No abstract available.
Drug Therapy* ; Empyema*

The role of cytokines and transcription factors on the regulation of megakaryocy topoiesis and platelet production are reviewed in this article. Megakaryocytopoiesis involves the proliferation and differentiation of megakaryocytic pro genitor cells into immature megakaryocytes, and the differentiation of immature megakaryocytes to mature megakaryocytes which produce platelets. The former is regulated mainly by thrombopoietin (TPO) and to a lesser degree by other cytokines such as interleukin-1 (IL-1), IL-3 and platelet-derived growth factor (PDGF), the later by TPO and probably IL-6 and IL-11. A number of transcription factors have been implicated in the control of megakaryocyte differentiation. GATA-1, FOG-1 and Fli-1 are essential regulators in early- and mid-stages of megakaryocytopoiesis. NF-E2 regulates late-stage of megakaryocytopoiesis and platelet production. However, the platelet release mechanism is poorly understood. Nitric oxide (NO) may act in the stage of platelet release through induction of apoptosis in megakaryocytes.
Animals ; Cytokines ; physiology ; DNA-Binding Proteins ; physiology ; Erythroid-Specific DNA-Binding Factors ; GATA1 Transcription Factor ; Hematopoiesis ; Humans ; Interleukins ; physiology ; Megakaryocytes ; physiology ; NF-E2 Transcription Factor ; NF-E2 Transcription Factor, p45 Subunit ; Platelet-Derived Growth Factor ; physiology ; Thrombopoiesis ; physiology ; Thrombopoietin ; physiology ; Transcription Factors ; physiology

Severe acute respiratory syndrome (SARS) has recently recognized as a new human infectious disease. A novel coronavirus was identified as the causative agent of SARS. This report summarizes the hematological findings in SARS patients and proposes a hypothesis for the pathophysiology of SARS coronavirus related abnormal hematopoiesis. Hematological changes in patients with SARS were common and included lymphopenia (68% - 90% of adults; 100% of children, n = 10), thrombocytopenia (20% - 45% of adults, 50% of children), and leukopenia (20% - 34% of adults, 70% of children). The possible mechanisms of this coronavirus on blood system may include (1) directly infect blood cells and bone marrow stromal cells via CD13 or CD66a; and/or (2) induce auto-antibodies and immune complexes to damage these cells. In addition, lung damage in SARS patients may also play a role on inducing thrombocytopenia by (1) increasing the consumption of platelets/megakaryocytes; and/or (2) reducing the production of platelets in the lungs. Since the most common hematological changes in SARS patients were lymphopenia and immunodeficiency. We postulate that hematopoietic growth factors such as G-CSF, by mobilizing endogenous blood stem cells and endogenous cytokines, could become a hematological treatment for SARS patients, which may enhance the immune system against these virus.
Adult ; Antigens, CD ; immunology ; Antigens, Differentiation ; immunology ; CD13 Antigens ; immunology ; Cell Adhesion Molecules ; Child ; Hematologic Diseases ; immunology ; physiopathology ; Hematopoiesis ; physiology ; Humans ; SARS Virus ; Severe Acute Respiratory Syndrome ; immunology ; physiopathology ; virology

The aim of this study was to investigate the effect of human bone marrow mesenchymal stem cells on human T-cell proliferation resulted from stimulation with PHA and possible immunomodulating mechanism. T cells were positively selected by CD3(+) magnetic beads, and were then co-cultured with irradiated MSCs overnight before the addition of PHA. T-cell proliferation was measured by BrdU assay and the degree of apoptosis was assessed by flow cytometry with Annexin V/PI. T cells co-cultured with or without MSCs were treated with PHA for 72 hours, then harvested. They were labeled with anti-CD4, anti-CD8, anti-CD25 antibodies and analyzed by flow cytometry. The results showed that MSCs inhibited T-cell proliferation, but did not induce T cell apoptosis. There were no significant changes in the ratio of CD4(+) and CD8(+) T cells of MSC-treated group, as compared with the control group. After stimulation with PHA, there was an increase in CD4(+) T cells and decrease of CD4(+)CD25(+) cells in MSC co-cultured group. It is concluded that the MSCs inhibit T-cell proliferation after stimulation with PHA, and show more inhibitive effects on CD8(+) and CD4(+) T cells, but CD25(+) regulatory T cells may not be involved in this process.
Bone Marrow Cells ; cytology ; CD4-CD8 Ratio ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Humans ; Mesenchymal Stromal Cells ; cytology ; physiology ; T-Lymphocyte Subsets ; cytology

The immunological role of megakaryocytes is not well known. This project studies the involvement of megakaryocytes on immuno-inflammatory processes and the possible mechanism via the adhesion molecule CD36 and the synthesis of relevant cytokines. The expression of adhesion protein CD36 on human platelets, megakaryocytes and megakaryocytic cell lines (Meg-01, Dami, CHRF-288-11 and M-07e) was analyzed by using flow cytometry, ELISA and immunocytochemical methods. The expression of interleukin-1 (IL-1) to interleukin-10 (IL-10), TNF-alpha, TNF-gamma and IFN-gamma on the four megakaryocytic cell lines was also determined by RT-PCR. The effect of IL-1beta, IL-3, IL-6 and TPO on murine megakaryocyte colony formation (CFU-MK) was studied by using a plasma clot culture system. The CFU-MK was confirmed by acetylcholine esterase staining. The results showed that: (1) CD36 was expressed on platelets, megakaryocytes and the four megakaryocytic cell lines, the relative expression level is as follows: platelets > megakaryocytes > Meg-01 > Dami > CHRF-288-11 > M-07e, suggesting that the level of CD36 expression correlates with the degree of maturity of megakaryocytic differentiation; (2) inflammatory cytokines TNF-alpha, IL-1beta, IL-3 and IL-6 were detected in all the four megakaryocytic cell lines, suggesting that different stages of megakaryocytes can be as a source of inflammatory cytokines; and (3) IL-1beta, IL-3 and IL-6, as well as TPO, play a stimulating effect on CFU-MK formation, suggesting that there is an "autocrine" effect on megakaryocytopoiesis. The data obtained suggest that megakaryocytes may involve in immuno-inflammatory processes via the synthesis of platelet adhesion molecules and inflammatory cytokines.

To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.
Animals ; Apoptosis ; drug effects ; Brain Chemistry ; Cell Line ; Cell Proliferation ; drug effects ; Erythropoietin ; pharmacology ; Humans ; Mice ; Neoplasm Proteins ; analysis ; Neurons ; drug effects ; Oncogene Proteins ; analysis ; Proto-Oncogene Proteins ; analysis ; Receptors, Cytokine ; analysis ; Receptors, Thrombopoietin ; Thrombopoietin ; pharmacology

The outcome of hepatocellular carcinoma (HCC) patients significantly differs between western and eastern population centers. Our group previously developed and validated the Chinese University Prognostic Index (CUPI) for the prognostication of HCC among the Asian HCC patient population. In the current study, we aimed to validate the CUPI using an international cohort of patients with HCC and to compare the CUPI to two widely used staging systems, the Barcelona Clinic Liver Cancer (BCLC) classification and the Cancer of the Liver Italian Program (CLIP). To accomplish this goal, two cohorts of patients were enrolled in the United Kingdom (UK; n = 567; 2006-2011) and Hong Kong (HK; n = 517; 2007-2012). The baseline clinical data were recorded. The performances of the CUPI, BCLC, and CLIP were compared in terms of a concordance index (C-index) and were evaluated in subgroups of patients according to treatment intent. The results revealed that the median follow-up durations of the UK and HK cohorts were 27.9 and 29.8 months, respectively. The median overall survival of the UK and HK cohorts were 22.9 and 8.6 months, respectively. The CUPI stratified the patients in both cohorts into three risk subgroups corresponding to distinct outcomes. The median overall survival of the CUPI low-, intermediate-, and high-risk subgroups were 3.15, 1.24, and 0.29 years, respectively, in the UK cohort and were 2.07, 0.32, and 0.10 years, respectively, in the HK cohort. For the patients who underwent curative treatment, the prognostic performance did not differ between the three staging systems, and all were suboptimal. For those who underwent palliative treatment, the CUPI displayed the highest C-index, indicating that this staging system was the most informative for both cohorts. In conclusion, the CUPI is applicable to both western and eastern HCC patient populations. The performances of the three staging systems differed according to treatment intent, and the CUPI was demonstrated to be optimal for those undergoing palliative treatment. A more precise staging system for early-stage disease patients is required.
Carcinoma, Hepatocellular ; Hong Kong ; Humans ; Liver Neoplasms ; Neoplasm Staging ; Prognosis ; United Kingdom

OBJECTIVETo observe the effects of water extract of Zuojin Pill ([characters: see text], ZJP) on inhibiting the growth of human gastric cancer cell line SGC-7901 and its potential mechanism.

METHODSEffects of ZJP on SGC-7901 cells growth were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, cell apoptosis and cell cycle were determined by flow cytometry, and apoptosis induction was detected by means of DNA gel electrophoresis. The cellular mechanism of drug-induced cell death was unraveled by assaying oxidative injury level of SGC-7901 cell, mitochondrial membrane potentials, expression of apoptosis-related genes, such as B cell lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cleaved caspase-3 and caspase-9.

RESULTSZJP exerted evident inhibitory effect on SGC-7901 cells by activating production of reactive oxygen species and elevating Bax/Bcl-2 ratio in SGC-7901 cells, leading to attenuation of mitochondrial membrane potential and DNA fragmentation.

CONCLUSIONSZJP inhibits the cancer cell growth via activating mitochondria-dependent apoptosis pathway. ZJP can potentially serve as an antitumor agent.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Cell Line, Tumor ; Cell Survival ; Colorimetry ; Comet Assay ; DNA Fragmentation ; Drugs, Chinese Herbal ; pharmacology ; Flow Cytometry ; Humans ; Mitochondrial Membranes ; drug effects ; Reactive Oxygen Species ; metabolism

PURPOSE: To estimate the current cancer burden in Korea, cancer incidence and mortality rates were projected for the year 2013. MATERIALS AND METHODS: Cancer incidence data from 1999 to 2010 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2011 were obtained from Statistics Korea. Cancer incidence in 2013 was projected by fitting a linear regression model to observed age-specific cancer incidence rates against observed years, then multiplying the projected age-specific rates by the age-specific population. For cancer mortality, a similar procedure was used, except that a Joinpoint regression model was used to determine at which year the linear trend changed significantly. RESULTS: In total, 247,732 new cancer cases and 74,179 cancer deaths are projected to occur in Korea in 2013. For all sites combined, the crude incidence rates are projected to be 489.8 and 492.2, and the age-standardized incidences to be 350.4 and 318.4 per 100,000 for males and females, respectively. CONCLUSION: Cancer has become an important public health concern in Korea, and as the Korean population ages, the cancer burden will continue to increase.
Female ; Forecasting ; Humans ; Incidence ; Korea ; Linear Models ; Male ; Public Health

PURPOSE: This article gives an overview of nationwide cancer statistics, including incidence, mortality, survival and prevalence, and their trends in Korea based on 2010 cancer incidence data. MATERIALS AND METHODS: Incidence data from 1993 to 2010 were obtained from the Korea National Cancer Incidence Database, and vital status was followed until 31 December 2011. Mortality data from 1983 to 2010 were obtained from Statistics Korea. Crude and age-standardized rates for incidence, mortality, prevalence, and relative survival were calculated. RESULTS: In total, 202,053 cancer cases and 72,046 cancer deaths occurred during 2010, and 960,654 prevalent cancer cases were identified in Korea as of 1 January 2011. The incidence of all cancers combined showed an annual increase of 3.3% from 1999 to 2010. The incidences of liver and cervical cancers have decreased while those of thyroid, breast, prostate and colorectal cancers have increased. Notably, thyroid cancer, which is the most common cancer in Korea, increased by 24.2% per year rapidly in both sexes. The mortality of all cancers combined showed a decrease by 2.7% annually from 2002 to 2010. Five-year relative survival rates of patients who were diagnosed with cancer from 2006 to 2011 had improved by 22.9% compared with those from 1993 to 1995. CONCLUSION: While the overall cancer incidence in Korea has increased rapidly, age-standardized cancer mortality rates have declined since 2002 and survival has improved.
Breast ; Colorectal Neoplasms ; Humans ; Incidence ; Korea ; Liver ; Prevalence ; Prostate ; Survival Rate ; Thyroid Gland ; Thyroid Neoplasms