Signal transduction inhibitors in the treatment of breast cancer

Signal transduction pathways are frequently altered in human breast cancer and are the targets of several novel therapies currently in clinical trials. Therapeutic strategies include extracellular blockade of tyrosine kinase receptors with the monoclonal antibodies C225 and trastuzumab. Competitive inhibitors of adenosine triphosphate binding sites on tyrosine and serine/threonine kinases are also being evaluated in phase I/II trials; these include ZD1839, OSI-774 and CI-1033. Flavopiridol and UCN-01 are nonspecific cell cycle kinase antagonists with preliminary evidence of breast cancer cell growth inhibition. Several inhibitors of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling are also in various stages of preclinical or clinical development. Additionally, inhibitors of farnesyl transferase have demonstrated activity in breast cancer cells irrespective of ras status. Current evidence suggests that targeting of signaling molecules is a promising new approach to treatment of breast cancer.     

Variation of concentration of heavy metals, calcium and magnesium with sex as determined by atomic absorption spectrophotometry

The concentrations of ten elements: Pb, Cd, Cr, Mn, Fe, Ni, Cu, Zn, Ca and Mg in hair, fingernails and toenails of girl and boy students between 20-24 years of age, living in nonindustrialized areas of Rajasthan state in India were analysed by Atomic Absorption Spectrophotometer. Adequate quality assurance was ensured by inter-laboratory exerciese, the results of which overall showed good consistency. With the exception of Cu, all metals were found to be significant in fingernails and toenails of boys as compared to boys hair while in case of girl students all metals except zinc in toenails were found to be significant in hair. Using Pearson's Correlation Coefficient we obtained information about high positive and negative correlations among metals in hair, finger nails and toenails of boy and girl students.     

Studying health consequences of microchimerism: methodological problems in studying health effects of procreation with multiple partners

A pregnancy requires a reasonably good health and may have positive as well as negative health consequences for the woman. Part of these health effects may depend on the immune response to the exchange of fetal cells (microchimerism). The number of biological fathers to a woman's children may thus have a health effect beyond the parity effect. A possible design for studying this is to compare health effects for women with or without multiple partners but with the same parity. We compared total and cause specific mortality in these two groups in order to estimate their comparability and thus the problem of confounding. By using population registries we identified all women who had children with at least two different partners from 1973 to 1996 in Denmark (64,704 exposed women). Among all women who had at least two births in the above mentioned time period, we selected a random sample of 100,000 women to obtain information on women having one father for their children. We linked this cohort to a number of registries, including the Cause of Death Registry. We studied cause-specific mortality up to 1997. Altogether 1373 women died during follow-up. Women who had children with more than one partner had a higher relative mortality rate, which was even higher if she had more than two partners. This finding persisted after excluding unnatural deaths and did not depend on time from exposure. Although some of the findings were adjusted for parity, age and social factors, it is highly unlikely that these large differences are entirely related to microchimerism. The study shows that caution is needed when studying health effects of procreation with multiple partners.     

Risk groups for hepatitis A virus infection

We report the conduct and results of a systematic search for evidence of risk of infection with hepatitis A virus (HAV) among blood transfusion recipients, travellers, the military, healthcare workers, sewage workers, foodhandlers, day care assistants, institutionalised subjects, blood transfusion recipients, drug addicts, homosexuals, prisoners and other risk groups such a liver transplantees. We report our recommendations for the use of the HAV vaccine in these groups.     

Eosinophilic gastritis simulating gastric carcinoma

A case of eosinophilic gastritis is reported in a 65-year-old woman. The disease presented with signs of delayed emptying, vomiting and substantial thickening of the antrum. Partial gastrectomy was performed because of the suspicion of gastric cancer and pyloric stenosis. Histopathology established the diagnosis of eosinophilic gastritis of mural type. Clinicopathological features of the disease, as well as its differential diagnosis are summarised in the discussion.     

Control of lead emissions from a battery repair shop in the city of Rio de Janeiro using the air as indicator

Lead levels in the air surrounding a battery repair shop (BRS) located in the Olaria neighborhood (Rio de Janeiro, Brazil) were monitored from April to July 1999. Most of the samples collected within 25 meters of the BRS exceeded the limit of 1.5 micro g.Pb.m-3 established by the United States Environmental Protection Agency (EPA). These results were published in a previous article (Quiterio et al., 2001). In the current study, installation of a Venture ventilation system and some changes in the operational procedure were proposed. After the modifications in the BRS, a new monitoring campaign was performed (August and September, 2000). Three points were selected for air collection, corresponding to the most critical points found in the previous assessments. The new concentrations ranged from 0.8 to 17.6 micro g.Pb.m-3, showing that lead emissions into the environment had decreased adequately. However, concentration at the chimney exhaust was still higher than EPA limits, and further improvements in the installations and procedures are definitely needed.     

Developmental and subcellular effects of chronic exposure to sub-lethal concentrations of ammonia,PAH and PCP mixtures in brown trout (Salmo trutta f. fario L.) early life stages

Brown trout (Salmo trutta f. fario L.) early life stages were studied for physiological effects caused by chronic exposure to sub-acute levels of unionised ammonia, a mixture of PCP and PAHs, and a combination of ammonia and the mixture of organics during the entire embryonic development. Nominal concentrations of tested compounds were based on field data. Accumulation data for PAHs and PCP in trout tissue reflected respective water concentrations of PCP and PAHs. Physiological responses were studied by early life stage tests (ELST) and by the analysis of the 70 kDa stress protein (hsp70). Endpoint responses in the ELST were: accelerated development, pre-hatching, and increased heart rates. For these endpoints, response levels were highest in the ammonia treatment, followed by the exposure to the PCP/PAH mixture. Weight was reduced in embryos treated with the PCP/PAH mixture, but not in the group treated with this mixture combined with ammonia. Induction of hsp70 by the test agents was found to be stage-specific with increased response levels at advanced developmental stages. In both the ELST and hsp70 analysis, response levels were lower in the combined ammonia/PCP/PAH treatment than in groups treated with either ammonia or the PCP/PAH mixture alone.     

Important effect of food on the bioavailability of oral testosterone undecanoate

STUDY OBJECTIVE: To assess the effects of food on the bioavailability of testosterone undecanoate, testosterone, and 5alpha-dihydrotestosterone (DHT) after administration of a new oral testosterone undecanoate formulation, Andriol Testocaps. DESIGN: Randomized, open-label, crossover study with a 1-week washout period. SETTING: Clinical pharmacology unit. SUBJECTS: Sixteen healthy postmenopausal women. INTERVENTION: Single oral doses of testosterone undecanoate 80 mg were administered either during a fasting period or after consumption of a standardized continental breakfast. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of testosterone undecanoate were assayed by liquid chromatography with mass spectrometry detection; testosterone and DHT were assayed by gas chromatography with mass spectrometry detection. Serum concentrations of testosterone, testosterone undecanoate, and DHT were low to negligible when testosterone undecanoate was administered to subjects in a fasting state; these values were significantly higher when the test drug was coadministered with food. For testosterone, the maximum serum concentration and area under the plasma concentration-time curve were 0.67 ng/ml and 5.37 ng x hr/ml, respectively, in the fasting state, versus 10.7 ng/ml and 56.4 ng x hr/ml, respectively, in the fed state. The same parameters were also significantly higher for testosterone undecanoate and DHT in the fed versus fasting subjects. CONCLUSION: Food increases the bioavailability of testosterone undecanoate, testosterone, and DHT. For proper absorption, Andriol Testocaps must be taken with meals.     

18F]Fluorodeoxyglucose positron emission tomography surveillance of hepatic metastases from prostate cancer following radiofrequency ablation: a case report

The liver is the organ most commonly involved with metastatic disease. Surgical resection of hepatic metastases is the only potentially curative therapy, but it is possible in only 20 per cent of the patients. Radiofrequency ablation (RFA) of hepatic lesions is a therapeutic option for unresectable hepatic metastases. Today there is no clear consensus about which imaging technique is the most reliable to monitor RFA therapy. [18F]Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a new imaging modality allowing evaluation of glucose metabolism that has become established for monitoring therapy and early detection of recurrence of various types of malignant tumors. We present a case report of a 61-year-old man treated for prostate carcinoma 3 years earlier who presented with rising serum prostate-specific antigen (PSA) levels. A CT scan demonstrated two hepatic metastases that were treated with RFA because the patient refused surgery. During 3 years of follow-up hepatic recurrence was monitored with serum PSA levels, CT of the abdomen, and FDG-PET imaging on multiple occasions. On three separate occasions FDG-PET revealed hypermetabolic foci despite no definite evidence of recurrence on CT. Furthermore FDG-PET imaging 2 months after the last RFA therapy showed two large photopenic areas without evidence of hypermetabolism consistent with successful RFA therapy. Serum PSA levels correlated better with FDG-PET than CT results. We conclude that in this patient FDG-PET imaging was more accurate than CT for monitoring recurrence of hepatic metastases from prostate carcinoma after RFA therapy. PET demonstrated hypermetabolic foci when there was recurrence and no evidence of hypermetabolism early after successful RFA therapy. In addition FDG-PET imaging helped to guide the placement of the RFA probe to the most metabolically active part of the tumor.     

Feasibility of abdomino-pelvic T1-weighted real-time thermal mapping of laser ablation

PURPOSE: To prove the hypothesis that T1-weighted (T1W) thermal mapping is reliable and achievable in magnetic resonance (MR)-guided laser tumor ablation. MATERIALS AND METHODS: Near real-time gray and color-scale T1W thermal maps in 111 MR-guided laser thermal ablations (LTA) of liver, kidney, and uterine tumors were studied. After laser fiber placement, near real-time gray and color-scale thermal maps were produced. Previous work showed T1 signal is inversely proportional to temperature below 55 degrees C (the point of irreversible necrosis). RESULTS: Thermal mapping was successful in 84% of uterine, 74% of hepatic, and 20% of renal ablations. For hepatic and uterine tumors, size and conspicuity of thermal lesions were significantly greater on subtracted colorized images rather than gray-scale raw image mapping (P = 0.001, paired Student's t-test). Patient movement (N = 24), fiber charring N = 2), magnetic field distortion, and reconstruction errors (N = 2) caused mapping failure. For both renal and hepatic tumors, comparison of near real-time T1W colorized thermal map and follow up gadolinium-enhanced MR imaging revealed moderate correlation (Pearson correlation coefficient of 0.55 and 0.5, respectively). CONCLUSION: In hepatic, renal, and uterine thermal maps, the color scale produced significantly greater sized lesions with significantly greater conspicuity than the gray scale. T1W thermal mapping was reliable and successfully achieved in 73.7% of procedures, and predicted the ablated area of the tumor moderately well.