RESUMO
Lung cancer is the most common cancer and the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer. Mutations of driver genes have major impacts on incidence and progression of lung cancer. Advances in molecular biology research and clinical research have promoted the discovery of rare tumor driver genes, as well as the development and application of new targeted drugs. Nearly 1% to 2% of NSCLCs harbor RET fusions, and this patient population may not respond well to traditional treatments like chemotherapy or radiation therapy. After the new highly selective RET inhibitors pralsetinib (BLU-667) and selpercatinib (LOXO-292) entered clinical application, the diagnosis and treatment of RET fusion positive NSCLC has made breakthrough progress. At present, there is a lack of guiding consensus on the standardized diagnosis and treatment of RET fusion-positive NSCLC in China. The Society of Cancer Precision of Chinese Anti-Cancer Association and Lung Cancer Expert Group of Chinese Medical Journal, invited 38 experts form respiratory medicine, medical oncology, oncology radiotherapy and pathology to form a consensus development group. Based on the existing research evidence, combined with China's clinical practice experience, a standardized process for the diagnosis and treatment of advanced RET fusion-positive NSCLC is proposed, including suitable populations and methods for RET gene fusion, treatment drug selection, treatment of resistance to highly selective RET inhibitors, and management of adverse reactions to treatment, with a view to providing guidance for clinicians.
Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , China , Consenso , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-ret/genéticaRESUMO
<p><b>OBJECTIVE</b>To explore the neuroprotective effects of electroacupuncture (EA) on hypoxic-ischemic encephalopathy (HIE) and to further investigate the role of glial cell line-derived neurotrophic factor (GDNF) family receptor member RET (rearranged during transfection) and its key downstream phosphatidylinositol 3 kinase (PI-3K)/protein kinase B (Akt) pathway in the process.</p><p><b>METHODS</b>A total of 220 seven-day-old SD rats (of either sex, from 22 broods) were randomly divided into two groups, one (30 rats) for sham-surgery group and the other (190 rats) for HIE model group. The HIE model was established using the left common carotid artery ligation method in combination with hypoxic treatment. The successfully established rats were randomly divided into five groups, including control model group, EA group, sham-EA group, antagonist group and antagonist plus electroacupuncture group, with 35 rats in each group. Baihui (GV 20), Dazhui (GV 14), Quchi (LI 11) and Yongquan (KI 1) acupoints were chosen for acupuncture. EA was performed at Baihui and Quchi for 10 min once a day for continuous 1, 3, 7 and 21 days, respectively. The rats were then killed after the operation and injured cerebral cortex was taken for the measurement of neurologic damage by hematoxylin-eosin (HE) staining and the degenerative changes of cortical ultrastructure by transmission electron microscopy. RET mRNA level and Akt protein level were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively.</p><p><b>RESULTS</b>EA could ameliorate neurologic damage of the first somatic sensory area (S1Tr) and alleviate the degenerative changes of ultrastructure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex.</p><p><b>CONCLUSION</b>EA has neuroprotective effects on HIE and could be a potential therapeutic strategy for HIE in the neonate. Activation of RET/Akt signaling pathway might be involved in this process.</p>
Assuntos
Animais , Feminino , Masculino , Western Blotting , Córtex Cerebral , Patologia , Eletroacupuntura , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Genética , Metabolismo , Hipóxia-Isquemia Encefálica , Genética , Patologia , Terapêutica , Degeneração Neural , Patologia , Neurônios , Patologia , Fármacos Neuroprotetores , Usos Terapêuticos , Proteínas Proto-Oncogênicas c-akt , Genética , Metabolismo , Proteínas Proto-Oncogênicas c-ret , Genética , Metabolismo , RNA Mensageiro , Genética , Metabolismo , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo RealRESUMO
REarranged during Transfection (RET) gene encodes a receptor tyrosine kinase and it was initially discovered as an in vitro transforming gene. For many years, RET has been involved in papillary thyroid carcinoma and medullary thyroid carcinoma. More recently, lung adenocarcinoma and chronic myelomonocytic leukemia samples have been found to display RET gene rearrangements. This knowledge is stimulating the search for protein kinase inhibitors to combat RET-driven malignancies.
Assuntos
Humanos , Adenocarcinoma , Carcinoma , Rearranjo Gênico , Leucemia Mielomonocítica Crônica , Pulmão , Neoplasias Pulmonares , Oncogenes , Fosfotransferases , Inibidores de Proteínas Quinases , Proteínas Tirosina Quinases , Transdução de Sinais , Glândula Tireoide , Neoplasias da Glândula Tireoide , TransfecçãoRESUMO
Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells, and accounts for 5% - 10% of all thyroid cancers. MTC is hereditary in about 25% of cases. Lymph node and distant metastasis can appear in an early time, so early diagnosis and treatment is essential. In this review, the main performance of laboratory and imaging are described. The current management and preventive measure are also described.