Thyroid Metastases from Triple-Negative Breast Cancer with High PD-L1 Expression - A Rare Presentation.

Thyroid metastases secondary to triple-negative breast cancer are sporadic. Diagnosis usually requires fine needle aspiration biopsy (FNAB) and immunohistochemistry. There are no treatment guidelines for this type of cancer, and to date, reports of chemotherapy combined with immunotherapy in thyroid metastases are very rare. Here, we first report the effectiveness of anti-PD-1 inhibitor in combination with chemotherapy for the treatment of metastatic thyroid cancer secondary to advanced triple-negative breast cancer with high expression of programmed cell death ligand 1 (PD-L1). Following six cycles of albumin paclitaxel (400mg d1/21 days) plus PD-1 antibody inhibitor (Sindilizumab 200mg d1/21 days), the patient experienced significant relief of neck swelling and obstructive feeding, both the thyroid metastases and the right breast lesion regressed completely following six cycles of treatment. Chemotherapy combined with immunotherapy may provide a new direction for unresectable advanced thyroid metastases.

Analysis of lncRNAs profiles associated with ferroptosis can predict prognosis and immune landscape and drug sensitivity in patients with clear cell renal cell carcinoma.

Ferroptosis is a novel kind of iron- and reactive oxygen-induced cell death, investigation into ferroptosis-associated long noncoding RNAs (FALs) in clear cell renal cell carcinoma (ccRCC) is scarce. The goal of the research was to look at FALs' possible predictive significance, as well as their interaction with the immune microenvironment and therapeutic responsiveness of ccRCC. The Cancer Genome Atlas database was employed to retrieve RNA sequencing data from 530 individuals with ccRCC. Patients with ccRCC were randomly assigned to one of two groups: training or testing. Pearson's correlation analysis through the identified ferroptosis-related genes was implemented to screen for FALs. Finally, a FALs signature composed of eight lncRNAs was discovered for predicting survival outcomes in ccRCC patients. ccRCC patients in the training, testing, and overall cohorts were separated into low-risk and high-risk groups based on their risk score. The FALs signature was identified to be an independent factor for overall survival in the multivariate Cox analysis (hazard ratio = 1.013, 95% confidence interval = 1.008-1.018, p < 0.001). A clinically prognostic nomogram was created depending on the FALs signature and clinical characteristics. The nomogram provides greater clinical practicability and may reliably estimate patients' overall survival. The FALs signature may additionally precisely represent ccRCC's immunological environment, immunotherapy reaction, and drug sensitivity. The eight FALs and their signature provide precise and reliable methods for evaluating the clinical effects of in ccRCC patients, and they could be biological markers and targets for therapy.

Pyroptosis and its role in cancer.

Programmed cell death (PCD) is mediated by specific genes that encode signals. It can balance cell survival and death. Pyroptosis is a type of inflammatory, caspase-dependent PCD mediated by gasdermin proteins, which function in pore formation, cell expansion, and plasma membrane rupture, followed by the release of intracellular contents. Pyroptosis is mediated by caspase-1/3/4/5/11 and is primarily divided into the classical pathway, which is dependent on caspase-1, and the non-classical pathway, which is dependent on caspase-4/5/11. Inflammasomes play a vital role in these processes. The various components of the pyroptosis pathway are related to the occurrence, invasion, and metastasis of tumors. Research on pyroptosis has revealed new options for tumor treatment. This article summarizes the recent research progress on the molecular mechanism of pyroptosis, the relationship between the various components of the pyroptosis pathway and cancer, and the applications and prospects of pyroptosis in anticancer therapy.

MIR503HG Overexpression Inhibits the Malignant Behaviors of Osteosarcoma Cells by Sponging miR-103a-3p.

Osteosarcoma (OS) is the most representative primary bone tumour in children and teenagers. This study explored the regulatory effects of long noncoding RNA MIR503HG (MIR503HG) on the biological functions of OS cells, and further investigated the potential mechanism of MIR503HG function exertion by analyzing the microRNA-103a-3p (miR-103a-3p) in OS cells and tissues. The expression of MIR503HG was examined using reverse transcription-quantitative PCR. OS cell proliferation was assessed by CCK-8 assay. Transwell assay was used to evaluate the migration and invasion of OS cells. The interaction between MIR503HG and miR-103a-3p was detected using the Dual-luciferase reporter assay. Forty-six paired OS tissues were collected, and the expression and correlation of MIR503HG and miR-103a-3p were evaluated. The expression of MIR503HG were significantly decreased in both OS cells and tissues. Over-expression of MIR503HG inhibited OS cell proliferation, migration and invasion. miR-103a-3p was directly targeted by MIR503HG in OS cells, and mediated the inhibitory effects of MIR503HG on OS cell malignant behaviors. miR-103a-3p expression was upregulated in OS tissues, which was negatively correlated with MIR503HG expression levels. The expression of MIR503HG was associated with OS patients' tumor size, differentiation, distant metastasis and clinical stage. Decreased MIR503HG in OS tissues and cell lines served as a tumor suppressor by inhibiting OS cell malignant behaviors through sponging miR-103a-3p. The findings of this study may provide evidence for the development of novel therapeutic targets of OS.

Comprehensive Analysis of Transcriptomic Profiles Identified the Prediction of Prognosis and Drug Sensitivity of Aminopeptidase-Like 1 (NPEPL1) for Clear Cell Renal Cell Carcinoma.

Aminopeptidase-like 1 (NPEPL1) is a member of the aminopeptidase group that plays a role in the development and progression of various diseases. Expression of NPEPL1 has been reported to be involved in prostate, breast, and colorectal cancers. However, the role and mechanism of NPEPL1 in clear cell renal cell carcinoma (ccRCC) are unclear. The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases were used to predict the relationship between clinicopathological features and NPEPL1 expression. Changes in immune status and drug sensitivity with NPEPL1 expression were analyzed by the "CIBERSORT" function in R software. The results found that NPEPL1 expression was upregulated in ccRCC tissues, with expression progressively increasing with ccRCC stage and grade. Patients with high NPEPL1 expression presented with a poor prognosis across different clinicopathological features. Univariate and multivariate Cox regression analyses indicated that aberrant NPEPL1 expression was an independent risk factor for ccRCC. The nomogram showed that NPEPL1 expression improved the accuracy of predicting the prognosis of ccRCC patients. The Gene Ontology (GO) term enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that NPEPL1 may be involved in the development of ccRCC through the voltage-gated calcium channel complex, channel activity, cAMP signaling pathway, and oxytocin signaling pathway. The coexpression analysis found that NPEPL1 altered tumor characteristics by interacting with related genes. The "CIBERSORT" analysis showed that elevated NPEPL1 expression was followed by an enrichment of regulatory T cells and follicular helper T cells in the microenvironment. The drug sensitivity analysis found patients with high NPEPL1 expression had a higher benefit from axitinib, cisplatin, and GSK429286A. In conclusion, upregulation of NPEPL1 expression was involved in ccRCC prognosis and treatment. NPEPL1 could be used as a therapeutic target to guide clinical dosing.

Severe cardiotoxicity in 2 patients with thymoma receiving immune checkpoint inhibitor therapy: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) are currently approved for a variety of cancers and their use is expanding from advanced disease to first-line metastatic and adjuvant therapies. With the wide application of immunotherapy, its adverse reactions are also the object we need to pay attention to. Among its adverse events, immune myocarditis has low morbidity, but a high fatality rate. Simultaneously, the unique biological properties of thymic epithelial tumors (TETs) increase the risk of immune-mediated toxicity. PATIENT CONCERNS: Patient 1 underwent chest computed tomography (CT) in April 2019 due to physical examination, which showed pleural metastasis of thymoma. Tissue puncture under CT guidance revealed type B2 thymoma. First-line chemotherapy with docetaxel combined with nedaplatin was administered, and apatinib was administered as a maintenance therapy after chemotherapy. After a regular review, progression of the disease was observed in April 12, 2021.Patient 2 underwent anterior mediastinal tumor resection on August 2, 2019, due to the completion of the CT examination during myasthenia gravis to suggest a thymic tumor. Postoperative pathology revealed type B3 thymoma. The patient underwent local radiotherapy from October 2019 to November 2019. After irregular reexamination, the patient's condition was stable. Disease progression has been observed in June 2021. DIAGNOSIS: Both patients were diagnosed with thymoma. INTERVENTIONS: Patient 1 was administered one cycle of gemcitabine, carboplatin, and sintilimab after disease progression. Patient 2 was treated with docetaxel and cisplatin for 2 cycles, and tislelizumab was added in the second cycle. OUTCOMES: Both patient 1 and patient 2 developed immune myocarditis after one cycle of immunotherapy. The difference was that patient 1 died within a few days. After a few days of active treatment for patient 2, the immune myocarditis did not improve significantly, and the patient chose to give up the treatment and go home. The shocking outcome is that the patient remains alive and stable. LESSONS: Oncologists should be wary of ICI-related myocarditis owing to its early onset, nonspecific symptoms, and fulminant progression, especially when ICIs are used in combination. The patient's cardiac condition should be assessed before administering ICIs.