Therapeutic Efficacy, Safety and Predictive Indicators of Eribulin Plus Anti-Angiogenic Medicine for Metastatic Breast Cancer.

OBJECTIVE: To evaluate the efficacy and safety of eribulin plus anti-angiogenic medicine in metastatic breast cancer (MBC), and explore the potential biomarkers. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medical Oncology, Xi'an International Medical Centre Hospital, Xi'an, China, from May 2022 to 2023. METHODOLOGY: A total of 40 MBC patients treated with eribulin were enrolled. Patients were divided into two groups based on whether they received eribulin monotherapy or combined therapy. Median progression-free survival (mPFS), the time from the start of erbium treatment to the time of disease progression, was calculated using the Kaplan-Meier method. RESULTS: The eribulin plus anti-angiogenic medicine treatment group had a significantly prolonged mPFS compared to the group without anti-angiogenic medicine treatment (7.0 months vs. 2.0 months, p <0.001). The multivariate analysis identified that the combination of anti-angiogenic therapy (HR = 0.043, p = 0.004) and the occurrence of grade 3-4 neutropenia after the treatment were two predictive factors for longer PFS (HR = 0.322, p = 0.009). In contrast, prior resistance to taxane was predictive of shorter PFS (HR = 4.583, p = 0.019). Other clinic-pathological factors were not significantly associated with PFS. Fisher's exact test showed no significant increase in treatment-related adverse events (all grades) after combination with anti-angiogenic medicine. CONCLUSION: The eribulin plus anti-angiogenic combination may act as a potential therapy for late-line MBC patients with clinically beneficial therapeutic effects. KEY WORDS: Metastatic breast cancer, Eribulin, Anti-angiogenic therapy, Predictive indicators of efficacy.

Endoscopic-ultrasound-guided biliary drainage with placement of electrocautery-enhanced lumen-apposing metal stent for palliation of malignant biliary obstruction: Updated meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced (ECE) delivery of lumen-apposing metal stent (LAMS) is gradually being recognized as a viable palliative technique for malignant biliary obstruction after endoscopic retrograde cholangiopancreatography (ERCP) failure. However, most of the studies that have assessed its efficacy and safety were small and heterogeneous. Prior meta-analyses of six or fewer studies that were published 2 years ago were therefore underpowered to yield convincing evidence. AIM: To update the efficacy and safety of ECE-LAMS for treatment of biliary obstruction after ERCP failure. METHODS: We searched PubMed, EMBASE, and Scopus databases from the inception of the ECE technique to May 13, 2022. Primary outcome measure was pooled technical success rate, and secondary outcomes were pooled rates of clinical success, reintervention, and adverse events. Meta-analysis was performed using a random-effects model following Freeman-Tukey double-arcsine transformation in R software (version 4.1.3). RESULTS: Fourteen eligible studies involving 620 participants were ultimately included. The pooled rate of technical success was 96.7%, and clinical success was 91.0%. Adverse events were reported in 17.5% of patients. Overall reintervention rate was 7.3%. Subgroup analyses showed results were generally consistent. CONCLUSION: ECE-LAMS has favorable success with acceptable adverse events in relieving biliary obstruction when ERCP is impossible. The consistency of results across most subgroups suggested that this is a generalizable approach.

Bone metastatic carcinoma with EGFR amplification and mutation: A case report and literature review.

RATIONALE: Mutations in the epidermal growth factor receptor (EGFR) gene are highly prevalent in non-small cell lung cancer, while rare in other cancers. Primarily it's hardly present in bone metastases from cancer of unknown primary (BMCUP). Currently, no specific treatment options for bone metastases from unknown primary cancers exist. PATIENT CONCERNS: The right shoulder and back pain of a 72-years-old man had been persistent for 2 weeks and had developed worse on 1 particular day. The right upper arm was compromised, which also hindered the arm's ability to raise and flex, and nighttime sleep was impacted. After applying the analgesic patch externally, the symptoms did not improve. No coughing or sputum production, chest tightness, shortness of breath, acid reflux, belching, abdominal pain, distension, diarrhea, backache, hematuria, black or bloody feces, or other discomforts appeared over the course of the illness. DIAGNOSES: The patient had a particular type of bone metastases from primary cancers with genetic test results indicating EGFR amplification and mutation. INTERVENTIONS: A third-generation tyrosine kinase inhibitors drug, oral Osimertinib 80 mg once a day with bisphosphonates anti-bone destruction treatment was performed on schedule. OUTCOMES: Following treatment, the patient's tumor-related symptoms were significantly improved by controlling the disease for up to 11 months and providing great pain relief. LESSON: EGFR-based genetic testing has emerged as a key measure for targeted therapy in non-small cell lung cancer. However, there are fewer relevant studies for other tumor types like BMCUP. Combined with literature reviews and our report, we provide evidence that targeting EGFR mutations according to the "basket theory" for the treatment of BMCUP is effective.

Unlocking phenotypic plasticity provides novel insights for immunity and personalized therapy in lung adenocarcinoma.

Background: Unlocking phenotype plasticity (UPP) has been shown to have an essential role in the mechanism of tumor development and therapeutic response. However, the clinical significance of unlocking phenotypic plasticity in patients with lung adenocarcinoma is unclear. This study aimed to explore the roles of unlocking phenotypic plasticity in immune status, prognosis, and treatment in patients with lung adenocarcinoma (LUAD). Methods: Differentially expressed genes (DEGs) and clinical information of UPP were selected from the cancer genome atlas (TCGA) database, and the GO, KEGG enrichment analyses were performed. The independent prognostic genes were determined by univariate and multivariate Cox regression, and the UPP signature score was constructed. Patients with LUAD were divided into high- and low-risk groups according to the median of score, and the immunocytes and immune function, the gene mutation, and drug sensitivities between the two groups were analyzed. Finally, the results were validated in the GEO database. Results: Thirty-nine significantly DEGs were determined. Enrichment analysis showed that UPP-related genes were related to protein polysaccharides and drug resistance. The prognostic results showed that the survival of patients in the high-risk group was poorer than that in the low-risk group (p < 0.001). In the high- and low-risk groups, single nucleotide polymorphism (SNP) and C > T are the most common dissent mutations. The contents of immune cells were significantly different between high- and low-risk groups. And the immune functions were also significantly different, indicating that UPP affects the immunity in LUAD. The results from TCGA were validated in the GEO. Conclusion: Our research has proposed a new and reliable prognosis indicator to predict the overall survival. Evaluation of the UPP could help the clinician to predict therapeutic responses and make individualized treatment plans in patients with LUAD.

SLC22A8: An indicator for tumor immune microenvironment and prognosis of ccRCC from a comprehensive analysis of bioinformatics.

Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies worldwide. SLC22A8 plays a key role in renal excretion of organic anions. However, its role in ccRCC remains unclear; therefore, this study aimed to elucidate the relationship between SLC22A8 and ccRCC. The The Cancer Genome Atlas-kidney renal clear cell carcinoma cohort was included in this study. The Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between SLC22A8 expression and clinicopathological characteristics. Multifactorial analysis and Kaplan-Meier survival curves were adopted for correlation between SLC22A8 expression and clinicopathological parameters and overall survival. Utilizing the UALCAN database, the correlation of the expression levels of SLC22A8 DNA methylation in ccRCC was explored. Immunological characterization of SLC22A8 regarding the ccRCC tumor microenvironment was carried out by the single sample Gene Set Enrichment Analysis algorithm and the CIBERSORT algorithm. With the CellMiner database, the analysis of the association between SLC22A8 gene expression and drug sensitivity was further performed. Eventually, gene ontology and Kyoto Encyclopedia of Gene and Genome enrichment analyses were applied to identify the functional and signaling pathways involved in SLC22A8. SLC22A8 expression is associated with age, grade, stage, and tumor status. SLC22A8 protein expression levels, phosphorylated protein levels, and DNA methylation expression levels were lower in ccRCC tissues than in normal tissues, and low methylation levels predicted poor overall survival. Comprehensive analysis of tumor immune infiltration and the tumor microenvironment indicated a higher level of overall immunity in the SLC22A8 low expression group. Gene Enrichment Analysis results showed that low expression of SLC22A8 was associated with immune pathways, such as phagocytosis recognition and humoral immune response. SLC22A8 expression was significantly correlated with survival and immune infiltration in ccRCC and can be used as a prognostic biomarker for ccRCC.