Background and Objective: Leukemic microenvironment has a major role in the progression of leukemia. Leukemic cells can induce reversible changes in microenvironmental components, especially the stromal function which...Background and Objective: Leukemic microenvironment has a major role in the progression of leukemia. Leukemic cells can induce reversible changes in microenvironmental components, especially the stromal function which results in improved growth conditions for maintaining the malignant leukemic cells. This study aimed to investigate the survival advantage of leukemic cells over normal hematopoietic cells in stromal microenvironment in long term. Methods: The mice were injected intraperitoneally with N-N’ ethylnitrosourea (ENU) to induce leukemia; the mice received injection of normal saline were used as control. At 180 days after ENU induction, the mice were killed and the bone marrows were cultured for 19 days. Colony-forming assays were used to analyze the formation of various cell colonies. The expression of Sca-1, CD146, VEGFR2, CD95, pStat3, pStat5, and Bcl-xL in marrow cells were detected by flow cytometry. Results: Long-term leukemic bone marrow culture showed abnormal elongated stromal fibroblasts with almost absence of normal hematopoietic cells. Adherent cell colonies were increased, but CFU-F and other hematopoietic cell colonies were significantly decreased in leukemia group (P< 0.001). Primitive progenitor-specific Sca-1 receptor expression was decreased with subsequent increased expression of CD146 and VEGFR-2 in leukemic bone marrow cells. Decreased Fas antigen expression with increased intracellular pStat3, pStat5 and Bcl-xL proteins were observed in leukemic bone marrow cells. Conclusions: Stromal microenvironment shows altered morphology and decreased maturation in leukemia. Effective progenitor cells are decreased in leukemia with increased leukemia-specific cell population. Leukemic microenvironment plays a role in promoting and maintaining the leukemic cell proliferation and survivability in long term.展开更多
The Tenth International Gastric Cancer Congress(IGCC) was held in Verona, Italy, from June 19 to 22, 2013. The meeting enclosed various aspects of stomach tumor management, including both tightly clinical approaches, ...The Tenth International Gastric Cancer Congress(IGCC) was held in Verona, Italy, from June 19 to 22, 2013. The meeting enclosed various aspects of stomach tumor management, including both tightly clinical approaches, and topics more related to basic research. Moreover, an overview on gastrointestinal stromal tumors was provided too, although here not discussed. Here we will discuss some topics related to molecular biology of gastric cancer(GC), inherent to prognostic, diagnostic and therapeutic tools shown at the conference. Results about well known subjects, such as E-cadherin loss of expression/function, were presented. They revealed that other mutations of the gene were identified, showing a continuous research to improve diagnosis and prognosis of stomach tumor. Simultaneously, new possible molecular markers with an established role for other neoplasms, were discussed, such as mesothelin, stomatin-like protein 2 and Notch-1. Hence, a wide overview including both old and new diagnostic/prognostic tools was offered. Great attention was also dedicated to possible drugs to be used against GC. They included monoclonal antibodies, such as MS57-2.1, drugs used in other pathologies, such as maraviroc, and natural extracts from plants such as biflorin. We would like to contribute to summarize the most impressive studies presented at the IGCC, concerning novel findings about molecular biology of gastric cancer. Although further investigations will be necessary, it can be inferred that more and more tools were developed, so as to better face stomach neoplasms.展开更多
AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were ...AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL)and 41 with nonalcoholic steatohepatitis (NASH).METHODS: Circulating levels of Bcl-2 were detected in 84 patients with ultrasono graphic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in γ-glutamyl-transpeptidase (γ-GT)strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls.RESULTS: Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ≤ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008).γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients presented a weak negative correlation between lobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metaboli-cally unhealthy overweight/obese patients (MUOs) was evidenced. HOMA, BMI and uric acid, in that sequence,best predicted serum Bcl-2 concentrations.CONCLUSION: MUOs could be detected by Bcl-2 levels.By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.展开更多
The concept of stem cells,their physiological existence,the intricate anatomical localization,the known and the unknown functions,and their exclusive utility for the purpose of regenerative medicine,are all now encomp...The concept of stem cells,their physiological existence,the intricate anatomical localization,the known and the unknown functions,and their exclusive utility for the purpose of regenerative medicine,are all now encompassed within an emergent question,'how compatible these cells are immunologically?' Indeed,the medical aspects of stem cells are dependent on a large number of queries based on the basic properties of the cells. It has greatly been emphasized to probe into the basic research on stem cells before any successful therapeutic attempts are made. One of the intricate aspects of the adult stem cells is its immunological behavior in relation to the microenvironmental associates,the stromal cells in the presence of a suitable target.展开更多
文摘Background and Objective: Leukemic microenvironment has a major role in the progression of leukemia. Leukemic cells can induce reversible changes in microenvironmental components, especially the stromal function which results in improved growth conditions for maintaining the malignant leukemic cells. This study aimed to investigate the survival advantage of leukemic cells over normal hematopoietic cells in stromal microenvironment in long term. Methods: The mice were injected intraperitoneally with N-N’ ethylnitrosourea (ENU) to induce leukemia; the mice received injection of normal saline were used as control. At 180 days after ENU induction, the mice were killed and the bone marrows were cultured for 19 days. Colony-forming assays were used to analyze the formation of various cell colonies. The expression of Sca-1, CD146, VEGFR2, CD95, pStat3, pStat5, and Bcl-xL in marrow cells were detected by flow cytometry. Results: Long-term leukemic bone marrow culture showed abnormal elongated stromal fibroblasts with almost absence of normal hematopoietic cells. Adherent cell colonies were increased, but CFU-F and other hematopoietic cell colonies were significantly decreased in leukemia group (P< 0.001). Primitive progenitor-specific Sca-1 receptor expression was decreased with subsequent increased expression of CD146 and VEGFR-2 in leukemic bone marrow cells. Decreased Fas antigen expression with increased intracellular pStat3, pStat5 and Bcl-xL proteins were observed in leukemic bone marrow cells. Conclusions: Stromal microenvironment shows altered morphology and decreased maturation in leukemia. Effective progenitor cells are decreased in leukemia with increased leukemia-specific cell population. Leukemic microenvironment plays a role in promoting and maintaining the leukemic cell proliferation and survivability in long term.
文摘The Tenth International Gastric Cancer Congress(IGCC) was held in Verona, Italy, from June 19 to 22, 2013. The meeting enclosed various aspects of stomach tumor management, including both tightly clinical approaches, and topics more related to basic research. Moreover, an overview on gastrointestinal stromal tumors was provided too, although here not discussed. Here we will discuss some topics related to molecular biology of gastric cancer(GC), inherent to prognostic, diagnostic and therapeutic tools shown at the conference. Results about well known subjects, such as E-cadherin loss of expression/function, were presented. They revealed that other mutations of the gene were identified, showing a continuous research to improve diagnosis and prognosis of stomach tumor. Simultaneously, new possible molecular markers with an established role for other neoplasms, were discussed, such as mesothelin, stomatin-like protein 2 and Notch-1. Hence, a wide overview including both old and new diagnostic/prognostic tools was offered. Great attention was also dedicated to possible drugs to be used against GC. They included monoclonal antibodies, such as MS57-2.1, drugs used in other pathologies, such as maraviroc, and natural extracts from plants such as biflorin. We would like to contribute to summarize the most impressive studies presented at the IGCC, concerning novel findings about molecular biology of gastric cancer. Although further investigations will be necessary, it can be inferred that more and more tools were developed, so as to better face stomach neoplasms.
文摘AIM: To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indices, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver (FL)and 41 with nonalcoholic steatohepatitis (NASH).METHODS: Circulating levels of Bcl-2 were detected in 84 patients with ultrasono graphic findings of "bright liver" and/or hyper-transaminasemia of unknown origin and/or increase in γ-glutamyl-transpeptidase (γ-GT)strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups (43 with FL and 41 with NASH). Twenty lean subjects, apparently healthy and young, were chosen as controls.RESULTS: Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein (CRP) concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index (BMI) values (P ≤ 0.0001) but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males (P = 0.0008).γ-GT activity was associated with homeostatic metabolic assessment (HOMA) (P = 0.0003) and with serum ferritin (P = 0.02). Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients presented a weak negative correlation between lobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metaboli-cally unhealthy overweight/obese patients (MUOs) was evidenced. HOMA, BMI and uric acid, in that sequence,best predicted serum Bcl-2 concentrations.CONCLUSION: MUOs could be detected by Bcl-2 levels.By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.
文摘The concept of stem cells,their physiological existence,the intricate anatomical localization,the known and the unknown functions,and their exclusive utility for the purpose of regenerative medicine,are all now encompassed within an emergent question,'how compatible these cells are immunologically?' Indeed,the medical aspects of stem cells are dependent on a large number of queries based on the basic properties of the cells. It has greatly been emphasized to probe into the basic research on stem cells before any successful therapeutic attempts are made. One of the intricate aspects of the adult stem cells is its immunological behavior in relation to the microenvironmental associates,the stromal cells in the presence of a suitable target.
