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09:16 EDT 27th May 2019 | BioPortfolio

The US National Library of Medicine and National Institutes of Health manage PubMed.gov which comprises of more than 29 million records, papers, reports for biomedical literature, including MEDLINE, life science and medical journals, articles, reviews, reports and  books.

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Showing PubMed Articles 1–25 of 634 from Cancer letters

Targeting the tumour immune microenvironment for cancer therapy in human gastrointestinal malignancies.

Gastrointestinal (GI) cancer is a malignancy of the GI tract and accessory digestive organs. GI cancer patients develop resistance to chemotherapy, targeted therapy drugs and immune therapies. Although immune checkpoint inhibitors have shown promising clinical results in melanoma, etc., immune checkpoint blockade responds in only a subset of colorectal cancer (CRC) patients with microsatellite instability-high (MSI-H) tumours. The tumour immune microenvironment (TIME) has a dynamic nature during malignant p...

PAK4 regulates stemness and progression in endocrine resistant ER-positive metastatic breast cancer.

Despite the effectiveness of endocrine therapies to treat estrogen receptor-positive (ER+) breast tumours, two thirds of patients will eventually relapse due to de novo or acquired resistance to these agents. Cancer Stem-like Cells (CSCs), a rare cell population within the tumour, accumulate after anti-estrogen treatments and are likely to contribute to their failure. Here we studied the role of p21-activated kinase 4 (PAK4) as a promising target to overcome endocrine resistance and disease progression in E...

Origins of DNA methylation defects in Wilms tumors.

Wilms tumor is an embryonic renal cancer that typically presents in early childhood and accounts for 7% of all pediatric cancers. Different genetic alterations have been described in this malignancy, however, only a few of them are associated with a majority of Wilms tumors. Alterations in DNA methylation, in contrast, are frequent molecular defects observed in most cases of Wilms tumors. How these methylation alterations are established in this tumor is not yet completely clear. The recent identification o...

A feedforward relationship between active Rac1 and phosphorylated Bcl-2 is critical for sustaining Bcl-2 phosphorylation and promoting cancer progression.

Active GTPase-Rac1 is associated with cellular processes involved in carcinogenesis and expression of Bcl-2 endows cells with the ability to evade apoptosis. Here we provide evidence that active Rac1 and Bcl-2 work in a positive feedforward loop to promote sustained phosphorylation of Bcl-2 at serine-70 (S70pBcl-2), which stabilizes its anti-apoptotic activity. Pharmacological and genetic inactivation of Rac1 prevent interaction with Bcl-2 and reduces S70pBcl-2. Similarly, BH3-mimetic inhibitors of Bcl-2 co...

Targeting the Shc-EGFR interaction with indomethacin inhibits MAP kinase pathway signalling.

Receptor tyrosine kinase (RTK)-mediated hyperactivation of the MAPK/Erk pathway is responsible for a large number of pathogenic outcomes including many cancers. Considerable effort has been directed at targeting this pathway with varying degrees of long term therapeutic success. Under non-stimulated conditions Erk is bound to the adaptor protein Shc preventing aberrant signalling by sequestering Erk from activation by Mek. Activated RTK recruits Shc, via its phosphotyrosine binding (PTB) domain (Shc), preci...

Small molecule inhibitor agerafenib effectively suppresses neuroblastoma tumor growth in mouse models via inhibiting ERK MAPK signaling.

Neuroblastoma (NB) is the most common extracranial solid tumor in early childhood. Despite intensive multimodal therapy, nearly half of children with high-risk disease will relapse with therapy-resistant tumors. Dysregulation of MAPK pathway has been implicated in the pathogenesis of relapsed and refractory NB patients, which underscores the possibility of targeting MAPK signaling cascade as a novel therapeutic strategy. In this study, we found that high expressions of RAF family kinases correlated with adv...

Nanoparticles for Nucleic Acid Delivery: Applications in Cancer Immunotherapy.

Immunotherapy has recently emerged as a powerful tool for cancer treatment. Early clinical successes from cancer immunotherapy have led to a growing list of FDA approvals, and many new therapies are in clinical and preclinical development. Nucleic acid therapeutics, including DNA, mRNA, and genome editing systems, hold significant potential as a form of immunotherapy due to its robust uses in cancer vaccines, adoptive T-cell therapies, and gene regulation towards the goal of treating cancer. However, these ...

The ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemo-resistance, EMT and cancer stemness in hepatocellular carcinoma.

ATP-binding cassette (ABC) transporters mediate multidrug resistance and cancer stem cell properties in various model systems. Yet, their biological significance in cancers, especially in hepatocellular carcinoma (HCC), remains unclear. In this study, we investigated the function of ABCF1 in HCC and explored its potential as a therapeutic target. ABCF1 was highly expressed in fetal mouse livers but not in normal adult livers. ABCF1 expression was upregulated in HCCs. These results demonstrate that ABCF1 fun...

A tRNA fragment, 5'-tiRNA, suppresses the Wnt/β-Catenin signaling pathway by targeting FZD3 in breast cancer.

tRNA-derived fragments offer a recently identified group of non-coding single-stranded RNAs that are often as abundant as microRNAs in cancer cells and play important roles in carcinogenesis. However, the biological functions of them in breast cancer are still unclear. Hence, we focused on investigating whether tiRNAs could play a key role in the progression of breast cancer. We have identified 5'-tiRNA with significantly low expression in breast cancer tissues. The down-regulation of serum 5'-tiRNA was pos...

Tumor vasculature remodeling by radiation therapy increases doxorubicin distribution and efficacy.

The tumor microenvironment regulates cancer initiation, progression and response to treatment. In particular, the immature tumor vasculature may impede drugs from reaching tumor cells at a lethal concentration. We and others have shown that radiation therapy (RT) induces pericyte recruitment, resembling vascular normalization. Here, we asked whether radiation-induced vascular remodeling translates into improved tissue distribution and efficacy of chemotherapy. First, RT induced vascular remodeling, accompan...

Hepatoma-derived growth factor supports the antiapoptosis and profibrosis of pancreatic stellate cells.

Pancreatic cancer is refractory and is characterized by extensively surrounding and intratumor fibrotic reactions that are contributed by activated pancreatic stellate cells (PSCs). Herein, we show that CCAAT/enhancer-binding protein δ (CEBPD) responds to transforming growth factor-β1 (TGF-β1) through reciprocal loop regulation and that activated hypoxia inducible factor-1α (HIF-1α) further contributes to the upregulation of the hepatoma-derived growth factor (HDGF) gene. Secreted HDGF contributes to t...

Interferon regulatory factor-1 reverses chemoresistance by downregulating the expression of P-glycoprotein in gastric cancer.

The emergence of multiple drug resistance (MDR) is the main cause of chemotherapy failure in gastric cancer. In this study, to generate MDR gastric cancer cell lines, we exposed MKN45 and AGS gastric cancer cells to cisplatin, fluorouracil, and adriamycin. Through transcriptome sequencing, we found that interferon regulatory factor-1 (IRF-1) was expressed at significantly lower levels in the MDR cell lines than in the parental cell lines. We then established stable clones of MKN45 and SGC7901 cells with a d...

Organoid technology in cancer precision medicine.

Organoid technology has been remarkably improved over the last decade. Various organoids have been derived from different types of tissues and recapitulate their organ-specific gene expression signatures, particular tissue spatial structures and functions of their original tissue. The patient-derived organoids (PDOs) have been used to elucidate crucial scientific questions, including the relationships between genetic/epigenetic alterations and drug responses, cell plasticity during disease progressions, and...

Combined Bcl-2/Src inhibition synergize to deplete stem-like breast cancer cells.

Breast cancer cells with stem cell properties play an important role in tumor progression and thus are key targets for therapy. Here, we show that combined Bcl-2/Src inhibition synergizes to deplete stem-like cells. While Src inhibition increases pro-apoptotic PUMA, we find that a significant amount interacts with Bcl-2 and Bcl-xL, promoting resistance to cell death. Consistent with this, the clinically-approved Bcl-2 selective drug venetoclax was sufficient to overcome resistance by preventing PUMA/Bcl-2 b...

Treg-mediated acquired resistance to immune checkpoint inhibitors.

T Regulatory cells (Tregs) act as a double-edged sword by regulating immune homeostasis (protective role) and inhibiting immune responses in different disease settings (pathological role). They contribute to cancer development and progression by suppressing T effector cell (Teff) functions. Decreased ratios of intratumoral CD8 T cells to Tregs have been associated with poor prognosis in most cancer types. Targeting immune checkpoints (ICs), such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and pr...

Special Issue Editorial:Recent Progress of MicroRNA Research in Immunity.

Malignant ascites-derived exosomes promote peritoneal tumor cell dissemination and reveal a distinct miRNA signature in advanced gastric cancer.

Peritoneal dissemination (PD) is the most frequent metastasis with poor prognosis in patients with advanced gastric cancer (GC). However, the molecular mechanisms of PD remain poorly defined. Exosomes play a pivotal role in cancer progression. Thus, this study aims to investigate the effects of malignant ascites (MA)-derived exosomes from GC patients on tumor cells and to elucidate the underlying mechanism. In vitro and in vivo analysis showed that compared to exosome-depleted supernatants, exosomes from MA...

Porphyrin-lipid Assemblies and Nanovesicles Overcome ABC Transporter-Mediated Photodynamic Therapy Resistance in Cancer Cells.

Photodynamic therapy (PDT) involves light activation of the photosensitizer to generate reactive molecular species that induce cell modulation or death. Based on earlier findings showing that photosensitizer benzoporphyrin derivative (BPD) is an ABCG2 substrate, we are investigating the ability of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) to transport BPD. In a panel of breast cancer cell lines overexpressing P-gp, MRP1, or ABCG2, BPD transport occurs only in cells overexpre...

BIRC5 is a target for molecular imaging and detection of human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer mortality with a dismal overall survival rate and an urgent need for detection of minute tumors. Current diagnostic modalities have high sensitivity and specificity for larger tumors, but not for minute PDAC. In this study, we test the feasibility of a precision diagnostic platform for detecting and localizing minute human PDAC in mice. This platform includes: 1) defining BIRC5 as an early PDAC-upregulated gene and utilizing an enhanced BIRC...

Vps4A mediates the localization and exosome release of β-catenin to inhibit epithelial-mesenchymal transition in hepatocellular carcinoma.

We previously reported that Vps4A acted as a tumor suppressor by influencing the microRNA profiles of exosomes and their parental cells in hepatocellular carcinoma (HCC). However, the underlying mechanism and if Vps4A contributes to sorting proteins into exosomes are not well known. Here, we performed mass spectrometry analysis of the immunoprecipitated Vps4A complex and confirmed that Vps4A was associated with β-catenin and CHMP4B. Through this interaction, Vps4A promoted the plasma membrane (PM) localiza...

FOXO3a knockdown promotes radioresistance in nasopharyngeal carcinoma by inducing epithelial-mesenchymal transition and the Wnt/β-catenin signaling pathway.

Mutations in the forkhead box O 3a (FOXO3a) gene are closely related to the progression of several types of cancers. However, few studies explore the relationship between FOXO3a and nasopharyngeal carcinoma (NPC). Our findings demonstrate that silencing FOXO3a promotes tumor radioresistance of NPC in vitro and in vivo through inducing EMT and activating Wnt/β-catenin signal pathway. These data establish that FOXO3a can be a novel and reliable NPC marker and a potential therapeutic target against NPC.

FA-NBs-IR780: Novel multifunctional nanobubbles as molecule-targeted ultrasound contrast agents for accurate diagnosis and photothermal therapy of cancer.

Early accurate diagnosis and targeted therapy for cancer are essential to improve the prognosis of patients. With the emergence of molecular imaging, molecule-targeted ultrasound imaging for the non-invasive and precise detection of cancer has attracted increased attention. The investigation of molecule-targeted ultrasound contrast agents (UCAs) with excellent performance is urgently needed. In this study, we synthetized folic acid and IR-780 on self-made nanobubbles and prepared novel UCAs, named FA-NBs-IR...

LYRM2 directly Regulates Complex I Activity to Support Tumor Growth in Colorectal Cancer by Oxidative Phosphorylation.

Oxidative phosphorylation (OXPHOS) in cancer has attracted a considerable attention in the past decades, and accumulated evidence has suggested that it plays an important role in tumor proliferation, metastasis and drug resistance. However, the mechanisms involved in these effects are still ambiguous to date. In this study, we found that LYR motif containing 2 (LYRM2), a novel molecule, is up-regulated in colorectal cancer and promotes tumor growth both in vivo and in vitro. Furthermore, we discovered that ...

Disruption of oncogenic liver-intestine cadherin (CDH17) drives apoptotic pancreatic cancer death.

Liver-intestine cadherin (CDH17) has been known to function as a tumor stimulator and diagnostic marker for almost two decades. However, its function in highly malignant pancreatic cancer (PC) has yet to be elucidated. Using different strategies including siRNA, shRNA, and CRISPR technology, we successfully induced knockdown and knockout of CDH17 in Panc02-H7 cells and established the corresponding stable cell lines. With these cells, we demonstrated that loss of CDH17 function not only suppressed Panc02-H7...

Targeting the Deubiquitinase STAMBPL1 Triggers Apoptosis in Prostate Cancer Cells by Promoting XIAP Degradation.

The zinc metalloprotease STAM-binding protein-like 1 (STAMBPL1) has been identified as a deubiquitinase by specifically cleaving Lys-63-linked polyubiquitin chains, but its cellular function remains unclear. Here we described the potential role of STAMBPL1 in suppression of the intrinsic apoptosis. We observed substantially high amounts of STAMBPL1 proteins in androgen-independent prostate cancer PC3 and DU145 cell lines. STAMBPL1 RNAi depletion triggered caspase-3/-7-dependent apoptosis in PC3 and DU145 ce...


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