No abstract

MOG-ON is not rare in Chinese demyelinating patients. It underwent a severe vision loss at onset but had relatively better visual recovery than patients with AQP4-ON. MOG-ON might have an unique pathogenesis different from AQP4-ON.

No abstract

Neuroendocrine carcinoma (NEC) of the breast, a distinct type of mammary carcinoma whose terminology was not proposed until 2003, has not been well recognized or studied. The aim of our study is to evaluate the clinicopathological features and outcomes of this type of tumor. We conducted a comparative study on 107 NEC patients and 475 invasive ductal carcinoma, not otherwise specified(IDC, NOS) patients from the Department of Pathology, Huashan Hospital, Fudan University, to determine the demographic, pathological, and clinical features at presentation, along with patient outcomes and prognostic factors. With an older age at presentation, NECs are more likely to be estrogen receptor(ER)/ progesterone receptor (PR) positive and human epidermal growth factor receptor 2 (HER-2) negative, and have a higher propensity for local recurrence and poorer overall survival(OS). Higher T classification, M classification, TNM stage, the expression of Ki67, and the absence of PR expression are prognostically of poorer OS and distant recurrence-free survival(DRFS). Distant metastasis is also a dependent prognostic factor. NEC of the breast is a distinct type of neoplasm with higher malignancy. Novel therapies such as the endocrine therapy should be explored and studies with larger case number and longer follow-up will be needed.

Introduction:Neratinib is a potent irreversible pan-ErbB tyrosine kinase inhibitor that has demonstrated antitumour activity and an acceptable safety profile in patients with human epidermal growth factor receptor (HER)-2-positive breast cancer and other solid tumours.Methods:This was a phase I/II, open-label, two-part study. Part 1 was a dose-escalation study to determine the maximum tolerated dose (MTD) of neratinib plus paclitaxel in patients with solid tumours. Part 2 evaluated the safety, efficacy, and pharmacokinetics of the combination at the MTD in patients with HER2-positive breast cancer.Results:Eight patients were included in the dose-escalation study; no dose-limiting toxicities were observed, and an MTD of oral neratinib 240 mg once daily plus intravenous paclitaxel 80 mg m−2 on days 1, 8, and 15 of each 28-day cycle was determined. A total of 102 patients with HER2-positive breast cancer were enrolled in part 2. The overall median treatment duration was 47.9 weeks (range: 0.1–147.3 weeks). Common treatment-emergent adverse events (all grades/grade ⩾3) included diarrhoea (92%/29% none grade 4), peripheral sensory neuropathy (51%/3%), neutropenia (50%/20%), alopecia (46%/0%), leukopenia (41%/18%), anaemia (37%/8%), and nausea (34%/1%). Three (3%) patients discontinued treatment due to an adverse event (mouth ulceration, left ventricular ejection fraction reduction, and acute renal failure). Among the 99 evaluable patients in part 2 of the study, the overall response rate (ORR) was 73% (95% confidence interval (CI): 62.9–81.2%), including 7 (7%) patients who achieved a complete response; an additional 9 (9%) patients achieved stable disease for at least 24 weeks. ORR was 71% among patients with 0/1 prior chemotherapy regimen for metastatic disease and no prior lapatinib, and 77% among those with 2/3 prior chemotherapy regimens for metastatic disease with prior lapatinib permitted. Kaplan–Meier median progression-free survival was 57.0 weeks (95% CI: 47.7–81.6 weeks). Pharmacokinetic analyses indicated no interaction between neratinib and paclitaxel.Conclusion:The combination of neratinib and paclitaxel was associated with higher toxicity than that of neratinib as a single agent, but was manageable with antidiarrhoeal agents and dose reductions in general. The combination therapy also demonstrated a high rate of response in patients with HER2-positive breast cancer. A phase III trial is ongoing to assess the benefit and risk of this combination in the first-line setting.

Objective: To investigate the role of myeloid-derived suppressor cells (MDSC) in cancer progression after the stress of operative removal and the potential treatment value of MDSC depletion.Summary Background Data: Surgery is the most important treatment strategy in breast cancer. Recent research has provided evidence that operations may promote cancer metastases under some circumstances.Methods: A mouse model of breast cancer (administration of the murine breast cancer 4T1 cells subcutaneously) and the stress of operation were used to compare immune responses and survival outcomes. Flow cytometry was performed to detect the expression of CD11b and Gr1 MDSCs in tumor tissues and lung metastases. Cytokine levels were detected with three-color flow cytometry and enzyme-linked immunosorbent assay (ELISA). MDSCs were isolated and co-cultured with 4T1 cells to identify any morphological change with immunofluorescence. The anti Gr-1 antibody was used to detect the function of the anti-Gr1 treatment in breast cancer.Results: The operative stress impaired the overall survival, leading to an increased number of MDSCs that preferentially infiltrated the tumor microenvironment and promoted tumor metastasis. In both in vitro and in vivo assays, MDSCs induced the epithelial-mesenchymal transition (EMT) of tumor cells through the up-regulation of TGF-beta1, VEGF, and IL-10. Furthermore, a treatment strategy of MDSC depletion was found to reduce pulmonary metastases after operations.Conclusions: The stress of operation could impair the overall survival in mice. The infiltrated MDSCs appear to induce EMT of tumor cells and increase metastases through the up-regulation of TGF-beta1, VEGF, and IL-10 levels. MDSC depletion could be a promising treatment strategy to prevent immune evasion after operations.

Chronic stress could induce cancer metastasis by constant activation of the sympathetic nervous system, while cellular mechanism remains obscure. The aim of this research is to explore the metastasis associated negative effect of chronic stress. The analysis of transcriptome sequencing implied that activation of STAT3 signaling pathway by downregulated miR-337-3p might be a potential mechanism to induce epithelial to mesenchymal transition (EMT) of cancer cell and promote metastasis under chronic stress. We also verified this biological process in further experiments. Downregulation of miR-337-3p could downregulate E-cadherin expression and upregulate vimentin expression in vitro and in vivo. STAT3, related signal pathways of which are involved in metastasis regulation, was directly targeted by miR-337-3p. In conclusion, the above results denoted that activation of miR-337-3p/STAT3 axis might be a potential pathway for the increasing metastasis of breast cancer under chronic stress.

No abstract