Understanding the mechanism of HIV-1 latency is crucial to eradication of the viral reservoir in HIV-1-infected individuals. However, the role of histone methyltransferase (HMT) G9a-like protein (GLP) in HIV-1 latency is still unclear. In the present work, we established four clonal cell lines containing HIV-1 vector. We found that the ...

BACKGROUND: HIV-1 is inhibited early after entry into cells expressing some simian orthologues of the tripartite motif protein family member TRIM5alpha. Mutants of the human orthologue (TRIM5alphahu) can also provide protection against HIV-1. The host protein cyclophilin A (CypA) binds incoming HIV-1 capsid (CA) proteins and enhances early stages of ...

ABSTRACT: BACKGROUND: Slit2 is a ~ 200 kDa secreted glycoprotein that has been recently shown to regulate immune functions. However, not much is known about its role in HIV (human immunodeficiency virus)-1 pathogenesis. RESULTS: In the present study, we have shown that the N-terminal fragment of Slit2 (Slit2N) (~120 kDa) ...

The cellular protein tetherin tethers the HIV-1 viral particles on the cellular membrane to inhibit the replication of HIV-1. However, the HIV-1 accessory protein Vpu counteracts the antiviral function of tetherin. In this study, two retroviral vector plasmids were constructed. One inhibited the vpu gene expression; the other one over-expressed ...

Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Acetylated or benzylated and/or with cyclohexylidene group ...

ABSTRACT: BACKGROUND: Lens epithelium--derived growth factor (LEDGF/p75) is a cellular co-factor of HIV-1 integrase (IN) that tethers the viral pre-integration complex to the host cell chromatin and determines the genome wide integration site distribution pattern of HIV-1. Recently, we demonstrated that HIV-1 replication was reduced in LEDGF/p75 knockout (KO) cells. ...

We present a case of sexual transmission of HIV-1 predicted to have CXCR4-tropism during male-to-male sexual exposure. Phylogenetic analyses exclude cell-free virus in the seminal plasma of the source partner and possibly point to the seminal cells as the origin of the transmission event.

Microbicides have been evaluated mostly against cell-free HIV-1. Since semen contains both cell-free and cell-associated HIV-1, HIV-1 transmission could occur via either or both sources. Therefore, it is important to examine the antiviral activity of microbicides against cell-associated HIV-1. The cyclic antimicrobial peptide Retrocyclin RC-101 has been shown previously to ...

Lapatinib targets human epidermal growth factor-receptor (EGFR) and Her2/neu receptor tyrosine-kinases and hence is under investigation in multimodal therapy concepts of advanced head and neck squamous cell carcinoma (HNSCC). We studied combined effects of lapatinib and cisplatin on colony formation (CF) of epithelial cells of individual HNSCC in short term ...

Probiotics have been shown to have a preventative role in colorectal carcinogenesis but research concerning their prophylactic potential in the later stages of colorectal cancer, specifically metastasis is limited. This study explored the potential of cell-free supernatants (CFS) from 2 probiotic Lactobacillus sp., Lactobacillus casei and Lactobacillus rhamnosus GG, to ...

The Werner syndrome protein (WRN) is a member of the RecQ helicase family. Loss of WRN results in a human disease, the Werner syndrome (WS), characterised by high genomic instability, elevated cancer risk and premature aging. WRN is crucial for the recovery of stalled replication forks and possesses both helicase ...

Phagoptosis, also called primary phagocytosis, is a recently recognised form of cell death caused by phagocytosis of viable cells, resulting in their destruction. It is provoked by exposure of 'eat-me' signals and/or loss of 'don't-eat-me' signals by viable cells, causing their phagocytosis by phagocytes. Phagoptosis mediates turnover of erythrocytes, neutrophils ...

Capsosiphon fulvescens is a well-known green sea algae that has been touted in recent years as a potential anticancer drug. In this study, C. fulvescens glycoprotein (Cf-GP) showed proapoptotic signaling in AGS cells. An MTS assay indicated that Cf-GP inhibited the proliferation of AGS cell lines in a dose-dependent manner. ...

Airway damage and remodelling are important components of lung pathology progression in cystic fibrosis (CF). Although repair mechanisms are engaged to restore the epithelial integrity, these processes are obviously insufficient to maintain lung function in CF airways. Our aims were therefore to study how the basic CFTR defect could impact ...

The oncogenic kinase PAK4 was recently found to be involved in the regulation of the G1 phase and the G2/M transition of the cell cycle. We have also identified that PAK4 regulates Ran GTPase activity during mitosis. Here, we show that after entering mitosis, PAK4-depleted cells maintain a prolonged metaphase-like ...

Type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) is the major enzyme in the prostate that reduces 4-androstene-3,17-dione (Δ(4)-Adione) to the androgen receptor (AR) ligand testosterone. AKR1C3 is upregulated in prostate cancer (PCa) and castrate resistant prostate cancer (CRPC) that develops after androgen deprivation therapy. PCa and CRPC often depend on intratumoral androgen ...

Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum. Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were ...

Cystic fibrosis (CF) is a monogenic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with lung and liver manifestations. Because of pitfalls of gene therapy, novel approaches for reconstitution of the airway epithelium and CFTR expression should be explored. In the present study, human amniotic mesenchymal ...

Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus that was originally identified from human prostate cancer patients and subsequently linked to chronic fatigue syndrome. Recent studies showed that XMRV is a recombinant mouse retrovirus; hence, its association with human diseases has become questionable. Here, we demonstrated that XMRV envelope ...

BACKGROUND: We previously reported that the level of high mobility group protein AT-hook 1 (HMGA1) is low in androgen-dependent prostate cancer (PCa) cells (LNCaP), but is high in androgen-independent PCa cells (DU145 and PC-3) and that HMGA1 is a strong candidate gene playing a potential role in the progression of ...

In this study, flutamide, an androgen receptor antagonist, was used as a tool to better understand the role of androgen receptor signaling and androgen signaling disruption during fetal and neonatal periods on porcine Leydig cell development and function. Flutamide, 50 mg kg(-1) d(-1) was administered into pregnant gilts during gestational ...

Ronquist G (Department of Internal Medicine, Clinical Chemistry, University Hospital, Uppsala, Sweden) Prostasomes - mediators of intercellular communication (Review). J Intern Med 2011 Prostasomes are nanosized microvesicles secreted by acinar epithelial cells of the prostate gland. Furthermore, they are intracellular microvesicles inside another larger vesicle, a so-called storage vesicle, equivalent ...

Background: The aim of the present work was to study the involvement of nuclear factor kappa B mediated by Interleukin-1 beta on cell proliferation and Prostate Specific Antigen production of LNCaP prostate cell lines and the possible cross talk with AKT signalling pathway. Methods: Nuclear factor kappa B and AKT ...

BACKGROUND: Prostate and seminal vesicle are two similar hormone responsive human organs that differ dramatically in their cancer incidence. DNA damage response (DDR) is required for maintenance of genomic integrity. METHODS: In this study we investigated the DDR and cell cycle checkpoint activation of these organs using orthotopic cultures of ...

Androgen receptor (AR) is the major therapeutic target for the treatment of prostate cancer (PCa). Anti-androgens to reduce or prevent androgens binding to AR are widely used to suppress AR-mediated PCa growth; however, the androgen depletion therapy is only effective for a short period of time. Here we found a ...

Galanin (GAL) is a neuropeptide that is widely expressed in neuroendocrine tissues, including the adenohypophysis. Since GAL is expressed at higher levels in females, little attention has been paid to the regulation of GAL secretion in males. Here, we show that testosterone regulates GAL secretion in the adenohypophysis of male ...

Current diagnostic tools cannot predict clinical failure and androgen-independent disease progression for patients with prostate cancer (PC). The survival signaling pathways of prostate cells play a central role in the progression of tumors to a neuroendocrine (NE) phenotype. NE cells demonstrate attributes that suggest that they are an integral part ...

Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, this therapy is associated with several undesired side-effects, including increased risk of cardiovascular diseases. To study if termination of long-term androgen ablation and restoration of testosterone levels could suppress the growth of relapsed hormone-refractory prostate tumors, we implanted ...

Patients with recurrent prostate cancer are commonly treated with androgen withdrawal therapy (AWT); however, almost all patients eventually progress to castration resistant prostate cancer (CRPC), indicating failure of AWT to eliminate androgen-sensitive prostate cancer. The overall goal of these studies is to determine whether dual inhibition of the receptor tyrosine ...

OBJECTIVES:: To investigate the effects of an antibiotic brefeldin A (BFA) on androgen-regulated cellular events in androgen-responsive prostate cancer cells, focusing on PSA (prostate-specific antigen) status, cell growth, and bioactivity of androgen receptor (AR). MATERIALS AND METHODS:: Androgen-responsive human prostate cancer LNCaP cells were employed and 5α-dihydrotestosterone (DHT) was used ...

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and ...

It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition ...

Androgens are responsible for maintaining epididymal structure and functions. However, little is known about how androgen action is mediated and the mechanisms underlying the restoration of the integrity of epididymal cells after androgen deprivation. We first provide an overview of what is known about androgen action in this tissue and ...

BACKGROUND: Treatment for primary prostate cancer (CaP) is the withdrawal of androgens. However, CaP eventually progresses to grow in a castration-resistant state. The mechanisms involved in the development and progression of castration-resistant prostate cancer (CRPC) remain unknown. We have previously generated LNCaP-IL6+ cells by treating LNCaP cells chronically with interleukin-6 ...

Extracts from Serenoa repens are widely used for the treatment of benign prostatic hyperplasia (BPH) and traditionally for prostatitis. In the present study we evaluated the biological effects of Serenoa repens extract (Prostasan®) on prostate cells beyond its known antiandrogenic actions. Prostasan® inhibited epidermal growth factor (EGF) and lipopolysaccharide (LPS) ...

Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human ...

The molecular mechanisms of apoptotic induction by benzyldihydroxyoctenone (BDH), a nonsteroidal antiandrogen, isolated from the culture broth of Streptomyces sp., have been previously published in prostate cancer LNCaP cells. Apoptotic induction of BDH-treated LNCaP cells was associated with downregulation of Bcl-xL that caused, in turn, cytochrome c release from mitochondria, ...

OBJECTIVE: • To conduct a preclinical evaluation of the ability of natural killer cells to cytolyze bladder cancer cells that were modified to show enhanced expression of natural-killer group 2, member D (NKG2D) ligands by R8-liposome-bacillus Calmette-Guéin (BCG)-cell wall skeleton (CWS) treatment. MATERIALS AND METHODS: • The T24 cells and RT-112 cells ...

Focal epiretinal radiation has emerged as a promising tool in the management of choroidal neovascularization associated with age-related macular degeneration. However, the dosages tested are not backed by cell culture studies used in the clinical setting empirically. Choroidal endothelial cells (RF6A) were maintained in a log scale and exposed to ...

Both the G2 chromosomal radiosensitivity assay and allelic differences in TP53 codon-72 have been associated with cancer predisposition. The relationship between the two endpoints was determined in 56 human EBV-transformed lymphoblastoid cell lines. Although there were overlapping distributions of sensitivity for the different genotypes, cell lines that were homozygous for ...

In order to generate genomic signals, the androgen receptor (AR) has to be transported into the nucleus upon androgenic stimuli. However, there is evidence from in vitro experiments that in castration-resistant prostate cancer (CRPC) cells the AR is able to translocate into the nucleus in a ligand-independent manner. The recent ...

Results from tissue recombination experiments documented well that stromal androgen receptor (AR) plays essential roles in prostate development, but epithelial AR has little roles in prostate development. Using cell specific knockout AR strategy, we generated pes-ARKO mouse with knock out of AR only in the prostate epithelial cells and demonstrated ...

Centrosomes are important cytoplasmic organelles involved in chromosome segregation, defects in which can result in aneuploidy, and contribute to tumorigenesis. It is known that DNA damage causes the supernumerary centrosomes by a mechanism in which centrosomes continue to duplicate during cell cycle arrest at checkpoints. We show here that ionizing ...

Gold nanoparticles (GNPs) have been shown to cause sensitization with kilovoltage (kV) radiation. Differences in the absorption coefficient between gold and soft tissue, as a function of photon energy, predict that maximum enhancement should occur in the kilovoltage (kV) range, with almost no enhancement at megavoltage (MV) energies. Recent studies ...

This study aimed to investigate the cancer stem cell (CSC) properties of radioresistant esophageal cancer cells and the radiosensitization effect of NS398, a cyclooxygenase (COX)-2 inhibitor, on them. Fractionated irradiation was applied to acquire radioresistant esophageal cancer cells. Clone formation assay was employed to detect cell radiosensitivity and cloning formation ...

Abstract It has been hypothesized that ionizing radiation-induced disruptions in mitochondrial O(2) metabolism lead to persistent heritable increases in steady-state levels of intracellular superoxide (O(2)(•-)) and hydrogen peroxide (H(2)O(2)) that contribute to the biological effects of radiation. Hamster fibroblasts (B9 cells) expressing a mutation in the gene coding for the ...

PURPOSE: In metastatic prostate cancer, DOC-2/DAB2 interactive protein (DAB2IP) is often downregulated and has been reported as a possible prognostic marker to predict the risk of aggressive prostate cancer (PCa). Our preliminary results show that DAB2IP-deficient PCa cells are radioresistant. In this study, we investigated the anticancer drug Epothilone B ...

Purpose: To investigate the possible cytotoxic interactions between the chemotherapeutic drug temozolomide (TMZ) and the cyclooxygenase-2 inhibitor meloxicam (MLC) or of both drugs combined with X-rays in three human glioma cell lines (D384, Hs 683 and U251). Materials and methods: Cells were exposed to TMZ (96 hours) and MLC was co-incubated during ...

M059J and M059K cells were isolated from different portions of the same human malignant glioma. M059J cells are more radiosensitive than M059K cells due to the absence of DNA-PKcs and low-expression of ATM. The mechanism concerning the absence of DNA-PKcs in M059J is due to the frameshift mutation in PRKDC ...

Abstract RKO36 cells exposed to either WR1065 or 10 cGy X rays show elevated SOD2 gene expression and SOD2 enzymatic activity. Cells challenged at this time with 2 Gy exhibit enhanced radiation resistance. This phenomenon has been identified as a delayed radioprotective effect or an adaptive response when induced by thiols or ...