LMTK3 escapes tumour suppressor miRNAs via sequestration of DDX5.

Lemur tyrosine kinase-3 (LMTK3) plays an important role in cancer progression and is associated with breast, lung, gastric and colorectal cancer. MicroRNAs (miRNAs) are small endogenous non-coding RNAs that typically repress target genes at post-transcriptional level and have an important role in tumorigenesis. By performing a miRNA expression profile, we identified a subset of miRNAs modulated by LMTK3.

Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression.

Background: MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of mRNAs and are aberrantly expressed in cancer with important roles in tumorigenesis. A broad analysis of the combined effects of altered activities of miRNAs in pancreatic ductal adenocarcinoma (PDAC) has not been done, and how miRNAs might affect tumour progression or patient outcomes is unclear.

Methods: We combined data from miRNA and mRNA expression profiles from PDAC and normal pancreas samples (each n=9) and used bioinformatic analyses to identify a miRNA-mRNA regulatory network in PDAC.

Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer.

Background: The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts a number of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes and cancer. Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into the potential role of this locus in cell survival and oncogenesis both in vivo and in vitro.

Methods: We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assess the relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignant human colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damage response.

Reduced dissemination of circulating tumor cells with no-touch isolation surgical technique in patients with pancreatic cancer.

Circulating tumor cells (CTCs) disseminate from the primary tumor and travel through the bloodstream and lymphatic system. The detection of and/or increase in the number of CTCs during a patient’s clinical course may be a harbinger of forthcoming overt metastasis. We aimed to examine the impact of 2 different surgical techniques, standard (ST) pancreaticoduodenectomy (PD) and no-touch isolation (NT) PD, on tumor behavior and outcome in patients with pancreatic cancer by using CTCs as biomarkers.

Is the detection of circulating tumor cells in locally advanced pancreatic cancer a useful prognostic marker?

Evaluation of: Bidard FC, Huguet F, Louvet C et al. Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial. Ann.

MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression.

Background & Aims: There has not been a broad analysis of the combined effects of altered activities of microRNAs (miRNAs) in pancreatic ductal adenocarcinoma (PDAC) cells, and it is unclear how these might affect tumor progression or patient outcomes.

Methods: We combined data from miRNA and messenger RNA (mRNA) expression profiles and bioinformatic analyses to identify an miRNA-mRNA regulatory network in PDAC cell lines (PANC-1 and MIA PaCa-2) and in PDAC samples from patients. We used this information to identify miRNAs that contribute most to tumorigenesis.

Downregulation of microRNA-515-5p by the estrogen receptor modulates sphingosine kinase 1 and breast cancer cell proliferation.

Sphingosine kinase 1 (SK1) plays an important role in estrogen-dependent breast tumorigenesis, but its regulation is poorly understood. A subset of microRNAs (miRNA, miR) is regulated by estrogen and contributes to cellular proliferation and cancer progression. Here, we describe that miR-515-5p is transcriptionally repressed by estrogen receptor α (ERα) and functions as a tumor suppressor in breast cancer.

miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts.

Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics.

Altered expression of the miRNA processing endoribonuclease Dicer has prognostic significance in human cancers.

Several studies have implicated miRNAs in the initiation and progression of human cancers. Examining the biogenesis pathways that generate these important regulatory molecules has revealed new mechanisms for tumor development. Altered expression of the endoribonuclease Dicer in many tumors has given new hope to unraveling the complex relationship between miRNA processing and cancer.

Loss of miR-126 is crucial to pancreatic cancer progression.

The tumor-suppressor miRNA 126 (miR-126) is downregulated in many tumors and has recently been placed at the heart of complex metastatic pathways. Hamada and colleagues have identified miR-126 as being downregulated in pancreatic ductal adenocarcinoma (PDAC) patient samples and cell lines. The protein ADAM9 has been implicated in the progression of various solid tumors including PDAC.

Retinoblastoma protein determines aggressiveness in triple-negative breast cancer.

Retinoblastoma protein (RB) is one of the most important tumor suppressors and functions in multiple biological pathways that are deregulated during tumor initiation and progression. Epithelial-to-mesenchymal transition (EMT) is a reversible embryonic process by which epithelial cells lose cell-cell contact and polarity, and its aberrant activation can trigger tumor progression and metastasis. Previously, it has been shown that depletion of RB initiates EMT by downregulating the adhesion molecule E-cadherin.

miRNAs in breast cancer: ready for real time?

Over the past decade, major advances in our comprehension of breast cancer biology have led to improved diagnostic and prognostic techniques and the development of novel targeted therapies. However, the efficacy of new treatments remains limited by a combination of drug toxicity, resistance and persisting insufficiencies in our understanding of tumor-signaling pathways; furthermore, the reliability of identified biomarkers is contentious. Following their recent discovery, miRNAs have been established as critical regulators of gene expression, and their putative roles as oncogenes and tumor-suppressor genes has provided a potential new dimension to our clinical approach to breast cancer diagnosis and treatment.

The clinico-pathologic role of microRNAs miR-9 and miR-151-5p in breast cancer metastasis.

Background: MicroRNAs (miRNAs) may function as suppressors or promoters of tumor metastasis according to their messenger RNA targets. Previous studies have suggested that miR-9 and miR-151-5p are associated with metastasis in breast cancer and hepatocellular carcinoma, respectively. We aimed to further establish the potential roles of miR-9 and miR-151-5p in tumor invasion and metastasis and investigate their use as biomarkers.

Monitoring early response to taxane therapy in advanced breast cancer with circulating tumor cells and [(18)F] 3´-deoxy-3´-fluorothymidine PET: a pilot study.

Aim: Early markers of response to chemotherapy, measured by blood markers and imaging, may ultimately lead to tailored therapies that avoid cumulative toxicity.

Materials & Methods: We performed a small pilot study to compare early changes in levels of circulatory tumor cells (CTCs) with changes in tumor proliferation, using metabolic imaging with [(18)F] 3´-deoxy-3´-fluorothymidine PET (FLT-PET) in women with advanced breast cancer, before and during docetaxel therapy.

Results: In those individuals in whom we could detect CTCs, a decrease in CTC count correlated with a decrease in FLT-PET signal, within 2 weeks.

Whole blood stem cell reinfusion and escalated dose melphalan in castration-resistant prostate cancer: a phase 1 study.

Purpose: Nontaxane-based chemotherapeutic options in castrate-resistant prostate cancer (CRPC) are limited despite the long natural history of the disease. We carried out a phase 1 dose-escalation study of the alkylating agent melphalan with autologous stem cell transplantation, comparing rapid changes in circulating tumor cells (CTC) and prostate-specific antigen (PSA) as a measure of response.

Experimental Design: Cohorts of individuals with advanced CRPC received high-dose intravenous melphalan, and autologous blood was returned to patients during treatment.

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors.

Background: MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated.

Integrated analysis of miRNA and mRNA profiles enables target acquisition in human cancers.

miRNAs play a role in post-transcriptional gene regulation by translational repression and/or mRNA degradation in a very tissue-specific manner. In order to understand the function of a miRNA, it is best to identify the genes that it regulates. Putative mRNA targets of miRNAs identified from seed sequence matches are available using computational algorithms in various web-based databases.

microRNAs as markers of survival and chemoresistance in pancreatic ductal adenocarcinoma.

microRNAs (miRs) are a recently recognized class of noncoding short RNAs, 17-25 nucleotides in length, that play a role in post-transcriptional gene regulation by translational repression and/or mRNA degradation. Various miRs have been highlighted in pancreatic cancer development and metastasis, and as potential clinical diagnostic/prognostic biomarkers. Recently, studies have indicated that miRs are responsible for resistance to chemotherapeutic agents.

[18F]-3'Deoxy-3'-fluorothymidine positron emission tomography and breast cancer response to docetaxel.

Purpose: To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [(18)F]-3'deoxy-3'-fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer.

Experimental Design: This was a prospective unblinded study in 20 patients with American Joint Committee on Cancer (AJCC) stage II-IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan 2 weeks after initiating the first or second cycle of docetaxel.

Determination of cut-offs for circulating tumor cell measurement in metastatic cancer.

The metastatic transformation of epithelial tumors progresses through various steps leading to the generation of circulating tumor cells (CTCs). Measurement of CTCs in the peripheral blood is being increasingly recognized as a promising tool in breast oncology. Several studies have evaluated the prognostic significance of CTCs in newly diagnosed metastatic breast cancer (MBC) patients.

Circulating tumor cells and plasma DNA analysis in patients with indeterminate early or metastatic breast cancer.

Background: Circulating tumor cells (CTCs) and tumor-specific alterations in cell-free plasma DNA can both be used as markers of prognosis in breast cancer. To date, there have been no studies that have compared these as markers for subclinical metastases in the follow-up of early breast cancer. In this study, we measured CTCs and plasma DNA in a published group of patients with multiple pulmonary nodules and indeterminate metastatic disease.

No evidence for a polyomavirus association or aetiology in AIDS-associated nonsmall cell lung cancer.

AIDS-associated lung cancer has an increasing incidence, unaccounted for by smoking, and occurs consistently at a younger age than matched controls. We investigated whether known and new cancer-associated polyomaviruses, including the newly identified Merkel cell virus, may play a role in its etiopathogenesis. Although viruses target conserved pathways in cellular evolution, we are unable to suggest that the viruses studied here induce novel mechanisms of oncogenic dysregulation in AIDS-associated lung cancer.

Clinical utility of circulating tumor cell measurement in the diagnosis of indeterminate lesions of the pancreas.

The quantification of circulating tumor cells has been historically problematic due to the different methods applied to their measurement. Following the development of standardized technology, they are now becoming well-established prognostic and predictive markers in patients with breast, colon and prostate cancer. While they represent a real-time noninvasive test, their use in diagnostics has seldom been reported.