Delayed thrombocytopenia as a rare but serious adverse event secondary to immune checkpoint inhibitor: a case report.

Immune checkpoint inhibitors (ICIs) are a recent breakthrough in antitumor drugs, although their overall safety has not been fully defined. Compared to conventional chemotherapy, ICIs exhibit different patterns of immunotoxicity, and immune-related adverse events (irAEs) have an immunological basis that is more toxic than usual and have a broad spectrum of manifestations involving different organ systems. Early recognition of symptoms and timely intervention are very important in managing immune-related adverse events (irAEs). In this study, we report a case of delayed immune thrombocytopenia in a patient treated with nivolumab for small cell lung cancer (SCLC). We found that thrombocytopenia was associated with the presence of platelet antibodies, autoantibodies, and thyroglobulin antibodies, accompanied by a decrease in the number of helper T cells and regulatory T cells. Platelets returned to normal after the removal of antibodies by plasma exchanges and methylprednisolone. We hypothesized that thrombocytopenia in patients was an antibody-driven and T-cell-mediated process. Although these observations indirectly suggest that cytokine changes contribute to immune dysregulation during irAE, prospective validation is needed to explain the confounding etiologies that may contribute to cytokine dysregulation. Therefore, studying the relationship between T cell subpopulations, cytokines and irAE in a larger population may be crucial for identifying biomarkers for ICI.

MicroRNA-361-3p Inhibit the Progression of Lymphoma by the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: MicroRNA is involved in the development of lymphoma. It is reported that miR-361-3p has a tumor inhibitory effect, but its role in lymphoma is still unclear. The purpose of this study is to examine whether miR-361-3p can inhibit the development of lymphoma and further explore the related potential mechanism. METHODS: In this study, we first analyzed the biological function of miR-361-3p in transfected Raji that mimicked miRNA. We also analyzed the biological function of the whole population in stably expressed miR-361-3p transgenic cells. Next, we conducted a complete micro-gene network to test the genetic profile of differential expression of stable gene-modified cells. RESULTS: We found that miR-361-3p expression was often reduced in lymphoma cell lines. Cellular assays have shown a significant role in inhibiting the growth of miR-361-3p by inhibiting lymphoma proliferation and migration, and severely inhibiting the Wnt/ß-catenin series protein signal. Bioinformatics analysis shows that Wnt10A is a new target of miR-361-3p, which is confirmed by our mechanism research. It is confirmed that restoring Wnt10A can reduce the tumor inhibition of Wnt/ß-catenin during lymphoma progression and restore the normal signal of Wnt/ß-catenin series proteins. DISCUSSION: Our data indicate that miR-361-3p inhibits the Wnt/ß-catenin protein signal by locking Wnt10A, which is an important factor in inhibiting the tumor in the pathogenesis of lymphoma. The miR-361-3p/Wnt10A axis may be a promising target for the treatment of lymphoma.

The effective role of sodium copper chlorophyllin on the dysfunction of bone marrow mesenchymal stem cells in multiple myeloma via regulating TGF-ß1.

BACKGROUND: The osteoblast differentiation of bone marrow-derived stem cells (BMSCs) is impaired in multiple myeloma (MM). We investigated the effects of sodium copper chlorophyllin (SCC) on osteoblast differentiation ability of BMSCs from MM. METHODS: Clinical bone marrow samples were collected. Fluorescence Activated Cell Sorter (FACS) was used to identify surface markers of BMSCs. BMSCs were treated with different concentrations of SCC and cell viability was detected by MTT assay. Relative mRNA and protein expressions of transforming growth factor-ß1 (TGF-ß1), SMAD2/3, osteogenic differentiation indicators (RUNX2 and OCN) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Alkaline phosphatase (ALP) was stained for activity detection. Formation of calcium nodus of BMSCs was examined by Alizarin Red S staining. RESULTS: CD90 and CD105 were high-expressed, but CD34 and CD45 were not expressed in BMSCs. BMSCs in MM group showed a lower expression of TGF-ß1 and a lower degree of osteogenic differentiation. SCC enhanced activities of BMSCs, ALP activity, and formation of calcium nodus, activated TGF-ß1, SMAD2/3 pathway and increased RUNX2 and OCN expressions in BMSCs. Silencing TGF-ß1 reversed the effects of SCC on BMSCs in MM. CONCLUSION: SCC could effectively improve the proliferation and osteogenic differentiation of BMSCs in MM through regulating TGF-ß1.

Effects of triptolide on bone marrow-derived mesenchymal stem cells from patients with multiple myeloma.

Triptolide (TPL), an extract of the Chinese herb Tripterygium wilfordii Hook F, is a potent anti-inflammatory agent that further possesses anticancer activity. Its antiproliferative effects are well established. Only few studies have focused on TPL as a potential treatment in multiple myeloma (MM). In the current study, bone marrow-derived mesenchymal stem cells (BMMSCs) from patients with MM were isolated and treated with TPL at varying concentrations. Thalidomide is currently used as a positive control drug in the treatment of MM. Cell Counting kit-8 assays were performed to assess proliferation activity and flow cytometry with Annexin V-fluorescein/propidium iodide was used to detect cell apoptosis of TPL-treated BMMSCs. Reverse transcription-quantitative polymerase chain reaction assays were applied to measure interleukin (IL)-6, IL-1ß and stem cell factor (SCF or Kit ligand) mRNA expression and western blot assays were performed to analyze transcription factor p65 (P65) expression in TPL-treated BMMSCs. ELISA was applied to measure vascular endothelial growth factor (VEGF) levels in the supernatant of the cultured and treated BMMSCs. TPL treatment significantly inhibited BMMSC proliferation compared with the untreated control (P<0.05). At 48 h following TPL treatment, a Cell Counting kit-8 study was performed and the IC50 value was determined at 101.55±2.45 ng/ml. Apoptotic rates were observed to increase with increasing concentrations of TPL (P<0.001), and IL-6, IL-1ß and SCF mRNA expression was significantly decreased with increasing TPL (P<0.001). P65 expression following TPL treatment was significantly decreased compared with the untreated control (P<0.05). VEGF levels were significantly reduced in the presence of increasing amounts of TPL (P<0.05). These findings suggest that TPL inhibited BMMSC growth and improved the bone marrow hematopoietic microenvironment by decreasing IL-6, IL-1ß and SCF mRNA expression, subsequently inhibiting the proliferation of MM cells. Therefore, TPL may be used in the future to treat patients with MM.

Decitabine for the treatment of atypical chronic myeloid leukemia: A report of two cases.

Atypical chronic myeloid leukemia (aCML) is a hematopoietic stem/progenitor cell disorder, predominantly involving neutrophils. At present, a limited number of studies regarding the treatment of aCML have been published, and the therapies that are currently available exhibit unsatisfactory outcomes. In the present study, the cases of two aCML patients treated with decitabine (DCA) therapy who achieved remission are presented. A 48-year-old male, who presented with fatigue and a cough that had lasted two months, and a 69-year-old male who presented with dizziness, fatigue and shortness of breath with exercise, were diagnosed with aCML following bone marrow examination, flow cytometry and chromosome banding analysis. The two patients were treated with four cycles of DCA chemotherapy (20 mg/m2, days 1-5) and remission was achieved in each patient. The present study evaluated the clinical manifestations, diagnostic criteria and relevant treatment regimens of aCML, which may provide insights for the treatment of affected patients. Routine blood and bone marrow examinations were performed weekly prior to each cycle. Symptoms were relieved in both patients after the first cycle and the two patients were followed up for 3 months after completion of the final cycle. The findings of the current case report indicate that DCA may present an efficacious treatment for aCML.