Epidemiological and animal studies demonstrated a link between gastric cancer (GC) or mucosal associated lymphoid tissue (MALT) lymphoma and chronic infection with Helicobacter pylori (H. pylori). ...The exact mechanism responsible for the development of GC and MALT-lymphoma in H. pylori-infected patients still remains obscure. This report is designed to overview the molecular biology, especially the gene expression and histochemical manifestation of gastrin and other growth factors such as transforming growth factor alpha (TGF alpha) and hepatocyte growth factor (HGF) in the GC before and after eradication of H. pylori. Furthermore, gene expression of cyclooxygenase-1 (COX-1) and COX-2 and apoptosis-related proteins such as Bax and Bcl-2 are discussed.
The findings originate from two series of patients; Series I involving 337 GC patients and 400 age- and gender-matched controls and series 2 including 20 MALT-lymphoma patients and 40 matched controls.
An overall H.pylori-seropositivity reached about 80% in GC and about 90% in MALT-lymphoma, significantly higher than in non-cancer controls (60%). The prevalence of CagA-positive strains was about twice as high (about 70%) in GC and MALT-lymphomas as in sex- and age-matched controls. Expression of gastrin was detected in antrum of all tested patients but also in majority (90%) of GCs and MALT-lymphomas tumor tissue. HGF and TGF alpha were expressed more frequently in GC tissue than in normal fundic mucosa. COX-1 was similarly expressed in GC and MALT as in intact mucosa, while COX-2 mRNA was detected only in tumor tissue, being attenuated by H.pylori eradication in GC and abolished by this therapy in MALT-lymphoma. The plasma levels of alpha-amidated gastrin in GC and MALT were several folds higher than in controls. Gene expression of bcl-2 was detected in all, while bax--only in about 50% of GC samples.
Infection with H. pylori, especially that expressing CagA-positivity, is primum movens in developing GC and MALT-lymphoma and the upregulation of growth factors, particularly of gastrin, and COX-2 and dysregulation of the Bax/Bcl-2 system seem to contribute to gastric cancerogenesis.
The aim of this study was to investigate the time course of angiographic restenosis rate and late loss after successful percutaneous coronary intervention and vascular brachytherapy with ...β-irradiation using strontium-90/yttrium-90 in 98 patients who were prospectively enrolled into a quantitative angiographic and clinical follow-up protocol at 6, 12, and 24 months after the index procedure, regardless of their symptom status. Actuarial restenosis rates measured 11.2 ± 5% at 6 months of follow-up, 24.5 ± 5% at 12 months, and 28.5 ± 6% at 24 months, respectively. Late loss of the stent segment during the first 6 months measured 0.38 ± 0.40 mm (6 to 12 months: 0.25 ± 0.38 mm; 12 to 24 months: 0.16 ± 0.32 mm), of the injured segment 0.27 ± 0.21 mm (6 to 12 months: 0.21 ± 0.26 mm; 12 to 24 months: 0.13 ± 0.24 mm), of the irradiated segment 0.18 ± 0.29 mm (6 to 12 months: 0.19 ± 0.31 mm; 12 to 24 months: 0.11 ± 0.27 mm), and of the analysis segment 0.18 ± 0.36 mm (6 to 12 months: 0.17 ± 0.29 mm; 12 to 24 months: 0.11 ± 0.20 mm). Restenosis after angioplasty and β-irradiation of in-stent restenotic lesions is not complete within 6 months but is sustained with a gradual decrease over 24 months.
Possible adverse interactions between an usually inconspicuous genetic trait and early environmental factors favoring the development of obesity were investigated in rats heterozygous for the leptin ...receptor defect "fatty" (fa). Pups were exposed to early postnatal overfeeding by reducing litter size from normally 10-12 to only 4. Rearing +/+ and +/fa pups from day 3 to 21 in small litters increased fat-free dry mass and body fat, but only in the latter did a significant interaction with genotype occur. Pronounced differences in the responsiveness of +/+ and +/fa pups to "prophylactic" leptin treatment (from day 1 to 21) were observed, with +/fa females from small litters being nearly as fat and unresponsive as previously reported for normally reared fa/fa pups. Clear heterozygous differences in total hypothalamic leptin binding, but no litter size effect, paralleling the differences in leptin responsiveness, were observed. By early postnatal overfeeding an usually inconspicuous genetic trait may thus become etiologic for the development of obesity via physiological changes other than the decreased leptin binding characterizing the genetic defect.
Understanding the driving forces behind spiral arms in protoplanetary disks remains a challenge due to the faintness of young giant planets. MWC 758 hosts such a protoplanetary disk with a two-armed ...spiral pattern that is suggested to be driven by an external giant planet. We present new thermal infrared observations that are uniquely sensitive to redder (i.e., colder or more attenuated) planets than past observations at shorter wavelengths. We detect a giant protoplanet, MWC 758c, at a projected separation of ~100 au from the star. The spectrum of MWC 758c is distinct from the rest of the disk and consistent with emission from a planetary atmosphere with Teff = 500 +/- 100 K for a low level of extinction (AV<30), or a hotter object with a higher level of extinction. Both scenarios are commensurate with the predicted properties of the companion responsible for driving the spiral arms. MWC 758c provides evidence that spiral arms in protoplanetary disks can be caused by cold giant planets or by those whose optical emission is highly attenuated. MWC 758c stands out both as one of the youngest giant planets known, and also as one of the coldest and/or most attenuated. Furthermore, MWC 758c is among the first planets to be observed within a system hosting a protoplanetary disk.
Nonmonotonic current transients at constant temperature, following a pulsed charge injection, have been observed in silicon diodes heavily irradiated with gamma rays. The features of the transients ...have been studied at different temperatures and using various reverse biases. The particular shape of the measured transients is interpreted, with the help of numeric simulations, in terms of a strong time dependency of the space charge density due to the discharge of radiation induced deep traps. In particular, a nonmonotonic transient is generated if the discharge of a dominant trap determines the change of the space charge sign (type inversion). In this case the active volume of the sample, from which the current is collected, is increased during the discharge and causes the sample to become fully depleted for a short time. During this time interval the active volume reaches its maximum value and a peak is produced in the transient shape. The measurement of this peak provides a sensitive way to detect type inversion in semiconductor devices and to determine the responsible energy levels. The correlation of nonmonotonic transients with thermally stimulated current spectra and the distortion produced in deep level transient spectroscopy spectra are discussed in detail.
Only a few approaches are available to address the mechanisms of cell death in vivo which are induced by anticancer treatment in patients with malignancies. In this study in vitro chemosensitivity ...testing of primary peripheral blood leukemic cells of five patients suffering from different leukemic non-Hodgkin's lymphomas was combined with the analysis of the in vivo rate of apoptosis by flow-cytometry (Annexin V and depolarisation of mitochondrial membrane potential (MMP) by JC-1). Furthermore, changes in expression patterns of apoptosis related proteins during chemotherapeutic treatment were detected by Western Blot. Gene expression profiling (HG-U133A, Affymetrix, Santa Clara, CA) was employed to identify common marker genes of in vivo drug response.
In vitro chemosensitivity was tested using the cytotoxic agents which the patients were scheduled to receive and was strongly correlated with effective reduction of leukemic lymphoma cells in patients resulting in complete remissions in all five cases. Due to the rapid clearance of apoptotic tumor cells in vivo neither the analysis of the in vivo rate of apoptosis and depolarisation of MMP nor the assessment of expression of regulators of apoptosis showed concordant results concerning the drug response. However, assessment of gene expression during therapy could identify a set of 30 genes to significantly discriminate between samples from patients before treatment compared to samples from the same patients after receiving cytotoxic therapy. Among these 30 genes we found a high proportion of genes associated with apoptotic cell death, cell proliferation and cell cycle signalling including complement lysis inhibitor (clusterin/CLU), beta-catenin interacting protein (ICAT), peroxisome proliferator activated receptor alpha (PPARα), TNF alpha converting enzyme (ADAM17/TACE), homeo box A3 (HOX1), inositol polyphosphatase 5-phosphatase type IV (PPI5PIV) and inhibitor of p53 induced apoptosis alpha (IPIA-Alpha/NM23-H6). These results indicate that in vitro chemosensitivity testing and gene expression profiling can successfully be utilised to analyse in vivo drug response in patients with leukemic NHL's and can be used to explore new pathway models of drug-induced cell death in vivo which are independent of different lymphoma subtypes and different treatment regimens.
Medical treatment for hepatocellular carcinoma (HCC) remains elusive. While an acyclic retinoid improved tumor-free survival after hepatoma resection, tamoxifen finally proved ineffective. ...Combination therapy of both agents has not been investigated in vitro and in vivo.
MH7777A hepatoma cells were incubated with tamoxifen (TAM) and 9-cis retinoic acid (CRA) alone or in combination. Proliferation rate and apoptosis were assessed by BrdU incorporation and flow cytometry. In vivo efficacy was studied using the Morris hepatoma model in immunocompetent rats. End points were macroscopic tumor growth, metastasis and immunohistochemistry for proliferative and apoptotic tumor cells (PCNA and TUNEL staining).
In vitro, CRA and TAM monotherapy was effective only in the highest concentration. Combination therapy significantly enhanced apoptosis rate and growth inhibition in hepatoma cells. While in vivo monotherapy did not reduce tumor growth or metastasis, their combination reduced tumor size after 28 days by 64.5±28%. This was paralleled by an increase in TUNEL positive and a decrease in PCNA positive cells.
The combination of TAM and CRA enhances their anti-tumoral efficacy in vitro as well as in vivo, while monotherapy is ineffective. This combination could be a promising adjunctive therapy of HCC.
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