ABSTRACT
BACKGROUND: Chronic myelomonocytic leukemia (CMML), a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms, has a generally poor prognosis, and easily progresses to acute myeloid leukemia. The simultaneous incidence of hematologic malignancies and solid tumors is extremely low, and CMML coinciding with lung malignancies is even rarer. Here, we report a case of CMML, with ASXL1 and EZH2 gene mutations, combined with non-small cell lung cancer (lung squamous cell carcinoma). CASE SUMMARY: A 63-year-old male, suffering from toothache accompanied by coughing, sputum, and bloody sputum for three months, was given a blood test after experiencing continuous bleeding resulting from a tooth extraction at a local hospital. Based on morphological results, the patient was diagnosed with CMML and bronchoscopy was performed in situ to confirm the diagnosis of squamous cell carcinoma in the lower lobe of the lung. After receiving azacitidine, programmed cell death protein 1, and platinum-based chemotherapy drugs, the patient developed severe myelosuppression and eventually fatal leukocyte stasis and dyspnea. CONCLUSION: During the treatment and observation of CMML and be vigilant of the growth of multiple primary malignant tumors.
ABSTRACT
BACKGROUND: The development of peripheral T-cell lymphoma (PTCL) after chemotherapy for Hodgkin's lymphoma (HL) is rare, and highly aggressive TCL/leukemia has not been reported to date. The relationship between HL and PTCL needs further exploration to understand the pathogenesis of metachronous lymphoma (ML) and find effective treatment options. We report a patient with ML, whose biopsy of a right cervical lymph node initially confirmed classical HL (CHL). CASE SUMMARY: We report a patient with ML, whose biopsy of a right cervical lymph node initially confirmed CHL, with typical reed-sternberg cells expressing CD30 and PAX-5. T-cell leukemia/lymphoma occurred 3 years after treatment, and a lymph node biopsy at the onset confirmed PTCL, nonspecific type, expressing CD3, CD4 and CD8. The patient was treated with standard doses of chemotherapy, programmed cell death-ligand 1 monoclonal antibody, and chidamide, all of which failed to achieve complete remission. The patient was diagnosed with refractory state, and eventually died of leukocyte stasis. CONCLUSION: The accuracy of the diagnosis needs to be confirmed when chemotherapeutic drugs are not effective.
ABSTRACT
Background: Studies have shown that the natural products of Astragalus membranaceus (AM) can effectively interfere with a variety of cancers, but their mechanism of action on breast cancer remains unclear. Triple-negative breast cancer (TNBC) is associated with a severely poor prognosis due to its invasive phenotype and lack of biomarker-driven-targeted therapies. In this study, the potential mechanism of the target composition acting on TNBC was explored by integrated pharmacological models and in vitro experiments. Materials and Methods: Based on the Gene Expression Omnibus (GEO) database and the relational database of Traditional Chinese Medicines (TCMs), the drug and target components were initially screened to construct a common network module, and multiattribute analysis was then used to characterize the network and obtain key drug-target information. Furthermore, network topology analysis was used to characterize the betweenness and closeness of key hubs in the network. Molecular docking was used to evaluate the affinity between compounds and targets and obtain accurate combination models. Finally, in vitro experiments verified the key component targets. The cell counting kit-8 (CCK-8) assay, invasion assay, and flow cytometric analysis were used to assess cell viability, invasiveness, and apoptosis, respectively, after Astragalus polysaccharides (APS) intervention. We also performed western blot analysis of key proteins to probe the mechanisms of correlated signaling pathways. Results: We constructed "compound-target" (339 nodes and 695 edges) and "compound-disease" (414 nodes and 6458 edges) networks using interaction data. Topology analysis and molecular docking were used as secondary screens to identify key hubs of the network. Finally, the key component APS and biomarkers PIK3CG, AKT, and BCL2 were identified. The in vitro experimental results confirmed that APS can effectively inhibit TNBC cell activity, reduce invasion, promote apoptosis, and then counteract TNBC symptoms in a dose-dependent manner, most likely by inhibiting the PIK3CG/AKT/BCL2 pathway. Conclusion: This study provides a rational approach to discovering compounds with a polypharmacology-based therapeutic value. Our data established that APS intervenes with TNBC cell invasion, proliferation, and apoptosis via the PIK3CG/AKT/BCL2 pathway and could thus offer a promising therapeutic strategy for TNBC.
