Treatment of bladder carcinoma with irradiation combined with misonidazole

One hundred patients suffering from cancer of the bladder were treated by external beam irradiation, 400 cGy twice a week to a total dose of 4800 cGy. One half of the patients were randomized to receive the electron affinic sensitizer agent, misonidazole, at a dose of 1 gr/m2 and a total dose of 12 gr/m2. There was no statistically significant difference in tumor responses and in recurrence--free survival time between the patients who received irradiation and misonidazole as compared to those who received irradiation and placebos.     

AUDITORY BRAINSTEM RESPONSES (ABR) IN HIGH-RISK NEONATES

ABSTRACT. In the present study, auditory brainstem responses (ABR) were recorded in 60 highrisk neonates in the intensive care unit selected by the following criteria: Birth-weight <2000 g, hyperbilirubinemia requiring phototherapy or exchange transfusion, idiopathic respiratory distress syndrome, artificial ventilation, asphyxia, sepsis or meningitis, intracranial haemorrhage, neurological symptoms and potential ototoxic medication (aminoglycoides, furosemide). The infants tested ranged in gestational age from 27-44 weeks. The ABR testing was performed in a sound-proof room using the Madsen (ERA-74) equipment. Four infants did not reveal responses to 70 dB HL ("nonresponders"), and the total of 10 neonates (16.6%) had abnormal ABR-tests, when the physiological changes related to gestational age and conceptional age (gestational age plus the age after birth) were taken into account. The 10 neonates with abnormal tests were reexamined after discharge, and in six there were no improvement of threshold sensitivity. Three of the "nonresponders" were retested several times within the two years after birth (one died at age 18 months of pertussis), and none of them revealed ABR at stimulus intensity of 70 dB HL. They all attend an audiological training program started at age of six months as a consequence of the early diagnosis of impaired auditory function. It is our opinion that a routine ABR-evaluation should be performed on high risk neonates (criteria mentioned above) in the newborn intensive care unit. Retesting of infants with abnormal responses within three months, and several times within the next two years if abnormal responses persist, is important. Transient impairment of auditory functions is not uncommon in these infants. However, the children with persisting hearing impairment should be discovered early to attend an early audiological training program.     

Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic cancer patients: a phase I-II study

The present trial is a phase I-II study based on a new liposomal cisplatin (lipoplatin). Previous preclinical and clinical data (phase I pharmacokinetics) led to the investigation of a combined treatment modality involving lipoplatin and gemcitabine. The gemcitabine dose was kept standard at 1000 mg/m2 and the lipoplatin dose was escalated from 25 mg/m2 to 125 mg/m2. The treatment was administered to advanced pretreated pancreatic cancer patients who were refractory to previous chemotherapy which included gemcitabine. Lipoplatin at 125 mg/m2 was defined as dose limiting toxicity (DLT) and 100 mg/m2 as the maximum tolerated dose (MTD) in combination with 1000 mg/m2 of gemcitabine. Preliminary objective response rate data showed a partial response in 2/24 patients (8.3%), disease stability in 14 patients (58.3%) for a median duration of 3 months (range 2-7 months) and clinical benefit in 8 patients (33.3%). Liposomal cisplatin is a non-toxic alternative agent to bare cisplatin. In combination with gemcitabine, it has an MTD of 100 mg/m2 and shows promising efficacy in refractory pancreatic cancer.     

Modulation of vascular endothelium by imatinib: a study on the EA.hy 926 endothelial cell line

In this study the EA.hy 926 endothelial cell line--simulating endothelial cells--was treated with imatinib in order to define a possible anti-angiogenic role for imatinib. Dose and time response experiments were performed. Cell morphology was studied, while migration efficiency, intercellular permeability and VE-cadherin expression were assayed, both in the presence and in the absence of imatinib. Imatinib-induced EA.hy 926 cell apoptosis was also examined. Results showed that imatinib reduced the endothelial cell population, changed cell monolayer morphology and reduced cell-to-cell cohesiveness. Migration efficiency was significantly decreased while intercellular permeability was 2.76-fold increased in the presence of imatinib. Indirect immunofluorescence microscopy showed nearly complete down-regulation of VE cadherin in imatinib-treated cells. Furthermore, apoptotic activity was detected in imatinib-treated cells. Altogether our results support an antiangiogenic profile for imatinib that possibly contributes to its therapeutic potential.     

Myoepithelial cell cocktail (p63+SMA) for the evaluation of sclerosing breast lesions

Sclerosing breast lesions may sometimes mimic the appearance of infiltrating carcinoma due to the entrapment of ductular structures in a fibrotic core. The immunohistochemical detection of the outer myoepithelial cell layer that is indicative of a non-infiltrating lesion is a valuable clue for the diagnosis of such ambiguous cases. The myoepithelial cell markers smooth muscle actin (SMA) and p63 are most commonly used since their specificity and sensitivity are well established. However, recent studies have indicated that some morphologically distinct myoepithelial cells fail to stain for SMA and that p63 positivity can be rarely expressed by a subset of malignant epithelial cells. Moreover, SMA can also be positive in stromal myofibroblastic cells and normal vessels that can be found close to the entrapped ductules and might be erroneously interpreted as myoepithelial cells. In this study, we used a double-immunolabeling technique combining both SMA and p63 antibodies (myoepithelial cell cocktail), in order to investigate whether this technique is advantageous over either marker used alone, in diagnosing sclerosing breast lesions. Our results indicate that p63 alone is not a useful myoepithelial cell marker if applied in large sclerosing breast lesions, however, in smaller lesions it is still of high value. On the contrary, SMA proved significantly useful in the evaluation of myoepithelial cells in larger but not in smaller complex sclerosing lesions. The myoepithelial cell cocktail has a staining sensitivity identical to that of SMA. Nevertheless, in a certain number of cases the cocktail might be useful in differentiating myoepithelial cells from stromal myofibroblasts or vascular smooth muscle cells due to the false impression of a higher staining intensity of the cocktail resulting from the expression of both nuclear and cytoplasmic/membranous antibodies that occupy a wider area of the cell under control.     

Use of monoclonal antibodies to identify cerebrospinal fluid lymphoblasts in children with acute lymphoblastic leukemia

The identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of children with acute lymphoblastic leukemia (ALL). We adapted a latex sphere rosetting technique to allow us to identify simultaneously cell surface markers and cell morphology in 199 CSF samples from 34 patients and 14 control subjects. In patients without leukemic meningitis, the majority of CSF lymphocytes (69%) were found to be mature T cells positive for OKT11. A much smaller number of cells (8%) were found to be B cells positive for la. In these children, only 3% of CSF lymphoid cells expressed the common acute lymphoblastic leukemia antigen (CALLA). Similar results were found in the control subjects. By contrast, 28 CSF samples from nine children with varying numbers of CSF lymphoblasts had much greater proportions of CALLA- and la-positive CSF cells (24% to 96%). Leukemic meningitis was present in one of these patients and later developed in four others. However, three patients with small numbers of lymphoblasts present but with low proportions of CALLA-positive CSF cells (less than 5%) subsequently had normal CSF examinations. We found the use of this rosetting technique valuable in providing information complementary to that obtained from cell morphology alone about the possible malignant nature of small numbers of lymphoblast-like CSF cells seen on cytocentrifuge preparations in children with ALL.     

Variability of interalveolar septal remodeling after bleomycin treatment in mice

Although bleomycin-induced cellular injury in the lung parenchyma is followed by the development of patchy fibrosis, the authors hypothesized that remodeling of the interalveolar septum (IAS) following bleomycin is a diffuse process not limited to the formation of discrete fibrotic areas. To determine the spectrum of changes in the IAS induced by bleomycin treatment, lungs were harvested from mice at 1, 2, 3, and 4 weeks following intratracheal administration of 0.04, 0.06, or 0.08 units of bleomycin. Light microscopy with quantitative morphometric techniques and electron microscopy were used to evaluate the IAS alterations. At 4 weeks after treatment, there was evidence of diffuse IAS remodeling. By morphological analysis, two types of structural remodeling of the IAS were observed. One type showed thickening with extracellular matrix deposition and hyperplasia of lining epithelial cells. The other type showed localized thinning of the interstitium with capillary loss and reduction in number and in size of epithelial cells. The authors have defined these variants as septal thickening and septal atrophy, respectively. The findings indicate that studies investigating the pathogenesis of lung fibrosis should focus on septal remodeling as well as analysis of fibrotic foci and measurement of collagen content.     

Dietary calcium, phosphorus, vitamin D, dairy products and the risk of colorectal adenoma and cancer among French women of the E3N-EPIC prospective study

A protective effect of calcium and/or dairy products on colorectal cancer has been reported in epidemiological studies but the findings are considered inconsistent. In particular, it is unclear whether they act at a particular step of the adenoma-carcinoma sequence. To investigate the effect of dairy product consumption and dietary calcium, vitamin D and phosphorus intake on the adenoma-carcinoma sequence in the French E3N-EPIC prospective study. The population for the study of risk factors for adenomas was composed of 516 adenoma cases, including 175 high-risk adenomas, and of 4,804 polyp-free subjects confirmed by colonoscopy. The population for the colorectal cancer study was composed of 172 cases and 67,312 cancer-free subjects. Diet was assessed using a self-administered questionnaire completed at baseline. There was a trend of decreasing risk of both adenoma (ptrend=0.04) and cancer (ptrend=0.08) with increasing calcium intake, with RRs for adenoma and cancer of 0.80 (IC 95%=0.62-1.03) and 0.72 (95% CI=0.47-1.10), respectively, in the fourth quartile compared to the first. A protective effect of dairy products on adenoma (RRQ4 vs. Q1=0.80, 95% CI=0.62-1.05, ptrend=0.04) was observed and of milk consumption on colorectal cancer (RRQ4vs. Q1=0.54, 95% CI=0.33-0.89, ptrend=0.09), although the latter did not reach significance. Phosphorus intake also decreased the risk of adenoma (RRQ4 vs. Q1=0.70, 95% CI=0.54-0.90, ptrend=0.005). No vitamin D effect was identified. Our data support the hypothesis that calcium, dairy products and phosphorus exert a protective effect at certain steps of the adenoma-carcinoma sequence.