RESUMEN
Background: Because lung cancer is the main cause of cancer deaths and lung adenocarcinoma (LUAD) accounts for more than 40% of all lung malignancies, it is essential to develop clinically useful biomarkers for the disease. The aim of this investigation is to assess the potential application of tubulin alpha-1b (TUBA1B) as a biomarker for diagnosing and monitoring the outcome of LUAD. Methods: The clinical data of the LUAD patients was retrospectively analyzed. Immunohistochemistry (IHC) analysis of a tissue microarray containing 90 LUAD cases was implemented to examine the expression of TUBA1B. The protein and mRNA levels of TUBA1B in serum were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) analysis respectively. UALCAN was employed to confirm the expression levels and survival probability of TUBA1B in LUAD patients. Results: Compared to adjacent non-cancerous tissues in the microarray, the expression of TUBA1B in LUAD tissues was much higher. The expression of TUBA1B in LUAD was statistically correlated with lymph node status (P = .031). Moreover, patients with higher TUBA1B expression had shorter overall survival (P < .0001). Furthermore, cox multi-factor analysis also suggested that TUBA1B may be an independent predictor for LUAD prognosis (P = .030). The results of TCGA data analysis by UALCAN were consistent with the microarray results, except for that TUBA1B was also significantly correlated with clinical tumor stages. Protein levels of TUBA1B in serum were obviously elevated in LUAD patients than control (P < .0001), and the area under the ROC curve was 0.99. TUBA1B also showed better sensitivity of 92.9% for LUAD than common clinical biomarkers. Conclusion: TUBA1B may be a non-invasive prognostic and diagnostic biomarker for LUAD patients.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Tubulina (Proteína)/genética , Estudios Retrospectivos , Adenocarcinoma del Pulmón/genética , Pronóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , BiomarcadoresRESUMEN
OBJECTIVE: To investigate the possible causes of abnormal hemoglobin electrophoresis results. METHODS: The hemoglobin electrophoresis results of 5 696 patients in the First Affiliated Hospital of Chengdu Medical College from September 2018 to July 2021 were collected, and the abnormal results and clinical significance were analyzed. RESULTS: The results of 486 patients (accounting for 8.53%) were abnormal, of which 300 cases had increased HbA2, 135 cases had decreased HbA2, 44 cases had increased F alone, and 7 cases had abnormal hemoglobin bands. Among the 486 patients, 246 patients were thalassemia gene positive (the positive rate was 50.62%), including 29 cases of α thalassemia, 208 cases of ß thalassemia and 9 cases of αß thalassemia. Among the patients with elevated HbA2, 68.67% were detected ß thalassemia, 3.00% αß thalassemia, 9.33% were suspected to be caused by macrocytosis, 6.33% by thyroid dysfunction, and 12.67% by uncertainty of the method. Among the patients with reduced HbA2, 21.48% were detected α thalassemia, 60.00% iron deficiency anemia, 8.15% were suspected to be caused by thyroid dysfunction, and 10.37% by uncertainty of the method. Among the patients with elevated F alone, the results of thalassemia gene detection were negative, 40.91% of them were suspected to be caused by macrocytosis, 27.27% by hereditary persistence of fetal hemoglobin, 29.55% by special physiological condition of pregnant women, and 2.27% by hyperthyroidism. Abnormal hemoglobin bands were detected in 7 patients, including 4 cases of hemoglobin D, 2 cases of hemoglobin E, and 1 case of hemoglobin J. CONCLUSION: Thalassemia, iron deficiency anemia, macrocytosis such as megaloblastic anemia and non-severe aplastic anemia, thyroid dysfunction, hereditary persistence of fetal hemoglobin, abnormal hemoglobin diseases, the uncertainty of the method are all important causes of abnormal hemoglobin electrophoresis results. In clinical work, the patient's indicators should be comprehensively analyzed to determine the possible cause.
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Anemia Ferropénica , Hemoglobinas Anormales , Talasemia alfa , Talasemia beta , Humanos , Femenino , Embarazo , Talasemia beta/genética , Hemoglobina Fetal/análisis , Electroforesis de las Proteínas Sanguíneas , Hemoglobina A2/análisis , Hemoglobinas Anormales/análisisRESUMEN
OBJECTIVE: To investigate gene mutation types of thalassemia in the population of this area and the relationship between hematological phenotype and age in ß-thalassemia. METHODS: 1 351 suspected cases of thalassemia were detected in the First Affiliated Hospital of Chengdu Medical College from June 2017 to June 2021. PCR-reverse dot blot hybridization(PCR-RDB) technique was used to detect the common α and ß thalassemia gene types, then the data of MCV, MCH, MCHC and Hb of confirmed cases were collected. The heterozygotes of ß-thalassemia were divided into 0-18 year group, 19-50 year group and >50 year group according to age, and the differences of hematological phenotypes among different groups were compared. RESULTS: Among the detected 1 351 samplesï¼ 523(38.71%) cases were diagnosed as thalassemia, 13 genotypes were detected in 260 cases (19.25%) with α-thalassemia; and 12 genotypes were detected in 252 cases (18.65%) with ß-thalassemia; 9 genotypes were detected in 11 cases with αß thalassemia. It was found that MCV and MCH were increased significantly in 0-18 year group, 19-50 year group and >50 year group, MCHC was highest in 0-18 year group, and Hb was the lowest in the >50 year group, and the difference was statistically significantï¼P<0.05ï¼. CONCLUSION: In this area, --SEA/αα was the major genotype of α-thalassemia, and CD41-42 /N and IVS-II-654/N were the major genotypes of ß-thalassemia. Morever, MCV and MCH were the lowest in the 0-18 year old group and the highest in the >50 years old group in heterozygotes of ß-thalassemia. The influence of age on hematological parameters in the primary screening of thalassemia provides a certain reference value in clinical diagnosis and treatment.
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Talasemia alfa , Talasemia beta , China/epidemiología , Genotipo , Heterocigoto , Humanos , Mutación , Fenotipo , Talasemia alfa/epidemiología , Talasemia alfa/genética , Talasemia beta/epidemiología , Talasemia beta/genéticaRESUMEN
AIM: To investigate the role of endoplasmic reticulum (ER) stress in cancer radiotherapy and its molecular mechanism. METHODS: Tunicamycin (TM) was applied to induce ER stress in human esophageal cancer cell line EC109, and the radiosensitization effects were detected by acute cell death and clonogenic survival assay. Cell cycle arrest induced by TM was determined by flow cytometric analysis after the cellular DNA content was labeled with propidium iodide. Apoptosis of EC109 cells induced by TM was detected by annexin V staining and Western blotting of caspase-3 and its substrate poly ADP-ribose polymerase. Autophagic response was determined by acridine orange (AO) staining and Western blotting of microtubule-associated protein-1 light chain-3 (LC3) and autophagy related gene 5 (ATG5). In order to test the biological function of autophagy, specific inhibitor or Beclin-1 knockdown was used to inhibit autophagy, and its effect on cell apoptosis was thus detected. Additionally, involvement of the phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway was also detected by Western blotting. Finally, male nude mice inoculated subcutaneously with EC109 cells were used to confirm cell model observations. RESULTS: Our results showed that TM treatment enhanced cell death and reduced the colony survival fraction induced by ionizing radiation (IR), which suggested an obvious radiosensitization effect of TM. Moreover, TM and IR combination treatment led to a significant increase of G2/M phase and apoptotic cells, compared with IR alone. We also observed an increase of AO positive cells, and the protein level of LC3-II and ATG5 was induced by TM treatment, which suggested an autophagic response in EC109 cells. However, inhibition of autophagy by using a chemical inhibitor or Beclin-1 silencing led to increased cell apoptosis and decreased cell viability, which suggested a cytoprotective role of autophagy in stressed EC109 cells. Furthermore, TM treatment also activated mTORC1, and in turn reduced Akt phosphorylation, which suggested the PI3K/Akt/mTOR signal pathway was involved in the TM-induced autophagic response in EC109 cells. Tumor xenograft results also showed synergistic retarded tumor growth by TM treatment and IR, as well as the involvement of the PI3K/Akt/mTOR pathway. CONCLUSION: Our data showed that TM treatment sensitized human esophageal cancer cells to radiation via apoptosis and autophagy both in vitro and in vivo.
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Estrés del Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/efectos de los fármacos , Neoplasias Esofágicas/terapia , Fármacos Sensibilizantes a Radiaciones/farmacología , Tunicamicina/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia/efectos de los fármacos , Autofagia/efectos de la radiación , Beclina-1 , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Retículo Endoplásmico/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de la radiación , Humanos , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Desnudos , Complejos Multiproteicos/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Tolerancia a Radiación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We report the availability of a digitized Chinese male and a digitzed Chinese female typical of the population and with no obvious abnormalities. The embalming and milling procedures incorporate three technical improvements over earlier digitized cadavers. Vascular perfusion with coloured gelatin was performed to facilitate blood vessel identification. Embalmed cadavers were embedded in gelatin and cryosectioned whole so as to avoid section loss resulting from cutting the body into smaller pieces. Milling performed at -25 degrees C prevented small structures (e.g. teeth, concha nasalis and articular cartilage) from falling off from the milling surface. The male image set (.tiff images each of 36 Mb) has a section resolution of 3072 x 2048 pixels ( approximately 170 micro m, the accompanying magnetic resonance imaging and computer tomography data have a resolution of 512 x 512, i.e. approximately 440 micro m). The Chinese Visible Human male and female datasets are available at http://www.chinesevisiblehuman.com. (The male is 90.65 Gb and female 131.04 Gb). MPEG videos of direct records of real-time volume rendering are at: http://www.cse.cuhk.edu.hk/~crc
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Simulación por Computador , Imagenología Tridimensional , Modelos Anatómicos , Adulto , Anatomía Transversal , Pueblo Asiatico , Cadáver , China , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Ilustración Médica , Tomografía Computarizada por Rayos XRESUMEN
The United States Visible Human Project (VHP) created a digital image data set of complete human male (data acquisition finished in November 1994) and female (data acquisition finished in December 1995) cadavers in magnetic resonance imaging (MRI), computed tomography (CT), and anatomical (anatomic serial section) modes. VHP aroused worldwide enthusiasm for Visible Human Research (VHR), and the data set is being used in a variety of research and educational domains. The Visible Korean Human (VKH) male was produced in March 2001. To accelerate worldwide VHR and to promote virtual anatomy as a revolutionary break with conventional anatomy, more visible human data sets representative of different populations of the world are in demand. The Chinese Visible Human (CVH) male (created in October 2002) and female (created in February 2003) project achieved greater integrity of images, easier blood vessel identification, and were free of organic lesion (unlike the other visible human projects). We performed data acquisition, three-dimensional (3D) reconstruction, and visualization with improved technology to create CVH male and female. CVH is the first volumetric data representing a complete normal adult human male and female of an Asian population. This article presents the history of Chinese Visible Human cadavers and the methods and technology used to produce the data set.