BackgroundOccult breast cancer (OBC) is a rare type of breast cancer that has not been well studied. The clinicopathological characteristics and treatment recommendations for OBC are based on a limited number of retrospective studies and thus remain controversial.Patients and methodsWe identified 479 OBC patients and 115,739 non-OBC patients from 2004 to 2014 in and the Surveillance, Epidemiology, and End Results (SEER) database. The clinicopathological characteristics and survival outcomes were compared between OBC and non-OBC patients. We used the propensity score 1:1 matching analysis to evaluate OBC vs non-OBC comparison using balanced groups with respect to the observed covariates. We further divided the OBC population into four groups based on different treatment strategies. Univariable and multivariable analyses were used to calculate and compare the four treatment outcomes within the OBC population.ResultsOBC patients were older, exhibited a more advanced stage, a higher rate of negative estrogen receptor and progesterone receptor status, a higher rate of HER2-positive status, and a higher rate of ≥10 positive lymph nodes, and were less likely to undergo surgical treatment than non-OBC patients. After adjustments for clinicopathological factors, the OBC patients exhibited a significantly better survival than the non-OBC patients (P<0.001). This result was confirmed in a 1:1 matched case–control analysis. Within the four OBC treatment groups, we observed no difference in survival among the mastectomy group, the breast-conserving surgery (BCS) group, and the axillary lymph node dissection (ALND)-only group. The multivariable analysis revealed that the sentinel lymph node dissection-only group had the worst prognosis (P<0.001). Conclusion: OBC has unique clinicopathological characteristics and a favorable prognosis compared with non-OBC. BCS plus ALND and radiotherapy showed a survival benefit that was similar to that of mastectomy for OBC patients.
The DosR regulon is believed to be a key factor in latency adaptation of Mycobacterium tuberculosis and is strongly induced by multiple stresses, including hypoxia. Previous studies have revealed reversible acetylation of the conserved core DNA-binding lysine residue 182 (K182) of DosR in M. tuberculosis. In this study, we demonstrated that acetylated K182 plays an important role in the DNA-binding ability of DosR and that acetylation of K182 completely abolished the affinity of DosR for DNA in vitro. Antibodies that specifically recognized acetyllysine at position 182 of DosR were used to monitor DosR acetylation. We found that in vitro acetylation of K182 could be removed by deacetylase Rv1151c and that either the deacetylase-deletion strain ∆npdA or treatment with a deacetylase inhibitor resulted in increased levels of K182 acetylation in vivo. The physiological significance of DosR acetylation was demonstrated by decreased levels of acetylated K182 in M. tuberculosis in response to hypoxia and by the effects of K182 acetylation on the transcript levels of DosR regulon genes. Since the DosR regulon plays a critical role during host infection by M. tuberculosis, our findings suggest that targeting DosR acetylation may be a viable strategy for antituberculosis drug development.
Background and Objectives: The influence of age at diagnosis of breast cancer upon the prognosis of patients with different immunohistochemical (IHC)-defined subtypes is still incompletely defined. Our study aimed at examining the association of age at diagnosis and risk of breast cancer-specific mortality (BCSM). Methods: 172,179 eligible breast cancer patients were obtained for our study cohort using the Surveillance, Epidemiology, and End Results database from 2010 to 2015. Patients were classified into four IHC-defined subtypes according to their ER, PgR, and HER2 status. Kaplan-Meier plots were used to describe BCSM among patients in different age groups. A Cox proportional hazards model was used for multivariate analysis. A multivariable fractional polynomial model within the Cox proportional hazards model was used to evaluate the relationship between age at diagnosis and the risk of BCSM. Results: For the whole cohort, the median follow-up time was 43 months. Patients younger than 40 years and those older than 79 years presented with the worst BCSM (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.03-1.23, and HR 3.52, 95% CI 3.23-3.83, respectively, p < 0.01, with age 40-49 years as the reference). The log hazard ratios of hormone receptor (HoR)(+)/HER2(-) patients formed a quadratic relationship between age at diagnosis and BCSM, but not in the other three subtypes of breast cancer. In the HoR(+)/HER2(-) subtype, patients younger than 40 years had worse BCSM than those aged at 40-49 years (HR 1.26, 95% CI 1.10-1.45, and p < 0.01). Conclusions: Women diagnosed with HoR(+)/HER2(-) breast cancer younger than 40 years or older than 79 years of age suffer higher rates of cancer-specific mortality. Young age at diagnosis may be particularly prognostic in HoR(+)/HER2(-) breast cancer.
Background: Taxanes are frontline chemotherapeutic drugs for patients with triple-negative breast cancer (TNBC); however, chemoresistance reduces their effectiveness. We hypothesized that the molecular profiling of tumor samples before and after neoadjuvant chemotherapy (NAC) would help identify genes associated with drug resistance. Methods: We sequenced 10 samples by RNA-seq from 8 NAC patients with TNBC: 3 patients with a pathologic complete response (pCR) and the other 5 with non-pCR. Differentially expressed genes that predicted chemotherapy response were selected for in vitro functional screening via a small-scale siRNAs pool. The clinical and functional significance of the gene of interest in TNBC was further investigated in vitro and in vivo , and biochemical assays and imaging analysis were applied to study the mechanisms. Results: Synaptotagmin-like 4 (SYTL4), a Rab effector in vesicle transport, was identified as a leading functional candidate. High SYTL4 expression indicated a poor prognosis in multiple TNBC cohorts, specifically in taxane-treated TNBCs. SYTL4 was identified as a novel chemoresistant gene as validated in TNBC cells, a mouse model and patient-derived organoids. Mechanistically, downregulating SYTL4 stabilized the microtubule network and slowed down microtubule growth rate. Furthermore, SYTL4 colocalized with microtubules and interacted with microtubules through its middle region containing the linker and C2A domain. Finally, we found that SYTL4 was able to bind microtubules and inhibit the in vitro microtubule polymerization. Conclusion: SYTL4 is a novel chemoresistant gene in TNBC and its upregulation indicates poor prognosis in taxane-treated TNBC. Further, SYTL4 directly binds microtubules and decreases microtubule stability.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.