject(s)
Carbonic Anhydrase IX/metabolism , Doxorubicin/therapeutic use , Mammary Neoplasms, Animal/drug therapy , Mammary Neoplasms, Animal/metabolism , Paclitaxel/therapeutic use , Survivin/metabolism , Tubulin/metabolism , Animals , Doxorubicin/pharmacology , Female , Paclitaxel/pharmacology , Rats, Sprague-Dawley
9.
Int J Mol Sci ; 22(10)2021 May 13.
Article in English | MEDLINE | ID: mdl-34068371

ABSTRACT

This study aimed to describe glutathione peroxidase 4 (GPx4) in rat oocytes, preimplantation embryos, and female genital organs. After copulation, Sprague Dawley female rats were euthanized with anesthetic on the first (D1), third (D3), and fifth days of pregnancy (D5). Ovaries, oviducts, and uterine horns were removed, and oocytes and preimplantation embryos were obtained. Immunohistochemical, immunofluorescent, and Western blot methods were employed. Using immunofluorescence, we detected GPx4 in both the oocytes and preimplantation embryos. Whereas in the oocytes, GPx4 was homogeneously diffused, in the blastomeres, granules were formed, and in the blastocysts, even clusters were present mainly around the cell nuclei. Employing immunohistochemistry, we detected GPx4 inside the ovary in the corpus luteum, stroma, follicles, and blood vessels. In the oviduct, the enzyme was present in the epithelium, stroma, blood vessels, and smooth muscles. In the uterus, GPx4 was found in the endometrium, myometrium, blood vessels, and stroma. Moreover, we observed GPx4 positive granules in the uterine gland epithelium on D1 and D3 and cytoplasm of fibroblasts forming in the decidua on D5. Western blot showed the highest GPx4 levels in the uterus and the lowest levels in the ovary. Our results show that the GPx4 is necessary as early as in the preimplantation development of a new individual because we detected it in an unfertilized oocyte in a blastocyst and not only after implantation, as was previously thought.


Subject(s)
Blastocyst/enzymology , Embryo Implantation , Embryonic Development , Gene Expression Regulation, Developmental , Gene Expression Regulation, Enzymologic , Oocytes/enzymology , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Animals , Blastocyst/cytology , Endometrium/enzymology , Female , Male , Oocytes/cytology , Ovary/enzymology , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Pregnancy , Rats , Rats, Sprague-Dawley , Uterus/enzymology
10.
Int J Mol Sci ; 21(17)2020 Aug 31.
Article in English | MEDLINE | ID: mdl-32878231

ABSTRACT

This study aimed to detect the presence of glutathione peroxidase 8 (GPx8) in rat during preimplantation period of pregnancy. Females were killed on first (D1), third (D3), and fifth (D5) day of pregnancy. The presence of GPx8 in embryos was detected under the confocal microscope, the presence of GPx8 in genital organs was confirmed immunohistochemically, and the amount of GPx8 was determined using densitometry. We found that GPx8 is dispersed in the cytoplasm of oocytes, while after fertilization, it is concentrated in granules. From 4-cell stage till blastocyst, GPx8 reaction was found in the perinuclear region. In the ovary, GPx8 was seen in granulosa-lutein cells, in plasma of blood vessels, and inside Graafian follicles. In oviduct, GPx8 was detected in the plasma and in the extracellular matrix (ECM). Moreover, epithelial cells of isthmus were positive. In uterus, GPx8 was observed in the uterine glands, in the plasma, and in ECM. On D5, the enzyme disappeared from the uterine glands and appeared in fibroblasts. Densitometry revealed that the highest amount of GPx8 was on D1 and subsequently declined. To our knowledge, this is the first paper describing GPx8 presence in the oocytes, preimplantation embryos, and female genital organs in mammals. Our results improve the understanding of antioxidant enzymes presence during pregnancy in defense against oxidative stress, which is considered to be one of the main causes of infertility.


Subject(s)
Embryo, Mammalian/metabolism , Embryonic Development , Gene Expression Regulation, Developmental , Genitalia, Female/metabolism , Oocytes/metabolism , Peroxidases/metabolism , Animals , Embryo, Mammalian/cytology , Female , Genitalia, Female/cytology , Oocytes/cytology , Peroxidases/genetics , Pregnancy , Rats , Rats, Sprague-Dawley
11.
Med Sci Monit ; 24: 5422-5426, 2018 Aug 04.
Article in English | MEDLINE | ID: mdl-30076780

ABSTRACT

BACKGROUND Studies on monoamine oxidase B (MAO-B) expression in renal cell carcinoma (RCC) are lacking. This study focused on the immunohistochemical evaluation of MAO-B in RCC. MATERIAL AND METHODS Sixty-three RCC samples were compared on basic clinical and histopathological parameters, including histopathological type and tumor grade. RCC samples were divided according to the histopathological type into 2 groups: conventional type (51 samples) and other types (12 samples). For MAO-B detection, a standard immunohistochemical procedure was employed. RESULTS In healthy kidney samples, MAO-B was detected predominantly in tubules. Fifty-two cancer tissue samples were MAO-B negative and 11 tissue samples were MAO-B low positive. Enzymes were detected only in the cytoplasm. We did not find any significant correlation between the percentage of positive MAO-B specimens and nuclear grade. Additionally, Fisher's test did not reveal any difference in numbers of positive and negative MAO-B samples between the 2 RCC types (P>0.05). CONCLUSIONS From our results, it was clear that MAO-B expression played no significant role in stimulation of renal cancer development. We found that MAO-B occurred only in 19% of kidney tumors and that the positivity of protein expression was low. Moreover, it seems that the disappearance of this enzyme in RCC is a consequence of replacement of healthy tissue by cancer cells. On the other hand, one can assume that the loss of MAO-B expression could be associated with severe pathological processes in the kidney.


Subject(s)
Carcinoma, Renal Cell/pathology , Monoamine Oxidase/metabolism , Monoamine Oxidase/physiology , Adult , Aged , Carcinoma, Renal Cell/metabolism , Female , Humans , Immunohistochemistry/methods , Kidney/pathology , Kidney Neoplasms/pathology , Male , Middle Aged
12.
Eur J Pharmacol ; 788: 21-28, 2016 Oct 05.
Article in English | MEDLINE | ID: mdl-27292162

ABSTRACT

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the activity and localization of superoxide dismutases (SODs) and catalase (CAT) in rat testis. After 30 days of intraperitoneal administration of either saline (control) or R-(-)-deprenyl dissolved in saline at concentrations of 0.0025mg/kg (low dose of deprenyl, LDD) or 0.25mg/kg (high dose of deprenyl, HDD), males were killed by thiopental, and their testes were collected. We found that deprenyl administration significantly increased the activity of antioxidant enzymes, and this effect varied by dosage. LDD caused significant elevation of all monitored enzymes, but HDD did not increase the activity of SOD2. Employing immunohistochemistry, we detected enzymes predominantly in Leydig cells (SOD1, SOD2, CAT), in late spermatids and residual bodies (SOD1, SOD2), and in primary spermatocytes (SOD2). Histopathological examination did not reveal testicular damage in experimental groups compared to control. Deprenyl proved to be a potent stimulator of antioxidant enzymes in rat testes; therefore, it could be used in the therapy of male infertility. On the other hand, it is crucial to choose a proper dose, since lower dose was more competent compared to a dosage that was one hundred times higher.


Subject(s)
Antioxidants/metabolism , Catalase/metabolism , Selegiline/administration & dosage , Selegiline/pharmacology , Superoxide Dismutase/metabolism , Testis/drug effects , Testis/metabolism , Animals , Male , Rats , Rats, Wistar , Testis/cytology , Testis/enzymology
13.
Eur J Pharmacol ; 754: 148-52, 2015 May 05.
Article in English | MEDLINE | ID: mdl-25725114

ABSTRACT

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the reproductive parameters of rat males. After 30 days of intraperitoneal administration of saline or 0.0025mg/kg (10(-5)mol/l) of R-(-)-deprenyl dissolved in saline, males were mated with females of the same strain. Subsequently, animals were killed by thiopental, and their blood and sperm were collected. We found that epididymis of males exposed to R-(-)-deprenyl had higher sperm count (P<0.05), and females who mated with these males gave birth to a greater number of offspring (P<0.05) compared to control. The blood of experimental animals contained higher levels of testosterone (P<0.05), FSH (P<0.01), and total antioxidants (P<0.01). We did not detect sperm DNA fragmentation in control or in experimental males. Interestingly, round spermatids were often observed inside seminiferous tubules of experimental animals, but obviously without any negative consequences on male fertility. Our findings could be verified on a sample of human male volunteers treated for infertility, because human organism tolerate higher doses of R-(-)-deprenyl, which is a selective inhibitor of monoamine oxidase B employed in our experiment and used in the therapy of Parkinson׳s disease, rather well.


Subject(s)
Monoamine Oxidase Inhibitors/adverse effects , Reproduction/drug effects , Selegiline/adverse effects , Animals , Antioxidants/metabolism , DNA Fragmentation/drug effects , Epididymis/drug effects , Female , Fertility/drug effects , Follicle Stimulating Hormone/blood , Luteinizing Hormone/blood , Male , Rats , Spermatozoa/drug effects , Testosterone/blood
14.
Acta Histochem ; 116(8): 1390-8, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25258012

ABSTRACT

We detected MRP1 (multidrug resistance-associated protein 1) and GSTp1 (glutathione-S-transferase p1) protein expression in samples of non-small cell lung cancer (NSCLC) and our results were compared to basic clinicopathological parameters. The indirect immunohistochemical method was used for localization of monitored proteins. A total of 135 tissue samples of NSCLC were characterized according to histopathological type of tumor. Next, we compared our results with basic clinicopathological parameters (histopathological type of tumor, tumor grade and TNM stage of disease). In MRP1 and GSTp1 positive tumor cells, strong brown cytoplasmic immunostaining was visible. In our set of samples 71% showed MRP1 positivity, while according to histopathological type the squamous cell carcinoma reached the highest level of positivity (76%). Our GSTp1 results showed that similarly to MRP1, 70% of samples were GSTp1 positive. According to histopathological type the adenocarcinoma samples showed the highest GSTp1 expression (77%). For precise statistical evaluation the Kruskal-Wallis, Chi-square and Mann-Whitney tests were used. We did not find any statistically significant correlations between MRP1 and clinicopathological parameters. In the group of GSTp1, by Mann-Whitney test we found a statistically significant correlation between GSTp1 and histological grade (p=0.025) in adenocarcinoma samples. As this was only one group of statistically significant correlation we wanted to confirm this finding. For this we applied also Chi-square test which revealed no statistically significant dependence (p=0.077). No statistically significant relation was seen in the coexpression of both proteins (p=0.753). Despite this, the majority of samples simultaneously expressed MRP1 and GSTp1 proteins. In conclusion, our results show that MRP1 and GSTp1 proteins represent independent prognostic features in NSCLC. Nevertheless, the clinical outcome in individual patients is often difficult to predict. Identification of the factors that characterize the resistant cases would permit immediate treatment of the patients with alternative therapeutic approaches.


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Glutathione S-Transferase pi/metabolism , Lung Neoplasms/metabolism , Multidrug Resistance-Associated Proteins/metabolism , Humans , Immunohistochemistry , In Vitro Techniques
15.
Article in English | MEDLINE | ID: mdl-23073516

ABSTRACT

BACKGROUND: Investigation of p53 immunoreactivity in formalin-fixed paraffin-embedded tissues of normal renal tissue and renal cell carcinoma with respect to histopathologic subtype and nuclear grade of RCC. METHODS: 42 tissue sections of RCC and 5 samples of normal renal tissue were stained for p53 expression using immunohistochemical assay. The results were analyzed in relation to nuclear grade and histopathologic subtype. RESULTS: In total, p53 expression was found to be 4 to 5 times higher (30.8%) in other types of RCC than in the clear-cell type of RCC (6.9%). Further, there was no statistically significant difference in p53 overexpression among the histopathologic subtypes (P>0.05, P=0.063). No association was found between the expression of p53 and nuclear grade (P>0.05, P=0.17). Interestingly, our study also showed weak cytoplasmic positivity in renal tubular epithelium. CONCLUSION: Our findings suggest that p53 might play an important role in tumour development or progression and it might be used as a new predictor and therapeutic target for RCC.


Subject(s)
Carcinoma, Renal Cell/chemistry , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/chemistry , Kidney Neoplasms/pathology , Tumor Suppressor Protein p53/analysis , Female , Humans , Kidney/chemistry , Male , Middle Aged , Neoplasm Grading
16.
Acta Histochem ; 115(3): 273-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22925562

ABSTRACT

One of the best characterized resistance mechanisms of human cancer is multidrug resistance (MDR) mediated by P-glycoprotein (Pgp/MDR1) and multidrug-resistant related protein (MRP1). In addition to Pgp/MDR1 and MRP1, p53 inactivation or mutation might play a relevant role in therapeutic failure. This study involved 25 children (17 girls and 8 boys) aged 7 months to 10 years treated for unilateral Wilms' tumor. 25 tissue samples of Wilms' tumor and 5 samples of normal human kidneys were obtained from the Department of Pathological Anatomy, Jessenius Faculty of Medicine in Martin, Slovak Republic. We used an indirect immunohistochemical method to determine expression of Pgp/MDR1, MRP1 and wild-type p53 in 25 tissue samples of nephroblastoma. The minority of nephroblastoma specimens showed positivity for both MDR proteins, as well as for wild-type p53. 24% of tissue samples revealed positive results for Pgp/MDR1, 48% for MRP1 and 8% for wild-type p53. Furthermore, our study showed a statistically significant difference between p53 and MRP1 protein expression (p<0.01), but not between p53 and Pgp/MDR1 (p>0.05). No correlation was found between the expression of both multidrug resistance proteins (Pgp/MDR1 and MRP1) and the expression of wild-type p53. Immunohistochemical detection of the expression of MDR proteins and wild-type p53 at the time of diagnosis might assist in choosing specific chemotherapeutics to improve prognosis and therapy.


Subject(s)
Kidney Neoplasms/metabolism , Multidrug Resistance-Associated Proteins/analysis , Tumor Suppressor Protein p53/analysis , Wilms Tumor/metabolism , ATP Binding Cassette Transporter, Subfamily B/analysis , ATP Binding Cassette Transporter, Subfamily B/biosynthesis , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Infant , Kidney Neoplasms/pathology , Male , Multidrug Resistance-Associated Proteins/biosynthesis , Tumor Suppressor Protein p53/biosynthesis , Wilms Tumor/pathology
17.
Med Sci Monit ; 18(12): BR482-6, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23197227

ABSTRACT

BACKGROUND: Studies of the biochemical properties of MAO-A (monoamine oxidase) are numerous, but the information about determination of MAO-A in human normal and tumour renal tissue is limited. Our objectives in the present study were to determine the localization of MAO-A in normal kidney and level of expression of this protein in tumour kidney. MATERIAL/METHODS: Enzyme immunohistochemical method was chosen for detection of MAO-A in 63 clinical samples of all histopathological types of RCC (renal cell carcinoma). Our results were compared to basic clinical and histopathological parameters such as histopathological type and tumour grade. We also compared MAO-A expression between normal and tumour tissue samples. RESULTS: We confirmed the elevated expression of MAO-A in high-grade tumours of renal cell carcinoma specimens. The percentage of MAO-positive samples progressively increased from 9% in grade 2 to 45% in grade 3. We also noted high levels of MAO-A immunoreactivity in epithelial cells of proximal tubules in normal renal tissue. MAO-A was absent or very low in epithelial cells of distal tubules and glomerular capsule, as well as in endothelial cells of renal vessels. CONCLUSIONS: Taken together, our results and findings of other studies show that MAO-A expression in high-grade tumours may have a direct role in maintaining a dedifferentiated phenotype and promoting aggressive behaviour. The ability of clorgyline (an MAO-A inhibitor) to counteract oncogenic pathways and promote differentiation suggests that MAO-A inhibitors, which have been used for many years in clinical practise for treating neurological disorders, could be therapeutic options for advanced stages of tumours.


Subject(s)
Carcinoma, Renal Cell/enzymology , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/enzymology , Kidney Neoplasms/pathology , Monoamine Oxidase/metabolism , Aged , Cytoplasm/pathology , Female , Humans , Immunohistochemistry , Kidney/enzymology , Kidney/pathology , Male , Middle Aged , Neoplasm Grading
18.
Med Sci Monit ; 17(12): BR354-63, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22129893

ABSTRACT

BACKGROUND: This study aimed to examine the relationship between XRCC1, p53 and MDR1 protein, along with polymorphisms of their genes and their prognostic values in breast cancer. The following clinical and pathological parameters were evaluated: histopathological type of tumor, grade, stage, Her2/neu expression, ER, PR positivity and involvement of regional lymph nodes. MATERIAL/METHODS: Expression of proteins was determined in 39 samples of breast cancer by immunohistochemistry. Nucleotide polymorphisms were analyzed by PCR-RFLP. For statistical analysis, chi-square test (Yates), Fisher's exact test, and correlation test were used to analyze the data. RESULTS: The highest protein expression was immunohistochemically found in MDR1 protein, with 54% of samples testing positive. In addition, the evaluation of MDR1 expression revealed higher positive immunoreactivity in lobular (LIC) and other types of tumor in comparison to ductal (DIC) type. The expression of p53 and XRCC1 protein was equal, but lower compared to MDR1, both testing positive in 36% of all tissue samples. Comparison of XRCC1 protein and histopathological type of tumor revealed that DIC and LIC types were mostly XRCC1-negative, while other types, papillary and mucinous were more likely to be XRCC1-positive. Interestingly, when evaluating LIC samples separately, a negative correlation between the Her2/neu and expression of XRCC1 was detected. Apparently, all Her2/neu-positive samples were XRCC1-negative (6/86%). The correlation test indicated a negative correlation between Her2/neu-positive samples and XRCC1-negative specimens (r = 1, p < 0.05). Statistical analysis did not reveal a correlation of p53 expression with clinical and pathological parameters. Similarly, no statistically significant difference was found between the tested polymorphisms and protein expression. CONCLUSIONS: We did not find statistically significant correlation between tested polymorphisms and their protein expression.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Breast Neoplasms/genetics , DNA-Binding Proteins/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Polymorphism, Genetic , Tumor Suppressor Protein p53/genetics , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , DNA-Binding Proteins/metabolism , Female , Gene Expression Regulation, Neoplastic , Genes, Neoplasm , Humans , Immunohistochemistry , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Prognosis , Receptor, ErbB-2/metabolism , Tumor Suppressor Protein p53/metabolism , X-ray Repair Cross Complementing Protein 1
19.
Tumori ; 97(1): 79-85, 2011.
Article in English | MEDLINE | ID: mdl-21528669

ABSTRACT

OBJECTIVES: p53 and XRCC1 protein expression were evaluated in 54 samples of nonsmall cell lung cancer. PATIENTS AND METHODS: The immunohistochemical method was used for detection of the monitored proteins. Tissue samples were divided according to histopathological tumor type. The results were then compared with basic clinical and histopathological parameters (histopathological type, nuclear grade and TNM tumor stage IA, IB). RESULTS: Statistically significant correlations were found between histopathological type and p53 expression, since P < 0.05 (P = 0.015). Comparing p53 expression with grade resulted in a strong positive correlation (P < 0.0396, R2 = 0.9223). The percentage of p53-positive tumors progressively increased from 0% in grade 1 to 75% in grade 4. No correlation was found between p53 expression and tumor stage. In case of XRCC1, the highest level was found in squamous cell lung carcinoma, where 71% of samples was positive. In case of large cell carcinoma samples, it was 67%, and in adenocarcinoma 52% of samples showed XRCC1 immunoreactivity. No statistically significant correlation was found between histopathological type, grade or early stage (IA, IB) of non-small cell lung cancer and expression of XRCC1 protein profile without neoadjuvant therapy. CONCLUSIONS: We found a statistically significant correlation between p53 expression and histopathological tumor type. It is possible that stabilized p53 protein plays an important role in the development of squamous and large cell carcinoma. Our findings also suggest that p53 expression cumulates with the dedifferentiation of cancer cells. It is possible that the expression of XRCC1 is not fixed and could be changed by the status of cancer cells and in relation to therapy. Relevant data about pre- versus post-chemotherapy and XRCC1 expression are needed to evaluate the influence of XRCC1 on drug resistance.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Non-Small-Cell Lung/chemistry , Carcinoma, Non-Small-Cell Lung/pathology , DNA-Binding Proteins/analysis , Lung Neoplasms/chemistry , Lung Neoplasms/pathology , Tumor Suppressor Protein p53/analysis , Adenocarcinoma/chemistry , Adenocarcinoma/pathology , Adult , Aged , Carcinoma, Large Cell/chemistry , Carcinoma, Large Cell/pathology , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Predictive Value of Tests , Prognosis , X-ray Repair Cross Complementing Protein 1
20.
Reprod Sci ; 17(8): 734-41, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20595704

ABSTRACT

We have evaluated the impact of chronic administration of clorgyline, a potent monoamine oxidase A inhibitor and a former antidepressant, on the preimplantation embryo development in Wistar rats. Females were injected intraperitoneally daily for 30 days with saline (control animals), or with a low-dose clorgyline (LDC, 0.1 mg/kg per d) or with a high-dose clorgyline (HDC, 1 mg/kg per d). Embryos were isolated on day 5 of pregnancy and urine was collected by puncture of the urinary bladder. The number of embryos per female did not differ between experimental groups and control, but we have recorded a decreased number of embryos in HDC group compared to LDC (P < .05). We have found that LDC significantly reduced the presence of healthy embryos and increased the presence of the degenerated embryos (P < .001). The administration of the LDC resulted in the lowest cell number in blastocysts. We have observed significantly increased serotonin levels in HDC group compared to both control (P < .05) and LDC animals (P < .01). Norepinephrine (NE) levels in both experimental groups were significantly elevated compared to controls. Dopamine levels did not differ between groups (P > .05). We speculate that lesser negative effect of HDC compared to LDC on the preimplantation embryo development could be the consequence of the lower NE levels and/or elevated serotonin levels. Potential mechanisms mediating clorgyline-induced impaired preimplantation embryo development are proposed.


Subject(s)
Antidepressive Agents/pharmacology , Biogenic Monoamines/urine , Clorgyline/pharmacology , Embryonic Development/drug effects , Monoamine Oxidase Inhibitors/pharmacology , Animals , Antidepressive Agents/administration & dosage , Antidepressive Agents/adverse effects , Blastocyst/drug effects , Blastocyst/pathology , Clorgyline/administration & dosage , Clorgyline/adverse effects , Dose-Response Relationship, Drug , Female , Monoamine Oxidase Inhibitors/administration & dosage , Monoamine Oxidase Inhibitors/adverse effects , Pregnancy , Rats , Rats, Wistar
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