All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutatio...All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutations is associated with increased risk of relapse.The aim of this study was to analyze the prognostic impact of FLT3-ITD on APL patients who received remission induction with ATRA,idarubicin(IDA)and/or ATO,followed by ATRA plus ATO along with anthracycline,as consolidation therapy.A total of 72 patients newly diagnosed with APL were included in this study.83.3%of the patients achieved complete remission(CR)after induction therapy.FLT3-ITD mutations were detected in 16(22.2%)patients and closely related to bcr-3 PML-RARa transcript(P<0.001).The 5-year overall survival(OS)rate was 100%in both FLT3-ITDposltlve and FLT3-ITD^(negatlve)groups,and there was no significant difference in 5-year event-free survival(EFS)between the two groups(78.3%vs.83.3%,P=0.85).ATRA plus ATO and anthracycline-based chemotherapy achieved great outcome in newly diagnosed APL regardless of the FLT3-ITD mutation status.展开更多
BACKGROUND： Recent studies have suggested that regeneration of the central nerve fiber following spinal cord injury occurs under specific conditions. OBJECTIVE： To study the effects of Nogo-neutralizing antibody （...BACKGROUND： Recent studies have suggested that regeneration of the central nerve fiber following spinal cord injury occurs under specific conditions. OBJECTIVE： To study the effects of Nogo-neutralizing antibody （IN-1）, in combination with neurotrophin-3 （NT-3）, on axonal regeneration and motor function following spinal cord injury in the rat. DESIGN, TIME AND SETTING： A randomized, controlled, animal study combining immunohistochemistry was performed at the Laboratory of Neuroanatomy of Xiangya Medical College, and Central Laboratory of Xiangya the Third Hospital, Central South University from January 2006 to December 2007. MATERIALS： Eighteen healthy, Sprague Dawley rats were randomly divided into three groups, with six rats per group： control, IN-l, and IN-1/NT-3. Hemisectioned spinal cord injury models were established by cutting the posterior 2/3 of spinal cord, which is equivalent to the Ts level. METHODS： A polyethylene tubing was inserted through into subarachnoid cavity, equivalent to the superior margin at the T8 level. Saline, IN-1, and IN-1/NT-3 were respectively injected into control, IN-1, and IN-1/NT-3 groups, three times/day for seven consecutive days. MAIN OUTCOME MEASURES： At 2 weeks post-surgery, biotin dextran amine （10%） was injected into the right sensorimotor cortex area. At day 28 post-surgery, spinal cord tissue was prepared for frozen sections Positive astrocytic expression was observed with glial fibrillary acidic protein （GFAP） immunohistochemical staining whose proliferation level was represented by gray value, i.e. the higher the gray value was, the less the positive cells were, and growth of positive fibers was observed with a biotin dextran amine histological reaction. Motor function was measured according to BBB scores pre-operatively, as well as at days 1, 7, 14, 21, and 28 post-operatively. RESULTS： Three rats died during experimentation. By random supplement, a total of 18 rats were included. GFAP-positive astrocytes were observed in all the three groups. In the control group, astrocytes were characterized according to active function, hyperplasia, proliferation, hypertrophy, and increasing processes as compared to IN-1 group and IN-1/IN-3 group. Astrocyte hyperplasia represented by gray value in the IN-1 group was less than the control group. Gray value of GFAP-positive products in the IN-1/IN-3 group was higher than other two groups （P 〈 0.05）. Biotin dextran amine tracing demonstrated no corticospinal tract fiber outgrowth following spinal cord injury; the fibers were incapable of passing through the glial scar in the control group. Several fibers were distributed in the proximal scar tissue region in the IN-1 group, and the regenerated fibers were disarranged. Many nerve fibers were distributed throughout the scar tissue, and even several biotin dextran amine-positive fibers were observed at the distal end of the injured segment. Post-operative Basso, Beattie, Bresnahan scores were greater than pre-operative ones, while Basso, Beattie, Bresnahan scores in the IN-1/NT-3 group were significantly greater than the other two groups at days 14, 21, and 28 post-surgery （P 〈 0.05）. CONCLUSION： IN-1, in combination with NT-3, promoted axonal regeneration following spinal cord injury, inhibited the colloidal effect, and enhanced the correlation between proximal and distal processes to recover motor function. The recovery effect of IN-1/NT-3 on motor function was superior that of to IN-1 alone.展开更多
A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neuro- trophic factor are all peptides or ...A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neuro- trophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the micro- spheres at 300-pm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implanta- tion, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and dis- tributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.展开更多
AIM: To analyze the expression of retinoic acid receptor responder 3 (RARRES3) protein in paraffin-embedded tissues of hepatocellular carcinoma (HCC) and cholangiocarcinoma(CC), and the correlation of RARRES3 producti...AIM: To analyze the expression of retinoic acid receptor responder 3 (RARRES3) protein in paraffin-embedded tissues of hepatocellular carcinoma (HCC) and cholangiocarcinoma(CC), and the correlation of RARRES3 production with tumor differentiation.METHODS: Expression of RARRES3 in tissues from 21CC (10 well-, 7 moderately- and 4 poorly-differentiated)and 32 HCC was determined by immunohistochemistry.RESULTS: Among 21 CC tissues, RARRES3 was detected in 8 (80%) of 10 well-differentiated tumors. Only 2 (18.2%)out of 11 tumors with moderate or poor differentiation showed positive RARRES3 expression. RARRES3 expression in well-differentiated CC was significantly higher than that in tumors with moderate or poor differentiation (Fisher exact test, P＜0.01). Expression of RARRES3 was not different between early (Ⅰ and Ⅱ) and late (Ⅲ and Ⅳ) stages of CC.Among 30 HCC tissues, 17 (56.7%) weakly expressed RARRES3 in HCC cells, and 25 (83.3%) normal tissues adjacent to HCC expressed the protein. RARRES3 expression was significantly decreased in HCC tissues compared to that in adjacent normal tissues (logistic regression analysis, OR = 0.27, 95% CI (0.11-0.62), P＜0.01).CONCLUSION: Expression of RARRES3 is positively correlated to well-differentiated CC, which supports the role of RARRES3 in malignant epithelial differentiation of the tumor. The decrease in RARRES3 expression in tissues of HCC and CC with moderate and poor differentiation suggests that altered RARRES3 expression may play a role in the carcinogenesis of the liver and biliary tract.展开更多
文摘All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutations is associated with increased risk of relapse.The aim of this study was to analyze the prognostic impact of FLT3-ITD on APL patients who received remission induction with ATRA,idarubicin(IDA)and/or ATO,followed by ATRA plus ATO along with anthracycline,as consolidation therapy.A total of 72 patients newly diagnosed with APL were included in this study.83.3%of the patients achieved complete remission(CR)after induction therapy.FLT3-ITD mutations were detected in 16(22.2%)patients and closely related to bcr-3 PML-RARa transcript(P<0.001).The 5-year overall survival(OS)rate was 100%in both FLT3-ITDposltlve and FLT3-ITD^(negatlve)groups,and there was no significant difference in 5-year event-free survival(EFS)between the two groups(78.3%vs.83.3%,P=0.85).ATRA plus ATO and anthracycline-based chemotherapy achieved great outcome in newly diagnosed APL regardless of the FLT3-ITD mutation status.
基金the Foundation of Hunan Public Health Bureau, No.B2005-076
文摘BACKGROUND： Recent studies have suggested that regeneration of the central nerve fiber following spinal cord injury occurs under specific conditions. OBJECTIVE： To study the effects of Nogo-neutralizing antibody （IN-1）, in combination with neurotrophin-3 （NT-3）, on axonal regeneration and motor function following spinal cord injury in the rat. DESIGN, TIME AND SETTING： A randomized, controlled, animal study combining immunohistochemistry was performed at the Laboratory of Neuroanatomy of Xiangya Medical College, and Central Laboratory of Xiangya the Third Hospital, Central South University from January 2006 to December 2007. MATERIALS： Eighteen healthy, Sprague Dawley rats were randomly divided into three groups, with six rats per group： control, IN-l, and IN-1/NT-3. Hemisectioned spinal cord injury models were established by cutting the posterior 2/3 of spinal cord, which is equivalent to the Ts level. METHODS： A polyethylene tubing was inserted through into subarachnoid cavity, equivalent to the superior margin at the T8 level. Saline, IN-1, and IN-1/NT-3 were respectively injected into control, IN-1, and IN-1/NT-3 groups, three times/day for seven consecutive days. MAIN OUTCOME MEASURES： At 2 weeks post-surgery, biotin dextran amine （10%） was injected into the right sensorimotor cortex area. At day 28 post-surgery, spinal cord tissue was prepared for frozen sections Positive astrocytic expression was observed with glial fibrillary acidic protein （GFAP） immunohistochemical staining whose proliferation level was represented by gray value, i.e. the higher the gray value was, the less the positive cells were, and growth of positive fibers was observed with a biotin dextran amine histological reaction. Motor function was measured according to BBB scores pre-operatively, as well as at days 1, 7, 14, 21, and 28 post-operatively. RESULTS： Three rats died during experimentation. By random supplement, a total of 18 rats were included. GFAP-positive astrocytes were observed in all the three groups. In the control group, astrocytes were characterized according to active function, hyperplasia, proliferation, hypertrophy, and increasing processes as compared to IN-1 group and IN-1/IN-3 group. Astrocyte hyperplasia represented by gray value in the IN-1 group was less than the control group. Gray value of GFAP-positive products in the IN-1/IN-3 group was higher than other two groups （P 〈 0.05）. Biotin dextran amine tracing demonstrated no corticospinal tract fiber outgrowth following spinal cord injury; the fibers were incapable of passing through the glial scar in the control group. Several fibers were distributed in the proximal scar tissue region in the IN-1 group, and the regenerated fibers were disarranged. Many nerve fibers were distributed throughout the scar tissue, and even several biotin dextran amine-positive fibers were observed at the distal end of the injured segment. Post-operative Basso, Beattie, Bresnahan scores were greater than pre-operative ones, while Basso, Beattie, Bresnahan scores in the IN-1/NT-3 group were significantly greater than the other two groups at days 14, 21, and 28 post-surgery （P 〈 0.05）. CONCLUSION： IN-1, in combination with NT-3, promoted axonal regeneration following spinal cord injury, inhibited the colloidal effect, and enhanced the correlation between proximal and distal processes to recover motor function. The recovery effect of IN-1/NT-3 on motor function was superior that of to IN-1 alone.
基金financially supported by a grant from the Natural Science Foundation of Hunan Province of China,No.13JJ6016
文摘A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neuro- trophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the micro- spheres at 300-pm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implanta- tion, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and dis- tributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.
基金Supported by the Tri-Service General Hospital (TSGH-C91-14),Department of Defense (N91079)National Science Council (NSC91-2314-B016-108) Taipei, Taiwan, China
文摘AIM: To analyze the expression of retinoic acid receptor responder 3 (RARRES3) protein in paraffin-embedded tissues of hepatocellular carcinoma (HCC) and cholangiocarcinoma(CC), and the correlation of RARRES3 production with tumor differentiation.METHODS: Expression of RARRES3 in tissues from 21CC (10 well-, 7 moderately- and 4 poorly-differentiated)and 32 HCC was determined by immunohistochemistry.RESULTS: Among 21 CC tissues, RARRES3 was detected in 8 (80%) of 10 well-differentiated tumors. Only 2 (18.2%)out of 11 tumors with moderate or poor differentiation showed positive RARRES3 expression. RARRES3 expression in well-differentiated CC was significantly higher than that in tumors with moderate or poor differentiation (Fisher exact test, P＜0.01). Expression of RARRES3 was not different between early (Ⅰ and Ⅱ) and late (Ⅲ and Ⅳ) stages of CC.Among 30 HCC tissues, 17 (56.7%) weakly expressed RARRES3 in HCC cells, and 25 (83.3%) normal tissues adjacent to HCC expressed the protein. RARRES3 expression was significantly decreased in HCC tissues compared to that in adjacent normal tissues (logistic regression analysis, OR = 0.27, 95% CI (0.11-0.62), P＜0.01).CONCLUSION: Expression of RARRES3 is positively correlated to well-differentiated CC, which supports the role of RARRES3 in malignant epithelial differentiation of the tumor. The decrease in RARRES3 expression in tissues of HCC and CC with moderate and poor differentiation suggests that altered RARRES3 expression may play a role in the carcinogenesis of the liver and biliary tract.
