IGF-1 and IGFBP-3: Risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

IGF-1 and IGFBP-3 may influence risk of prostate cancer through their roles in cellular growth, metabolism and apoptosis, however, epidemiologic results have been inconsistent. The role of obesity in prostate cancer risk is not clearly understood, but hyperinsulinemia-related increases in bioactive IGF-1 levels, associated with obesity, could be a component of the relationship between the IGF-axis and prostate cancer. We conducted a nested case-control study in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF-1 and IGFBP-3 and risk of prostate cancer. A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis. There was no clear overall association between IGF-1, IGFBP-3 and IGF-1:IGFBP-3 molar ratio (IGFmr) and prostate cancer risk, however, IGFmr was associated with risk in obese men (BMI > 30, p-trend = 0.04), with a greater than 2-fold increased risk in the highest IGFmr quartile (OR 2.34, 95% CI 1.10-5.01). Risk was specifically increased for aggressive disease in obese men (OR 2.80, 95% CI 1.11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men.     

Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund’s adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors. Asim Saha and Smarajit Pal contributed equally to this work. This work was presented as abstract in the San Antonio Breast Cancer Symposium, 2005. Breast Cancer Research and Treatment 94, supplement 1:4093.     

Behandlung des akuten ST-Hebungsinfarkts in Netzwerkstrukturen

Management of acute ST elevation myocardial infarction (STEMI) demands rapid and complete reperfusion of the infarct-related artery (IRA). With postinfarction prognosis depending on time delay from onset of symptoms to complete reperfusion (TIMI 3 flow) of the IRA, primary percutaneous coronary intervention (PPCI) performed by an experienced team has been shown to be superior to thrombolytic therapy with lower mortality, less frequent occurrence of nonfatal reinfarction and stroke, and thus represents the preferred treatment strategy according to the national and international guidelines.For regional implementation of PPCI, particularly in rural areas, information and transfer logistics within networks of care and direct transport of an infarction patient to a PCI hospital rather than to the closest hospital are a challenge. With successful implementation of network logistics and standardized therapeutic pathways, current guidelines and requested timelines versus thrombolysis could be met. The implemented logistics comprised 24 h/7 days stand-by services of an experienced PCI team, direct telephone hotline contact between rescue service/emergency physician and interventional cardiologist on call, and direct open access to a catheterization laboratory at any time.Within the Drip&Ship network Rostock, to date (July 2007) 1,022 consecutive patients with PCI for STEMI were documented and analyzed over 5 years; of these, 490 patients were transferred from a community hospital to the PCI center and 532 patients were admitted directly to the interventional center. In 95.1% of all transferred and in 94.8% of all directly admitted patients, PCI was successfully accomplished upon arrival. A normalized flow to the IRA after PCI was documented in 96% of both groups, no patient was subjected to thrombolytic therapy. At 12-month follow-up, there were no differences between both groups with respect to infarct size and mortality. Moreover, there was no evidence of differences in left ventricular ejection fraction between groups. Thus, transportation of STEMI patients within an established PCI network did not result in any prognostic disadvantage. Efficient network logistics with transportation for PPCI in acute STEMI ensure both safety and outcome profiles similar to patients treated by PCI in metropolitan areas.     

Effect of Lactobacillus rhamnosus GG in persistent diarrhea in Indian children: a randomized controlled trial

AIM: To evaluate the role of Lactobacillus rhamnosus GG (LGG) as probiotic in persistent diarrhea (PD) in children of North Bengal, India. SETTING: Hospital-based study. DESIGN: Randomized, double-blind controlled trial. PATIENTS AND METHODS: All patients of PD admitted over a period of 2 years were included in the study as per predefined inclusion criteria. They were randomized to receive oral rehydration solution (ORS) alone, or ORS plus LGG powder containing 60 million cells, twice daily for a minimum period of 7 days or till diarrhea has stopped along with correction of dehydration with ORS and/or intravenous fluids as per WHO protocol and antibiotics in culture positive patients. The duration and frequency of purge and vomiting were studied. Data were analyzed by SPSS-10 software. Statistical significance was calculated by Student t test and chi2 test. RESULTS: The study comprised of 235 patients randomized into 2 groups, cases (117) and controls (118). Both the groups were similar with respect to age, number of breastfed infants, presentation with dehydration, degree of protein energy malnutrition, and distribution of infections. Stool culture was positive in 90 (38.3%) patients, Escherichia coli being the commonest organism followed by Shigella spp. and Clostridium difficile. The mean duration of diarrhea was significantly lower in the cases than in controls (5.3 vs. 9.2 d). The average duration of hospital stay was also significantly lesser in cases. No complication was observed from the dose of LGG used. CONCLUSIONS: LGG (dose of 60 million cells) could decrease the frequency and duration of diarrhea and vomiting and reduced hospital stay in patients of PD.     

The distribution of interstitial cells of Cajal in the ileum is not altered by infection with Schistosoma mansoni

BACKGROUND & OBJECTIVES: The interstitial cells of Cajal (ICC) act as pacemakers that generate slow waves and function as a relay between smooth muscle cells of the gastrointestinal (GI) tract. Recent reports indicate the crucial role played by the ICC in defining GI motility during human disease status like pyloric stenosis, Hirschsprung's disease and ulcerative colitis. Experimental data showed that Nippostrongylus infection in the rat caused an altered GI motility pattern accompanied by a complete loss of ICC-deep muscular plexus. The aim of the present study was to delineate if ICC were similarly affected during Schistosoma mansoni infections, thereby responsible for the disturbed GI motility patterns triggered in the afflicted mammalian host. METHODS & RESULTS: Immunohistochemistry was done using whole mounts and sections from naive and S. mansoni infected mice ileum. Primary antibodies detected Kit-immunoreactivity (Kit-ir representing ICC), PGP-9.5 (protein gene product 9.5 representing a neuronal marker), SK3 (ionic channel marker for non-Kit fibroblast like cells), and Cx43 (gap junction protein representing a muscle marker). Single/double immunofluorescence staining and confocal microscopy depicted that muscle thickness (Cx43-ir) and inflammatory infiltrate increased with infection. Kit-ir ICC and SK3-ir fibroblast like cells (FLC) were present at all normal locations as seen in controls and during acute and chronic stages of infection. INTERPRETATION & CONCLUSION: No disappearance of either ICC population was noted. A preferential (although not exclusive) location of inflammatory infiltrate in contact with SK3-ir FLC in the muscle layer was observed. The present study thus delineated that ICC are not affected during S. mansoni infections, and thereby may not be responsible for mediating the disturbed GI motility patterns caused by schistosomiasis.     

Acanthus ilicifolius plant extract prevents DNA alterations in a transplantable Ehrlich ascites carcinoma-bearing murine model

AIM: To investigate the chemopreventive efficacy of the Indian medicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinoma (EAC)- bearing murine model. METHODS: Male Swiss albino mice were divided into four groups: Group A was the untreated normal control; Group B was the EAC control mice group that received serial, intraperitoneal (ip) inoculations of rapidly proliferating 2 x 105 viable EAC cells in 0.2 mL of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract (ALE) of the plant at a dose of 2.5 mg/kg body weight by single ip injections, once daily for 10, 20 and 30 consecutive days following tumour inoculation (ALE control); and Group D was the EAC ALE- treatment group. The chemopreventive potential of the ALE was evaluated in a murine model by studying various biological parameters and genotoxic markers, such as tumour cell count, mean survival of the animals, haematological indices, hepatocellular histology, immunohistochemical expression of liver metallothionein (MT) protein, sister-chromatid exchanges (SCEs), and DNA alterations.RESULTS: Treatment of the EAC-bearing mice with the ALE significantly (P < 0.001) reduced viable tumour cell count by 68.34% (228.7 x 106 ± 0.53) when compared to EAC control mice (72.4 x 106 ± 0.49), and restored body and organ weights almost to the normal values. ALE administration also increased (P < 0.001) mean survival of the hosts from 35 ± 3.46 d in EAC control mice to 83 ± 2.69 d in EAC ALE-treated mice. Haematological indices also showed marked improvement with administration of ALE in EAC-bearing animals. There was a significant increase in RBC count (P < 0.001), hemoglobin percent (P < 0.001), and haematocrit value (P < 0.001) from 4.3 ± 0.12, 6.4 ± 0.93, and 17.63 ± 0.72 respectively in EAC control mice to 7.1 ± 0.13, 12.1 ± 0.77, and 30.23 ± 0.57 respectively in EAC ALE-treated group, along with concurrent decrement (P < 0.001) in WBC count from 18.8 ± 0.54 in EAC control to 8.4 ± 0.71 in EAC ALE. Furthermore, treatment with ALE substantially improved hepatocellular architecture and no noticeable neoplastic lesions or foci of cellular alteration were observed. Daily administration of the ALE was found to limit liver MT expression, an important marker of cell proliferation with concomitant reduction in MT immunoreactivity (62.25 ± 2.58 vs 86.24 ± 5.69, P < 0.01). ALE was also potentially effective in reducing (P < 0.001) the frequency of SCEs from 14.94 ± 2.14 in EAC control to 5.12 ± 1.16 in EAC ALE-treated group. Finally, in comparison to the EAC control, ALE was able to suppress in vivo DNA damage by abating the generations of ‘tailed’ DNA by 53.59% (98.65 ± 2.31 vs 45.06 ± 1.14, P < 0.001), and DNA single-strand breaks (SSBs) by 38.53% (3.14 ± 0.31 vs 1.93 ± 0.23, P < 0.01) in EAC-bearing murine liver. CONCLUSION: Our data indicate that, ALE is beneficial in restoring haematological and hepatic histological profiles and in lengthening the survival of the animals against the proliferation of ascites tumour in vivo. Finally, the chemopreventive efficacy of the ALE is manifested in limiting MT expression and in preventing DNA alterations in murine liver. The promising results of this study suggest further investigation into the chemopreventive mechanisms of the medicinal plant A. ilicifolius in vivo and in vitro.