Adriamycin in combination with dexamethasone and octreotide lacks activity on the treatment of a 4T1 metastatic breast cancer model.

The aim of this study was to evaluate whether the palliative treatment for metastatic disease with dexamethasone (DEX) plus octreotide (OCT) can improve the anticancer effects of the standard treatment with adriamycin (ADR) on a 4T1 metastatic breast cancer (MBC) model. 4T1 cells were first characterized for the expression of the somatostatin receptors 1-5 and were then inoculated onto the femur of BALB/C mice. Investigation protocols used 4T1 cell proliferation and invasion assays, analysis of radiographic images of the bone metastatic lesions, and overall survival of the diseased animals.

Detection of circulating tumor cells in breast cancer patients using multiplex reverse transcription-polymerase chain reaction and specific primers for MGB, PTHRP and KRT19 correlation with clinicopathological features.

Aim: The aim of this study was to correlate the clinicopathological features of breast cancer patients with the positive detection of parathyroid hormone-related protein (PTHRP), cytokeratin protein 19 (KRT19) and mammaglobin (MGB) using a multiplex reverse transcription polymerase chain reaction (RT-PCR) assay developed to detect circulating tumor cells (CTCs) in peripheral blood of patients with breast cancer.

Patients And Methods: Peripheral blood samples were collected from 54 breast cancer patients and 20 healthy blood donors. Subsequently, the samples were processed for RNA extraction and analyzed for the expression of PTHRP, KRT19 and MGB using specific primers and multiplex RT-PCR.

Dexamethasone plus octreotide regimen increases anticancer effects of docetaxel on TRAMP-C1 prostate cancer model.

Aim: The aim of this study was to evaluate whether the neoadjuvant use of the dexamethasone (DEX) plus octreotide (OCT) regimen can improve the direct anticancer effects of docetaxel (DOC) in the TRAMP-C1 prostate cancer model.

Materials And Methods: TRAMP-C1 cells were first characterized for the expression of SSTR1-5 and then were inoculated onto the femur of C57Bl mice. Investigation protocols employed TRAMP-C1 cell proliferation and invasion assays, analysis of radiographic images of the bone lesions and overall survival of the diseased animals.

IGF1Ec expression in MG-63 human osteoblast-like osteosarcoma cells.

Aim: The insulin-like growth factor 1 (IGF1) gene gives rise to multiple transcripts, using an elaborate alternative splicing mechanism. The aim of this study was to shed light on the expression and role of the IGF1 system in human MG-63 osteoblast-like osteosarcoma cells.

Materials And Methods: The expression of the IGF1Ea, IGF1Eb and IGF1Ec isoforms was characterized using reverse transcription polymerase chain reaction (RT-PCR), quantitative real time-PCR (qRT-PCR) and western blot analysis.

Expression of the insulin-like growth factor 1 (IGF-1) and type I IGF receptor mRNAs in human HLE-B3 lens epithelial cells.

Background/aim: The E peptide of the IGF-1Ec transcript has been documented to stimulate the growth of different cell lines, via a type I IGF-1 receptor (IGF-1R)-independent mechanism. The aim of the present study was to determine the implication of the IGF-1Ec isoform into the posterior capsule opacification process in human lens epithelium.

Materials And Methods: The expression of the IGF-1 system was characterized in human HLE-B3 lens epithelium cells and the mitogenic activity of IGF-1 and synthetic E peptide and the effects of growth hormone (GH) and dihydrotestosterone (DHT) were examined, using qualitative real-time PCR, RT-PCR, Western blot analysis and trypan blue exclusion assays in wild-type and IGF-1R knock-out HLE-B3 cells.

Multiplex RT-PCR-based detections of CEA, CK20 and EGFR in colorectal cancer patients.

Aim: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting circulating tumor cells in the peripheral blood of colorectal cancer (CRC) patients.

Methods: Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival.

Detection of the circulating tumor cells in cancer patients.

As the presence of tumor cells circulating in the blood is associated with systemic disease and shortened survival, the establishment of a method to detect circulating tumor cells (CTCs) is of critical importance for a more concise staging and follow-up of cancer patients. Recently, the most robust strategies for the determination of CTCs are the PCR-based methods and the CellSearch® system that exploits the immunofluorescent characterization and isolation of cancer cells. Herein, we analyzed the experimental strategies used for determining CTCs with respect to accuracy, sensitivity and reproducibility in cancers of the breast, colon, prostate and melanoma.

Methods of detection of circulating melanoma cells: a comparative overview.

Disease dissemination is the major cause of melanoma-related death. A crucial step in the metastatic process is the intravascular invasion and circulation of melanoma cells in the bloodstream with subsequent development of distant micrometastases that is initially clinically undetectable and will eventually progress into clinically apparent metastasis. Therefore, the use of molecular methods to detect circulating melanoma cells may be of value in risk stratification and clinical management of such patients.

uPA, uPAR and TGFβ₁ expression during early and late post myocardial infarction period in rat myocardium.

The expression patterns of transforming growth factor beta 1 (TGFβ₁), urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) were analysed after artery ligation-induced myocardial infarction (MI) in the rat myocardium. uPA and uPAR expressions were significantly increased both at transcriptional and protein level during early phase post MI period (uPA at 1 hour and uPAR at 24 hours post infarction). TGFβ1 mRNA expression profile revealed a significant increase of TGFβ1 expression from day 4 up to 8 weeks post infarction.

Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro.

Different insulin-like growth factor-1 (IGF-1) isoforms, namely IGF-1Ea, IGF-1Eb and IGF-1Ec (MGF), have been proposed to have various functions in muscle repair and growth. To gain insight into the potentially differential actions of IGF-1 isoforms in the regulation of muscle regeneration, we assessed the time course of their expressions at both mRNA and protein levels after exercise-induced muscle damage in humans. In addition, we characterized mature IGF-1 and synthetic MGF E peptide signalling in C2C12 myoblast-like cells in vitro.

The glutamatergic system expression in human PC-3 and LNCaP prostate cancer cells.

Background: The glutamatergic system (Glu system) comprises the Glu receptors (GluRs), the Glu transporters (GluTs) and glutamine synthetase (GS).

Materials And Methods: Using PCR-based detection and Western blot analysis, the expression of Glu system components was assessed in human androgen-independent PC-3 and androgen-dependent LNCaP prostate cancer cells.

Results: iGluRs, such as NR1, NR2A, NR2C, NR2D and NR3B; mGLuRs such as mGluR1, mGluR2, mGluR3, mGluR4 and mGluR5; GluTs such as EAAT1, EAAT2, EAAT3 and EAATS; and GS mRNA were steadily expressed in both cell lines.

Circulating tumor cells in colorectal cancer: detection methods and clinical significance.

Colorectal cancer is one of the most frequently diagnosed malignancies in both men and women. Although curative resection is the major treatment option, approximately half of all patients eventually develop distant metastases. Thus, the need for early detection of occult metastases has led to extensive investigation with regard to the detection of disseminated tumor cells in biological fluids, including peripheral blood or bone marrow of cancer patients.

In vivo models for heart failure research.

The medical treatment of heart failure (HF) is associated with 50% survival at 5 years, thus being one of the major causes of mortality in Western countries. An understanding of the pathophysiology of HF is essential for the development of novel efficient therapies. Consequently, the use of animal models is indispensable.

Detection of circulating tumor cells in prostate cancer patients: methodological pitfalls and clinical relevance.

Disseminated malignancy is the major cause of prostate cancer-related mortality. Circulating tumor cells (CTCs) are essential for the establishment of metastasis. Various contemporary and molecular methods using prostate-specific biomarkers have been applied to detect extraprostatic disease that is undetectable by conventional imaging techniques, assessing the risk for disease recurrence after therapy of curative intent.

Molecular markers detecting circulating melanoma cells by reverse transcription polymerase chain reaction: methodological pitfalls and clinical relevance.

Herein, we expound the theory of circulating melanoma cells (CMCs) and their detection with reverse transcription polymerase chain reaction as a molecular staging approach. We discuss the molecular markers that have been used for CMC detection focusing on the use of these markers for multiplex detection analysis. Finally, we comment on the contradictory data of CMC detection studies in the literature and we propose possible solutions which may contribute to the clinical significance of CMC detection in patient management.

The kisspeptin (KiSS-1)/GPR54 system in cancer biology.

Kisspeptin (KiSS-1) gene, initially described as a melanoma metastasis suppressor gene, encodes a number of peptides (kp-54, kp-14, kp-13, kp-10), which are endogenous ligands to a G protein-coupled receptor, referred as hOT7T175 or AXOR12 or GPR54. So far intensive investigation has provided substantiate evidence supporting the role of KiSS-1/GPR54 system in cancer biology as well as in the regulation of the reproductive function and trophoblast invasion. The precise mechanism by which KiSS-1/GPR54 system is affecting cancer cell growth and metastasis includes complex endocrine, paracrine and autocrine actions.

Molecular diagnosis of the viral component in cardiomyopathies: pathophysiological, clinical and therapeutic implications.

Background: Myocarditis is defined as the inflammation of myocardium associated with cardiac dysfunction. Despite this clear-cut definition, diagnosis and etiologic treatment continue to create considerable debate. Viral infections are frequent causes of myocarditis and there is evidence that persistent viral infection is associated with poor prognosis in different subtypes of cardiomyopathy.

Mechanisms of bone metastasis in prostate cancer: clinical implications.

Prostate cancer shows a strong predilection to spread to the bones. Once prostate tumour cells are engrafted in the skeleton, curative therapy is no longer possible and palliative treatment becomes the only option. Herein, we review the multifactorial mechanisms and complex cellular interactions that take place inside the bone metastatic microenvironment.

Characterization of a rabbit antihuman mechano growth factor (MGF) polyclonal antibody against the last 24 amino acids of the E domain.

The human insulin-like growth factor-1 (IGF-1) gene gives rise to multiple, heterogeneous mRNA transcripts by alternative splicing, thus producing different IGF-1 isoforms. The mechano growth factor (MGF) is an IGF-1 isoform that was found to be markedly up-regulated in exercised or damaged muscle. The specific E domain of the MGF splice variant may act as an independent growth factor.

Combined androgen blockade therapy can convert RT-PCR detection of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts from positive to negative in the peripheral blood of patients with clinically localized prostate cancer and increase biochemical failure-free survival after curative therapy.

Background: The clinical relevance of positive molecular staging as defined by reverse transcriptase-polymerase chain reaction (RT-PCR) detections of both prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts in the peripheral blood (PB) of patients with prostate cancer is still debatable.

Methods: We analyzed the biochemical failure-free survival (bFFS) of prostate cancer patients with positive molecular staging who underwent immediate curative therapy (Group I, n=39) compared to prostate cancer patients who did convert their positive molecular staging by the administration of combined androgen blockade (CAB) for 12 months prior to curative treatment (Group II, n=15).

Results: The median bFFS for Group I was 9 months (95% CI 5-13 months) and was significantly lower compared to Group II (>36 months, p<0.

Regulation of the mGluR5, EAAT1 and GS expression by glucocorticoids in MG-63 osteoblast-like osteosarcoma cells.

Introduction: Growth factors, cytokines, sex steroid hormones and glucocorticoids have differential and complex effects on skeletal metabolism. Recently, the presence of the glutamatergic (Glu) system in bone cells has provided new evidence for its possible role in bone physiology. Consequently, we have investigated the regulation of certain components of the Glu system by glucocorticoids in MG-63 osteoblast-like osteosarcoma cells, in vitro.

Molecular detection of tyrosinase transcripts in peripheral blood from patients with malignant melanoma: correlation of PCR sensitivity threshold with clinical and pathologic disease characteristics.

Background: Positive molecular detection of tyrosinase transcripts (TYR mRNA) in RNA extracts of peripheral blood (PB) samples from patients with malignant melanoma provides evidence of disease dissemination.

Methods: Total RNA extracted from PB was quantified and subjected to RT-PCR under ultra-sensitive and reduced-sensitivity PCR conditions using SSRT-II. Positive TYR mRNA detection in 78 melanoma patients and 40 healthy volunteers was correlated with clinical stage, Breslow's evaluation of tumor thickness, Clark's assessment of tumor invasion, the location of the primary tumor site, and tumor histology.

Serum testosterone: A potentially adjunct screening test for the assessment of the risk of prostate cancer among men with modestly elevated PSA values (> or =3.0 and <10.0 ng/ml).

Whether serum testosterone (T) can become an adjunct test able to validate the PSA-weighted risk of prostate cancer (PR.CA) in the "grey" diagnostic area (PSA =3.0 to <10.

Combination therapy using LHRH and somatostatin analogues plus dexamethasone in androgen ablation refractory prostate cancer patients with bone involvement: a bench to bedside approach.

The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.