Relationship between gene mutations and protein expressions of PDGFR α and C-kit in gastrointestinal stromal tumors.

OBJECTIVE: To investigate the relationship between gene mutations and protein expressions of PDGFR α and C-kit in gastrointestinal stromal tumors (GIST) and its significance in tumorigenesis. METHODS: Single strand conformation polymorphism-polymerase chain reaction (PCR-SSCP), immunohistochemistry and Western blot were used to detect the gene mutations in PDGFR α and C-kit and their protein expressions in 105 cases of GIST specimens. RESULTS: In 105 cases of GIST, PDGFR α gene mutation was found in 12 cases (11.4%), which was common in the stomach- derived spindle cell GIST. C-kit gene mutation was found in 58 cases (55.2%), which was common in the small intestine. Mutations of PDGFR α is in 12 cases of GIST were stronger than the C-kit mutations in GIST, normal gastrointestinal tissues and schwannomas. No significant correlation was found between mutations and C-kit protein expression (P>0.05), while the protein expression of PDGFR α was significantly correlated with mutations (P<0.0001). CONCLUSION: Mutations of PDGFR α and C-kit plays an important role in part of GIST tumorigenesis. Mutation sites were related with original sites and histological types. Most protein expressions were closely related to their gene mutations in GIST.

Transfusion-related acute lung injury in paediatric surgical patients: a retrospective study.

BACKGROUND: Little is known about the occurrence of transfusion-related acute lung injury(TRALI) in Chinese paediatric patients. As such, a retrospective review of medical records from January 2008 to December 2011 was undertaken. OBJECTIVE: To determine the incidence of TRALI and its risk factors in children (age <14 years). STUDY DESIGN AND METHODS: All medical records of Sheng Jing Hospital from January 2008 to December 2011 were reviewed retrospectively using the hospital's record system. Paediatric surgical patients who had been diagnosed clinically with acute lung injury were included. Transfusion data were collected, together with risk factors such as sepsis and aspiration. RESULTS: In total, 1495 patients were involved in the study. Thirty-five cases were analysed further as they had acute lung injury, pulmonary oedema and respiratory distress. TRALI was confirmed in two of these cases. The average duration of transfusion was found to be significantly longer in patients with TRALI compared with controls, and the percentage of female donors was significantly higher for patients with TRALI. CONCLUSION: The incidence of TRALI was found to be lower than reported previously, but TRALI is under-recognised, under-reported and undertreated.

A novel NF1 mutation in a Chinese patient with giant café-au-lait macule in neurofibromatosis type 1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Combination of IFNγ and chemotherapeutic agents increase TRAIL sensitivity of neuroblastoma cell lines.

OBJECTIVE: Aim of the study was to further evaluate the role of caspase 8 and death receptors (DR) in the TRAIL-induced apoptosis of neuroblastoma (NB) cell lines. METHODS: Caspase 8 mRNA expression was monitored by RT-PCR. Caspase 8, DR5 and DR4 protein expression were monitored by Western blot analysis. The effects of IFNγ, TRAIL, IFNγ+TRAIL, caspase 8 inhibitor+TRAIL and IFNγ+chemotherapeutic agents+TRAIL on the growth and apoptosis of NB cells were detected with MTT and flow cytometry. The relative caspase 8 activity was measured with colorimetric assay. RESULTS: Caspase 8 expression was induced by IFNγ in the NB cell line SKNDZ. TRAIL alone did not induce apoptosis compared with controls but a combination of IFNγ+TRAIL and IFNγ+chemotherapeutic agents+TRAIL significantly induced cell apoptosis in SY5Y cells. Etoposide and doxorubicin induced DR5 but not DR4 in NB cell lines. SKNDZ cells expressing caspase 8 after treatment with IFNγ were still resistant to TRAIL but sensitive to TRAIL after the induction of DR5. CONCLUSIONS: Sensitization of NB cells to TRAIL may be mediated by the upregulation of caspase 8 with IFNγ and DR5 with chemotherapeutic agents. This suggests that caspase 8 and death receptors play a very important role in TRAIL-induced apoptosis of NB cells and a combination of IFNγ, TRAIL and chemotherapeutic agents may be a new and interesting anticancer treatment strategy for NB.

Fluid therapy of acute brain edema in children.

The clinical experience with a new fluid therapy in children with acute brain edema complicated by infectious disease is reported. The clinical data of a retrospective group of 192 patients and a prospective study of 1,302 and 2,279 patients is summarized. One method of fluid therapy for children with acute brain edema is traditional; fluid intake is restricted to less than 1,200 mL/m(2) daily (60 mL/kg daily). Another method is the new fluid therapy regimen used in our prospective study, in which dehydration and fluid replenishment are individualized. On the first day the fluid intake of patients who survived varied from 40 to 208 mL/kg daily. The mortality rate in the two prospective groups was 19.66% in 1,302 patients and 17.2% in 2,279 patients, significantly lower than the 63.5% in the retrospective group (192 patients) (P <0.001). This result indicates that a wide range of fluid intake for children with acute brain edema is allowable during the first days of treatment. The appropriate dehydration and fluid replenishment should be individualized based on close observation of the patient's condition.