Bases biológicas del cáncer: una propuesta de contenidos mínimos para las carreras de la salud / Biological bases of cancer: a proposal of minimum contents for health schools

El cáncer constituye la segunda de causa de muerte a nivel mundial y se estima será la primera, superando a las cardiovasculares. El estudio de sus bases moleculares ha permitido el desarrollo de la quimioterapia clásica, como de nuevas terapias biológicas. Si bien estos avances han redundado en un aumento en la sobrevida, no ha impactado en una menor incidencia de los casos. Esto último se debe, en parte, al desconocimiento de los múltiples factores carcinogénicos existentes y los efectos de sus interacciones para cada uno de los tumores. En este sentido, es interesante notar que, en los currículos de las escuelas de salud de las universidades chilenas, el cáncer u oncología como tal, no constituye una cátedra en sí misma, siendo sus contenidos tangencialmente abordados en distintos momentos de la formación; en biología celular, medicina interna y cirugía, entre otros. Con estos antecedentes, el propósito de este trabajo es ofrecer un propuesta sencilla y accesible para los estudiantes, respecto de los contenidos que, a nuestro juicio, son esenciales para comprender las bases biológicas de esta enfermedad y enfrentar con mejores conocimientos el ciclo clínico posterior. A continuación, el lector se encontrará con principios fundamentales de la biología humana normal (como el ciclo celular y el dogma central de la biología molecular), que permiten obtener una visión global de los mecanismos fisiológicos cuya desregulación conlleva a una neoplasia maligna. Luego se entregarán algunas definiciones amplias en relación con los conceptos de neoplasia, tumor benigno y maligno. Para, finalmente, abordar las principales etapas que permiten el desarrollo del cáncer; (i) iniciación, (ii) promoción y (iii) progresión. En esta última, se profundizará por separado, en angiogénesis, degradación de la matriz extracelular, migración y evasión de la respuesta inmune. Este trabajo no aborda materias relacionadas con la hipótesis metabólica del cáncer.

Cancer constitutes the second most common cause of death worldwide and is expected to become the leading one, even above cardiovascular diseases. The understanding of the cellular and molecular basis of cancer has led not only to the proper development of chemotherapy but also of target therapies. Although these advances are related with improved survival rates among cancer patients, it has poorly impacted its incidences. In this regard, the lack of knowledge regarding the impact that the several carcinogenic factors and their interactions have on different types of cancers may explain at least in part the difficulties to reduce incidence rates. However, is worth noticing that in several health schools of chilean universities, cancer does not constitute a formal course, being only partially approached during other courses, such as cell biology, internal medicine, and surgery. Thus, the aim of our work is to provide students a simple and resumed manuscript about essential topics necessary to understand the biological basis of cancer. First, the reader will find some fundamentals about human biology including the cell cycle and the central dogma of molecular biology, which offers an overview of the physiological mechanisms leading to malignant neoplasia. Then, we will provide current definitions of neoplasia, benign and malignant tumors are provided. Finally, the different stages of tumor progression will be approached to allow the understanding of cancer development. These stages include (i) initiation, (ii) promotion, and (iii) progression. For the last one, metastasis, angiogenesis, extracellular matrix degradation, migration, and immune evasion will also be addressed. This work will not consider the metabolic hypothesis of cancer.

Genes involucrados en el cáncer pulmonar / Genes involved in lung cancer

Introducción: El cáncer pulmonar constituye un serio problema de salud mundial por su elevada prevalencia y mortalidad. En la carcinogénesis pulmonar están implicados oncogenes y genes supresores tumorales, que en una compleja interacción con factores ambientales favorecen la transformación cancerosa. Objetivo: Describir los principales genes implicados en el cáncer pulmonar. Métodos: Se buscaron referencias en las bases de datos PubMed Central, Annual Reviews y SciELO. Se revisaron preferentemente los artículos originales, las revisiones bibliográficas, las revisiones sistemáticas y los metaanálisis de los últimos cinco años. Análisis e integración de la información: En la carcinogénesis pulmonar se involucran los oncogenes JUN, FOS, ABL1, BRAF, RAF1, GNAS, KRAS, NRAS, HRAS, CSF 1R, MYC, EGFR, MET, ALK, CCNE1, DDR2, ERBB3, FGFR1, MDM2, ROS1, SOX2 y TP63 y los genes supresores tumorales TP53, CDKN2A, CDKN1A, RB1, CDK2AP1, ATM, ERCC2, BRCA1, CCND1, STK11, PDLIM2, PTEN, ARID1A, ASCL4, CUL3, EP300, KEAP1, KMT2D, NF1, NOTCH1, RASA1, ETD2 y SMARCA4. El conocimiento de la genética molecular del cáncer pulmonar es importante para la identificación de biomarcadores diagnósticos y pronósticos más eficaces y para el diseño de fármacos diana sobre genes específicos(AU)

Introduction: Lung cancer is a serious global health problem due to its high prevalence and mortality. Lung carcinogenesis involves oncogenes and tumor suppressor genes which interact in complex manners with environmental factors, paving the way for the cancerous transformation. Objective: Describe the main genes involved in lung cancer. Methods: References were searched for in the databases PubMed Central, Annual Reviews and SciELO. Particular attention was paid to original papers, bibliographic reviews, systematic reviews and meta-analyses published in the last five years. Data analysis and integration: Lung carcinogenesis involves the oncogenes JUN, FOS, ABL1, BRAF, RAF1, GNAS, KRAS, NRAS, HRAS, CSF 1R, MYC, EGFR, MET, ALK, CCNE1, DDR2, ERBB3, FGFR1, MDM2, ROS1, SOX2 and TP63, and the tumor suppressor genes TP53, CDKN2A, CDKN1A, RB1, CDK2AP1, ATM, ERCC2, BRCA1, CCND1, STK11, PDLIM2, PTEN, ARID1A, ASCL4, CUL3, EP300, KEAP1, KMT2D, NF1, NOTCH1, RASA1, ETD2 and SMARCA4. Knowledge about the molecular genetics of lung cancer is important to identify more efficient diagnostic and prognostic biomarkers and to design targeted drugs for specific genes(AU)

Relationship between the expression of proto oncogene c-Ski in non-small cell lung cancer and the early metastasis of tumor / 中国基层医药

Objective To explore the relationship between the expression of proto oncogene c -Ski in non-small cell lung cancer and the early metastasis of tumor .Methods From January 2015 to July 2016 , 97 patients with non -small cell lung cancer in the People's Hospital of Pingxiang were selected .The protein expression of c-Ski was examined with immunohistochemical SP and real -time PCR,the results were observed and compared.Results The positive rates of c-Ski protein and mRNA level in non -small cell lung cancer tissues and adjacent normal tissues were 18.6％and 79.4％,respectively,the difference was statistically significant (χ2 =71.80, P<0.01).The positive rate of c-Ski protein expressed in non -small cell lung cancer patients was related with age , clinical stage and pathologic classification ,the differences were statistically significant (χ2 =8.40,4.72,15.71,all P<0.05).Conclusion c-Ski may play an important role in the invasion and metastasis of non -small cell lung cancer,which can be used as a potential therapeutic target for non -small cell lung cancer in the future .

Advances of long non-coding RNA UCA1 in cancers / 国际肿瘤学杂志

Long non-coding RNA urothelial carcinoma associated 1 (UCA1) is initially discovered and named in bladder cancer tissue,which is highly expressed in multi types of tumor tissues,such as bladder cancer,ovarian cancer,lung cancer,suggesting that UCA1 acts as oncogene.UCA1 is confirmed to regulate tumor cell proliferation,apoptosis,invasion and migration,which plays an important role in the occurrence and development of cancers.UCA1 is expected to become a new biomarker for diagnosis,prognosis and drug susceptibility,which may be a promising therapeutic target of cancer.

Nódulo de mama como primeira manifestação de lipossarcoma mixóide metastático: relato de caso / Breast mass as first clinical manifestation of metastatic liposarcoma myxoid:case report

Os autores descrevem o relato do caso de uma paciente de 37 anos, do sexo feminino que apresentou, como primeira manifestação de um lipossarcoma metastático, a presença de nódulo de mama direita, localizado em quadrante supero lateral, palpável, fibroelástico, móvel e indolor de cerca de 3 cm. A avaliação através de exames de imagem (Ultrassonografia mamaria E – USG e mamografia e core biopsy) revelou nódulo de mama com características benignas e histologia compatível com fibroadenoma. Foi indicada a remoção cirúrgica do nódulo por desejo da paciente Como antecedente, a paciente apresentava tratamento cirúrgico com exerese de lipossarcoma mixóide intramuscular de coxa esquerda grau histológico 2 – pT2 pNx – associada a radioterapia. O achado anatomopatológico definitivo demonstrou que o nódulo de mama se tratava de um lipossarcoma mixóide de 3,8 cm com índice mitótico de 4/10 CGA cujo perfil imunohistoquímico com pesquisa de citoqueratinas AE1/AE3, proteína S100, CD34, receptores de estrogênio e progesterona e Ki 67 confirmou a histologia. Posteriormente, com estes achados, procedeu-se ao estadiamento completo com cintilografia óssea, tomografias computadorizadas de abdome, tôrax e Sistema Nervoso Central (SNC) que revelaram doençca plurimetastática. A glândula mamária pode ser sede de metástases de inúmeras neoplasias imaturas e propomos-nos a descrever a ocorrencia de um lipossarcoma mixoide metastático de coxa com sua apresentação clinica inicial mimetizando um nódulo benigno de mama.

The authors describe a female’s patient case report who presented, as first clinical presentation of metastatic myxoid liposarcoma, the presence of breast mass. We describe a case report of a 37 years old female patient who presented, as unique clinical manifestation, a right breast mass of 3.8 cm, palpable, fibroelastic, mobile and painless. The screening exams (breast ultrasound, mammograms, fine needle aspiration) revealed a benign breast mass (birads 2) and we performed a lumpectomy required by the patient. As medical records, the patient presented a surgical treatment for intramuscular left thigh’s myxoid liposarcoma, histologic grade 2 – pT2pNx – plus local radiation. The final pathology analysis, after surgery, revealed that the breast mass was a metastatic myxoid liposarcoma, 3,8 cm of diameter, mitotic index 4/10 with immunohistochemical profile (CK AE!/AE3, S100 protein, estrogen and progesterone receptors and Ki 67) compatible with this diagnosis. With these findings, we made a complete screening (abdomen, thorax and CNS CT-scan, bone scintigraphy) that revealed extensive metastatic disease. The mammary glands can be primary site of various metastatic diseases, so we describe the occurrence of breast mass as first manifestation of metastatic thigh’s myxoid liposarcoma.

Association of serum HER-2 level with metabolic syndrome in middle-aged and elderly population / 第二军医大学学报

Objective To investigate the association of circulating HER-2 level with metabolic syndrome in middle-aged and elderly population. Methods We conducted a population-based cross-sectional study with 687 participants aged 40 years or older from a community in Chongming District, Shanghai, China. Serum HER-2 levels were measured using ELISA. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adutt Treatment Panel III (NCEP ATP III) criteria for Asian-Americans. Results After adjusting for other influencing factors, we found that the participants with metabolic syndrome (n=370) had significantly higher HER-2 level compared with the control group (n=317) ([12. 4 ± 2. 3] ng/mL vs [8. 2 ± 1. 6] ng/mL, P<0. 001). The serum HER-2 level increased (P<0. 001) with the accumulation of the metabolic syndrome components. After adjusting for potential risk factors, multiple logistic regression analysis showed that the highest quartile of serum HER-2 was associated with increased risk of metabolic syndrome, with a fully adjusted odds ratio (OR) of 1. 35 (95' confidence interval [CI] - 1. 14-2. 31), P<0. 001). Conclusion Serum HER-2 is independently associated with metabolic syndrome in middle-aged and elderly Chinese in this study.

Breviscapine effects on the expression of proliferating cell nuclear antigen and c-fos in the testis of diabetic rat models / 中国组织工程研究

BACKGROUND:Breviscapine has been shown to impact the reproductive capacity in rats with type 2 diabetes mel itus, but few reports concerned its mechanism of action. OBJECTIVE:To study the effects of breviscapine on proliferating cel nuclear antigen and proto-oncogene c-fos expression in testis of type 2 diabetes mel itus rats. METHODS:Total y 36 healthy male rats were randomly divided into control group, model group and breviscapine group with 12 rats in each group. In the model group and breviscapine group, rat models of type 2 diabetes mel itus were established by continuous intraperitoneal injection of streptozotocin. Blood glucose reaching 16.7 mmol/L in rats was considered as the standard of model induction. In the control group, rats were given an equal volume of citrate buffer solution by single intraperitoneal injection. In the breviscapine group, rats were administered breviscapine 10 mg/(kg?d) for 4 consecutive weeks by intraperitoneal injection. Rats in the other two groups were injected with an equal volume of physiological saline at the same time point. RESULTS AND CONCLUSION:After 4 weeks of intervention, serum testosterone testing, immunohistochemistry and PCR results showed that serum testosterone levels, proliferating cel nuclear antigen, c-Fos protein and mRNA expression:control group>breviscapine group>model group (P<0.05);blood glucose concentration:the control group

Syndrome in question

Costello syndrome (CS) is a rare genetic disorder, first described by Costello in 1971, caused by mutations in the HRAS proto-oncogene. Clinical findings include facial dysmorphism, skin disorders, cognitive impairment, cardiac and musculoskeletal defects. There is an increased risk of malignancies in these patients, due to the proto-oncogene mutation, and also sudden death secondary to heart disease. We report a case with characteristic phenotype, highlighting the peculiar skin changes.

Expression and clinical significance of Wnt-5a gene in primary hepatocellular carcinomas / 中国医师杂志

Objective To investigate the expression of Wnt-5a gene in primary hepatocellular carcinoma (HCC) and to expose its role and clinical significance in the development of HCC.Methods Real time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed in 26 fresh HCC samples and the corresponding para-carcinoma tissues to detect mRNA expression of Wnt-5a gene.Wnt-5a protein was detected with immunohistochemical method in paraffin embedding tissues of 85 cases of HCCs and the corresponding para-carcinoma tissues,and 15 cases of hepatic cirrhosis.Results RT-PCR analysis showed that Wnt-5a mRNA (0.102 127 ±0.158 620) in the HCC tissues was more than that (0.020 106 ±0.022 075) in the para-carcinoma tissues (P＜0.05).The positive expression rate of Wnt-5a protein in HCC,para-carcinoma,and hepatic cirrhosis tissues were 21.2％ (18/85),81.26％ (69/85),and 86.7％ (13/15),respectively.The positive rate of Wnt-5a was significantly lower in the HCC than in the para-carcinoma and hepatic cirrhosis tissues (P ＜ 0.01).The expression of Wnt-5a was significantly associated with lower tumor node metastasis (TNM) stages and small alpha fetoproteins (AFP) content of blood serum (P ＜0.05).Conclusions The high expression of Wnt-5a mRNA was found in the gene transcription of HCC,while Wnt-5a protein was absent or low in HCC.It was suggested that the roles of Wnt-5a was interfered at the protein level rather than the transcriptional level in the HCC.

Alteraciones moleculares implicadas en la fisiopatogenia del cáncer y su utilidad para la investigación en medicina / Molecular changes involved in physiopathogeny of cancer and their utility for research in medicine

La neoplasia es una enfermedad genética que usa mecanismos de progresión e invasión similares a los de los tejidos normales cuando proliferan. Su aparición se debe a la suma de alteraciones genéticas que facilitan la progresión tumoral por fallos en los mecanismos de senescencia celular y apoptosis. Dentro de las principales alteraciones moleculares destacan la expresión aberrante de oncogenes, genes supresores tumorales, enzimas y factores de transcripción que promueven un ciclo celular anómalo. El objetivo de esta revisión es el de conocer algunos de los cambios moleculares implicados en el inicio, promoción y progresión de las neoplasias, con el fin de tener información de los genes útiles para realizar diagnósticos más tempranos del cáncer, que favorezcan el pronóstico de la enfermedad y que sean útiles para la investigación en biotecnología diagnóstica y en terapia génica.

Neoplasia, considered as a genetic disease that uses progression mechanisms similar to the normal tissues' when proliferates. Its presence is due to genetic alterations that facilitate tumor progression by failures in the mechanisms of cellular senescence and apoptosis. Within the main molecular alterations the most important are: aberrant expression of oncogenes, tumor suppressor genes, enzymes and transcription factors that promote abnormal cell cycle. The main objective of this paper is to review some of the molecular changes involved in the initiation, promotion and progression of neoplasms, in order to have genes useful information for earlier diagnosis of cancer, favoring the prognosis of genes disease, for diagnostic research in biotechnology and gene therapy.

Aerobic exercise affects c-Src mRNA expression and c-Src activity in aortic vascular endothelial cells of spontaneous hypertensive rat models / 中国组织工程研究

BACKGROUND:Proto-oncogene c-Src plays an important role in regulating cardiovascular diseases such as hypertension. At present, there were no studies concerning exercise intervention effects on c-Src expression in aortic endothelial cels so as to regulate hypertension. OBJECTIVE: To observe the effects of aerobic exercise on c-Src mRNA expression and c-Src activity in the aorta blood vessel endothelial cels of spontaneous hypertensive rats. METHODS: A total of 8 male Wistar rats were considered as normal control group. Sixteen spontaneous hypertensive rats were randomly assigned to 8 rats as spontaneous hypertension group and 8 rats as spontaneous hypertension exercise group. Rats in the spontaneous hypertension exercise group carried on 90 minutes unloaded aerobic swimming every day, 6 days a week, for 8 weeks. The rats in the normal control group and spontaneous hypertension group did not swim. Blood pressure of rats was measured once a week. 8 weeks later, the c-Src mRNA expression and c-Src activity were determined in aortic vascular endothelial cels of rats in each group. RESULTS AND CONCLUSION: Compared with spontaneous hypertension group, blood pressure was lower, but c-Src mRNA expression and c-Src activity were significantly higher in the spontaneous hypertension exercise group. The c-Src activity and c-Src mRNA expression were higher in the spontaneous hypertension exercise group than normal control group and spontaneous hypertension group (P < 0.01). Results indicated that aerobic exercise can promote the increase in c-Src activity and c-Src mRNA expression in aortic endothelial cels of spontaneous hypertensive rats.

Pim-3 gene and its related effect / 国际肿瘤学杂志

Pim-3,a new member of the the proto-oncogene pim family which expresses serine and threonine kinase activity,shows a high similar to pim-1 and pim-2 at the function,structure and sequence.Pim-3 plays an important regulative role in the cell cycle transform,cell apoptosis and occurrence of the malignant tumors by phosphorylating numerous specific substrates.

The repair effects of Pim-3 on liver in fulminant hepatic failure rat model / 中华传染病杂志

Objective To investigate the liver repair effects of Pim-3 gene in rat with fulminant hepatic failure (FHF). Methods Thirty-two rats were divided into four groups (eight for each group). Three groups of rats were pretreated with Ringer's solution, vector plasmid or Pim-3 gene recombinant plasmid respectively and, one day later, received intraperitoneal injections with lipopolysacchride (LPS) and D-galactosamine (D-GalN). The fourth group served as normal control.Eight hours after the LPS/D-GalN injection, the liver tissues and blood samples were collected. The contents of serum transaminase was tested by automatic blood biochemistry meter. The morphological changes were observed by light microscopy using hematoxylin and eosin (HE) staining. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β gene expression was detected by reverse transcriptionpolymerase chain reaction(RT-PCR). The serum levels of TNF-α and IL-1β were measured by enzyme linked immunosorbent assay (ELISA), and cell apoptosis by TdT-mediated dUTP nick end labeling (TUNEL) assay. Comparisons between groups were done by analysis of variance. ResultsThe over expressions of Pim-3 gene and reporter gene, green fluorescent protein (GFP) were induced by injection with recombinant plasmid solution.In comparison with the rats retreated with Ringer' s solution or vector plasmid, those pretreated with recombinant plasmid had a lower mortality and lower serum transaminase levels. The injection of recombinant plasmid significantly reduced hemorrhage, necrosis and inflammatory infiltration in the liver. Liver apoptotic index (AI) was dramatically lower in rats treated with recombinant vectors compared to the rats treated with Ringer's solution or vector plasmids [(10. 2±6.9)％ vs (83. 1±12.6) ％ and (79.9±13.4) ％ respectively, P＜0. 01]. In addition, the expression of exogenous Pim-3 gene remarkable inhibited the transcriptions and expressions of TNF-α and IL-1β. ConclusionsPim-3 gene can protect rats from LPS/D-GalN-induced FHF possibly by inhibiting expressions and secretions of inflammatory cytokines, such as TNF-α and IL-13, in liver tissues.

Preparation of the polyclonal antibody against KIAA0649 and its cellular localization / 北京大学学报(医学版)

Objective: To prepare and characterize the polyclonal antibody against KIAA0649 and identify the localization and the functional motif of KIAA0649. Methods: Three polypeptides were synthesized based on the bioinformatics analysis of KIAA0649 protein. New Zealand rabbits were immunized with the mixture of the three KIAA0649 peptides coupled with keyhole limpet hemocyanin ( KLH). The titer of the antisera was detected with ELISA. The antisera were purified with immuno-affinity chromatography when the titer reached 1:10~5. Western blot was performed with the purified antisera on the cell lysates of U2OS cells transfected with either Flag-KIAA0649 or KIAA0649-targeting siRNA. Immunofluorescence was performed with the purified antisera and anti-Flag antibody on the cells transfected with FlagKIAA0649. A series of Flag-K1AA0649 deletion mutants was constructed by PCR cloning. The cellular compartmentation of full-length Flag-KIAA0649 and its deletion mutants were analyzed with immunofluorescence. Results: The results of Western blot and immunofluorescence demonstrated that the antisera from the KIAA0649 polypeptides-immunized rabbits specifically recognized endogenous and exogenous KIAA0649. The full-length Flag-K1AA0649 displayed specific nuclear foci. The Flag-KIAA0649 deletion mutant containing PENF motif showed the same nuclear foci as the full length of Flag-KJAA0649, suggesting that the PENF motif could be the minimum functional motif of KIAA0649. Conclusion: We have obtained anti-KIAA0649 polyclonal antibody which will be useful for further investigation. The PENF motifcould be the minimum functional domain of KIAA0649.

Study on the relationship between CRKL activity and multidrug resistance in leukemia cell lines / 白血病·淋巴瘤

Objective To investigate the role of CRKL activity in leukemia cells with muhidrug resistance and find new factor related to multidrug resistance. Methods By flow cytometry, CRKL activity was compared in K562, HL-60 cells and its resistance cells. The change of CRKL activity was observed in sensitive cells treated with and withdrawal daunorubicin. Results With the comparison of K562, HL-60 sensitive cells, in K562, HL-60 resistant cell lines, the level of CRKL phosphorylation in K562, HL-60 resistance cells treated with daunombicin 72 hours increased markedly. The level of CRKL phosphorylation was time-dependent with chemotherapy drugs, not change of CRKL activity was found in Jurkat ceils.Conclusion The level of CRKL activity is new factor related to muhidrug resistance in leukemia cells.

RET targeted treatment of medullary thyroid carcinoma / 国际肿瘤学杂志

Medullary thyroid carcinoma(MTC), which includes sporadic type and hereditary type, is a kind of malignant tumor in thyroid parafollicular cells. MTC is the common clinical character of the multiple en-docrine neoplasia type 2 (MEN 2), including MEN 2A and MEN 2B, and familial medullary thyroid carcinoma(FMTC). The RET gene encodes a receptor tyrosine kinase, its mutations and polymorphisms can induce acti-vation of the BET tyrosine kinase domain via different signal pathways resulting the genesis of MTC. RET has been used as a target for MTC molecular therapy. However, a clinically useful therapeutic option for treating pa-tients with RET-associated cancer is still not available.

Change in Expression of Keratin and Proto-oncogene Induced by Beta-propiolactone in HaCaT Cell / 대한해부학회지

To investigate the relationship between the morphologic changes and the expression of keratin and proto-oncogene induced by Beta-propiolactone (BPL), we assessed on the expression of keratins (K8, K10, K13) and proto-oncogenes (c-fos, c-jun, c-myc) in human HaCaT cell line. The cells were treated with 0, 0.1, 1 microgram/ml BPL for 2 or 6 hours. Morphologic studies revealed that BPL changed the cells into fibrocyte-shaped, caused highly lobulated nuclei and reduced desmosomes in their number. Findings of immunofluorescence and Northern blotting indicated that BPL consistently decrease expression of K10 representing a normal differentiation marker of keratinocytes, while increasing expression of K8 and K13 associated with a pathologic differentiation. This reagent also up-regulated expression of c-fos and c-jun, and down-regulated expression of c-myc. Together with staining for each keratin or proto-oncogene and DNA content in flow cytometry, BPL increased K8 expression dramatically at S-G2-M phase. The induction of c-Fos at S-G2-M phase appeared within 2 hours, and c-Jun gradually occurred. However, c-Myc was inhibited regardless of phases of cell cycle. In conclusion, these changes caused by BPL demonstrate a close relationship between the morphologic evidence and the altered expression of each keratin and proto-oncogene.

Effects of Gax gene transfection on proto-oncogene expression and proliferation of PASMCs in rats under hypoxia conditions / 中国病理生理杂志

AIM:To explore the effects of Gax gene transfection on expressions of c-fos and c-jun mRNA and proliferation of pulmonary arterial smooth muscle cells (PASMCs) in rat under hypoxia. METHODS: PASMCs were transfected with Gax gene by Ad-Gax. Under normal oxygentention (21% O2) or hypoxia (2.5% O2) for 12 h condition, expressions of Gax mRNA and protein in PASMCs were detected by RT-PCR and immunocytochemistry. The expressions of c-fos and c-jun mRNA were evaluated by RT-PCR. [3H]-TdR incorporation was used to measure the PASMCs proliferation. RESULTS: The Gax overexpression in transfection group was confirmed by RT-PCR and immunocytochemistry. Under normal oxygentention or hypoxia, the c-fos and c-jun mRNA levels in transfection group were lower than those in the non-transfection group, respectively (P

Effect on the expression of proto-onogene c-mpl in megakaryocytes line-HEL by interleukin-13 / 中国病理生理杂志

AIM:To investigate the relevance of the proliferation of megakaryocytic cell line-HEL stimulated by the recombinant human interleukin-13 (IL-13) to the expression of pro-oncogene c-mpl in HEL cells. METHODS: MTT colorimetric assay and reverse transcrition polymerase chain reaction (RT-PCR) are separately used in this study to observe the effect on the proliferation of HEL cells and the expression of c-mpl mRNA in HEL cells by rhIL-13. RESULTS: RhIL-13 stimulated the proliferation of HEL cells and upregulated the expression of c-mpl mRNA in HEL cells. CONCLUSION: Our results suggest that rhIL-13 stimulated the proliferation of HEL cells and provide the evidence that its mechanism is partly because of increasing the pro-oncogene c-mpl expression in HEL cells.

Correlation between intraventricular pressure and early phase proto-oncogene expression in volume overload rats / 中国病理生理杂志

AIM: To investigate the effect of intraventricular pressure change by volume overload (VOL) on expression of proto-oncogene c- fos ,c- jun ,c- myc and egr-1 . METHODS: Left ventricular systolic pressure(LVSP) and left ventricular end diastolic pressure (LVEDP) of rat with VOL induced by aortacaval fistula operation and rats of control group were measured at 30 min, 1, 4, 6, 12 and 48 h after the operation,these mRNAs at the foregoing time points were measured by slot bloting method and quantified with densitometry. RESULTS: Be compared with the control group, VOL rats LVSP decreased ( P 0.05) after the operation.The proto-oncogene expression signals were not detected in the control,negative controls and VOL rats at 30 min after the operation. The c- fos, c- jun and egr-1 mRNA signals appeared earlier,at 1 h, and c- myc mRNA increased later at 4 h.All reached peak value at 4 h and then declined gradually.The c- fos mRNA were not detected at 48 h. The c- myc ,c- 0jun and egr-1 mRNA persisted throught the entire observation period from 1 h to 48 h. CONCLUSIONS: During VOL early phase the overload have effect on expression of the proto-oncogene mRNA,c- fos, c- jun and egr-1 mRNA appear earlier, c- myc later, egr -1,c- jun and c- myc persist longer period, but the expressions do not strengthen with the ventricule wall load increase.This sequential induction pattern may reflect the time course regularity of the proto-oncogenes expression induced by VOL,and indicate the proto-oncogenes expression initiate while the heart load accumulate some extent and duration and the load magnitude may not play a critical role.