ABSTRACT
Background: High dose Cyclophosphamide [Cy] and Vinorelbine Cyclophosphamide [Vino-Cy] are stem cell [SC] mobilisation options for patients with multiple myeloma [MM]. We present a comparison of mobilisation outcomes using these regimens
Patients and methods: Vino-Cy patients received Vinorelbine 25 mg/m[2] on day 1, cyclophosphamide 1500 mg/m[2] on day 2, and pegylated GCSF on day 4 or GCSF 10 mcg/kg/day from day 4 onwards. Cy patients were given cyclophosphamide 4000 mg/m[2] on day 1 and GCSF10 mcg/kg/day from day 5 onwards. The target CD34 + SC collection was 5 * 10[6] per kg/BW
Results: 149 patients were included. SC collection was lower in the Vino-Cy group [8.20 * 10[6]/ Kg BW] compared to the Cy group [11.43 * 10[6]/Kg BW], with adjusted geometric mean ratio of 0.59 [95% CI 0.41 to 0.86, p = 0.006]. Time taken to achieve an adequate PB SC count was shorter for Vino-Cy [9 +/- 1 day compared to 12 +/- 2 days for Cy, adjusted absolute mean difference -3.95, 95% CI -4.85 to -3.06, P < .001]. Mobilisation related toxicities [in particular, neutropaenic fever] were greater for Cy
Conclusion: Vino-Cy is a potential alternative to Cy given the need for effective mobilisation protocols with acceptable toxicity
ABSTRACT
Multiple myeloma (MM) is an incurable plasma cell neoplasm with an incidence of 100 patients per year in Singapore. Major advances have been made in the diagnosis, risk stratification and treatment of MM in the recent past. The reclassification of a subset of patients with smouldering MM, based on high-risk biomarkers, and the development of the revised international staging system are among the key new developments in diagnosis and staging. The use of novel agent-based treatment has resulted in significant improvements in the survival and quality of life of many patients with MM. Determining the optimal use of proteasome inhibitors, immunomodulators and, more recently, monoclonal antibodies is an area of ongoing investigation. In this guideline, we aim to provide an overview of the management of MM, incorporating the latest developments in diagnosis and treatment.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal , Chemistry , Biomarkers, Tumor , Medical Oncology , Reference Standards , Multiple Myeloma , Diagnosis , Therapeutics , Practice Guidelines as Topic , Proteasome Endopeptidase Complex , Quality of Life , Risk , Singapore , Societies, Medical , Stem Cell Transplantation , Transplantation ConditioningABSTRACT
[ABSTRACT]AIM:Toexplorethedevelopmentofhepaticsinusoidalcapillarizationintheearlystageofliverfi-brosis induced by carbon tetrachloride (CCl4) in rats.METHODS:Clean SD rats were randomly divided into normal con-trol group (group N, n=6) and liver fibrotic model group (group M, n=32).The rats in group N were intraperitoneal in-jected with saline and the rats in group M were intraperitoneal injected with CCl 4(2 mL/kg, twice a week for 4 weeks).At the end of the 3rd day and the 1st, 2nd and 4th weeks, all rats were killed and then the samples were collected .The patho-logical changes in the livers were observed by HE staining and Masson straining .The development of hepatic sinusoidal capillarization was observed by transmission electron microscopy (TEM) and immunohistochemical staining .The cell sur-face expression of vascular endothelium-associated marker CD31, collagen type Ⅳ(Col IV) and laminin (LN) was deter-mined.RESULTS:HE and Masson staining showed the formation of liver fibrosis after treatment with CCl 4 for 4 weeks. TEM showed that the fenestrate diameter of liver sinusoidal endothelial cells (LSECs) grew down, the fenestrate numbers of LSECs were decreased along with the development of liver fibrosis , and the consecutive basement membrane was formed at the end of the experiment .The expression of CD31 was significantly increased along with the development of defenestration , and the expression of Col IV and LN was significantly increased after the treatment with CCl 4 for 2 weeks and 4 weeks , re-spectively .CONCLUSION:The typical hepatic sinusoidal capillarization was detected in the early stage of liver fibrosis , and the deposition of LN in the liver sinusoidal walls was the mainly factor of formation of the consecutive basement mem -brane .
ABSTRACT
Objective:To study the effects of rat interleukin-10 (rIL-10) gene treatment on the expression of collagen , matrix metalloproteinase 13(MMP13) and their specific inhibitors the tissue inhibitor of metalloproteinase 1(TIMP1) in porcine serum in-duced liver fibrosis rats then to explore the anti-fibrotic effect of rL-10.Methods:Thirty SD rats were divided into normal control and fibrosis model group.Normal control group (group C) was intraperitoneally injected with 0.5 ml normal sodium twice a week for 8 week, while the fibrosis model group was injected with equal volume of pig serum for 8 week.At the beginning of the 5th week, fibrosis model group was further randomly divided into a fibrosis model subgroup ( group M ) , rIL-10 gene treatment subgroup ( group I ) and empty vector control subgroup(group P).Rats in group C and M were injected with Ringer’s solution as a reagent control via the tail vein weekly, rats in group I were injected with the rIL-10 plasmid pcDNA3-rIL-10, and rats in group P were injected with empty vector pcDNA3.All rats were sacrificed at the end of 8th week, and the liver tissue samples were collected to observe deposition of collegan in liver tissue by sirius red staining and detected the expression of MMP 13 and TIMP1 in the liver tissue by SP immunohistochemistry .Re-sults:Sirius red staining showed that the area of the collegan deposition was dramatically increased in fibrosis model subgroup and emp -ty vector control subgroup compared with the normal control group , and the area of the collagen deposition was dramatically decreased in rIL-10 gene treatment subgroup compared with the fibrosis model and empty vector control subgroup .Immunohistochemistry analysis showed that the expression of MMP 13 and TIMP1 in fibrosis model subgroup and empty vector control subgroup was significantly higher than the normal control group , but compared with normal control group , expression of MMP13 was significantly increased and expres-sion of TIMP1 was significantly decreased in rIL-10 gene treatment subgroup .Compared with fibrosis model subgroup and empty vector control subgroup, the expression of MMP13 and TIMP1 was dramatically decreased in rIL-10 gene treatment subgroup.Conclusion:rIL-10 gene treatment attenuates the area of collagen deposition in liver fibrosis rats associated with downregulation of TIMP 1.
ABSTRACT
Objective To investigate the clinicopathological features of renal cell carcinoma (RCC).Methods From December 1956 to August 2012,the clinicopathological features of RCC were studied in 705 cases and related literatures were reviewed.Results The diameter of RCC ranged from 0.6 to 18.0 cm,which the average size was 4.6 cm.The proportions of the clear cell,papillary,multilocular clear cell,chromophobe and unclassified histologic subtype were 88.9％ (627/705),4.1％ (29/705),3.3％ (23/705),1.3％ (9/705) and 2.4％ (17/705),respectively.According to the Fuhrman grading system,the proportions of grade 1,2,3,4 were 19.0％ (116/612),58.3％ (357/612),18.1％ (111/612)and 4.6％ (28/612),respectively.The rates of invasion into the renal pelvis,perirenal fat and vascular were 10.9％ (66/603),10.6％ (64/603) and 4.8％ (29/603),respectively.Of 705 cases,464 (76.6％)cases were in T1,65 (10.7％) cases in T2,73 (12.0％) cases in T3,and 4 (0.7％) cases in T4.As to the lymph node and distant metastasis,the rate was 2.8％ (17/606) and 3.5％ (21/606).The percentages of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ RCC were 74.3％ (450/606),9.9％ (60/606),11.7％ (71/606) and 4.1％(25/606),respectively.The 3-,5-,10-and 15-year disease-specific survival rate for RCC was 92.8％,86.9％,76.8％ and 55.5％,respectively.To those patients with clear cell RCC,the disease-specific survival at the same time point was 92.8％,88.1％,77.4％ and 55.4％,respectively.Multivariate analysis showed that the stage was the only independent prognostic factor for RCC.Conclusions Tumor stage of RCC is the independent prognostic factor for disease-specific survival.The evaluation of renal sinus invasion and lymph node should be noted in the diagnosis of RCC.
ABSTRACT
AIM:To investigate the expression of angiotensin-converting enzyme 2 (ACE2) in nephritic epithelium of primates. METHODS:The expression of ACE2 in Vero E6 cells was detected by the techniques of RT-PCR and immunocytochemistry (ICC) techniques. The distribution of ACE2 protein in kidney tissues of two Rhesus monkeys and two normal human cases was observed by immunohistochemistry (IHC) techniques. RESULTS:Vero E6 cells were found to express both ACE2 mRNA and protein. ACE2 protein was mainly located in epithelium of proximal tubules of Rhesus monkey and human kidney. CONCLUSION:The expression of ACE2 in epithelium of primate kidney may provide the condition for SARS-CoV entry,which may be one of the reasons for inducing renal damage in SARS patients.
ABSTRACT
Aim To establish a method of hydrodynamic-based transfection(HBT) and provide a means in rats of the gene therapy of liver diseases,which allowed an efficient expression of rIL-10 gene in rat liver.Methods Using rIL-10 gene as a reporter gene,different volumes and doses of plasmid DNA solutions were rapidly injected into rat tail vein,then the serum and the tissue of liver,kidney,lung,spleen and heart in different time were collected and the expression of rIL-10 was detected by the methods of RT-PCR,ELISA and immunochemistry.Results Using rIL-10 gene as a reporter gene,the results demonstrated that an efficient transfer and expression of rIL-10 in rat liver could be achieved by a rapid injection of a large volume of rIL-10 DNA solution into rat via tail vein.Maintaining a stable expression of rIL-10 in serum could be assessed by repeated administration.Conclusion The HBT was a simple,convenient and efficient method of gene transfer and expression in rats,which could be used as an effective means to study further gene therapy of rIL-10 in liver diseases.