To develop a radiomics signature based on preoperative MRI to estimate disease-free survival (DFS) in patients with invasive breast cancer and to establish a radiomics nomogram that incorporates the ...radiomics signature and MRI and clinicopathological findings.
We identified 294 patients with invasive breast cancer who underwent preoperative MRI. Patients were randomly divided into training (
= 194) and validation (
= 100) sets. A radiomics signature (Rad-score) was generated using an elastic net in the training set, and the cutoff point of the radiomics signature to divide the patients into high- and low-risk groups was determined using receiver-operating characteristic curve analysis. Univariate and multivariate Cox proportional hazards model and Kaplan-Meier analysis were used to determine the association of the radiomics signature, MRI findings, and clinicopathological variables with DFS. A radiomics nomogram combining the Rad-score and MRI and clinicopathological findings was constructed to validate the radiomic signatures for individualized DFS estimation.
Higher Rad-scores were significantly associated with worse DFS in both the training and validation sets (
= 0.002 and 0.036, respectively). The radiomics nomogram estimated DFS C-index, 0.76; 95% confidence interval (CI); 0.74-0.77 better than the clinicopathological (C-index, 0.72; 95% CI, 0.70-0.74) or Rad-score-only nomograms (C-index, 0.67; 95% CI, 0.65-0.69).
The radiomics signature is an independent biomarker for the estimation of DFS in patients with invasive breast cancer. Combining the radiomics nomogram improved individualized DFS estimation.
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Circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) are increasingly recognized for their potential utility in disease monitoring and therapeutic targeting. The clinical application of ...CTC/DTC requires better understanding of the biological mechanisms behind tumor dissemination, the survival of DTCs, and their activation to aggressive growth from dormancy. Recent research using animal models of DTCs and CTCs have provided novel insights into these processes. Here, we discuss these findings in the context of results obtained from the clinical analyses of CTCs and DTCs, which demonstrate that the animal models mimic, in many aspects, the complex situation in patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Metastatic disease is the primary cause of death for most cancer patients. Complex and redundant pathways involving the tumor cell and the microenvironment mediate tumor invasion at the primary site, ...survival and arrest in the bloodstream, and progressive outgrowth at a distant site. Understanding these pathways and their dynamic interactions will help identify promising molecular targets for cancer therapy and key obstacles to their clinical development. PUBLICATION ABSTRACT
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Genomic instability and mutations underlie the hallmarks of cancer-genetic alterations determine cancer cell fate by affecting cell proliferation, apoptosis and immune response, and increasing data ...show that mutations are involved in metastasis, a crucial event in cancer progression and a life-threatening problem in cancer patients. Invasion is the first step in the metastatic cascade, when tumour cells acquire the ability to move, penetrate into the surrounding tissue and enter lymphatic and blood vessels in order to disseminate. A role for genetic alterations in invasion is not universally accepted, with sceptics arguing that cellular motility is related only to external factors such as hypoxia, chemoattractants and the rigidity of the extracellular matrix. However, increasing evidence shows that mutations might trigger and accelerate the migration and invasion of different types of cancer cells. In this review, we summarise data from published literature on the effect of chromosomal instability and genetic mutations on cancer cell migration and invasion.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m1A) and 3-methylcytidine (m3C) ...demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. In vivo study confirms the regulation effects of ALKBH3 on growth of tumor xenograft. The m1A demethylated tRNA is more sensitive to angiogenin (ANG) cleavage, followed by generating tRNA-derived small RNAs (tDRs) around the anticodon regions. tDRs are conserved among species, which strengthen the ribosome assembly and prevent apoptosis triggered by cytochrome c (Cyt c). Our discovery opens a potential and novel paradigm of tRNA demethylase, which regulates biological functions via generation of tDRs.
Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer worldwide, and the survival rates of patients with HCC remains quite low after 5years. Long non-coding RNAs (LncRNAs) are a ...novel class of non-coding RNAs that are capable of regulating gene expression at various levels. Recent works have demonstrated that lncRNAs are often dysregulated in HCC, and the dysregulation of some of these lncRNAs are associated with the clinicopathological features of HCC. They regulate cell proliferation, apoptosis, autophagy, Epithelial-Mesenchymal Transition (EMT), invasion and metastasis of HCC by modulating gene expression and cancer-related signaling pathways, and thus contribute to the onset and progression of HCC. In this review, we provide a comprehensive survey of dysregulated lncRNAs in HCC, with particular focus on the functions and regulatory mechanisms of several essential and important lncRNAs, and discuss their potential clinical application as early diagnostic and/or prognostic biomarkers or therapeutic targets for HCC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Antibodies targeting PD-1 or its ligand 1 PD-L1 such as atezolizumab, have great efficacy in a proportion of metastatic urothelial cancers
. Biomarkers may facilitate identification of these ...responding tumors
. Neoadjuvant use of these agents is associated with pathological complete response in a spectrum of tumors, including urothelial cancer
. Sequential tissue sampling from these studies allowed for detailed on-treatment biomarker analysis. Here, we present a single-arm phase 2 study, investigating two cycles of atezolizumab before cystectomy in 95 patients with muscle-invasive urothelial cancer (ClinicalTrials.gov identifier: NCT02662309). Pathological complete response was the primary endpoint. Secondary endpoints focused on safety, relapse-free survival and biomarker analysis. The pathological complete response rate was 31% (95% confidence interval: 21-41%), achieving the primary efficacy endpoint. Baseline biomarkers showed that the presence of preexisting activated T cells was more prominent than expected and correlated with outcome. Other established biomarkers, such as tumor mutational burden, did not predict outcome, differentiating this from the metastatic setting. Dynamic changes to gene expression signatures and protein biomarkers occurred with therapy, whereas changes in DNA alterations with treatment were uncommon. Responding tumors showed predominant expression of genes related to tissue repair after treatment, making tumor biomarker interpretation challenging in this group. Stromal factors such as transforming growth factor-β and fibroblast activation protein were linked to resistance, as was high expression of cell cycle gene signatures after treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Berberin, extracted from Chinese herbal medicine Coptis chinensis, has been found to have anti-tumor activities. However, the underlying mechanisms have not been fully elucidated. Our current study ...demonstrated that berberin inhibited the in vitro and in vivo growth, migration/invasion of CRC cells, via attenuating the expression levels of COX-2/PGE2, following by reducing the phosphorylation of JAK2 and STAT3, as well as the MMP-2/-9 expression. We further clarified that an increase of COX-2/PGE2 expression offset the repressive activity of Berberin on JAK2/STAT3 signaling, and a JAK2 inhibitor AZD1480 blocked the effect of COX-2/PGE2 on MMP-2/-9 expression. In summary, Berberin inhibited CRC invasion and metastasis via down-regulation of COX-2/PGE2- JAK2/STAT3 signaling pathway.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Collective cell migration has a key role during morphogenesis and during wound healing and tissue renewal in the adult, and it is involved in cancer spreading. In addition to displaying a coordinated ...migratory behaviour, collectively migrating cells move more efficiently than if they migrated separately, which indicates that a cellular interplay occurs during collective cell migration. In recent years, evidence has accumulated confirming the importance of such intercellular communication and exploring the molecular mechanisms involved. These mechanisms are based both on direct physical interactions, which coordinate the cellular responses, and on the collective cell behaviour that generates an optimal environment for efficient directed migration. The recent studies have described how leader cells at the front of cell groups drive migration and have highlighted the importance of follower cells and cell-cell communication, both between followers and between follower and leader cells, to improve the efficiency of collective movement.
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IJS, NUK, SBMB, UL, UM, UPUK
Malignant gliomas are devastating tumours that frequently kill patients within 1 year of diagnosis. The major obstacle to a cure is diffuse invasion, which enables tumours to escape complete surgical ...resection and chemo- and radiation therapy. Gliomas use the same tortuous extracellular routes of migration that are travelled by immature neurons and stem cells, frequently using blood vessels as guides. They repurpose ion channels to dynamically adjust their cell volume to accommodate to narrow spaces and breach the blood-brain barrier through disruption of astrocytic endfeet, which envelop blood vessels. The unique biology of glioma invasion provides hitherto unexplored brain-specific therapeutic targets for this devastating disease.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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