RESUMO
Analysis of HER2 status of the tumor and expression of mTOR, AMPK showed a decrease in mTOR mRNA level in HER2+ tumors in comparison with HER- status. The appearance of PD-L1+ transformed cells in the tumor was associated with increased expression of the LC3B gene and elevated content of the corresponding protein measured after treatment.
Assuntos
Adenocarcinoma , Proteínas Associadas aos Microtúbulos , Neoplasias Gástricas , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antineoplásicos/uso terapêutico , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Farmacológicos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Resultado do TratamentoRESUMO
The peculiarities of gastric cancer development associated with the expression levels of components of the AKT/mTOR signaling cascade and PD, PD-L1, PD-L2 have not yet been identified. We revealed the fundamental changes in the expression AKT/mTOR and PD receptors and their ligands associated with dissemination of gastric cancer. An increase in the mRNA level of all components of this cascade was demonstrated. The expression of mTOR and AKT decreased against the background of enhanced expression of PTEN phosphatase. The increase in the expression of PD-1 receptors and PD-L1 and PD-L2 ligands was most pronounced in patients with distant metastases.
Assuntos
Antígeno B7-H1/genética , Proteína 2 Ligante de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/genética , Serina-Treonina Quinases TOR/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antígeno B7-H1/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Masculino , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas c-raf/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
In untreated rectal cancer patients, the chymotrypsin-like activity of proteasomes in tumor tissue was 3-fold higher than that in conventionally normal tissue, which is explained by up-regulation of expression of immunoproteasomes and total pool of proteasomes. After neoadjuvant chemoradiation therapy, expressions of the total pool of proteasomes and immunoproteasomes in the tumor as well as the relative ratios of these indices to those in conventionally normal tissue were smaller by 1.4-3.3 times in comparison with the untreated patients. These changes were paralleled with pronounced (4.5-fold) down-regulation of proteasome activity in the tumor and a 3.7-fold decrease of activity ratio for the proteasomes in tumor and in conventionally normal tissue. The number of immunoproteasome subunits and the chymotrypsin-like activity of proteasomes can be viewed as potential markers to prognosticate effectiveness of neoadjuvant chemoradiation therapy in rectal cancer patients.
Assuntos
Cisteína Endopeptidases/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Neoplasias Retais/genética , Neoplasias Retais/terapia , Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Quimiorradioterapia/métodos , Cisteína Endopeptidases/imunologia , Raios gama/uso terapêutico , Expressão Gênica , Humanos , Terapia Neoadjuvante/métodos , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/imunologia , Complexo de Endopeptidases do Proteassoma/efeitos da radiação , Neoplasias Retais/patologia , Neoplasias Retais/cirurgiaRESUMO
Chymotrypsin-like activity of proteasomes and total calpain activity were studied in patients with stage T2-4N0-3M0 gastric cancer and stage T2-4N0-2M0-1 colorectal cancer. Activities of proteasomes and calpains in gastric and colorectal cancer tissues were higher than in the corresponding normal tissues. Changes in activities of proteasomes and calpains were mutually related. The appearance of lymphogenic metastases in gastric cancer was associated with the increase in calpain activity. The progress of colorectal cancer and development of lymphogenic and hematogenic metastases were associated with elevated chymotrypsin-like activity of proteasomes.
Assuntos
Calpaína/metabolismo , Quimotripsina/metabolismo , Neoplasias Colorretais/metabolismo , Metástase Linfática/fisiopatologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Neoplasias Gástricas/metabolismo , Fluorometria , Humanos , Estatísticas não ParamétricasRESUMO
All-trans-retinoic acid (ATRA) is the main biologically active metabolite of retinol (vitamin A) that is required for the regulation of such processes as embryogenesis, tissue differentiation, proliferation, and others. Multiple alcohol, retinol and retinaldehyde dehydrogenases (ADHs, RDHs and RALDHs) as well as aldo-keto reductases (AKRs) catalyze the biosynthesis of retinoic acid in humans. For many normal and neoplastic tissues, the key ATRA-synthesizing enzymes remain unknown. We identified ATRA-generating genes that are expressed in normal and malignant gastric tissues using the transcriptomic database analysis. Quantitative changes in the expression levels of these genes in gastric cancer were determined by semi-quantitative RT-PCR and real-time PCR. Significant decreases in the mRNA levels of genes encoding enzymes that catalyze the reversible oxidation/reduction of retinol and retinaldehyde (ADH4, ADH1B, ADH1C, RDHL, AKR1B10, AKR1B1, and RDH12), as well as the oxidation of retinaldehyde (RALDH1) were revealed in most of the tumor samples. The sharp reduction in the expression levels of genes encoding the key enzymes that convert retinol and retinaldehyde to retinoic acid could lead to a significant decrease in the content of ATRA--the transcriptional regulator of many genes, which in turn can lead to a dysregulation of cell proliferation/differentiation and initiate cancer development.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Tretinoína/metabolismo , Vitamina A , Aldeído Desidrogenase/biossíntese , Aldeído Desidrogenase/genética , Família Aldeído Desidrogenase 1 , Diferenciação Celular/genética , Proliferação de Células , Transformação Celular Neoplásica/genética , Humanos , Retinal Desidrogenase/biossíntese , Retinal Desidrogenase/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Vitamina A/genética , Vitamina A/metabolismoRESUMO
Comparison of protein expression in intestinal and diffuse stomach tumors by 2D gel electrophoresis led to identification of three proteins (SOD2, S100A6, and TXN), which are overexpressed in tumors as compared to normal controls. It was shown, that overexpression of proteins SOD2 and TXN occurs much more frequently in diffuse tumors than in intestinal ones. A control panel of eleven proteins overexpressed in stomach tumors has been selected based on the data of comparative 2D analysis described in the literature. Bioinformatics search for mRNAs encoding proteins from the control panel in Oncomine database (which contains the results of determination of mRNA transcription level in tumor vs. normal samples) demonstrated the coincidence of proteomic and transcriptomic data for seven out of 11 proteins.
Assuntos
Biomarcadores Tumorais/biossíntese , Proteínas de Ciclo Celular/biossíntese , Proteínas de Neoplasias/biossíntese , Proteômica , Proteínas S100/biossíntese , Neoplasias Gástricas/metabolismo , Superóxido Dismutase/biossíntese , Tiorredoxinas/biossíntese , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/genética , Biologia Computacional , Eletroforese em Gel Bidimensional , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Intestinais/genética , Neoplasias Intestinais/metabolismo , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Proteína A6 Ligante de Cálcio S100 , Proteínas S100/análise , Proteínas S100/genética , Neoplasias Gástricas/genética , Superóxido Dismutase/análise , Superóxido Dismutase/genética , Tiorredoxinas/análise , Tiorredoxinas/genéticaRESUMO
An analysis of the end results of combined treatment for stage III non-small cell lung cancer, stage III gastric cancer and soft-tissue sarcoma has been carried out. Radical surgery was supplemented with intraoperative radiation therapy (IORT) with a single dose of 10-20 Gy. The radiation source was an original small-size betatron installed in the operating room. IORT did not interfere with wound healing nor did it involve increase in postoperative lethality. The 5-year survival rates for lung cancer patients who received IORT or surgery alone were 34.1 and 24.4%, respectively. The same indices for gastric cancer in IORT patients were 34.2% while in surgical cases--21.7%. Two-year non-relapse survival in patients with soft-tissue sarcomas showed a rise due to reduced recurrence incidence in irradiated areas.
