Triple Negative Breast Cancer (TNBC) is a highly heterogeneous subtype of breast cancer that lacks the expression of oestrogen receptors, progesterone receptors and human epidermal growth factor receptor 2. Although TNBC is sensitive to chemotherapy, the overall outcomes of TNBC are worse than for other breast cancers, and TNBC is still one of the most fatal diseases for women. With the discovery of antigens specifically expressed in TNBC cells and the developing technology of monoclonal antibodies, chimeric antigen receptors and cancer vaccines, immunotherapy is emerging as a novel promising option for TNBC. This review is mainly focused on the tumour microenvironment and host immunity, Triple Negative Breast Cancer and the clinical treatment of TNBC, novel therapies for cancer and immunotherapy for TNBC, and the future outlook for the treatment for TNBC and the interplay between the therapies, including immune checkpoint inhibitors, combination of immune checkpoint inhibitors with targeted treatments in TNBC, adoptive cell therapy, cancer vaccines. The review also highlights recent reports on the synergistic effects of immunotherapy and chemotherapy, antibody–drug conjugates, and exosomes, as potential multifunctional therapeutic agents in TNBC.
Background/Aims: Prostate cancer (PCa) is one of the main cancers that damage males’ health severely with high morbidity and mortality, but there is still no ideal molecular marker for the diagnosis and prognosis of prostate cancer. Methods: To determine whether the differentially expressed circRNAs in prostate cancer can serve as novel biomarkers for prostate cancer diagnosis, we screened differentially expressed circRNAs using SBC-ceRNA array in 4 pairs of prostate tumor and paracancerous tissues. A circRNA-miRNA-mRNA regulatory network for the differential circRNAs and their host genes was constructed by Cytoscape3.5.1 software. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was performed to confirm the microarray data. Results: We found 1021 differentially expressed circRNAs in PCa tumor using SBC-ceRNA array and confirmed the expression of circ_0057558, circ_0062019 and SLC19A1 in PCa cell lines and tumor tissues through qRT-PCR analysis. We demonstrated that combination of PSA level and two differentially expressed circRNAs showed significantly increased AUC, sensitivity and specificity (0.938, 84.5% and 90.9%, respectively) than PSA alone (AUC of serum PSA was 0.854). Moreover, circ_0057558 was correlated positively with total cholesterol. The functional network of circRNA-miRNA-mRNA analysis showed that circ_0057558 and circ_0034467 regulated miR-6884, and circ_0062019 and circ_0060325 regulated miR-5008. Conclusion: Our results demonstrated that differentially expressed circRNAs (circ_0062019 and circ_0057558) and host gene SLC19A1 of circ_0062019 could be used as potential novel biomarkers for prostate cancer.
Early relapse after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a tremendous influence on the long-term survival outcomes of ICC patients. The purpose of our study was to investigate risk factors for early tumor relapse and confirm whether early relapse was correlated with ICC patients' long-term survival outcomes. Three hundred and twenty-two consecutive ICC patients undergoing partial hepatectomy at Liver Surgery Department of Zhongshan Hospital (Fudan University, Shanghai, China) between January 2005 and December 2011 were included in this retrospectively study. The definition of early relapse had been described as tumor relapse within 24 months after hepatectomy in ICC patients. We identified a total of 168 ICC patients with early relapse and 23 ICC patients with late relapse after hepatectomy. From the time of relapse, the long-term survival outcomes were worse among patients who had early vs. late relapse (median OS 16.5 vs. 44.7 months, respectively; P < 0.0001). The overall survival of the early relapse group was lower than that of the late relapse group (P < 0.0001). Multivariate Cox regression analysis indicated that multiple tumors (hazard ratio [HR], 1.951; 95% CI, 1.382–2.755; P < 0.001), lymphonodus metastasis (HR, 1.517; 95% CI, 1.061–2.168; P = 0.022), and higher serum CA19-9 levels (HR, 1.495; 95% CI, 1.095–2.039; P = 0.011) were independent risk factors of early relapse. Moreover, multiple tumors (HR, 1.641; 95% CI, 1.120–2.406; P = 0.011), lymphonodus metastasis (HR, 2.008; 95% CI, 1.367–2.949; P < 0.001), elevated NLR (HR, 1.921; 95% CI, 1.331–2.774; P < 0.001) and higher serum CA19-9 levels (HR, 1.990; 95% CI, 1.409–2.812; P < 0.001) were independent predictors of overall survival for ICC patients with early relapse. Collectively, our findings demonstrated that multiple tumors, lymphonodus metastasis, and higher serum CA19-9 levels were associated with the increased risks of early relapse and worse prognoses of ICC after curative-intent resection.
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