A novel approach in the treatment of neuroendocrine gastrointestinal tumors: additive antiproliferative effects of interferon-gamma and meta-iodobenzylguanidine.

Background: Therapeutic options to effectively inhibit growth and spread of neuroendocrine gastrointestinal tumors are still limited. As both meta-iodobenzylguanidine (MIBG) and interferon-gamma (IFNgamma) cause antineoplastic effects in neuroendocrine gastrointestinal tumor cells, we investigated the antiproliferative effects of the combination of IFNgamma and non-radiolabeled MIBG in neuroendocrine gut STC-1 and pancreatic carcinoid BON tumor cells.

Methods And Results: IFNgamma receptors were expressed in both models.

Enhancement of peripheral benzodiazepine receptor ligand-induced apoptosis and cell cycle arrest of esophageal cancer cells by simultaneous inhibition of MAPK/ERK kinase.

Specific ligands of the peripheral benzodiazepine receptor (PBR) activate pro-apoptotic and anti-proliferative signaling pathways. Previously, we found that PBR ligands activated the p38 mitogen-activated protein kinase (MAPK) pathway in esophageal cancer cells, and that the activation of p38MAPK contributed to tumor cell apoptosis and cell cycle arrest. Here, we report that PBR ligands also activate the pro-survival MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway in esophageal cancer cells, which might compromise the efficacy of PBR ligands.

Recent results in understanding molecular pathways in the medical treatment of esophageal and gastric cancer.

Cancers of the esophagus and stomach constitute a major cause of cancer deaths worldwide. Despite improvements in both surgical techniques and (radio) chemotherapy regimens, these tumors remain a great therapeutic challenge. Thus, there is a need for innovative medical treatment strategies effective even in advanced disease.

Effect of adventitial VEGF(165) gene transfer on vascular thickening after coronary artery balloon injury.

Objective: Experimental studies have provided evidence that neovascularization is an important feature of plaque growth, and angiogenic gene therapy may, therefore, increase plaque growth. This study examined the effect of local (peri)adventitial vascular endothelial growth factor165 (VEGF) gene transfer on vascular thickening after coronary balloon injury.

Methods: Two coronary arteries of 15 pigs were subjected to balloon injury followed by either (peri)adventitial VEGF165 or beta-galactosidase (LacZ) plasmid/liposome-mediated gene transfer via needle injection catheter.

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839).

Therapeutic options to inhibit the growth and spread of neuroendocrine (NE) gastrointestinal tumours are still limited. Since gefitinib (4-(3-chloro-4-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline), an inhibitor of epidermal growth factor receptor-sensitive tyrosine kinase (EGFR-TK), had been shown to suppress potently the growth of various non-NE tumour entities, we studied the antineoplastic potency of gefitinib in NE gastrointestinal tumour cells. In human insulinoma (CM) cells, in human pancreatic carcinoid (BON) cells and in NE tumour cells of the gut (STC-1), gefitinib induced a time- and dose-dependent growth inhibition by almost 100%.

A novel tetracycline-controlled transactivator-transrepressor system enables external control of oncolytic adenovirus replication.

The use of restricted replication-competent adenoviruses (RRCAs) inducing tumor cell-specific lysis is a promising approach in cancer gene therapy. However, the use of RRCAs in humans carries considerable risk, since after injection into the patient, further regulation or inhibition of virus replication from the outside is impossible. Therefore, we have developed a novel system allowing external pharmacological control of RRCA replication.

Antihistamines for the common cold.

Background: Although antihistamines are prescribed in large quantities for the common cold, there is little evidence to whether these drugs are effective.

Objectives: To assess in patients with a common cold the effects of antihistamines in alleviating nasal symptoms, or in shortening of illness duration.

Search Strategy: We searched the Cochrane Acute Respiratory Infections Group Specialized Register and EMBASE up to December 2002; Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE up to February 2003.

Ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in oesophageal cancer cells: involvement of the p38MAPK signalling pathway.

Specific ligands of the peripheral benzodiazepine receptor (PBR) are known to induce apoptosis and cell cycle arrest in oesophageal cancer cells. However, the underlying mechanisms are still unknown. Here, we investigated the transcriptional alterations and activation of protein kinases in response to PBR-specific ligands.

Hypericin activated by an incoherent light source has photodynamic effects on esophageal cancer cells.

Background And Aims: Photodynamic therapy (PDT) is a new treatment modality for early esophageal neoplasia. With two absorption maxima in the visible light range (550 and 588 nm) hypericin is a very promising photosensitizer for PDT with incoherent light sources. We studied the effects of photosensitizing hypericin in both primary cell cultures and cell lines (squamous: Kyse-140 and adenocarcinoma: OE-33) of human esophageal cancer using an incoherent white light source.

Perinatal risk factors for schizophrenia: diagnostic specificity and relationships with maternal psychopathology.

Although a growing body of evidence supports the hypothesis that exposure to obstetric complications (OCs) increases the vulnerability for schizophrenia, some questions remain unanswered regarding the diagnostic specificity and the etiological significance of this association. Associations with a history of OCs have been reported for other severe psychiatric disorders, such as autism, anorexia nervosa, or psychotic affective disorder. Thus, OCs may increase in a relatively non-specific way the vulnerability for a range of severe mental disorders, the expression of this vulnerability depending on the interaction between OCs and other risk factors, such as the genetic liability for specific psychiatric disorder, or exposure to later environmental risk factors.

Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human esophageal cancer cells.

Esophageal cancer is the most markedly increasing tumor entity in Western countries. Due to very poor 5-year-survival, new therapeutic approaches are mandatory. Peripheral benzodiazepine receptors (PBR) have been implicated in growth control of various tumor models, but they have not been studied yet in esophageal cancer.

Identification of a single nucleotide polymorphism in the choline acetyltransferase gene associated with Alzheimer's disease.

The dysfunction of the cholinergic system in Alzheimer's disease (AD) supports the hypothesis that a decline in choline acetyltransferase (ChAT) activity in memory as well as in cognitive functions in AD might be functionally linked. To assess the physiological relevance of an allelic variation in the ChAT gene we investigated the presence of a possible polymorphism in AD patients and in elderly non-demented subjects as controls. By using polymerase chain reaction, single stranded conformation polymorphism or the LightCycler analysis we detected a single nucleotide polymorphism in the first common coding exon of the ChAT gene.

Synergistic activation of the human choline acetyltransferase gene by c-Myb and C/EBPbeta.

To elucidate regulatory mechanisms at the transcriptional level of the human choline acetyltransferase gene (hChAT) we performed cotransfections assays in NG108-15 and SN56 cells using ChAT-CAT reporter plasmids with c-Myb and C/EBPbeta expression plasmids. The hChAT gene has several promoters, one of which (promoter P2 or M-type) is both c-Myb and C/EBPbeta inducible as 3-4-fold trans-activation was obtained in both cell lines when using either c-Myb or C/EBPbeta expression vectors alone. The simultaneous expression of c-Myb and C/EBPbeta in the absence or presence of NGFI-C (egr4) leads respectively to a 15-fold and 32-fold synergistic transcriptional activation of promoter P2.

Overexpression of the peripheral benzodiazepine receptor is a relevant prognostic factor in stage III colorectal cancer.

Purpose: The peripheral benzodiazepine receptor (PBR) has been implicated in the growth control of colorectal cancer, where PBR-specific ligand-binding is increased 3-4-fold. However, the prognostic relevance of PBR (over) expression has not yet been evaluated in colorectal cancer.

Experimental Design: A 5-year follow-up was performed in 116 consecutive patients undergoing surgery for colorectal cancer with regional or distant metastases [Union International Contre le Cancer (UICC) stage III, 59 patients; UICC stage IV, 57 patients].

Meta-iodobenzylguanidine induces growth inhibition and apoptosis of neuroendocrine gastrointestinal tumor cells.

Neuroendocrine gastrointestinal tumors take up, decarboxylate and store large amounts of monoamines. Radioactive-labeled monoamines like the norepinephrine analogue meta-iodobenzylguanidine (MIBG) have been used for the imaging of neuroendocrine tumors for many years. MIBG is selectively taken up via norepinephrine transporters (NETs) localized in the plasma membrane of neuroendocrine gastrointestinal tumor cells and thereby offers the possibility for specific and innovative therapeutic approaches.

Obstetrical complications and the development of postpartum depressive symptoms: a prospective survey of the MATQUID cohort.

Objective: To prospectively investigate in a cohort of pregnant women the association between obstetrical complications (OCs) and depressive symptomatology in the early postpartum period.

Method: A total of 441 pregnant women attending the State Maternity Hospital in Bordeaux were interviewed during the third trimester of pregnancy, then at 3 days and 6 weeks after birth. Maternal depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS).

Does amoxicillin improve outcomes in patients with purulent rhinorrhea? A pragmatic randomized double-blind controlled trial in family practice.

Objective: To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea.

Study Design: Double-blind randomized placebo-controlled trial.

Population: The 416 patients included from 69 family practices were 12 years or older, presenting with acute upper respiratory complaints, and having a history of purulent rhinorrhea and no signs of complications of sinusitis.

Inhibition of the alpha-nu integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo.

Anti-angiogenetic cancer therapy is a potential new form for treatment of solid tumours. The alpha(v)-integrins (alpha(v)beta3, alpha(v)beta5) mediate the contact of activated endothelial cells to proteins of the extracellular matrix during tumour angiogenesis as a prerequisite for survival of endothelial cells. The aim of this study was to investigate the effects of application of a methylated cyclic RGD-peptide as an alpha(v)-integrin antagonist on angiogenesis, microcirculation, growth and metastasis formation of a solid tumour in vivo.

Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y(2)-receptors.

Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antiproliferative effects of P2-purinergic receptors in human oesophageal cancer cells.

Antibiotic prescribing in acute infections of the nose or sinuses: a matter of personal habit?

Background: A proper understanding of how and why GPs prescribe antibiotics in general practice is essential for the design of strategies aimed at making prescribing more rational.

Objective: The intention of this study is to contribute to such understanding by investigating which elements are important in the GP's decision to prescribe antibiotics for patients with acute infectious complaints of the nose and/or sinuses.

Methods: During their training in general practice, students observed the following elements while attending encounters between their trainer-GP and patients with a runny nose, blocked nose or cough: patient characteristics, contact characteristics, signs and symptoms, diagnosis and prescriptions.

Peptones stimulate intestinal cholecystokinin gene transcription via cyclic adenosine monophosphate response element-binding factors.

Cholecystokinin (CCK) is a potent intestinal hormone that regulates several digestive functions. Despite the physiological importance of CCK, the cellular and molecular mechanisms that govern its synthesis and secretion are not completely identified. Peptones, which are fair counterparts of the protein fraction in the intestinal lumen, are good stimulants of CCK secretion.

Normalization: contrast-gain control in simple (Fourier) and complex (non-Fourier) pathways of pattern vision.

Results from two types of texture-segregation experiments considered jointly demonstrate that the heavily-compressive intensive nonlinearity acting in static pattern vision is not a relatively early, local gain control like light adaptation in the retina or LGN. Nor can it be a late, within-channel contrast-gain control. All the results suggest that it is inhibition among channels as in a normalization network.

A comparison of the dynamics of simple (Fourier) and complex (non-Fourier) mechanisms in texture segregation.

Models of texture segregation frequently feature two processing mechanisms: simple, linear channels (1st-order, Fourier mechanisms) and complex channels (2nd-order, non-Fourier mechanisms). Using texture patterns designed to segregate primarily as a result of activity in one set of channels or the other, we employed the method of cued response to obtain speed-accuracy tradeoff (SAT) functions measuring the time course of texture segregation processing in simple and complex channels. Here, both simple-channel and complex-channel patterns are composed of Gabor-patch texture elements, thus equating input to simple channels and the first stage of complex channels.

Spatial summation in simple (Fourier) and complex (non-Fourier) texture channels.

Complex (non-Fourier, second-order) channels have been proposed to explain aspects of texture-based region segregation and related perceptual tasks. Complex channels contain two stages of linear filtering with an intermediate pointwise nonlinearity. The intermediate nonlinearity is crucial.