ABSTRACT
Objective: Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which binds to the EGF receptor, plays an important role in the occurrence and development of inflammation in various diseases. HB-EGF mediates the progression of ovarian cancer and is associated with disease prognosis. Thus, a specific humanized antibody to HB-EGF with high affinity is important. Methods: In this study, a humanized domain antibody (VH) against HB-EGF was discovered through phage display technology. The domain antibody was expressed in HB2151 cells and purified from the supernatant using protein L, and were used to test the its effect in invasion and migration of ovarian cancer SKOV3. Results: A domain antibody against HB-EGF was discovered, with a dissociation constant of â¼30 nM. Functional assays indicated that the domain antibody inhibited the functions of HB-EGF in promoting invasion and migration of SKOV3 cells. Conclusions: The selected domain antibody is a potential tool for developing novel drugs or therapies to combat ovarian cancer.
Subject(s)
Ovarian Neoplasms , Female , Humans , Heparin-binding EGF-like Growth Factor/immunology , Immunoglobulins/analysis , Immunoglobulins/immunology , Ovarian Neoplasms/metabolism , PrognosisABSTRACT
Chimeric antigen receptor T cell therapy (CART) has achieved excellent results in the past 10 years for treating of leukemia. Treatment of B cell acute lymphoblastic leukemia by anti-CD19 CART can reach a complete remission rate of 90%. Although CART has greatly improved the treatment of patients with leukemia and lymphoma, as many as one-third of the patients can suffer disease relapse after CART. The tumor surface marker CD19 is negative in most the patients who relapse, and these patients display high expression of CD19 before treatment. In this review, the current causes of CD19-negative relapses after CD19 CART against leukemia, and the mechanisms of target escape are briefly summarized. Also, methods and strategies for treating relapse to provide references for the treatment of leukemia relapse are also discussed.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Antigens, CD19/genetics , Antigens, CD19/metabolism , Cell- and Tissue-Based Therapy , Humans , Immunotherapy, Adoptive/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Receptors, Chimeric Antigen/genetics , RecurrenceABSTRACT
Existing data on the prognosis and clinicopathological features of patients with metastatic renal cell carcinoma (mRCC) are limited. This study aims to investigate the prognostic value and clinicopathological features of different metastatic sites in patients with mRCC. A dataset from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database consisting of 18 registries (1973-2015) was selected for a retrospective mRCC cohort study. Information was included on the metastatic sites in lung, bone, liver, and brain. Kaplan-Meier analysis was applied to compare the survival distribution. Univariate and multivariate Cox regression models were used to analyze survival outcomes. From the SEER database, a total of 10,410 patients with primary mRCC from 2010 to 2015 were enrolled in this cohort study. Analysis indicated that 54.9%, 37.7%, 19.5%, and 10.4% of patients were found to have lung, bone, liver, and brain metastasis, respectively. There was a significantly higher risk for sarcomatoid RCC patients to develop liver metastasis as compared to patients with clear cell RCC. The median survival for patients with lung, bone, liver, or brain metastasis was 7 months, 7 months, 4 months, and 5 months, respectively. Various clinicopathological features and prognostic values are associated with different metastatic sites. Understanding these differences may enable targeted pre-treatment assessment of primary mRCC and personalized curative intervention for patients.
Subject(s)
Bone Neoplasms/secondary , Brain Neoplasms/secondary , Carcinoma, Renal Cell/secondary , Kidney Neoplasms/pathology , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Aged , Bone Neoplasms/mortality , Brain Neoplasms/mortality , Carcinoma, Renal Cell/mortality , Female , Humans , Kidney Neoplasms/mortality , Liver Neoplasms/mortality , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , SEER ProgramABSTRACT
Digestive system cancers, including hepatocellular carcinoma, colorectal and gastric tumors, are characterized by high rates of incidence and mortality. Digestive cancers are difficult to diagnose during the early stages, and the side effects of chemotherapy are often severe and may outweigh the therapeutic benefits. Chimeric antibody chimeric antigen receptor T cell (CAR-T) therapy, a novel immunotherapy, has achieved excellent results for the treatment of hematological tumors. However, CAR-T treatment of solid tumors has struggled due to a lack of target specificity, a difficult tumor microenvironment, and T cell homing. Despite the challenges, CAR-T treatment of digestive cancers is progressing. Combining CAR-T with other targets and/or modifying the CAR may represent the most promising approaches for future treatment of digestive cancers.
