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1.
J Cancer Res Clin Oncol ; 150(5): 271, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780840

ABSTRACT

OBJECTIVE: Previous research has shown that both temozolomide (TMZ) and PD-1/L1 inhibitors (PD-1/L1) alone exhibit certain potential in the treatment of non-small cell lung cancer (NSCLC) with brain metastases (BM), in this study, we will explore combining the two in order to seek new effective treatment options for NSCLC with BM. MATERIAL AND METHODS: During 2021.1 to 2023.12, we collected the date of these pretreated-NSCLC with BM who accept the treatment of TMZ and PD-1/L1, the objective response ratio (ORR), progression-free survival (PFS) and overall survival (OS) were set as the primary endpoint, meanwhile, the toxicity of such regimen was also recorded. RESULTS: About 42 patients are enrolled, our primary analysis demonstrated that the ORR of such regimen toward NSCLC with BM was 26.19%, with Approximate intracranial and extracranial lesion ORR was 6% and 20% respectively, the DCR was about 64.29%, the mean PFS and OS was about 4 m and 8.5 m. Further analysis indicated that the efficiency correlated with the diagnosis-Specific Graded Prognostic Assessment (ds-GPA) score. Moreover, the toxicity can also be tolerated, indicating the application potential of such regimen against NSCLC with BM. CONCLUSIONS: Our results exhibited that with tolerated toxicity, the combination of TMZ and PD-1/L1 shows promising efficiency against NSCLC with BM, this would be of great significance for the treatment of NSCLC with brain metastasis. However, due to the limitation of sample and retrospective property, the real value of such regimen needed to be further confirmed in the future.


Subject(s)
Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Temozolomide , Humans , Temozolomide/therapeutic use , Temozolomide/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Brain Neoplasms/secondary , Brain Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Retrospective Studies , Male , Middle Aged , Female , Aged , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/administration & dosage , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Programmed Cell Death 1 Receptor/antagonists & inhibitors , B7-H1 Antigen/antagonists & inhibitors
2.
Anticancer Drugs ; 33(1): e730-e733, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34387589

ABSTRACT

EGFR and BRAF V600E mutations are both early driven and usually mutually exclusive. We report the case of a 59-year-old woman diagnosed with advanced lung adenocarcinoma harboring coexisting EGFR exon 18 G719A and BRAF V600E mutations. She experienced a long-term response to oral afatinib, with a progression-free survival rate of 33 months and an overall survival rate of 11 years. Lung adenocarcinoma with synchronous EGFR G719A and BRAF V600E mutations is rare and has not been previously reported. This case highlights the importance of an adequate response to afatinib and provides an optimal therapeutic option for such patients.


Subject(s)
Adenocarcinoma of Lung/drug therapy , Afatinib/therapeutic use , Antineoplastic Agents/therapeutic use , Lung Neoplasms/drug therapy , Adenocarcinoma of Lung/genetics , ErbB Receptors/genetics , Female , Humans , Lung Neoplasms/genetics , Middle Aged , Proto-Oncogene Proteins B-raf/genetics
3.
Biochem Biophys Res Commun ; 458(3): 476-482, 2015 Mar 13.
Article in English | MEDLINE | ID: mdl-25680464

ABSTRACT

Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitro proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain/pathology , Glioma/genetics , Glioma/pathology , Tetraspanins/genetics , Up-Regulation , Antineoplastic Agents, Alkylating/pharmacology , Apoptosis/drug effects , Brain/drug effects , Brain/enzymology , Brain/metabolism , Brain Neoplasms/drug therapy , Brain Neoplasms/enzymology , Cell Line, Tumor , Dacarbazine/analogs & derivatives , Dacarbazine/pharmacology , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Gene Expression Regulation, Neoplastic , Glioma/drug therapy , Glioma/enzymology , Humans , Neoplasm Grading , RNA Interference , Temozolomide , Tetraspanins/metabolism
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