Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts

Interferon-inducible protein 10 (IP-10) is an immunomodulatory chemokine recently recognized to have potent antiangiogenic activity in vivo. Due to difficulties in the stability, manufacture and chronic administration of recombinant forms of endogenous antiangiogenic proteins, antiangiogenic gene therapy has emerged as a promising new form of cancer treatment. We retrovirally transduced A375 human melanoma cells with the human IP-10 gene and injected cells subcutaneously into nude mice. IP-10-transduced cells also were mixed with null-transduced cells in varying proportions before injection. In vivo growth of IP-10-transduced melanoma cells was markedly diminished compared to parental or null-transduced cells (p = 0.0002, Kruskal-Wallis test). This growth inhibition was associated with a marked reduction in microvessel density. The degree of growth inhibition of tumors following injection of a mixed population of null- and IP-10-transduced cells was directly associated with the fraction of IP-10-transduced cells present. We conclude that retroviral transduction of human melanoma cells with the IP-10 gene leads to sufficient protein secretion to inhibit angiogenesis and tumor growth. These findings suggest that IP-10 gene therapy might be an effective therapy in patients with cancer.     

Endocarditis after nipple piercing in a patient with a bicuspid aortic valve

Piercing the skin for cosmetic reasons can be dangerous in young adults who have previously undergone surgery for congenital defects of the heart. We report the case of a 24-year-old man in whom coarctation of the aorta had been corrected 15 years earlier. Two months after piercing his left nipple without antibiotic prophylaxis, he developed a local mastitis, followed by bacterial endocarditits that required replacement of the aortic valve.     

Mortality from cancer of the head and neck,lung and esophagus in eastern Austria between 1960 and 1989

In eastern Austria, mortality from cancer of the mouth and pharynx, larynx, esophagus and lung between 1960 and 1989 developed differently by site and gender. In males, a decrease in lung cancer contrasted with an increase in mouth/pharynx cancer, while rates for cancer of the larynx and esophagus changed only slightly. At all sites, similar double-wave shaped cohort effects were discernible, with a period of decreasing risk separating two periods of increasing risks. The extents of these cohort effects, especially in the later rise of mouth/pharynx neoplasms, shaped the respective mortality curves. In females, lung cancer was found to increase over the whole period, while mouth/pharynx cancer increased during the last decade with risks increasing from cohort to cohort. Larynx rates became somewhat greater during the last two decades. Esophageal cancer demonstrated a steady decrease. For tobacco-related cancers, deglutitional sites were affected in a growing proportion. The combined topical effects of tobacco and alcohol suggest an increasing influence of the co-factor alcohol upon the occurrence of upper aerodigestive cancers in eastern Austria.     

Pathologische Fraktur bei fibrösem Histiozytom der proximalen Radiusmetaphyse

In this paper the authors report on a rare site for a benign bone lesion. They describe the clinical, radiological diagnostic, and therapeutic procedures for a benign fibrous histiocytoma (BFH) of the proximal radial metaphysis. Good results of operative treatment after excochleation, transplantation of an autologous bone chip, and stabilization with the IP-XXS nail are presented.     

The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer—a pooled analysis of the randomised clinical trials PlanB and SUCCESS C

Background Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy.Methods Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models.Results AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89–1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80–1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86–1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77–1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3–4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology.Conclusion For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.Subject terms: Randomized controlled trials, Breast cancer     

Should children at risk for familial adenomatous polyposis be screened for hepatoblastoma and children with apparently sporadic hepatoblastoma be screened for APC germline mutations?

BACKGROUND: Hepatoblastoma (HB) is the most frequent liver tumor in childhood, occurring in the first few years of life. Surgery combined with chemotherapy has resulted in dramatic improvements in prognosis. However, even today, about one quarter of affected children do not survive the disease. Compared to the general population, the risk of HB is 750-7,500 times higher in children predisposed to familial adenomatous polyposis (FAP), an autosomal-dominant cancer predispostion syndrome caused by germline mutations in the tumor suppressor gene APC. Only limited data exist about the frequency of APC germline mutations in cases of apparently sporadic HB without a family history of FAP. PROCEDURE: In our sample of 1,166 German FAP families, all known cases of HB were registered. In addition, 50 patients with apparently sporadic HB were examined for APC germline mutations. RESULTS: In the FAP families, seven unrelated cases of HB are documented; three had been detected at an advanced stage. In patients with apparently sporadic HB, germline mutations in the APC gene were identified in 10%. CONCLUSIONS: These data raise the issue of the appropriate screening for HB in children of FAP patients. To date, the efficiency of surveillance for HB is unclear. In Beckwith-Wiedemann syndrome (BWS), recent studies suggest an earlier detection of both Wilms tumor and HB by frequent screening. We discuss the rationale and implications of a screening program; besides the examination procedure itself, screening for HB in children of FAP patients would have important consequences for the policy of predictive testing in FAP. In a substantial fraction of sporadic HB, the disease is obviously the first manifestation of a de novo FAP. These patients should be identified by routine APC mutation screening and undergo colorectal surveillance thereafter.     

Development of an in vitro blood-brain barrier model based on immortalized porcine brain microvascular endothelial cells

Immortalized porcine brain microvessel endothelial cells (PBMEC/C1-2) were used to develop a model for measurement of blood-brain barrier permeation of central nervous system active drugs. Previous studies showed that a system using C6 astrocyte glioma conditioned medium leads to cell layers with transendothelial electrical resistance values up to 300 Omega cm(2) and a permeability coefficient P(e) of 3.24 +/- 0.14 x 10(-4) cm/min for U-[(14)C]sucrose, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro. However, commercially available inserts for the Transwell system were not permeable for highly lipophilic compounds, such as diazepam. Systematic studies with different insert showed, that inserts with a pore width of 1 microm proved to be optimal for permeation studies of lipophilic compounds. Permeability studies with a set of three benzodiazepines further supported this finding.     

Development of bioelectrical impedance analysis prediction equations for body composition with the use of a multicomponent model for use in epidemiologic surveys

BACKGROUND: Previous studies to develop and validate bioelectrical impedance analysis (BIA) equations to predict body composition were limited by small sample sizes, sex specificity, and reliance on reference methods that use a 2-component model. OBJECTIVE: This study was designed to develop sex-specific BIA equations to predict total body water (TBW) and fat-free mass (FFM) with the use of a multicomponent model for children and adults. DESIGN: Data from 5 centers were pooled to create a sample of 1474 whites and 355 blacks aged 12-94 y. TBW was measured by dilution, and FFM was estimated with a multicomponent model based on densitometry, isotope dilution, and dual-energy X-ray absorptiometry. RESULTS: The final race-combined TBW prediction equations included stature(2)/resistance and body weight (R(2) = 0.84 and 0.79 and root mean square errors of 3.8 and 2.6 L for males and females, respectively; CV: 8%) and tended to underpredict TBW in black males (2.0 L) and females (1.4 L) and to overpredict TBW in white males (0.5 L) and females (0.3 L). The race-combined FFM prediction equations contained the same independent variables (R(2) = 0.90 and 0.83 and root mean square errors of 3.9 and 2.9 kg for males and females, respectively; CV: approximately 6%) and tended to underpredict FFM in black males (2.1 kg) and females (1.6 kg) and to overpredict FFM in white males (0.4 kg) and females (0.3 kg). CONCLUSION: These equations have excellent precision and are recommended for use in epidemiologic studies to describe normal levels of body composition.     

Intraocular lenses in aviators: a review of the U.S. Army experience

Intraocular lenses are known to be efficacious in the correction of aphakia, but their suitability and durability in Army aviators has not been previously evaluated. Eight experienced pilots (preoperative flight time average: 7,660 hours), who had intraocular lens implants following removal of cataractus lenses, were studied. All had returned to flight duty, seven as pilots, with a total of 2,700 hours postoperative flight time accumulated. All were very pleased with the surgery and with the effectiveness of their lenses. Minor problems included: halos around lights in low illumination (5/8 pilots), erythropsia (2/8), and difficulties with a fixed focal length (2/8). Two aviators reported significant visual problems: complications associated with a platinum loop iris supported intraocular lens, and discomfort and glare stemming from traumatic corneal scarring. A detailed ophthalmological examination revealed abnormalities (5/8 pilots), but none which would be directly attributed to flying. Modern intraocular lenses appear to be an acceptable means of correcting aphakia in Army aviators.     

Palliative endoscopic therapy for rectal cancer with neodymium:YAG laser.

Neodymium: YAG laser has become an alternative to conventional palliative therapy for rectal cancer. Between January 1986 and December 1989, 31 patients were treated with endoscopic laser evaporation for rectal cancers with obstruction (n = 17), bleeding (n = 3) and non-obstructive luminal narrowing (n = 11). Contraindications against surgery were multiple metastases (n = 16), poor general health (n = 7), refusal by patient (n = 5) and extensive local invasion (n = 3). Laser treatment was tolerated well with an initially good response in 29 patients. Palliation could be maintained in 20 patients with laser only; two patients had an unsatisfactory control of symptoms and in eight cases a diverting colostomy was eventually required, largely due to extramural tumor growth. Complications were limited to one stenotic scar. There were no laser-related deaths. Patients survived on average 10.8 (0.1-49) months, 2-year survival was 26%. We conclude that endoscopic neodymium: YAG laser therapy is an efficient and safe palliative method to control intraluminal, obstructing or bleeding rectal cancers.