A Xenogenic Bone Derivative as a Potential Adjuvant for Bone Regeneration and Implant Osseointegration: An Study.

Several clinical conditions may limit the success of bone regeneration and/or implant osseointegration. For this reason, many compounds have been tested for their ability to stimulate this biological process. Synthetic hydroxyapatite (HA), mimicking natural bone hydroxyapatite, and extra-cellular matrix proteins, such as type I collagen, are potential candidates.

Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis.

Aim: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC).

Methods: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry.

Results: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased.

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes.

Autocrine/paracrine stimulation of KIT has been observed in colorectal carcinoma (CRC) cell lines. We investigated the expression of KIT and stem cell factor (SCF) in CRC in comparison with premalignant colon lesions and normal colonic mucosa to assess the prognostic and therapeutic relevance of this receptor/ligand system in CRC. Transcript levels of c-kit and the two SCF splicing variants were determined quantitatively by real-time RT-PCR using cDNA obtained from normal, premalignant and malignant snap frozen colon tissue specimens.

Antagonistic interactions between gemcitabine and 5-fluorouracil in the human pancreatic carcinoma cell line Capan-2.

Although the recently-developed Gemcitabine (GEM) has renewed interest in clinical research in pancreatic carcinoma, it offers modest improvement of tumor-related symptoms and marginal survival advantage, even when combined with other currently-available chemotherapeutic agents such as 5-Fluorouracil (5-FU). We hypothesized that this disappointing result could be due to an interaction between the two drugs affecting cytotoxic activity. We measured in-vitro growth inhibition, cell cycle distribution, gene and protein expression of apoptosis regulators bcl-2, bcl-x and survivin, NFkappaB and telomerase activities of human pancreatic carcinoma cell line Capan-2 following exposure to GEM and 5-FU singly or combined, by MTT assay and median effect analysis, flow cytometry, real-time RT-PCR, Western blotting, electrophoretic mobility shift assay (EMSA) and telomeric repeat amplification protocol (TRAP) assay, respectively.

Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells.

Ag presentation by dendritic cells (DC) is essential to effective antitumor T cell responses in cancer patients. Depending on their origin, maturation state, and the ambient cytokine milieu, DC can differentiate into distinct subpopulations, which preferentially either induce Th1 cell activation (CD11c+,CD123- myeloid DC (MDC)) or immunosuppressive T cell development (CD11c-,CD123+ plasmacytoid DC (PDC)). The present study was undertaken to characterize the effects of pancreatic carcinoma cell-derived cytokines on immature monocyte-derived DC (iMo-DC) in vitro and in vivo.

Botulinum toxin treatment of oesophageal achalasia in the old old and oldest old: a 1-year follow-up study.

Background: Intrasphincteric injection of botulinum toxin (BTX) has become one of the most frequent therapeutic approaches for the treatment of oesophageal achalasia. This treatment seems particularly effective in elderly patients who are not candidates for more invasive procedures.

Aims: There are few or no data on BTX treatment of achalasia in the old old and oldest old.

Circulating vascular endothelial growth factor and interferon-gamma-inducible protein-10 levels in pancreatic cancer during chemotherapy.

Background: Chemotherapeutic anticancer properties are thought to derive from apoptosis pathway activation and/or cell division arrest, but animal models have also evidenced anti-angiogenic activity in some agents.

Patients And Methods: The impact of gemcitabine, irinotecan and oxaliplatin + 5-FU upon the serum markers vascular endothelial growth factor (VEGF) (pro-angiogenic) and IFN-gamma-inducible protein (IP)-10 (anti-angiogenic) was evaluated by ELISA in locally advanced and/or metastatic cancer versus clinical efficacy and survival.

Results: Patients had higher serum levels of both markers versus controls.

Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival.

Cytokine shedding by tumor cells into the local microenvironment modulates host immune response, tumor growth, and metastasis. The study aimed to verify the hypothesis that the immunological microenvironment of pancreatic carcinoma exists in a prevalently immunosuppressive state, influencing survival. We analyzed expression profiles of pro-inflammatory (IL-1beta, IL-2, IL-6, IL-8, IL-12 p40, IL-18 and IFN-gamma) and anti-inflammatory (IL-10, IL-11, IL-13 and TGF-beta isoforms) cytokines.

Noncardiac chest pain of esophageal origin in patients with and without coronary artery disease.

Background/aims: Non-cardiac chest pain is a frequent finding in patients admitted to emergency departments, and it has been shown that many of these patients may have an esophageal cause for their pain. However, little data are available on patients primarily referred to the cardiology unit, and especially those with coronary artery disease. The purpose of this study was to assess the role of esophageal dysfunction in chest pain patients with and without coronary artery disease.

Human pancreatic carcinoma cells secrete bioactive interleukin-18 after treatment with 5-fluorouracil: implications for anti-tumor immune response.

Recently we observed that pancreatic carcinoma cell lines constitutively express Interleukin-18 (IL-18). Bioactive IL-18 induces Interferon (IFN)-gamma production, Fas Ligand (FasL) expression, and inhibits angiogenesis, raising the issue of anti-tumor effects of a tumor-derived cytokine and motivating a more detailed analysis of IL-18 production in pancreatic carcinoma cells. This analysis included the study of effects of chemotherapeutic drugs (5-fluorouracil [5-FU], gemcitabine, cisplatin) commonly used in the treatment of pancreatic cancer patients on IL-18 production and processing.

Ablation of phosphoinositide 3-kinase-gamma reduces the severity of acute pancreatitis.

In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-gamma (PI3K gamma) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3K gamma, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet.

Constitutive expression of interleukin-18 in head and neck squamous carcinoma cells.

Background: Interleukin (IL)-18 is a potent immunomodulatory cytokine promoting TH-1 and cytotoxic immune responses through interferon (IFN)-gamma induction. The aim of this study was to investigate the production of IL-18 by squamous cell carcinoma of the head and neck (HNSCC).

Methods: The expression of IL-18 was analyzed by reverse transcriptase-polymerase chain reaction, Western blot, and ELISA in untreated and 5-fluorouracil (5-FU)-treated HNSCC cell lines.

Inhibition of cell survival and invasive potential of colorectal carcinoma cells by the tyrosine kinase inhibitor STI571.

Inhibiting tyrosine kinases has recently emerged as a therapeutic modality in several forms of neoplasia. The tyrosine kinase inhibitor STI571 (IMATINIB MESYLATE; GLEEVEC; GLIVEC) is a case in point as it has shown promise in the treatment of malignancies expressing the BCR/ABL fusion protein. In addition to BCR/ABL, STI571 inhibits the tyrosine kinase moieties of several cell surface receptors including the platelet-derived growth factor (PDGF) receptors and c-Kit.

Long-term study on the effects of visual biofeedback and muscle training as a therapeutic modality in pelvic floor dyssynergia and slow-transit constipation.

Purpose: Biofeedback training has been shown as an effective therapeutic measure in patients with pelvic floor dyssynergia, at least in the short term. Long-term effects have received less attention. Moreover, its effects in patients with slow-transit constipation have been scarcely investigated.

Mechanisms of the priming effect of low doses of lipopoly-saccharides on leukocyte-dependent platelet aggregation in whole blood.

Several studies focused on the ability of bacterial lipopolysac-charides (LPS) in triggering platelet and/or leukocyte activation. The aim of this study was to investigate the molecular mechanisms involved in the aggregation of platelets and in their interaction with leukocytes in whole blood after stimulation with low doses of LPS. LPS did not directly induce platelet aggregation in whole blood, but they primed the aggregation of platelets induced by epinephrine, adenosine diphosphate and arachidonic acid.

Decreased expression of stem cell factor in esophageal and gastric mucosa after esophagogastric anastomosis for cancer: potential relevance to motility.

Background: Esophageal replacement with gastric tube is a well-established reconstruction of the alimentary tract after esophagectomy in cancer patients. The resulting molecular events in the transposed gastric tube and residual esophagus have yet to be investigated. Stem cell factor (SCF) was recently shown to be critical for signaling in gastrointestinal motility.

Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.

Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques.

The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils.

Thrombolytic agents, used to restore blood flow to ischaemic tissues, activate several enzymatic systems with pro-inflammatory effects, thus potentially contributing to the pathogenesis of ischaemia-reperfusion injury. Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been implicated in the pathogenesis of this process. We previously showed that the infusion of streptokinase (SK) induces the intravascular release of PAF in patients with acute myocardial infarction (AMI), and that cultured human endothelial cells (EC) synthesized PAF in response to SK and plasmin (PLN).

Human leukocyte interferon-alpha treatment for chronic HCV-related hepatitis in hemophilic patients previously intolerant to other interferons-alpha.

Thirty patients affected by hemophilia A or B or von-Willebrand's disease and chronic posttransfusional active HCV hepatitis who developed major side effects during the course of a previous treatment with recombinant interferon-alpha (IFN-alpha) were studied. In all patients IFN-alpha therapy had to be discontinued and those who achieved a primary serologic and viral response to HCV relapsed within a few months. After a washout period, patients were retreated with human leukocyte IFN-alpha, 6 MU thrice weekly for 12 months.