ABSTRACT: BACKGROUND: To understand the role of proteases involved in human thyroid cancer progression and tissue invasion, thyrocytes from other species could potentially be used provided their characteristics are similar. It is not known whether dipeptidyl peptidase IV and aminopeptidase N activities, which are overexpressed in human thyroid cancer, are, ...

High-risk human papillomaviruses (HR-HPVs) infections is highly associated with the development of cervical cancer. It is now recognized that telomere length maintenance or extension is indispensable for carcinogenesis. The early oncoproteins E6 and E7 are the main malignant transformation factors of HR-HPVs and they maintain telomeres by different mechanisms, of ...

RalA and RalB are small GTPases which support malignant development and progression in experimental models of bladder, prostate and squamous cancer. However, demonstration of their clinical relevance in human tumors remains lacking. Here, we developed tools to evaluate Ral protein expression, activation and transcriptional output and evaluated their association with ...

MicroRNAs (miRNAs), highly conserved, non-coding endogenous RNA and nearly ~22 nucleotides (nt) in length, are well-known to regulate several apoptotic pathways in cancer. In this study, we computationally constructed the initial human apoptotic PPI network by several online databases, and further integrated these high-throughput datasets into a Naïve Bayesian model ...

In normal human somatic cells, telomere dysfunction causes cellular senescence, a stable proliferative arrest with tumour suppressing properties. Whether telomere dysfunction-induced senescence (TDIS) suppresses cancer growth in humans, however, is unknown. Here, we demonstrate that multiple and distinct human cancer precursor lesions, but not corresponding malignant cancers, are comprised of ...

Human telomerase is a ribonucleoprotein complex that functions as a telomere terminal transferase by adding multiple TTAGGG hexamer repeats using its integral RNA as the template. There is a very strong association between telomerase activity and malignancy in nearly all types of cancer, suggesting that telomerase could be used not ...

Objective: Our objective was to construct a recombinant bacillus Calmette-Guérin vaccine (rBCG) that secretes human interferon-alpha 2b (IFNα-2b) and to study its immunogenicity and in vitro antitumor activity against human bladder cancer cell lines T24 and T5637. Methods: The signal sequence BCG Ag85B and the gene IFNα-2b were amplified from ...

The unlimited proliferation potential of cancer cells requires the maintenance of their telomeres. This is frequently accomplished by reactivation of telomerase. However, in a significant fraction of tumors an alternative lengthening of telomeres (ALT) mechanism is active. The molecular mechanism of the ALT pathway remains elusive. In particular, the role ...

Nodal is a TGF-β-related embryonic morphogen that is expressed in multiple human cancers. Detection of Nodal expression in these tissues can be challenging if issues related to Nodal transcription and protein processing are not considered. Here, we discuss certain characteristics related to Nodal expression and function and how these can ...

Prostate cancer is the most commonly diagnosed malignancy in men in developed countries. ErbB2, a tyrosine kinase receptor overexpressed in many human cancer types, contributes to prostate cancer progression by activating the androgen receptor in a steroid poor environment, thus promoting androgen-independent cell growth. The consequent development of hormone refractory ...

Background:Although the role of human papilloma virus (HPV) in cervical squamous cell carcinoma (CSCC) is well established, the role in head and neck SCC (HNSCC) is less clear. MicroRNAs (miRNAs) have a role in the cancer development, and HPV status may affect the miRNA expression pattern in HNSCC. To explore ...

Fast cancer diagnosis represents a real necessity in applied medicine due to the importance of this disease. Thus, theoretical models can help as prediction tools. Graph theory representation is one option because it permits us to numerically describe any real system such as the protein macromolecules by transforming real properties ...

Aldo-keto reductase 1C3 (AKR1C3) is a human enzyme that catalyzes the NADPH-dependent reduction of steroids and prostaglandins. AKR1C3 overexpression is associated with the proliferation of hormone-dependent cancers, most notably breast and prostate cancers. Nonsteroidal anti-inflammatory drugs (NSAIDs) and their analogues are well characterized inhibitors of AKR1C3. Here, the X-ray crystal ...

Two monoclonal antibodies (Mabs), RP215 and GHR106, were selected for the preclinical evaluations of anti-cancer drugs targeting various human cancers including those of the ovary, cervix, lung, and liver. Both Mabs were shown to react with pan cancer markers, which are over-expressed on the surface of almost all human cancers. ...

Introduction: MicroRNAs (miRNAs), a class of small, regulatory and non-coding RNA molecules, display aberrant expression patterns and functional abnormalities in all kinds of human diseases including cancers. As important emerging modulators in cellular pathways, miRNAs play a key role in tumorigenesis. Correcting these miRNA deficiencies by either up-regulating or down-regulating ...

Systemic delivery of fenretinide in oral cancer chemoprevention trials has been largely unsuccessful due to dose-limiting toxicities and sub-therapeutic intra-oral drug levels. Local drug delivery, however, provides site-specific therapeutically-relevant levels while minimizing systemic exposure. These studies evaluated the pharmacokinetic and growth-modulatory parameters of fenretinide mucoadhesive patch application on rabbit buccal ...

Experiments with cultures of human tumor cell lines, xenografts of human tumors into immunodeficient mice, and mouse models of human cancer are important tools in the development and testing of anti-cancer drugs. Tumors are complex structures composed of genetically and phenotypically heterogeneous cancer cells that interact in a reciprocal manner ...

A founding premise of the human genome project was that knowledge of the spectrum of abnormalities that comprise cancers and other human diseases would lead to improved disease management by identifying molecular abnormalities that could guide disease detection and diagnosis, suggest new therapeutic strategies and be developed as markers to ...

Over the past 10 years the realisation that genetic mouse models of cancer may play a key role in preclinical drug development has gained strong momentum. Moreover sequencing studies of human tumours have provided key insights into the mutational complexity of epithelial cancer, unleashing important clues for researchers to generate ...

The human N-terminal acetyltransferases (NATs) catalyze the transfer of acetyl moieties to the N-termini of 80-90% of all human proteins. Six NAT types are present in humans, NatA-NatF, each is composed of specific subunits and each acetylates a set of substrates defined by the N-terminal amino-acid sequence. NATs have been ...

Multidrug resistance (MDR) is one of the major concerns in the treatment of cancer and one of the major causes of therapy failure. The overexpression of an ABC transporter, the ABCB1, is often associated with MDR in cancer. Previously it was observed that hydantoin compounds can modulate the activity of ...

ABSTRACT Background: Cancer is one of the leading causes of deaths in the world. Current chemotherapeutic agents are associated with serious side effects in patients therefore researchers are trying to find an alternative agent that is effective against cancer as well as less toxic. Resveratrol (3,5,4'-trihydroxystilbene), commonly found in red ...

MicroRNAs (miRNAs) are a class of 21-23 nucleotide RNA molecules that play critical roles in the regulation of various cancers, including human lung cancer. Among them, miR-26a has been identified as a tumor-related regulator in several cancers, but its pathophysiologic properties and correlation with the development of human lung cancer ...

Vast resources are expended during the development of new cancer therapeutics, and selection of optimal in vivo models should improve this process. Genetically engineered mouse models (GEMM) of cancer have progressively improved in technical sophistication and, accurately recapitulating the human cognate condition, have had a measureable impact on our knowledge ...

Deregulation of protein synthesis is a common event in human cancer and a key player in translational control is eIF4E. Elevated expression levels of eIF4E promote cancer development and progression. Recent findings suggest that eIF4E activity is a key determinant of the PI3K/Akt/mTOR and Ras/Raf/MEK/ERK mediated tumorigenic activity and targeting ...

Abstract MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that are evolutionarily conserved and widely distributed among species. Their major function is to negatively regulate mRNA target genes, and miRNA expression has been found to be deregulated in all human cancers, where miRNAs play critical roles in tumorigenesis, ...

Dysregulation of microRNAs (miRNAs) has been widely shown to be associated with the development and progression of cancer. Recent studies discovered a handful of miRNAs with great potential to act as therapeutic targets in various human cancers. Inhibition or overexpression of these oncomirs may regulate the expressions of their associated ...

Enhanced receptor selectivity: Carbonic anhydrase inhibitors are relevant for both, cancer diagnosis and therapy. Combining non-radioactive Re compounds with their radioactive (99m) Tc homologs enables the use of identical molecules for therapy and imaging (theragnostic). The syntheses and in vitro evaluation of [(Cp-R)M(CO)(3) ] (CP=cyclopentadienyl, M=Re, (99m) Tc) with R ...

Telomere attrition unleashes genomic instability, promoting cancer development. Once established, however, the malignant clone often re-establishes genomic stability through overexpression of telomerase. In two papers, one in this issue of Cell and one in the subsequent issue, DePinho and colleagues explore the consequences of telomerase re-expression and its validity as ...

Prostate cancer is a prevalent disease that affects the aging male population. Whilst there have been significant advances of our biological understanding of the disease, clinical translation of promising agents continues to lag behind. In part, this is due to a paucity of relevant experimental and pre-clinical models required to ...

Increases in the level of cyclooxygenase (COX)-2 and prostanoids such as prostaglandin E(2) (PGE(2)) are considered biomarkers of colorectal cancer. Therefore, non-steroidal anti-inflammatory drugs (NSAID) have been used to reduce the risk of cancer development by reducing prostanoid biosynthesis as COX inhibitors. Along with their activity as COX inhibitors, NSAID ...

MicroRNAs (miRNAs) are endogenous short non-coding RNA molecules that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs are aberrantly expressed in many human cancers and that they play　significant roles in the initiation, development and metastasis of ...

Exome sequencing of human breast cancers has revealed a substantial number of candidate cancer genes with recurring but infrequent somatic mutations. To determine more accurately their mutation prevalence, we performed a mutation analysis of 36 novel candidate cancer genes in 96 human breast cancers. Somatic mutations with potential impact on ...

A healthy human body contains at least tenfold more bacterial cells than human cells and the most abundant and diverse microbial community resides in the intestinal tract. Intestinal health is not only maintained by the human intestine itself and by dietary factors, but is also largely supported by this resident ...

Flavonoids are widely distributed in nature and a prevalent component of the human diet. Numerous biological activities have been reported. Some clinical trials or meta-analyses have suggested positive associations between flavonoid intake and human health, whereas others have not supported such a relationship. We currently highlight some responses that may ...

Organic anion transporting polypeptide 1B3 (OATP1B3) is a hepatocyte plasma membrane protein that transports various endogenous and xenobiotic compounds. Although it is exclusively expressed in the human liver under normal conditions, OATP1B3 can be also expressed in various human cancer tissues that have been associated with prognosis and clinical outcomes. ...

Phosphoinositide-3-kinase (PI3K) is an important target for cancer therapeutics due to the deregulation of its signaling pathway in a wide variety of human cancers. We describe herein a novel series of imidazo[1,2-a]pyrazines as PI3K inhibitors.

The current paradigm for cancer risk assessment in the United States (U.S.) typically requires selection of representative rodent bioassay dose-response data for extrapolation to a single cancer potency estimate for humans. In the absence of extensive further information, the chosen bioassay result generally is taken to be that which gives ...

An ethyl acetate extract of the roots of Rumex dentatus L. was investigated. Three compounds were identified by their spectroscopic data as chrysophanol (1), 6-methyl-7-acetyl-1, 8-dihydroxy-3-methoxy naphthalene-1-O-β-D(L)-glucoside (2) and 6-methyl-7-acetyl-1, 8-dihydroxy naphthalene-1-O-β-D(L)-glucoside (3) were found in the plant for the first time. Compounds 2 and 3 are novel compounds. Their ...

The use of small molecules to target miRNAs is a new type of therapy for human diseases, particularly cancers. We proposed a novel high-throughput approach to identify the biological links between small molecules and miRNAs in 23 different cancers and constructed the Small Molecule-MiRNA Network (SMirN) for each cancer to ...

Pancreatic cancer has one of the worst prognoses among all types of cancers. The survival rate is less than 5 per cent; this is due to difficulty in diagnosing at an early stage. Despite the improvements in diagnostic imaging techniques such as computed tomography, magnetic resonance imaging, etc., the early ...

Knowledge gained from the identification of genetic and epigenetic alterations that contribute to the progression of prostate cancer in humans is now being implemented in the development of functionally relevant translational models. GEM (genetically modified mouse) models are being developed to incorporate the same molecular defects associated with human prostate ...

The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is now implicated in a wide range of human cancers. Results from recent clinical trials with ALK inhibitors provide promise for patients harboring oncogenic ALK lesions. This review will discuss our current understanding of ALK in human cancer and the implication of ...

The chicken anaemia virus-derived protein Apoptin/VP3 (CAV-Apoptin) has the important ability to induce tumour-selective apoptosis in a variety of human cancer cells. Recently the first human Gyrovirus (HGyV) was isolated from a human skin swab. It shows significant structural and organisational resemblance to CAV and encodes a homologue of CAV-Apoptin/VP3. ...

The human genome contains microRNAs (miRNAs), small noncoding RNAs that orchestrate a number of physiologic processes through regulation of gene expression. Burgeoning evidence suggests that dysregulation of miRNAs may promote disease progression and cancer pathogenesis. Virus-encoded miRNAs, exhibiting unique molecular signatures and functions, have been increasingly recognized as contributors to ...

The manufacture, use and disposal of various plastics can pose numerous health risks, including the risk of cancer. A model example of carcinogenic risk from plastics is provided by polyvinyl chloride, since it is composed of the known human carcinogen vinyl chloride (VC). In recent years, much has been learned ...

Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of ...

The so-called "Seed and Soil" hypothesis proposed by Stephen Paget in 1889 to explain the metastatic behavior of cancer cells and the homing of certain cancers to "selected" sites has been a well-recognized phenomenon for over a century. What advances have been made to increase our understanding of this phenomenon ...

The anticancer effects of traditional Chinese medicine (TCM) have attracted the attention of the public vis-à-vis existing cancer therapies with various side effects. Lycium barbarum fruit, commonly known as Gou Qi Zi in China, is a potential anticancer agent/adjuvant. Its major active ingredients, L. barbarum polysaccharides (LBP), scopoletin and 2-O-β-D: ...

The enormous biologic complexity of human cancer has stimulated the development of more appropriate experimental models that could resemble in a natural and spontaneous manner the physiopathologic aspects of cancer biology. Companion animals have many desired characteristics that fill the gap between in vitro and in vivo studies, and these characteristics have ...