Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping mutation.However,its bioavailability in the cerebrospinal fluid(CSF)in hu...Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping mutation.However,its bioavailability in the cerebrospinal fluid(CSF)in humans has not been fully elucidated.Moreover,information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited.Here,we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation.He was urgently hospitalized due to leptomeningeal metastasis.We administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance status.The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF,with a penetration rate(CSF/plasma)of 1.83%.These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.展开更多
Background Glanzmann thrombasthenia （GT） is an autosomal recessive bleeding disorder characterized by the tendency to hemorrhage and the inability of platelets to aggregate in response to agonists. GT is caused by a...Background Glanzmann thrombasthenia （GT） is an autosomal recessive bleeding disorder characterized by the tendency to hemorrhage and the inability of platelets to aggregate in response to agonists. GT is caused by a defect of the platelet glycoprotein lib/Ilia complex. The objective of this study was to describe the clinical features and the genetic cause of GT in a 6-year-old girl from south China. Methods A three-generation family was studied. The proband patient aged 6 years and her parents undertook examinations of platelet counts, blood film, bleeding time, platelet aggregation, and flow cytometry. All coding exons of the ITGA2B and ITGB3 genes were amplified by polymerase chain reaction （PCR）, and direct sequencing was performed for mutational screening on the patient and normal controls consisted of 52 healthy blood donors. Reverse transcription PCR was conducted to test for exon skipping. Results The proposita patient showed dispersing platelets, prolonged bleeding time, and severely reduced platelet aggregation in response to the physiological agonists adenosine diphosphate （ADP）, epinephrine, collagen, and ristocetin. Flow cytometric measurements showed that the contents of allb and 133 were significantly decreased. Sequencing results demonstrated two different types of heterozygous mutations existed in the allb gene （c.2930delG and IVS15-1delG）. The compound mutations were also confirmed in the patient＇s mother and father separately. Conclusions The allbβ3 deficiency of the proband was caused by two compound ITGA2B mutations, which were first reported in Chinese GT patients. The IVS15-1delG was first confirmed to cause an exon skipping.展开更多
文摘Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping mutation.However,its bioavailability in the cerebrospinal fluid(CSF)in humans has not been fully elucidated.Moreover,information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited.Here,we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation.He was urgently hospitalized due to leptomeningeal metastasis.We administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance status.The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF,with a penetration rate(CSF/plasma)of 1.83%.These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.
文摘Background Glanzmann thrombasthenia （GT） is an autosomal recessive bleeding disorder characterized by the tendency to hemorrhage and the inability of platelets to aggregate in response to agonists. GT is caused by a defect of the platelet glycoprotein lib/Ilia complex. The objective of this study was to describe the clinical features and the genetic cause of GT in a 6-year-old girl from south China. Methods A three-generation family was studied. The proband patient aged 6 years and her parents undertook examinations of platelet counts, blood film, bleeding time, platelet aggregation, and flow cytometry. All coding exons of the ITGA2B and ITGB3 genes were amplified by polymerase chain reaction （PCR）, and direct sequencing was performed for mutational screening on the patient and normal controls consisted of 52 healthy blood donors. Reverse transcription PCR was conducted to test for exon skipping. Results The proposita patient showed dispersing platelets, prolonged bleeding time, and severely reduced platelet aggregation in response to the physiological agonists adenosine diphosphate （ADP）, epinephrine, collagen, and ristocetin. Flow cytometric measurements showed that the contents of allb and 133 were significantly decreased. Sequencing results demonstrated two different types of heterozygous mutations existed in the allb gene （c.2930delG and IVS15-1delG）. The compound mutations were also confirmed in the patient＇s mother and father separately. Conclusions The allbβ3 deficiency of the proband was caused by two compound ITGA2B mutations, which were first reported in Chinese GT patients. The IVS15-1delG was first confirmed to cause an exon skipping.
