ABSTRACT
BACKGROUND: Brain metastases (BM) are very rare in gastric adenocarcinoma (GaC), and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness. However, its pathogenesis remains unclear. Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor (MET) amplification. Therefore, treatment with savolitinib, a small molecule inhibitor of c-Met, was selected. CASE SUMMARY: A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain. Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy. The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department. Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification. After discussing treatment options with the patient, savolitinib tablets were administered. After a month of treatment, the intracranial lesions shrank considerably. CONCLUSION: BM is very rare in advanced GaC, especially in meningeal cancer, that is characterized by rapid disease deterioration. There are very few effective treatment options available; however, technological breakthroughs in genomics have provided a basis for personalized treatment. Furthermore, MET amplification may be a key driver of BM in gastric cancer; however, this conclusion requires further investigation.
ABSTRACT
BACKGROUND: Over the past 20 years, we have gained a deep understanding of the biological heterogeneity of diffuse large B cell lymphoma (DLBCL) and have developed a range of new treatment programs based on the characteristics of the disease, bringing us to the era of immune-chemotherapy. However, the effectiveness and molecular mechanisms of targeted-immunotherapy remain unclear in DLBCL. Targeted-immunotherapy may be beneficial for specific subgroups of patients, thus requiring biomarker assessment. CASE SUMMARY: Here, we report a case of MCD subtype DLBCL with MYD88L265P and CD79B mutations, considered in the initial stage as lymphoplasmic lymphoma (LPL) or Waldenstrom macroglobulinemia (WM). Flow cytometry supported this view; however, the immunohistochemical results of the lymph nodes overturned the above diagnosis, and the patient was eventually diagnosed with MCD subtype DLBCL. The presence of a monoclonal IgM component in the serum and infiltration of small lymphocytes with a phenotype compatible with WM into the bone marrow led us to propose a hypothesis that the case we report may have transformed from LPL/WM. CONCLUSION: This highlights the possible transformation from WM to DLBCL, CD79B mutation may be a potential biomarker for predicting this conversion.
ABSTRACT
OBJECTIVE: To detect the expression levels of CD4(+) CD25(+) CDl27(low) Treg cells, TGF-ß and Notch1 mRNA in peripheral blood of the patients with idiopathic thrombocytopenic purpura (IPT) before and after treatment, and to investigate their significance in the pathogenesis of ITP. METHODS: Peripheral blood was collected from 30 newly diagnosed patients with ITP and 20 normal controls, then the number of CD4(+) CD25(+) Treg and CD4(+) CD25(+) CDl27(low) Treg were detected by the flow cytometry. Plasma TGF-ß level was determined by ELISA. Total RNA was extracted and the expression level of Notch1 mRNA was measured by real-time Q-PCR. RESULTS: The expression levels of CD4(+) CD25(+) CDl27(low) Treg and CD4(+) CD25(+) Treg in newly diagnosed ITP group were significantly lower than those in normal controls. After treatment, the proportion of Tregs increased to (5.17% ± 0.74%) and (4.16% ± 0.68%), and was higher than that in newly diagnosed patients. The TGF-ß level in peripheral blood of newly-diagnosed patients was obviously lower than that in normal controls, and was (961.53 ± 60.10) ng/L after treatment and was significantly higher than that in newly diagnosed patients; the expression level of Notch1 mRNA in peripheral blood of patients in newly-diagnosed group was obviously lower than that in control, and was (1.35 ± 0.10) after treatment that was higher than that in newly-diagnosed group. After treatment, the proportion of Treg cells, level of TGF-ß and erpression level of Notch1 mRNA in effective group were higher than those in effective group, improved group and ineffective group, and there was significant difference (P <0.01). The expression level of TGF-ß and Notch1 mRNA in ITP patients possitively correlated to CD4(+) CD25(+) CDl27(low) (P <0.01). CONCLUSIONS: The levels of CD4(+) CD25(+) CDl27(low) Treg, TGF-ßand Notch1 mRNA in peripheral blood of the patients with ITP are significantly lower than those of normal control, suggesting that there is significant abnormal immunoregulation in ITP patients. In the ITP patients the levels of CD4(+) CD25(+) CDl27(low) Treg postively correlated with Notch1 mRNA expression, indicating that Notch signal may be revalent to Treg's immunosuppression function.
Subject(s)
Purpura, Thrombocytopenic, Idiopathic , T-Lymphocytes, Regulatory , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , RNA , RNA, Messenger , Real-Time Polymerase Chain Reaction , Receptor, Notch1 , Transforming Growth Factor betaABSTRACT
Mycophenolate mofetil (MMF) is a newly developed immunosuppressor, widely used in allogeneic bone marrow transplant. The purpose of this study was to evaluate the effects of mycophenolic acid (MPA), the active metabolite of MMF in vivo, on the maturation and immunologic function of murine bone marrow-derived dendritic cells (DC), and to explore the underlying mechanisms of MMF in graft versus host disease. Cultured DC were treated with MPA at doses of 0.01 and 0.1 micro mol/L. The immunophenotype of DC in control and treated groups was analyzed by flow cytometry. The capability of antigen presentation and the stimulatory activity of the DC on allogeneic T cells were tested by incorporation of (3)H-TdR and mixed lymphocyte reaction respectively. IL-12 production in culture supernatant and the levels of Th1/Th2 cytokines such as IL-2, IFN-gamma, IL-4 and IL-10 in mixed lymphocyte reaction (MLR) supernatant were examined by ELISA assay. The results showed that DCs cultured in the presence of MPA expressed low levels of CD40, CD80 and CD86, and exhibited weak activity in stimulating the proliferation of allogeneic T cells and antigen presenting function with a concurrent reduction of IL-12 production. Allogeneic T cells stimulated by MPA-treated DC expressed higher levels of Th2 cytokines such as IL-4 and IL-10 but lower levels of Th1 cytokines such as IL-2 and IFN-gamma than those stimulated by DC without MPA treatment. It is concluded that MPA, and hence MMF, exerts a negative effect on the maturation and immunologic functions of DC in culture, and drives a shift of Th1 to Th2 cytokines in MLR.
