Cells can secrete extracellular vesicles (EVs) to communicate with neighboring or distant cells by EVs which are composed of a lipid bilayer containing transmembrane proteins and enclosing cytosolic ...proteins, lipids, and nucleic acids. Breast Cancer is the most frequently diagnosed malignancy with more than 1 million new cases each year and ranks the leading cause of cancer mortality in women worldwide. In this review, we will discuss recent progresses of the roles and mechanisms of cancer-derived EVs in metastatic breast cancer, with a special attention on tumor microenvironment construction, progression, and chemo/radiotherapy responses. This review also covers EV roles as biomarker and therapeutic target in clinical application.
Pancreatic cancer is one of the most lethal tumors across the world with an overall 5-year survival rate of 9%, and great efforts have been devoted in early diagnosis and treatment in the past ...decades. Competing endogenous RNAs are novel and specific regulatory mechanisms of gene expression, and researches have indicated its important roles in tumor regulation. In this study, we explored the circ-0050102 expression in pancreatic cancer and its impacts on tumor malignant phenotypes and further investigated the correlations among circ-0050102, miR-1182 and NPSR1. Results of real-time quantitative PCR showed that circ-0050102 expressed higher in pancreatic cancers compared with that in adjacent normal tissues. In cell functional experiment, downregulation of circ-0050102 could suppress cell proliferation, migration and invasion ability, boost cell apoptosis and arrest cell cycle in both PANC-1 and CFPAC-1 cells. Furthermore, allogeneic transplantation in nude mice was performed and results showed that the inhibition of circ-0050102 could slow down tumor formation in vivo. Mechanism research suggested that circ-0050102 could downregulate miR-1182, while miR-1182 could not influence the expression of circ-0050102, and miR-1182 could directly target at NPSR1 and suppress it. Moreover, circ-0050102 could reverse the effects of si-NPSR1 on pancreatic cancer cells. In conclusion, we identified that circ-0050102 played an important role in promoting pancreatic cancer by regulating the miR-1182/NPSR1 pathway.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory human malignancies. F-box only proteins (FBXO) are the core components of SKP1-cullin 1-F-box E3 ubiquitin ligase, which have ...been reported to play crucial roles in tumor initiation and progression
ubiquitination-mediated proteasomal degradation. However, the clinical implications and biological functions of FBXOs in PDAC have not been fully clarified. Herein we perform a comprehensive analysis for the clinical values and functional roles of FBXOs in PDAC using different public databases. We found that FBXO1 (CCNF), FBXO20 (LMO7), FBXO22, FBXO28, FBXO32, and FBXO45 (designated six-FBXOs) were robustly upregulated in PDAC tissues, which predicted an adverse prognosis of PDAC patients. There was a significant correlation between the expression levels of six-FBXOs and the clinicopathological features in PDAC. The transcriptional levels of six-FBXOs were subjected to the influence of promoter methylation levels. There were more than 40% genetic alterations and mutations of six-FBXOs, which affected the clinical outcome of PDAC patients. Furthermore, the expression of six-FBXOs was associated with immune infiltrations and activated status, including B cells, CD8
T cells, CD4
T cells, NK cells, macrophages, and dendritic cells. The functional prediction revealed that the six-FBXOs were involved in ubiquitination-related pathways and other vital signaling pathways, such as p53, PI3K/Akt, and Hippo pathway. Therefore, six-FBXOs are the promising prognostic biomarkers or potential targets for PDAC diagnosis and treatment.
Photodynamic therapy (PDT) is a clinically implemented modality to combat malignant tumor, while its efficacy is largely limited by several resistance factors from tumor microenvironment (TME), such ...as hypoxia, anti-oxidant systems, and ATP-dependent tumor adaptive resistances. The aim of this work is to construct a multifunctional nanoplatform to remodel multiple resistant TME for enhanced PDT. Here, a targeting nano-reactor was facilely constructed to reverse the multiple resistances of PDT by incorporating glucose oxidase (GOx) and chlorin e6 (Ce6) into poly (D, L-lactic-co-glycolic acid) (PLGA)/ metal-organic framework (MOF) core-shell nanoassembly, with surface deposition of hyaluronic acid (HA) stabilized MnO.sub.2. The nano-reactor could selectively target tumor cells by virtue of surface HA modification, and once internalization, a few reactions were initiated to modulate TME. Glucose was consumed by GOx to inhibit ATP generation, and the produced H.sub.2O.sub.2 was catalyzed by MnO.sub.2 to generate O.sub.2 for tumor hypoxia alleviation and photodynamic sensitization, and glutathione (GSH) was also effectively depleted by MnO.sub.2 to suppress the tumor antioxidant defense. Consequently, the nano-reactor achieved robust PDT with amplified tumor therapy via intravenous injection. This nano-reactor offers a multifunctional nanoplatform to sensitize TME-limited tumor treatment means via reversing multiple resistances.
Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. The optimal surgical procedure and prognostic factors for PC remain controversial.
Clinical information and ...parafibromin staining results from 53 patients with PC were reviewed retrospectively from 1997 to 2018. Immunohistochemical staining for parafibromin was performed on formalin-fixed, paraffin-embedded tissue samples. The influence of clinical parameters, surgical procedure, and parafibromin staining of tumor tissues on prognosis were evaluated.
A total of 53 patients with PC were enrolled in this study. The male to female ratio was 1.94:1. En bloc resection was performed as initial surgery for 18 patients (34.0%), and 35 patients (66.0%) underwent local resection. Parafibromin staining was negative in the tumor tissues of 24 PC patients (45.3%). Thirty-three patients suffered from local recurrence or distant metastasis, and overall mortality was 16/53 at a median follow-up time of 80 months (range, 7 to 282 months). Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio HR, 4.13; 95% confidence interval CI, 1.73 to 9.87;
= .001) was related to recurrence or metastasis and that age >50 years (HR, 5.66; 95% CI, 1.58 to 20.31;
= .008) was related to mortality. The extent of resection was not related to recurrence or overall survival.
The majority of PC patients have a relatively long survival with multiple recurrences. Absence of parafibromin staining was a factor that influenced PC recurrence. The main factor influencing PC outcomes may be the biological characteristics rather than surgical extent.
= confidence interval;
= disease-free survival;
= hazard ratio;
= overall survival;
= parathyroid carcinoma;
= World Health Organization.
Background: Parathyroid carcinoma (PC) is a rare endocrine malignancy with poor outcomes. Over 60% of PC patients experience repeated disease recurrence or metastasis. The significance of cervical ...lymph node dissection (LND) for PC remains inconclusive. Methods: PC patients diagnosed at Peking Union Medical College Hospital between 1992 and 2021 were reviewed retrospectively. Clinical data, initial tumor histological staging, parafibromin histochemical staining results, Ki67 index, CDC73 gene mutation status and outcome information were collected systemically. The risk factors for recurrence and lymph node or distant metastasis were explored. Results: Sixty-eight PC patients receiving LND were enrolled. Cervical lymph node metastasis was identified in 19.4% of patients at initial surgery and 25.0% of patients including reoperations for recurrences. The independent risk factor for PC recurrence was a Ki67 index ≥ 5% (HR4.41, 95% confidence interval (CI)1.30–14.95, p = 0.017). Distant metastasis was an independent prognostic factor for PC patient overall survival (HR 5.44, 95% CI 1.66–17.82, p = 0.005). High-risk Schulte staging (p = 0.021) and CDC73 abnormalities (p = 0.012) were risk factors for cervical lymph node metastasis. Conclusion: Most PCs were slow-growing, but lymph node metastasis was not rare. For patients planning to undergo remedial surgery after previous local resection of PC, central LND is suggested for tumors with high-risk Schulte staging or CDC73 abnormalities.
Hyperparathyroidism is the third most common endocrine disease. Parathyroid adenoma (PA) accounts for approximately 85% of cases of primary hyperparathyroidism, but the molecular mechanism is not ...fully understood. Herein, we aimed to investigate the genetic and transcriptomic profiles of sporadic PA.
Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) of 41 patients with PA and RNA-seq of 5 normal parathyroid tissues were performed. Gene mutations and characterized expression changes were identified. To elucidate the molecular mechanism underlying PA, unsupervised consensus clustering of RNA-seq data was performed. The correlations between the sequencing data and clinicopathological features of these patients were analyzed.
Previously reported PA driver gene mutations, such as
(9/41),
(4/41),
(3/41),
(3/41),
(2/41) and
(2/41), were also identified in our cohort. Furthermore, somatic mutation of
, which had not been reported in PA, was found in 4 samples. RNA-seq showed that the expression levels of 84 genes were upregulated and 646 were downregulated in PA samples compared with normal samples. Unsupervised clustering analysis of RNA-seq data clustered these patients into 10 subgroups related to mutation or abnormal expression of a group of potential pathogenic genes.
,
,
,
,
and
mutations in PA were revealed. According to the RNA-seq data clustering analysis, cyclin D1, β-catenin, VDR, CASR and GCM2 may be important factors contributing to the PA gene expression profile.
Pancreatic cancer is an aggressive and challenging malignancy with limited treatment options, largely attributed to the dense tumor stroma and intrinsic drug resistance. Here, we introduce a novel ...iron-containing nanoparticle formulation termed PTFE, loaded with the ferroptosis inducer Erastin, to overcome these obstacles and enhance pancreatic cancer therapy. The PTFE nanoparticles were prepared through a one-step assembly process, consisting of an Erastin-loaded PLGA core stabilized by a MOF shell formed by coordination between Fe3+ and tannic acid. PTFE demonstrated a unique capability to repolarize tumor-associated macrophages (TAMs) into the M1 phenotype, leading to the regulation of dense tumor stroma by modulating the activation of tumor-associated fibroblasts (TAFs) and reducing collagen deposition. This resulted in enhanced nanoparticle accumulation and deep penetration, as confirmed by in vitro multicellular tumor spheroids and in vivo mesenchymal-rich subcutaneous pancreatic tumor models. Moreover, PTFE effectively combated tumor resistance by synergistically employing the Fe3+-induced Fenton reaction and Erastin-induced ferroptosis, thereby disrupting the redox balance. As a result, significant tumor growth inhibition was achieved in mice-bearing tumor model. Comprehensive safety evaluations demonstrated PTFE's favorable biocompatibility, highlighting its potential as a promising therapeutic platform to effectively address the formidable challenges in pancreatic cancer treatment.
This study presents a deep tumour penetration and synergistic iron metabolic response drug delivery system. Through the synergistic effect of iron ions and Erastin, PTFE regulated TAFs and tumor dense stroma by inducing M2-to-M1 polarization of macrophages, thereby improving nanoparticle permeability and overcoming drug delivery barriers. Meanwhile, the formulation disrupts the redox balance at the tumor site, inducing ferroptosis in cancer cells, and presents a promising therapeutic strategy for pancreatic cancer. Display omitted
Percutaneous kyphoplasty (PKP) is now widely performed to treat VCF, which is usually caused by osteoporosis. Previous researches have reported unsuspected malignancies found by biopsy. However, the ...safety and cost-effective profiles of routine biopsy during PKP are unclear. The purpose of this study was to evaluate the feasibility of routine biopsy during PKP in treatment of VCF.
Ninety-three patients (September 2007-November 2010) undergoing PKP without biopsy were reviewed as the control group. One hundred and three consecutive patients (November 2010-September 2013) undergoing PKP with biopsy of every operated vertebral level were prospectively enrolled as the biopsy group. The rate of unsuspected lesions was reported, and the severe adverse events, surgical duration, cement leakage rate and pain control were compared between the two groups.
No statistically significant differences were found between the two groups, regarding the severe adverse events, surgical duration, cement leakage rate and pain control. Four unsuspected lesions were found in the biopsy group, three of which were malignancies with a 2.9% (3/103) unsuspected malignancy rate. The economic analysis showed that routine biopsy was cost-effective in finding new malignancies comparing with a routine cancer screening campaign.
Routine biopsy during PKP was safe and cost-effective in finding unsuspected malignancies. We advocate routine biopsy in every operated vertebral level during PKP for VCF patients.
PDF
