Review old bone, new tricks
AbstractDespite the significant progress made over the past decade with combination of molecular profiling data and the development of new clinical strategies, our understanding of metastasis remains elusive. Bone metastasis is a complex process and a major cause of mortality in breast and prostate cancer patients, for which there is no effective treatment to-date. The current review summarizes the routes taken by the metastatic cells and the interactions between them and the bone microenvironment. We emphasize the role of the specified niches and cues that promote cellular adhesion, colonization, prolonged dormancy, and r...
Source: Clinical and Experimental Metastasis - July 30, 2022 Category: Cancer & Oncology Source Type: research

Electrochemotherapy of skin metastases from malignant melanoma: a PRISMA-compliant systematic review
AbstractThe main treatment of MM metastases are systemic therapies, surgery, limb perfusion, and intralesional talimogene laherparepvec. Electrochemotherapy (ECT) is potentially useful also due to the high response rates recorded in cancers of any histology. No randomized studies comparing ECT with other local therapies have been published on this topic. We analyzed the available evidence on efficacy and toxicity of ECT in this setting.  PubMed, Scopus, and Cochrane databases were screened for paper about ECT on MM skin metastases. Data about tumor response, mainly in terms of overall response rate (ORR), toxicity (both f...
Source: Clinical and Experimental Metastasis - July 22, 2022 Category: Cancer & Oncology Source Type: research

Gemcitabine induces polarization of mouse peritoneal macrophages towards M1-like and confers antitumor property by inducing ROS production
In this study,  mouse-derived PMs were treated with GEM ex vivo to analyze the polarization status. Production of GEM-induced reactive oxygen species (ROS) and reactive nitrogen species was evaluated using DCFH-DA, DAF-FM, and Griess assay. Antitumor effects of PMs on UN-KC-6141and UN-KPC-961 murine PC cells were evaluated in presence and absence of GEM in vitro. Similarly, effect of GEM on human THP-1 macrophage polarization and its tumoricidal effect was studied in vitro. Furthermore, the effect of GEM-treated PMs on peritoneal metastasis of UN-KC-6141 cells was evaluated in a syngeneic mouse model of PC. GEM upregulate...
Source: Clinical and Experimental Metastasis - July 15, 2022 Category: Cancer & Oncology Source Type: research

Understanding the cell survival mechanism of anoikis-resistant cancer cells during different steps of metastasis
AbstractAnchorage-independent survival of cancer cells is associated with metastasis as it enables cells to travel to secondary target sites. Tissue integrity is generally maintained by detachment-induced cell death called ‘anoikis’, but cancer cells undergoing the multistep metastatic process show resistance to anoikis. Anoikis resistance enables these cells to survive through the extracellular matrix (ECM) deprived phase, which starts when cancer cells detach and move into the circulation till cells reach to the secondary target site. Comprehensive analysis of the molecular and functional biology of anoikis resistanc...
Source: Clinical and Experimental Metastasis - July 13, 2022 Category: Cancer & Oncology Source Type: research

Establishment and Image based evaluation of a New Preclinical Rat Model of Osteoblastic Bone Metastases
AbstractBone remodeling is disrupted in the presence of metastases and can present as osteolytic, osteoblastic or a mixture of the two. Established rat models of osteolytic and mixed metastases have been identified changes in structural and tissue-level properties of bone. The aim of this work was to establish a preclinical rat model of osteoblastic metastases and characterize bone quality changes through image-based evaluation. Female athymic rats (n  = 22) were inoculated with human breast cancer cells ZR-75-1 and tumor development tracked over 3–4 months with bioluminescence andin-vivoµCT imaging. Bone tissue-lev...
Source: Clinical and Experimental Metastasis - July 11, 2022 Category: Cancer & Oncology Source Type: research

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review
AbstractFor peritoneal metastases (PM), there are few curative treatment options, and they are only available for a select patient group. Recently, new therapies have been developed to deliver intraperitoneal chemotherapy for a prolonged period, suitable for a larger patient group. These drug delivery systems (DDSs) seem promising in the experimental setting. Many types of DDSs have been explored in a variety of animal models, using different cytostatics. This review aimed to provide an overview of animal studies using DDSs containing cytostatics for the treatment of gastro-intestinal PM and identify the most promising the...
Source: Clinical and Experimental Metastasis - June 23, 2022 Category: Cancer & Oncology Source Type: research

Long non-coding RNA NRSN2-AS1, transcribed by SOX2, promotes progression of esophageal squamous cell carcinoma by regulating the ubiquitin-degradation of PGK1
AbstractAberrant expression of long non-coding RNAs (lncRNAs) plays pivotal roles in tumorigenesis of human malignant cancers, including esophageal squamous cell carcinoma (ESCC). However, the specific role of lncRNA NRSN2-AS1 in ESCC has not been investigated. Our analysis of clinical data revealed that NRSN2-AS1 was upregulated in ESCC tissues and negatively correlated with patient survival. Luciferase reporter assays and chromatin immunoprecipitation assays demonstrated that NRSN2-AS1 is transcribed by SOX2. In vitro functional experiments showed that NRSN2-AS1 can promote ESCC cell proliferation, migration, and invasio...
Source: Clinical and Experimental Metastasis - June 17, 2022 Category: Cancer & Oncology Source Type: research

PLXDC2 enhances invadopodium formation to promote invasion and metastasis of gastric cancer cells via interacting with PTP1B
In this study, we found that PLXDC2 was highly expressed in gastric cancer tissues, and the expression levels were positively correlated with clinicopathological features, but negatively with the patients ’ outcome. Cox regression analysis identified PLXDC2 as an independent prognostic indicator for the patients. Knockdown of PLXDC2 markedly suppressed the in vitro invasion and in vivo metastasis of gastric cancer cells, while overexpression of PLXDC2 resulted in opposite effects. Mechanistically, PLXDC2 enhanced the level of phosphorylated Cortactin (p-Cortactin) by physically interacting with protein tyrosine phosphata...
Source: Clinical and Experimental Metastasis - June 4, 2022 Category: Cancer & Oncology Source Type: research

Anti-invasive effects of minoxidil on human breast cancer cells: combination with ranolazine
AbstractA plethora of ion channels have been shown to be involved systemically in the pathophysiology of cancer and ion channel blockers can produce anti-metastatic effects. However, although ion channels are known to frequently function in concerted action, little is known about possible combined effects of ion channel modulators on metastatic cell behaviour. Here, we investigated functional consequences of pharmacologically modulating ATP-gated potassium (KATP) channel and voltage-gated sodium channel (VGSC) activities individually and in combination. Two triple-negative human breast cancer cell lines were used: MDA-MB-2...
Source: Clinical and Experimental Metastasis - May 28, 2022 Category: Cancer & Oncology Source Type: research

Downregulation of LINC00886 facilitates epithelial –mesenchymal transition through SIRT7/ELF3/miR-144 pathway in esophageal squamous cell carcinoma
AbstractLINC00886 has been reported to be down-regulated in laryngeal squamous cell carcinoma, and aberrant DNA methylation status of it has been screened in several tumor types. However, the roles of LINC00886 in esophageal squamous cell carcinoma (ESCC) remained unclarified. The present study was to investigate the expression level, epigenetic inactivation mechanisms, and functions of LINC00886 in ESCC tumorigenesis. Frequent down-regulation of LINC00886 was verified in esophageal cancer cells and ESCC tissues. There are CpG islands spanning the promoter and exon 1 regions of LINC00886 gene, and DNA hypermethylation of p...
Source: Clinical and Experimental Metastasis - May 26, 2022 Category: Cancer & Oncology Source Type: research

Prostate cancer addiction to oxidative stress defines sensitivity to anti-tumor neutrophils
AbstractBone metastatic prostate cancer (BM-PCa) remains one of the most difficult cancers to treat due to the complex interactions of cancer and stromal cells. We previously showed that bone marrow neutrophils elicit an anti-tumor immune response against BM-PCa. Further, we demonstrated that BM-PCa induces neutrophil oxidative burst, which has previously been identified to promote primary tumor growth of other cancers, and a goal of this study was to define the importance of neutrophil oxidative burst in BM-PCa. To do this, we first examined the impact of depletion of reactive oxygen species (ROS), via systemic deletion o...
Source: Clinical and Experimental Metastasis - May 23, 2022 Category: Cancer & Oncology Source Type: research

FTO mediated ERBB2 demethylation promotes tumor progression in esophageal squamous cell carcinoma cells
AbstractN6-methyladenosine (m6A) is the most prevalent and internal modification that occurs in the messenger RNAs of eukaryotes. However, knowledge of the impact of these modifications on gene expression regulation remains limited. By using the in vitro MeRIP-seq and RNA-seq assays, we discovered that the mRNA demethylase FTO was significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and cells. Knockdown of FTO drastically suppressed the proliferation, migration, and invasion of ESCC cells. Furthermore, by using transcriptome-wide m6A-seq and RNA-seq assays, we identified ERBB2 is the target of FT...
Source: Clinical and Experimental Metastasis - May 7, 2022 Category: Cancer & Oncology Source Type: research

Stereotactic body radiotherapy (SBRT) and concomitant systemic therapy in oligoprogressive breast cancer patients
AbstractBreast cancer is a heterogenous disease with a deep tailoring level. Evidence is accumulating on the role of stereotactic body radiotherapy (SBRT) in the management of oligometastatic disease, however this is limited in breast cancer. The aim of the present study is to show the effectiveness of SBRT in delaying the switch to a subsequent systemic treatment in oligoprogressive breast cancer patients. Retrospective analysis from two Institutions. Primary endpoint: time to next systemic treatment (NEST). Secondary endpoints: freedom from local progression (FLP), time to the polymetastatic conversion (tPMC) and overall...
Source: Clinical and Experimental Metastasis - May 5, 2022 Category: Cancer & Oncology Source Type: research

miR-106a-5p carried by tumor-derived extracellular vesicles promotes the invasion and metastasis of ovarian cancer by targeting KLF6
This study investigated the mechanism of miR-106a-5p carried by OC cell-derived EVs in OC. miR-106a-5p expression in OC tissues and cells was measured. EVs were extracted from SKOV3 cells and normal cells. The internalization of EVs in OC cells was observed. OC cells were treated with SKOV3-EVs or SKOV3-EVs overexpressing miR-106a-5p to detect the proliferation, migration, and invasion. The expression levels of miR-106a-5p, KLF6, and PTTG1 were detected and their binding relationships were identified. Combined experiments were designed to detect the effects of KLF6 and PTTG1 on OC cells. A xenograft tumor experiment was pe...
Source: Clinical and Experimental Metastasis - April 21, 2022 Category: Cancer & Oncology Source Type: research

Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression
AbstractHepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. The study aimed to perform a data mining analysis of the expression and regulatory role of key genes in HCC to reveal novel potential biomarkers of diagnosis prognosis, or progression since their availability is still almost lacking. Starting from data of our cohort of patients (HCV-positive HCC pts undergoing liver transplantation (LR, n  = 10) and donors (LD, n = 14), deeply analyzed previously, in which apelin, osteopontin, osteoprotegerin, NOTCH-1, CASP-3, Bcl-2, BAX, PTX3, and NPTX2 were analyzed, we applied sta...
Source: Clinical and Experimental Metastasis - April 16, 2022 Category: Cancer & Oncology Source Type: research