Objective To understand the research progress and future prospects of the growth arrest specific protein 6/Axl receptor tyrosine kinase (Gas6/Axl) signaling pathway in gastrointestinal malignant tumors. Method Retrieve relevant literature on the Gas6/Axl signaling pathway in gastrointestinal malignant tumors and analyze and summarize. Results The Gas6/Axl signaling pathway was abnormally upregulated and activated in gastrointestinal malignancies, leading to malignant cell proliferation, invasion, and metastasis, thereby promoting the occurrence and development of gastrointestinal malignancies. At present, in the field of gastrointestinal cancer, the research of Gas6/Axl signaling pathway mainly involved tumor angiogenesis, tumor drug resistance, mesenchymal epithelial transformation, and tumor microenvironment. Conclusions The Gas6/Axl signaling pathway plays a critical role in governing various cellular processes and downstream effects. Its aberrant expression contributes to the development and advancement of gastrointestinal malignancies through diverse mechanisms. Thoroughly exploring the involvement of the Gas6/Axl signaling pathway in gastrointestinal tumors is of utmost significance, as it holds the potential to unveil novel therapeutic targets for effective management of gastrointestinal malignancies.
The incidence and mortality of esophageal cancer in China rank the fifth and fourth, respectively, with squamous carcinoma accounting for more than 90%. Currently, the treatment of esophageal squamous carcinoma mainly includes surgery, chemotherapy, radiotherapy, and endoscopic treatment. However, the 5-year survival rate is only about 20%. At present, the treatment of esophageal squamous carcinoma seems to reach a plateau. Thus, it is urgent to develop new and more effective drugs and treatments. In this paper, the clinical research progresses of epidermal growth factor receptor (EGFR)- targeted therapy of esophageal squamous carcinomas were summarized, including anti-EGFR monoclonal antibodies, such as cetuximab and nimotuzumab, and EGFR-tyrosine kinase inhibitor, such as gefitinib, erlotinib, and ecclinib.
Patients with locally advanced thyroid cancer often face challenges in achieving radical surgery during initial diagnosis. This has become a significant hurdle in the treatment of thyroid cancer. With the continuous development of systemic therapy for thyroid cancer, several studies have demonstrated that neoadjuvant therapy can shrink tumors in some patients, thereby increasing the chances of complete resection and improving prognosis. Targeted therapy plays a crucial role as a core component of neoadjuvant treatment. Simultaneously, the potential efficacy of immunotherapy has gained attention, showing promising prospects. We aim to summarize the research progress and existing issues regarding neoadjuvant therapy for locally advanced thyroid cancer. We look forward to more high-quality clinical studies providing robust evidence for neoadjuvant therapy in locally advanced thyroid cancer, expanding the breadth of treatment options.
Objective To investigate the expressions of vascular endothelial growth factor-C (VEGF-C) and its receptor Flt-4 in hepatocellular carcinoma (HCC), in order to analyze the relationships among their expressions, angiogenesis, lymph-genesis, and clinicopathologic features of HCC. Methods Sixty-two cases of HCC and 15 cases of normal hepatic tissue were studied with immunohistochemical method in order to inspect the expressions of VEGF-C and Flt-4, and to calculate the microvessel density (MVD) marked by CD34 and the lymphatic vessel density (LVD) marked by Flt-4. Besides their correlations, their relations with clinicopathologic features of HCC were further analyzed. Results The positive rates of VEGF-C and Flt-4 were obviously higher in HCC than those in normal hepatic tissue (Plt;0.05, Plt;0.01). The expression of VEGF-C in HCC was remarkably related with portal vein tumor emboli, histological differentiation of HCC, and postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). The expression of Flt-4 in HCC was also related with histological differentiation and postoperative recurrence (Plt;0.05, Plt;0.01). MVD was related with tumor size, TNM clinical stage, histological differentiation, portal vein tumor emboli, and postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). LVD was related with histological differentiation, postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). Additionally, there was positive correlation between VEGF-C and Flt-4, MVD or LVD, Flt-4 and MVD or LVD, MVD and LVD, respectively (Plt;0.01). Conclusions VEGF-C and Flt-4 are highly expressed in HCC, and are related with postoperative recurrence, are positive correlated with MVD and LVD. It suggests that VEGF-C/Flt-4 might has an effect on progression and prognosis of HCC through promoting angiogenesis and lymph-genesis.
ObjectiveTo explore the clinical features of myasthenia gravis (MG) harboring both acetylcholine receptor antibody (AChRAb) and muscle-specific tyrosine kinase antibody (MuSKAb) positivity.MethodsWe searched PubMed, Web of Science, Embase and China National Knowledge Infrastructure databases (from inception to November 2016), to collect the case reports of MG with both AChRAb and MuSKAb positivity. Along with one case discovered in Department of Neurology, West China Hospital, the clinical data of the cases were retrospectively analyzed.ResultsA total of 13 double-seropositive MG patients were enrolled in this study, demonstrating a marked female predominance (including 1 male and 12 females) and a younger age at onset [(31.07±24.77) years]. During the disease course, 10 of the included patients presented severe bulbar involvement, dyspnea and neck weakness, with myasthenic crisis in 6 individuals. Among the 11 patients with detailed records, abnormal thymus glands comprised 4 thymus hyperplasia and one thymoma. While the response to oral pyridostigmine was unsatisfactory in 11 double-seropositive MG patients, ranging from mild benefit to overt intolerance; the patients treated with plasma exchange (3/3), rituximab (1/1) or corticosteroid (7/12) improved dramatically, with other immumosuppressants and intravenous immunoglobulin partially responsive. Moreover, 5 patients undergoing thymectomy improved markedly or partially.ConclusionsCompared with MG patients with MuSKAb positivity merely, the condition of the double-seropositive MG patients seem to be more severe and further inclined to myasthenic crisis. The incidence of abnormal thymus, such as thymus hyperplasia, is higher. Thymectomy may be an effective treatment for such patients.
The tyrosine kinase activity of epidermal growth factor receptor (EGFR) plays a key role in tumor cell proliferation, invasion, migration, and drug resistance. Studies have shown that non-small cell lung cancer patients with somatic driver gene EGFR mutations are sensitive to and can benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Nevertheless, EGFR-TKIs-related adverse events should not be ignored. Common adverse events such as diarrhea, acne-like rash and paronychia are usually manageable; although the incidence of interstitial lung disease is low, once it occurs, it is a serious threat to patients' life, and its pathogenesis is still unclear. There is very limited animal experimental and clinical research evidence on the potential mechanism of EGFR-TKIs-related interstitial lung disease in the available literature. Based on this, this article reviews the association between EGFR-TKIs and interstitial lung disease, at the same time, also discusses the research progress of EGFR-TKIs-related interstitial lung disease in combination with cytotoxic drugs or immunotherapeutic drugs and EGFR-TKIs, in order to provide a reference for the prevention and treatment of EGFR-TKIs-related interstitial lung disease in clinical practice in the future.
Objective To evaluate the effects of two different epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs) , Gefitinib and Erlotinib, on lung fibrosis induced by bleomycin.Methods Forty BALB/c female mice were randomly divided into four groups, ie. a control group( saline given orally and intratracheally) , a fibrosis group( saline given orally with bleomycin instillation) , a Gefitnib group( Gefitnib 20 mg/kg given orally with bleomycin instillation) , and an Erlotinib group ( Erlotinib25 mg/kg given orally with bleomycin instillation) . Bleomycin ( 3 mg/kg) was intratracheally instilled on the first day. Gefitinib or Erlotinib was given orally daily and normal saline as control. Then they were sacrificed by abdominal aortic bleeding 14 days after the bleomycin instillation. The left lung was stained with HE and Masson’s trichrome staining respectively for pathological examination. Total EGFR and phosphorylated EGFR were detected by immunohistochemistry. Hydroxyproline ( HYP) assay was performed in the right lung.Results Both Gefitinib and Erlotinib significantly reduced lung collagen accumulation and the content of HYP. Immunohistochemistry revealed that phosphorylation of EGFR in lung mesenchymal cells induced by bleomycin was inhibited. Furthermore, there was no difference between Gefitinib and Erlotinib in inhibiting lung fibrosis. Conclusion Our findings suggest that, in the preclinical setting, EGFR-TKIs may have aprotective effect on lung fibrosis induced by bleomycin.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
Abstract:Objective To observe the expression of calcium-dependent proline-rich tyrosine kinase-2（Pyk2） in myocardium of rheumatic heart disease, the relationship between its role and cardiac fibrosis and clinical significance. Methods The blue myocardium collagen stain were analysed after Masson staining in 30 patients with rheumatic heart disease （RHD group） and 6 normal myocardium specimens （control group）. The contents of hyaluronic acid （HA）, laminin（LN） and type IV collagen（IV-C） were detected by radio-immunity method,and the expressions of Pyk2 protein and messenger ribonucleic acid（mRNA） were explored by immunohistochemistry methods and reverse transcriptase polymerase chain reaction （RT PCR）,then the correlations of these results were statistically analyzed. Results The contents of HA,LN and IV C in RHDgroup increased compared to control group（174.95±76.14μg/L vs. 70.06±15.63μg/L, 153. 86 ± 20. 72μg/L vs. 90.01±14. 11μg/L, 95. 26±7.66μg/L vs. 63. 21±10.62μg/L; P= 0.003, 0. 013, 0. 035）. The Pyk2 absorption and the ratio of Pyk2 mRNA/glyceraldehyde phosphate dehydrogenase （GAPDH） in RHD group were significantly higher than those in control group （0. 325 ± 0. 032 vs. 0.106±0.013, 0.870±0.085 vs. 0.573±0.042; P=0.048, 0.006）.There were positive correlativity between the expression of Pyk2 protein and HA, LN and IV-C （r=0. 611, 0. 743, 0. 829, P〈0. 01）, there were positive correlativity between the expression of Pyk2 mRNA and LN, IV-C （r=0. 794, 0. 766, P〈0.05）. Conclusion Pyk2 may play a key role in the proceeding of cardiac fibrosis in rheumatic heart disease by increasing collagen synthesis in myocardium.
ObjectiveTo investigate role and mechanism of protein tyrosine phosphatase 1B (PTP1B) in jejunoileal bypass to treating rats with type 2 diabetes mellitus (T2DM). MethodsTwenty-four T2DM SD rats and 24 normal SD rats were selected randomly by using random number table, then the SD rats with T2DM were randomly divided into jejunoileal bypass operation (DJBO, n=12) group and sham operation (DSO, n=12) group, the SD rats with normal food diet were randomly divided into jejunoileal bypass operation (NJBO, n=12) group and sham operation (NSO, n=12) group. Subsequently, fasting body weight (FBW), fasting plasma glucose (FPG), fasting insulin (FINS), and homeostasis model-insulin resistant (HOMA-IR) index of rats in each group were tested at different time points (before operation, on week 4 and 8 after operation). In addition, expression of PTP1B protein in skeletal muscle was determined by immunohistochemical staining and Western blot method respectively. Results① The FBW before making T2DM model had no significant difference between the rats with high-fat diet and with normal diet (P > 0.05), which on week 4 or 8 after making T2DM model in the rats with high-fat diet was significantly heavier than that in the rats with normal diet (P < 0.05). ② Before jejunoileal bypass operation, the FBW, FPG, FINS, and HOMA-IR index in the DJBO group and the DSO group were significantly higher than those in the NJBO group and the NSO group (P < 0.05), respectively, which had no significant differences between the DJBO group and the DSO group (P > 0.05) and between the NJBO group and the NSO group (P > 0.05). ③ Compared with the values before jejunoileal bypass operation, the FBW, FPG, FINS, and HOMA-IR index on week 4 or 8 after jejunoileal bypass operation were significantly decreased in the DJBO group (P < 0.05); the FBW was significantly increased on week 4 or 8 after jejunoileal bypass operation in the DSO group and the NSO group (P < 0.05), and on week 8 after jejunoileal bypass operation in the NJBO group (P < 0.05). The other indexes had no significant differences between before and after jejunoileal bypass operation in the DSO group, the NSO group, or the NJBO group (P > 0.05). ④ On week 8 after jejunoileal bypass operation, the expression of PTP1B protein in the DSO group was significantly higher than that in the DJBO group, the NSO group or the NJBO group (P < 0.05), which in the DJBO group was significantly higher than that in the NSO group (P < 0.05) or the NJBO group (P < 0.05), which had no significant difference between the NJBO group and the NSO group (P > 0.05). ConclusionJejunoileal bypass could effectively improve insulin resistance and decrease FPG level and FBW of T2DM rats through inhibiting expression of PTP1B protein in skeletal muscle of rat with T2DM.