PubMed Journal Database | Cancer letters 
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Showing PubMed Articles 1–25 of 417 from Cancer letters
We aimed to develop an anti-angiogenic model for breast cancer by combining (1) siRNA-based therapy delivered by self-complementary adeno-associated virus serotype 2 (scAAV2) vectors to target tumor vasculature, and (2) noninvasive monitoring to tumor response to anti-angiogenesis by photoacoustic (PA) imaging. scAAV2 vector containing 7 surface exposed tyrosine to phenylanine capsid mutations was able to transduce microvascular endothelial cells with high efficiency. siRNAs against UPR (unfolded protein re...
Metastasis is the primary mediator of prostate cancer (PCA) lethality and poses a significant clinical obstacle. The identification of factors involved in the metastasis of PCA is imperative. We demonstrate herein that trefoil factor 1 (TFF1) promotes PCA cell migration and invasion in vitro and metastasis in vivo. The capacity of TFF1 to enhance cell migration/invasion is mediated by transcriptional repression of E-CADHERIN. Consideration of targeted inhibition of TFF1 to prevent metastasis of prostate car...
Cucurbitacin B (CuB), has recently emerged as a potent anticancer agent; however, its efficacy in non-small-cell lung cancer (NSCLC) and the mechanism(s) initiating its biological effects remain largely unclear. In this study, CuB potently suppressed the growth of four NSCLC cells (H1299, A549, HCC-827 and H661) in vitro and the highly aggressive H1299 xenograft in vivo. CuB significantly altered the actin cytoskeletal assembly, induced G2/M cell-cycle arrest and mitochondrial apoptosis through the modulati...
MLL gene aberrations are frequently diagnosed in infant acute myeloid leukemia (AML). We previously described the MLL-NEBL and NEBL-MLL genomic fusions in an infant AML patient with a chromosomal translocation t(10;11)(p12;q23). NEBL was the second Nebulin family member (LASP1, NEBL) which was found to be involved in MLL rearrangements. Here, we report on our attempts to unravel the oncogenic properties of both fusion genes. First, RT-PCR analyses revealed the presence of the MLL-NEBL and NEBL-MLL mRNAs in...
Transforming acidic coiled-coil protein 3 (TACC3) is a member of the TACC family, essential for mitotic spindle dynamics and centrosome integrity during mitosis. Mounting evidence suggests that deregulation of TACC3 is associated with various types of human cancer. However, the molecular mechanisms by which TACC3 contributes to the development of cancer remain largely unknown. Here, we propose a novel mechanism by which TACC3 regulates epithelial-mesenchymal transition (EMT). By modulating the expression of...
In this study, we investigated the mechanism of brucine in tumor angiogenesis. We found that brucine inhibits VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures in HUVECs in a dose-dependent manner. Brucine suppresses VEGF- induced p-VEGFR2 kinase activity and inhibits neovascularization in vivo. Brucine inhibits the downstream protein kinases of VEGFR2, including Src, FAK, ERK, AKT and mTOR. And further downregulates levels of VEGF, NO, IL-6, IL-8, TNF-α...
There is a need for a comprehensive anti-cancer strategy that simultaneously targets abnormal proliferation, angiogenesis rates, and development of chemotherapy resistance. We have identified a small molecule, OT-404, that effectively inhibited proliferation and angiogenesis of either chemo-sensitive or -resistant human cancer cells and enhanced cancer cell sensitivity to different chemotherapy. In vivo studies of human tumor xenografts in nude mice showed that OT-404, used alone or encapsulated into nanopa...
KRC-408, a novel c-Met inhibitor, suppresses cell proliferation and angiogenesis of gastric cancer.
Among many cancer therapeutic targets, c-Met receptor tyrosine kinase has recently given particular attention. This kinase and its ligand, hepatocyte growth factor (HGF), play a central role in cell proliferation and the survival of several human cancers. Thus, we developed KRC-408 as a novel c-Met inhibitor and investigated its anti-cancer effects on human gastric cancer. KRC-408 inhibited the phosphorylation of c-Met and its constitutive downstream effectors such as phosphatidylinositol 3-kinase (PI3K), A...
Entrapped doxorubicin nanoparticles for the treatment of metastatic anoikis-resistant cancer cells.
Metastasized and chemoresistant secondary breast cancer treatment commonly shows very low efficacy. A new efficient treatment method is required to overcome the limitation against the secondary breast cancer. In this study, anoikis-resistant breast cancer cells, MDA-MB-231 and MCF-7 were developed as models of chemoresistant and metastatic breast cancer. Doxorubicin encapsulating human serum albumin nanoparticles (HSA+DOX NPs) were fabricated to confirm the benefits of nanoparticles at the treatment of anoi...
miR-206 inhibits gastric cancer proliferation in part by repressing cyclinD2.
In this study, we detected miR-206 expression in gastric cancer (GC) and further investigated its effects on GC cell growth in vitro and in vivo. miR-206 expression was found to be significantly decreased in 30 GC samples and GC cell lines by real time-PCR. Restoration of miR-206 reduced cell growth and colony forming ability in GC cells with G0/G1 cell cycle arrest. Further studies demonstrated that miR-206 could suppress GC cells proliferation at least partially through targeting the cyclinD2 (CCND2). The...
Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer.
Breast cancer development largely depends upon the essential contributions from the tumor microenvironment, where several inflammatory cell populations (e.g. macrophages) orchestrate breast cancer development. The majority of tumor-associated macrophages (TAMs) exhibit alternatively activated M2 properties, produce abundant anti-inflammatory factors and facilitate tumor development. Clinical evidences compellingly indicate the association between high TAMs influx and poor prognosis in patients with breast c...
In this study, we investigated the antitumor effects of deguelin in several human breast cancer cells in vitro and in vivo. Deguelin inhibited cell viability and the anchorage-dependent and anchorage-independent colony formation of triple-negative (MDA-MB-231 and MDA-MB-468) and triple-positive (MCF-7) breast cancer cells, and it significantly reduced the growth of MCF-7 cell xenograft tumors. The induction of apoptosis, inhibition of insulin-like growth factor-1 receptor (IGF-1R) signaling activation, and...
Early detection and treatment of head and neck cancer has led to increased patient survival. However such patients are at a high risk for multiple primary neoplasm(s) (MPN). In order to study the genetic susceptibility to MPN, 22 candidate SNPs were genotyped based on which a distinctive Genotype Score was created using Additive, Dominant and Recessive models. Using lymphoblastoid cell lines (LCLs) generated from these individuals, the Genotype Score was correlated with carcinogen sensitivity in vitro. LCLs...
Gastrin, cholecystokinin2 receptor (CCK2R), and cyclooxygenase-2 (COX-2) have been implicated in the carcinogenesis and progression of gastric cancer. Our study demonstrated that antagonist or siRNA against CCK2R blocked amidated gastrin (G17)-induced activation of STAT3 and Akt in gastric cancer cell lines. G17-increased COX-2 expression and cell proliferation were effectively blocked by CCK2R antagonist and inhibitors of JAK2 and PI3K. In addition, knockdown of STAT3 expression significantly attenuated G1...
High-risk neuroblastomas often harbor structural chromosomal alterations, including amplified MYCN, and usually have a near-di/tetraploid DNA index, but the mechanisms creating tetraploidy remain unclear. Gene-expression analyses revealed that certain MYCN/MYC and p53/pRB-E2F target genes, especially regulating mitotic processes, are strongly expressed in near-di/tetraploid neuroblastomas. Using a functional RNAi screening approach and live-cell imaging, we identified a group of genes, including MAD2L1, whi...
Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) chronicity and dietary exposure to aflatoxin, a mutagen targeting codon 249 of tumor suppressor TP53 (R249S mutation). Based on a case-control in Thailand, we have measured R249S and the status of HBX gene in plasma DNA of 176 cases and 133 referents. Detection of HBX complete sequences was associated with R249S in HCC with no documented prior cirrhosis but not in HCC developing in a context of cirrhosis or in non-cancer chronic liver...
CHC promotes tumor growth and angiogenesis through regulation of HIF-1α and VEGF signaling.
Pancreatic adenocarcinoma is an aggressive disease with a high mortality rate. In this study, we have newly generated a monoclonal antibody (mAb), Pa65-2, which specifically binds to pancreatic cancer cells and tumor blood vessels. The target protein of Pa65-2 is identified as human clathrin heavy chain (CHC). In vitro and In vivo study showed that suppression of CHC either by shRNA or by Pa65-2 inhibited tumor growth and angiogenesis. One of the key functions of CHC was to bind with the hypoxia-inducing fa...
Nasopharyngeal carcinoma (NPC) is an EBV-associated cancer. We analysed Siah1 expression as well as LMP1 and HIF1α expression by immuno-histochemical staining in 74 NPC biopsy specimens and found that the expression of Siah1 was significantly correlated with advanced tumour status and stage. Moreover, Siah1-positive and HIF1α-positive cases had significantly worse prognoses. The expression score for LMP1 was remarkably correlated with that of Siah1, whereas there was little correlation between LMP1 expres...
Inhibition of GSH synthesis potentiates temozolomide-induced bystander effect in glioblastoma.
Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor prognosis. Current standard treatment includes chemotherapy using DNA alkylating agent temozolomide (TMZ) concomitant with surgical resection and/or irradiation. However, GBM patients exhibit various levels of the elevated expression of DNA repair enzyme, due to MGMT causing resistance to TMZ. Determination of the MGMT-positive population of primary tumor is important to evaluate the therapeutic efficacy of TMZ. Here we gener...
C-terminal region of HBx is crucial for mitochondrial DNA damage.
HBx is strongly associated with hepatocellular carcinoma development through transcription factor activation and reactive oxygen species (ROSs) production. However, the exact role of HBx during hepatocellular carcinogenesis is not fully understood. Recently, it was reported that C-terminal truncated HBx is associated with tumor metastasis. In the present study, we confirmed that the C-terminal region of HBx is required for ROS production and 8-oxoguanine (8-oxoG) formation, which is considered as a reliable...
Human osteopontin is subject to alternative splicing, which generates three isoforms, termed OPNa, OPNb and OPNc. These variants show specific expression and roles in different cell contexts. We present an overview of current knowledge of the expression profile of human OPN splicing isoforms (OPN-SIs), their tissue-specific roles, and the pathways mediating their functional properties in different pathophysiological conditions. We also describe their putative application as biomarkers, and their potential u...
Transcriptional and epigenetic regulation of human microRNAs.
MicroRNAs (miRNAs) are members of non-coding RNAs. They are involved in diverse biological functions. MiRNAs are precisely regulated in a tissue- and developmental-specific manner, but dysregulated in many human diseases, in particular cancers. Transcriptional regulation, post-transcriptional regulation, as well as genetic alterations, are the three major mechanisms controlling the spatial and temporal expression of miRNAs. Emerging evidence now indicates that transcriptional and epigenetic regulations play...
Despite ongoing attempts to improve the overall breast cancer (BC) survival rate, BC cells' (BCCs) predilection for metastasizing to the bone marrow has enabled BCCs to not only remain dormant, but also evade detection. BCCs are able to acquire quiescence by establishing gap junctional intercellular communication (GJIC) with the stroma through the assembly of connexins (Cxs). The chemoattractant CXCL12 also appears to play a role in GJIC based on its tendency to decrease when GJIC is formed between BCCs and...
Previous studies have demonstrated the involvement of transcriptional factor forkhead box M1 (FoxM1) in cellular senescence of hepatocellular carcinoma (HCC). In the present study, we revealed that oxaliplatin could induce senescence in HCC cells, since advanced HCC patients with lower expression of FoxM1 were more sensitive to oxaliplatin therapy. Our data indicated that due to the repression by p53, FoxM1 played a critical role in oxaliplatin-induced senescence via regulating cycle-related proteins p21, p...
Microvessel density and p53 mutations in advanced-stage epithelial ovarian cancer.
We planned to determine the relationship between angiogenesis and p53 mutational status in advanced-stage epithelial ovarian cancer. Using 190 tumor samples from patients with stage III and IV ovarian cancer we performed p53 sequencing, immunohistochemistry, and CD31 microvessel density (MVD) determination. MVD was elevated in tumors with p53 null mutations compared to p53 missense mutation or no mutation. Disease recurrence was increased with higher MVD in both unadjusted and adjusted analyses. In adjusted...
