In the present study, we have used three molecular methods (ASP-real-time PCR, ASP-DNA-FLA PCR and direct sequencing) to detect the DDR2 gene mutation in 143 patients with NSCLC metastases to the central nervous system (CNS).
We have utilized in situ hybridization and immunocytochemistry techniques to examine the expression of both alpha 2-macroglobulin (alpha 2-MR) and the 39 kDa receptor-associated protein (RAP) in 8 benign (BPH) and 34 malignant human prostate tissues, including 4 metastases.
α2-Macroglobulin (α2M) is thought to be involved in cancer metastasis and inflammatory reaction through its functions as a proteinase inhibitor and carrier protein for interleukin-6 (IL-6).
Likewise, mutations that weaken the A2M-APP (amyloid precursor protein) association may increase the proliferative effect of APP through preventing β-amyloid degradation by the A2M receptor, and mutations that abolish the A2M-Kallikrein-13 (KLK13) interaction may lead to cell proliferation and metastasis through the destructive effect of KLK13 on the extracellular matrix.
Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.
Together, these experiments provide preclinical evidence that the FDA-approved DNA methylation inhibitor DAC may be repurposed to treat patients with osteosarcoma based on its efficacy to decrease proliferation, to induce osteoblast differentiation, and to reduce metastasis to visceral organs.<b>Significance:</b> These findings describe the effects of DNA methyltransferase inhibition on ERα and its potential role as a tumor suppressor in osteosarcoma.<i>See related commentary by Roberts, p. 1034</i><i>See related article by El Ayachi and colleagues; Cancer Res 79(5);982-93</i>.
AAMP has a significant influence on the biological functions of breast cancer cells and its high expression correlates with poor prognosis and metastasis.
Moreover, in the red module, 34 network hub genes for metastasis risk were identified, six of which (ABAT, AGXT, ALDH6A1, CYP4A11, DAO and EHHADH) were also hub nodes in the protein-protein interaction network of the module genes.
Tissue factor (TF) expressed at the protein level includes two isoforms: The membrane‑bound full‑length TF (flTF) and the soluble alternatively spliced TF (asTF). flTF is the major thrombogenic form of TF, whereas asTF is more closely associated with tumor growth, angiogenesis, metastasis and cell growth.
We further demonstrate that fluidity can be regulated by cellular cholesterol flux, as the cholesterol efflux channel ABCA1 potentiated metastatic behaviors in vitro and in vivo The requirement for fluidity was further supported by the finding in breast cancer patients that ABCA1 was overexpressed in 41% of metastatic tumors, reducing time to metastasis by 9 years.
Metastasis suppressing activity also was observed in the highly malignant mouse 10T(1/2) derived RMP-6 cell line, which was transformed by a combination of oncogenic ras, myc, and mutant p53.
Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC.
Using mRNA expression profiles retrieved from microarrays deposited in the Gene Expression Omnibus Profiles database, RT-qPCR measurement and bioinformatics analysis, we further indicated that high expression of HBB might predict a poorer 5-year survival, high expression of ALDH1A2 and ABCA8 might predict a poor outcome; while ALDH1A2, ADH1B, HBB and ABCA8, in particular the former two genes, might be associated with drug resistance, and ALDH1A2 and NELL2 might contribute to invasiveness and metastasis in ovarian cancer.
Persistence of previously detected MDR1-positivity after treatment (7/9 compared with 0/2 cases) was significantly associated with axillary node metastasis (P < 0.05).
Moreover, the incidence of P-glycoprotein overexpression was found to be higher among patients with localized disease at the clinical onset than in patients with evidence of metastasis at the time of diagnosis.
Two patients with increased levels of MDR1 before chemotherapy did not respond to the treatment and distant metastasis and death occurred in these patients.
Taken together, our results proved that miR-770 could suppress the doxorubicin-resistance and metastasis of TNBC cells, which broaden our insights into the underlying mechanisms in chemo-resistance and metastasis, and provided a new prognostic marker for TNBC cells.
Since these levels were lower than expected for RCC, we asked whether the metastases possessed a phenotype different from primary RCC and examined MDR-1 expression in 5 paired cell lines derived from primary and metastatic RCC.
Our results suggest that pharmacological inhibition of ABCB1 and ABCG2 during osimertinib therapy might potentially be considered to further benefit patients with brain (micro-)metastases positioned behind an intact blood-brain barrier, or with substantial expression of these transporters in the tumor cells, without invoking a high toxicity risk.
The identification of organ-specific cytokines that can upregulate expression of mdr-1 (or other resistant mechanisms) may suggest an approach to overcome the resistance of some metastases to particular chemotherapeutic agents.
We sought to determine how often P-glycoprotein is involved in the drug-resistance of urothelial cancer, and whether MDR1 gene expression is correlated with tumor grade, invasiveness, or metastasis.
There was also a strong correlation between Nrf2 overexpression and tumor size, histological grade, lymph node and distant metastasis while P-gp upregulation was shown to be associated only with the histological grade and tumor size (Chi-square, all p<0.05).