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The state of the microcirculatory bed remains one of the determining factors in course of inflammatory bowel diseases (IBD). The presence of small foci of ischemia could realize in dystrophic-necrobiotic consequences, which can also underlie the development or strengthening of the inflammatory process. Based on above, the goal of our study was to determine the impact of the development of mucosal ischemia in the colon on the activity of proliferative processes during inflammation. The study was performed on 12 adult WAG rats with modeling IBD by oral administration of 2.5% solution Dextran Sulfate Sodium. Serial slides of the colon where made with stained with hematoxylin and eosin, according to Rego, immunohistochemical examination (IHC) to Ki67. Volume of ischemic area and Ki67 expression were detected. Statistical comparison was performed. Inspection microscopy in the DSS experimental group determined alterative-desquamative changes in the surface epithelium and epithelium of intestinal glands (crypt); diffuse polymorphic cellular infiltration in the mucous membrane, which in some places spread to the submucosal base, that are morphological manifestations of IBD. Foci of ischemia had been detected in that group with 13.09±0.67% volume as just microfocal changes were observed in intact animals (p < 0.05). Detection of proliferative activity depending on ischemic signs was realized in different level of Ki67 expression. So, lowest level of Ki67 was estimated in mucosa above ischemia (18.06±3.33%). Most pronounced expression of Ki67 was observed in IBD group in area which no connected with ischemia and was even 57.71±4.68% (p < 0.05). Ki67 was strongly expressed in epithelial cells of the colon both in intact tissue and in modeling IBD with significant increasing expression more than twice in inflammatory group (p < 0.05) but spreading of activity process was uneven. Collation of slides with ICH and Rego staining realized in estimation of strong negative correlation between Ki67 expression and ischemia (r=-0.819).
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Enfermedades Inflamatorias del Intestino , Ratas , Animales , Antígeno Ki-67/metabolismo , Microcirculación , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal/metabolismo , IsquemiaRESUMEN
The manifestation of the side cardiotoxic effect of anthracycline antibiotics limits their use in the treatment of malignant processes in some patients. The review analyzes the main causes of the susceptibility of cardiomyocytes to the damaging effect of anthracyclines, primarily associated with an increase in the processes of free radical oxidation. Currently, research is widely carried out to find ways to reduce anthracycline cardiotoxicity, in particular, the use of cardioprotective agents in the complex treatment of tumors. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to improve the function and metabolism of the cardiovascular system under various pathological impacts, therefore, it is proposed to use them to reduce cardiotoxic complications of chemotherapy. Statins exhibit direct (hypolipidemic) and pleiotropic effects due to the blockade of mevalonic acid synthesis and downward biochemical cascades that determine their cardioprotective properties. The main point of intersection of the pharmacological activity of anthracyclines and statins is the ability of both to regulate the functioning of small GTPase from the Rho family, and their effect in this regard is the opposite. The influence of statins on the modification and membrane dislocation of Rho proteins mediates the indirect antioxidant, anti-inflammatory, endothelioprotective, antiapoptotic effect. The mechanism of statin inhibition of doxorubicin blockade of the DNA-topoisomerase complex, which may be important in preventing cardiotoxic damage during chemotherapy, is discussed. At the same time, it should be noted that the use of statins can be accompanied by adverse side effects: a provocation of increased insulin resistance and glucose tolerance, which often causes them to be canceled in patients with impaired carbohydrate metabolism, so further studies are needed here. The review also analyzes data on the antitumor effect of statins, their ability to sensitize the tumor to treatment with cytostatic drug. It has been shown that the relationship between anthracycline antibiotics and statins is characterized not only by antagonism, but also in some cases by synergism. Despite some adverse effects, statins are one of the most promising cardio- and vasoprotectors for use in anthracycline cardiomyopathy.
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Miocitos Cardíacos , Antraciclinas/efectos adversos , Antibacterianos , Cardiotoxicidad , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversosRESUMEN
OBJECTIVE: To investigate microsatellite instability in smooth muscle tumors of uncertain malignant potential and to compare the results with clinical and morphological data. SUBJECT AND METHODS: Histological and immunohistochemical studies were conducted in 26 patients aged 30-63 years (mean age, 37 years) with leiomyomatosis; which revealed intravenous leiomyomatosis in 20 cases, metastasizing leiomyoma in 2, disseminated peritoneal leiomyomatosis in 3, and smooth muscle tumor of uncertain malignant potential in 1 case. Microsatellite instability was studied by fragment analysis on a genetic analyzer using a test system of six markers: D10S1146, D10S218, D10S24, D10S1213, D3S1295, and D9S942. RESULTS: Microsatellite repeat changes characteristic of leiomyosarcomas (heterozygosity loss and/or microsatellite instability in at least one locus studied) were found in 6 patients; all were clinically and morphologically diagnosed as having intravenous leiomyomatosis. In 3 of these 6 cases, leiomyomatosis was accompanied by metastases to the lungs and spread to the peritoneum; heart damage was noted in 2 cases. The data analysis did not allow identification of any significant clinical and morphological criteria for this group. CONCLUSION: Leiomyomatosis is not a transitional form from benign leiomyoma to leiomyosarcoma, as evidenced by the difference in the status of molecular markers. Analysis of molecular genetic changes in DNA from tumor tissue samples cannot categorically clarify the nature of the disease by identifying the signs of genetic instability; however, there is a need for further accumulation of experience in studying tumors of this group and in identifying the possible association with disease prognosis.
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Leiomiomatosis , Leiomiosarcoma , Tumor de Músculo Liso , Neoplasias Uterinas , Adulto , Femenino , Humanos , Leiomiomatosis/patología , Leiomiosarcoma/patología , Persona de Mediana Edad , Pronóstico , Tumor de Músculo Liso/patología , Neoplasias Uterinas/patologíaRESUMEN
AIM: Assessment of diagnostic significance of informativeness and security of ultrasonography with contrast enhancement drug SonoVue in the diagnosis of Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS AND METHODS: The pilot conducted a prospective study which involved 15 patients with inflammatory bowel disease (IBD). All patients gave written consent to participate in the study and processing of personal data. The study included adult patients with an established diagnosis of UC and CD, with proven clinical activity of the disease. Activity was evaluated based on clinical and laboratory data on the scale of best (CDAI >150) for patients with CD and on a scale of Trulove-Witts (2-3 stage) and the Mayo index (DAI) for patients with UC. All the patients underwent colonoscopy with biopsy, ultrasound examination of abdominal cavity organs with the study of the vascularization of the intestinal wall (color Doppler, power Doppler, contrast study). RESULTS: The use of contrast showed additional features in the instrumental evaluation of activity of inflammatory process, identification of complications and assessment of prognosis. CONCLUSION: The results of ultrasound of the bowel with contrast can be used to assess the activity and stage of disease in patients with UC or CD.
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Colitis Ulcerosa , Enfermedad de Crohn , Ultrasonografía , Adulto , Colitis Ulcerosa/diagnóstico por imagen , Enfermedad de Crohn/diagnóstico por imagen , Humanos , Proyectos Piloto , Estudios ProspectivosRESUMEN
BACKGROUND: The prevalence of anemia in hospitalized seniors has been linked to poor functional outcomes, increased mortality, and longer hospital stays, and has been associated with advancing age, male sex, and cognitive impairment. Despite the potential for complications, anemia often is undiagnosed and/or untreated in seniors. OBJECTIVES: Examine (a) the distribution of anemia diagnosis and treatment in patients in a rehabilitation hospital, and (b) patients' cognitive and functional outcomes. DESIGN: Retrospective chart review of medical records of 132 patients. MEASUREMENTS: The presence and type of anemia were determined based on the World Health Organization criteria for adults and Smith's algorithm, respectively. The Mini-Mental State Exam (MMSE) was used to measure cognitive status. Functional impairment was assessed using the Functional Independence Measure (FIM). RESULTS: The mean age of the sample was 82.20 years, with 68% being female, the mean MMSE and FIM scores were 23.95 (SD = 4.3) and 82.82 (SD = 15.63), respectively. In total, 67% of males and 46% of females were anemic (P < 0.05). The majority of anemias were caused by nutritional deficiencies. The percent of anemic females receiving treatment for anemia was higher (71%) than the percent of anemic males (46%) (P < 0.05). The majority of the patients improved functionally regardless of anemia status. CONCLUSIONS: Results indicated that a substantial number of patients in a geriatric hospital were anemic, with significant percentage going untreated. The overall improvement in patients' functional abilities suggests that remedial rehabilitation of frail seniors has an impact on recovery during their hospital stay.
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The article discusses results of the structural and functional analysis of molecular genetic abnormalities in various malignant tumors. Investigations have discovered more than 20 new markers for sporadic breast cancer. Several of them formed the test system, allowing the diagnosis with a specificity of 100%. Appearance of TMPRSS2/ERG4 chimeric gene is a frequent tumor-specific event, its expression is correlated with more aggressive forms of prostate cancer, may serve as a molecular marker for tumor cells and androgen assessment of tumor response to hormonal therapy. The effective systems for the early diagnosis of cervix and endometrium cancer were developed as well. Mutations in the VHL, deletions of chromosome 3 and methylation of several genes can predict the course and selection of effective therapy of clear cell kidney cancer, a number of molecular markers were identified for early diagnosis and prognosis of recurrence of bladder cancer. For diagnosis, prognosis and treatment of brain tumors we developed an effective complex system of markers. Protocol of molecular genetics investigation reveals the cause of the disease by more than 90% of patients with retinoblastoma. In order to study abnormal methylation in tumor genomes an innovative technology AFLOAT has been developed that allows to efficiently identify new markers with diagnostic value. Test systems of molecular genetic and epigenetic markers for early diagnosis and prognosis as well as for cancer therapy optimization have shown to be effective, have been approved for use in clinical practice and are being introduced into practical healthcare.
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Biomarcadores de Tumor/genética , Diagnóstico Precoz , Pruebas Genéticas/métodos , Neoplasias , Terapia Combinada , Genoma , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia , PronósticoRESUMEN
It was found that in an osteoporotic bone the fraction of nanosized pores decreases, the mineral phase amorphizes, hydrated shells around mineralized particles of the bone matrix thicken, and adhesion forces increase. This contributes to the formation of water clusters similar to bulk water clusters compared to the healthy bone tissue and leads to the accumulation of more viscous liquid with increased intermolecular interaction forces in the pores of the bone matrix. Given this, the rates of chemical reactions proceeding in the water phase of ultrathin channels of general parts of collagen fibrils decrease. Ultimately, nanopores of collagen-apatite interfaces lose, to a certain extent, the capability of catalyzing the hydroxyapatite crystallization.
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The t(X;18)(p11;q11) translocation has been shown to be the specific alteration for synovial sarcomas. The translocation leads to production of chimeric protein SYT/SSX by fusion of SYT and SSX genes involved. The expression analysis of SYT/SSX1 and SYT/SSX2 chimeric transcripts was performed in formalin-fixed soft tissue tumour specimens and the diagnostic validity of immunohistochemistry, FISH and RT-PCR methods was compared. The chimeric transcripts were detected in 12 from 16 synovial sarcomas: 7 SYT/SSX1 and 5 SYT/SSX2 fusion variants; by fluorescence hybridization in situ (FISH) the translocation was found in 13 from 16 sarcoma samples. As synovial sarcoma represents a diagnostically challenging group, genetic analysis of translocations and chimeric transcripts is an extremely useful confirmatory diagnostic tool providing higher sensitivity than immunohistochemistry markers do.
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Biomarcadores de Tumor/genética , Cromosomas Humanos Par 18/genética , Proteínas de Fusión Oncogénica/genética , Patología Molecular/métodos , Sarcoma Sinovial/genética , Neoplasias de los Tejidos Blandos/genética , Adolescente , Adulto , Anciano , Secuencia de Bases , Biomarcadores de Tumor/análisis , Cromosomas Humanos Par 18/química , Cartilla de ADN/química , Cartilla de ADN/genética , Femenino , Formaldehído , Expresión Génica , Fusión Génica , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas de Fusión Oncogénica/análisis , Adhesión en Parafina , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/patología , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patología , Fijación del Tejido , Transcripción Genética , Translocación GenéticaRESUMEN
Cytotoxic properties of a liposomal form of the HLDF6 hexapeptide, representing an HL-60 cell differentiation factor fragment, have been studied on a murine primary lymphosarcoma cell culture. It is established that the liposomal HLDF6 peptide is capable of inhibiting proliferation and enhancing death of the cells of both LS and RLS lymphosarcoma strains distinguished by their sensitivity to cytostatic agents. The effect of the preparation is determined by its antiproliferative and apoptogenic actions on the cells. Free HLDF6 peptide showed a lower cytotoxic activity with respect to the tumor cells as compared to the liposomal preparation.
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Antineoplásicos/farmacología , Proteínas de Neoplasias/química , Oligopéptidos/farmacología , Animales , Apoptosis , Línea Celular Tumoral , Liposomas , Ratones , Oligopéptidos/administración & dosificación , Oligopéptidos/químicaRESUMEN
This paper presents the results of an analysis the chimeric genes FUS/CHOP and EWS/CHOP in patients diagnosed as having liposarcoma in order to make a differential diagnosis in both soft tissue tumors and various variants of liposarcoma. Liposarcomas were found in 5 of 7 cases of primary tumors: 4 chimeric transcripts of the FUS/CHOP type (5-2), a variant of alternative splicing of the FUS/CHOP type (5-2) with depletion in 14 p.n. anda rare variant of the EWS/CHOP type (7-2). Fluorescence in situ hybridization (FISH) confirmed translocations in the tumor samples with the chimeric genes being detected. Reverse transcription-polymerase chain reaction and FISH revealed no chimeric genes specific to myxoid sarcoma in a group of patients with other variants of liposarcoma. Thus, the findings support the strict specificity of the chimeric genes FUS/CHOP and EWS/CHOP for myxoid liposarcoma and the expression of these genes in most tumors of this type.
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Regulación Neoplásica de la Expresión Génica , Liposarcoma/metabolismo , Liposarcoma/patología , Proteínas de Fusión Oncogénica/biosíntesis , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Proteína EWS de Unión a ARN/biosíntesis , Proteína FUS de Unión a ARN/biosíntesis , Factor de Transcripción CHOP/biosíntesis , Adulto , Anciano , Empalme Alternativo , Diagnóstico Diferencial , Femenino , Humanos , Liposarcoma/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
We have examined the existence of intratumoral genetic heterogeneity for LOH on chromosomes 9p21 (p16, p15, p19), 13p14 (RB1), 10q23 (PTEN), 17p (TP53), microsatellite instability and K-RAS point mutations on four different segments of sporadic colorectal cancers. The intratumoral genetic heterogenity was detected in 9/11 (81%) colorectal adenocarcinomas and morphologically validated. These results show that colorectal cancer is highly heterogeneous for these molecular markers. Furthermore, the analysis has shown the order (succession) of the appearance of these molecular anomalies during tumorigenesis on sporadic CRC, and supposed, that K-RAS point mutations, and anomalies of p16-RB1-cyclin D pathway could occur before LOH on 10q23 (PTEN) and microsatellite instability during tumor progression.
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Adenocarcinoma/genética , Cromosomas Humanos/genética , Neoplasias Colorrectales/genética , Pérdida de Heterocigocidad , Proteínas de Neoplasias/genética , Mutación Puntual , Adenocarcinoma/metabolismo , Anciano , Inestabilidad Cromosómica/genética , Cromosomas Humanos/metabolismo , Neoplasias Colorrectales/metabolismo , Ciclina D , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Ciclinas/genética , Ciclinas/metabolismo , Femenino , Humanos , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Proteína Oncogénica p21(ras)/genética , Proteína Oncogénica p21(ras)/metabolismo , Proteína de Retinoblastoma/genética , Proteína de Retinoblastoma/metabolismoRESUMEN
We have developed a modification of methylation sensitive arbitrarily primed PCR, one of the methods of differentially methylated CpG islands in cancer cells genomes screening. Seven genes undergoing abnormal epigenetic regulation in breast cancer, SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, CACNG4 and PSMF1, have been identified by this method. Methylation and loss of expression frequencies were evaluated for each of the identified genes on 100 paired (cancer/morphologically intact control) breast tissue samples. Significant frequencies of abnormal methylation were detected for SEMA6B, BIN1, and LAMC3 (38%, 18%, and 8% correspondingly). Methylation of the above genes was not characteristic for morphologically intact breast tissues. Downregulation of SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, CACNG4 and PSMF1 in breast cancer was as frequent as 44-94% by real-time PCR expression assay. The most pronounced functional alterations were demonstrated for SEMA6B and LAMC3 genes, which allows recommending their inclusion into the panels of carcinogenesis diagnostic panels. Fine methylation mapping was performed for the genes most frequently methylated in breast cancer (SEMA6B, BIN1, LAMC3), providing a fundamental basis for the development of effective methylation tests for these genes.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Islas de CpG , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Genes Relacionados con las Neoplasias , Secuencia de Bases , Epigénesis Genética , Femenino , Expresión Génica , Humanos , Datos de Secuencia MolecularRESUMEN
The results of an investigation of the RB 1, p16 and p53 genes in sporadic breast cancer through molecular and immunohistochemical studies are presented.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Ciclo Celular/genética , Genes p16 , Proteína de Retinoblastoma/genética , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Femenino , Eliminación de Gen , Humanos , Inmunohistoquímica , Repeticiones de Microsatélite , Proteína p14ARF Supresora de Tumor/genéticaRESUMEN
The article discusses an approach of high school professors to teaching physicians during raising the level of physicians skill.
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Curriculum , Atención a la Salud , Educación Médica Continua/métodos , Médicos , Enseñanza , Médicos/normas , Enseñanza/métodos , UcraniaRESUMEN
TNR/11q#1 is a polymorphic trinucleotide (GCC)n repeat located within the minimal region of the 11q deletion in chronic lymphocytic leukemia (CLL). It was recently shown that certain alleles of this repeat are associated with a worse prognosis in CLL patients. To investigate the role of TNR/11q#1 variants as risk-modifying factors in leukemogenesis, we conducted a case-control study on 113 acute lymphotic leukemia (ALL) patients, 82 CLL patients and 146 healthy controls of Russian origin. Comparison of allele and genotype distributions in the control, ALL and CLL groups, performed by Fisher's exact test with two-sized P-value, showed significant decrease in the presence of the GCC(6) allele in the ALL and CLL groups compared to controls. Moreover, 'rare' alleles GCC(7-8) and GCC(13-14) were significantly overrepresented in the ALL group versus controls. We found that CLL risk genotypes were those with both alleles containing more than 6 GCC repeats (P = 0,0212, odds ratio = 1,68 (95% CI, 1,121...2,531)). ALL risk genotypes include three allele combination variants: 1) both alleles containing more than 6 GCC repeats (P = 0,0019, odds ratio = 1,756 (95% CI 1,223...2,502)); 2) one of the alleles containing 7 or 8 repeats (P = 0,0155, odds ratio = 18,22 (95% CI 1,93...136.37)); 3) one of the alleles containing more than 12 repeats (P = 0,0209, Odds ratio = 2,599 (95% CI 1,161...5,815)). Association of certain alleles and genotypes of the TNR/11q#1 repeat with both acute and chronic lymphocytic leukemia suggests the presence of a cancer related gene, involved in a wide spectrum of neoplasia, in the vicinity of this repeat.
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Alelos , Cromosomas Humanos Par 11/genética , Predisposición Genética a la Enfermedad , Leucemia Linfocítica Crónica de Células B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Repeticiones de Trinucleótidos/genética , Adulto , Estudios de Casos y Controles , Niño , Genotipo , Humanos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The review considers the epigenetic defects and their diagnostics in several hereditary disorders and tumors. Aberrant methylation of the promoter or regulatory region of a gene results in its functional inactivation, which is phenotypically similar to structural deletion. Screening tests were developed for Prader-Willi, Angelman, Wiedemann-Beckwith, and Martin-Bell syndromes and mental retardation FRAXE. The tests are based on allele methylation analysis by methylation-specific or methylation-sensitive PCR. Carcinogenesis-associated genes (RB1, CDKN2A, ARF14, HIC1, CDI, etc.) are often methylated in tumors. Tumors differ in methylation frequencies, allowing differential diagnostics. Aberrant methylation of tumor suppressor genes occurs in early carcinogenesis, and its detection may be employed in presymptomatic diagnostics of tumors.
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Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Neoplasias/diagnóstico , Neoplasias/genética , Impresión Genómica , Humanos , Repeticiones de TrinucleótidosRESUMEN
It is shown that in a number of cases the summing up of military hospital work has the formal character. It consists the following: for the week (30.0 +/- 5.4%), for the day (18.0 +/- 2.4%), for the month (15.0 +/- 2.1%) and for the quarter (12.0 +/- 1.6%); for the education period (5.0 +/- 1.1%) and for the school year (3.0 +/- 0.9%). The experts consider that the main causes of chiefs' formal attitude to summing-up are the following: lack of sufficient volume of necessary information (25%), high official load (20%), low professional level of the chiefs dealing with the given problem (15%), other causes (40%).