Neoadjuvant sorafenib,gemcitabine, and cisplatin administration preceding cystectomy in patients with muscle-invasive urothelial bladder carcinoma: An open-label,single-arm,single-center,phase 2 study

Background

Outcomes of neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder carcinoma (MIUBC) should be improved. Sorafenib was combined with gemcitabine and cisplatin chemotherapy (SGC) in an open-label, single-arm, phase 2 trial (NCT01222676).

A personal technique: mammaplasty with J scar

Mastopexy and reduction mammaplasty techniques have evolved with time, pursuing the aim of an effective and reliable technique that produces a well-shaped breast and reduces the amount of scarring. The authors believe that the L mammaplasty achieves the best results in terms of a short scar and a good, stable shape. They present their technique of a modified L mammaplasty with a resulting scar in the shape of a J, which implies a central breast resection with the nipple-areola complex transposed on a superior pedicle. The correct execution of the preoperative markings and the shaping of the gland tissue are mandatory to obtaining the desired result. The technique has been used during the past 7 years on 326 patients, providing satisfactory results with short scars and virtually no complications.     

Radiosensitization of human melanoma cells by ribozyme-mediated inhibition of survivin expression

Survivin is a structurally unique member of the inhibitors of apoptosis protein family and is involved in the control of cell division and inhibition of apoptosis. The notion that survivin is overexpressed in most human tumors but absent in normal adult tissues with only a few exceptions has led to the proposal of survivin as a promising therapeutic target for novel anticancer therapies. In this context, we generated a hammerhead ribozyme targeting the 3' end of the CUA110 triplet in the survivin mRNA. Two human melanoma cell lines (JR8 and M14) overexpressing survivin were stably transfected with the pRc/CMV vector carrying the ribozyme sequence. Two polyclonal cell populations proven to endogenously express ribozyme and characterized by a markedly lower survivin protein level (-60% and -50%, respectively) than JR8 and M14 parental cells were selected for the study. Ribozyme-expressing cells showed a significantly (p<0.01) increased sensitivity to gamma-irradiation (as detected by clonogenic cell survival) compared to JR8 and M14 cells. Moreover, in the JR8 cell line, the extent of radiation-induced apoptosis (in terms of percentage of apoptotic nuclei in cells stained with propidium iodide and level of caspase-3 catalytic activity) was markedly greater in ribozyme-expressing cells than in parental cells. These results demonstrate for the first time that attenuation of survivin expression renders human melanoma cells more susceptible to gamma-irradiation.     

The Po River Delta (north Italy) indoor epidemiological study: effects of pollutant exposure on acute respiratory symptoms and respiratory function in adults

The authors studied the effects of relatively low doses of nitrogen dioxide and respirable suspended particulate matter (i.e., < 2.5 mu) on acute respiratory symptoms and on peak expiratory flow in 383 adults (15-72 yr of age) who lived in the Po River Delta area, located near Venice. During 2 wk-1 wk in winter and 1 wk in summer--the authors monitored each participant's house to measure nitrogen dioxide (in parts per billion) and respirable suspended particulate (microgram/m3) concentration. Information on sex, age, height, weight, daily activity patterns, active and passive smoking, chronic respiratory diseases, daily peak expiratory flow, and presence of acute respiratory symptoms during the weeks monitoring occurred were also collected. Peak expiratory flow variation was studied as mean amplitude percentage (i.e., amplitude/mean) and percentage of diurnal variation (maximum/minimum). The exposure indices to nitrogen dioxide (nitrogen dioxide--index of exposure) and to respirable suspended particulate matter (respirable suspended particulate matter-index of exposure) were computed as the product of pollutant concentration and time of exposure. The authors considered indices as "low" or "high" on the basis of the median value. The median nitrogen dioxide was 20 ppb in winter and 14 ppb in summer; the highest nitrogen dioxide levels occurred in the kitchen in the winter (33 ppb) and summer (20 ppb). The median respirable suspended particulate matter was 68 micrograms/m3 in winter and 45 micrograms/m3 in summer. Only in winter were there significant associations between bronchitic/asthmatic symptoms and "high" nitrogen dioxide and respirable suspended particulate matter indices. In subjects who did not smoke, a significant influence of the "high" respirable suspended particulate matter-index of exposure was also observed in summer. With respect to peak expiratory flow and its variability, respirable suspended particulate matter-index of exposure was associated with an increase of both amplitude/mean and maximum/mean; however, with respect to the nitrogen dioxide--index of exposure, the association was significant only in subjects with chronic respiratory diseases (i.e., asthma and bronchitis). These relationships were significant only in winter. In conclusion, the results of the current study indicate that there is an association between relatively low doses of pollutants and acute respiratory symptoms and peak expiratory flow in adults.     

The role of ultrasound-guided aspiration biopsy of peripheral pulmonary nodules: our experience

BACKGROUND: Peripheral lung lesions are difficult to diagnose with conventional methods: ultrasound-guided aspiration biopsy is an interesting prospect having been reported to have good sensitivity and specificity. PATIENTS AND METHODS: From January 1991 to August 2001 we investigated, in 268 patients, the role of ultrasound-guided transthoracic fine needle aspiration for cytological diagnosis of peripheral lung lesions. Nodule sizes ranged from 1 to 10 cm. RESULTS: From 268 patients, we obtained 174 positive specimens for malignancy, of which 155 were positive for primary lung tumors and 19 for metastasis; 76 negative; 9 inadequate; and 9 aspecific. One patient developed pneumothorax after needle aspiration and one patient emophtoe. The nodule size did not affect complication rate and diagnostic outcome. CONCLUSION: This diagnostic procedure appears to be effective, safe and feasible, even in bedridden patients. The cost is low (70Euro), the examination is fast (5-6 minutes) and well-tolerated and, if the specimen is inadequate or non-specific, it is possible to repeat the examination. Ultrasound-guided aspiration biopsy can replace the TC-guided biopsy in patients with peripheral lung nodules.     

Study of formulation variables influencing the drug release rate from matrix tablets by experimental design.

Experimental design was utilized to simultaneously investigate the effect of varying the type of diluent (insoluble Calcium phosphate or water-soluble arabic gum) and the diluent/matrix ratio on the drug release behaviour from both lipophilic (glyceryl behenate, Compritol) or hydrophilic (hydroxypropylmethylcellulose) matrix tablets. Ketoprofen, theophylline and sodium sulphadiazine were selected as model drugs on the basis of their respectively very low, medium and high water-solubility, in order to evaluate the influence of this parameter as well. The selected response variables were the dissolution efficiency (i.e. the area under the dissolution curve) after one and six hours and the time necessary to dissolve 10% drug. Tablets obtained by direct compression of drug-diluent-matrix ternary mixtures prepared according to the experimental plan provided for by an asymmetric screening matrix, were tested for drug release properties using a USP paddle apparatus. Graphic analysis of the effects allowed identification, for each examined drug, of the formulation factors active on the selected responses and determination of the proper level of the variables to be selected for the response improvement. The different results obtained with the three examined drugs pointed out the role of the drug solubility in determining the influence of formulation parameters on drug release rate from matrix tablets.     

Morphometric study of collagen maturation in chick compact bone

An ultrastructural-morphometric study was carried out on the process of osteoid maturation in growing surfaces of parallel-fibered chick bone. The aim was to investigate the distribution, size and amount of collagen fibrils (CFs), as well as the proteoglycan (PG) content, throughout the osteoid seam and in the adjacent bone. The results show that the organic components secreted by osteoblasts undergo complete maturation inside the osteoid seam only. Proceeding from the secreting plasma membrane of osteoblasts (osteoidogenic surface) towards the mineralizing surface, we found that CFs gradually increase in diameter but not in number per surface unit. As a consequence, the proportion of osteoid seam occupied by CF increases too, at the expense of the interfibrillar substance. PG content also decreases inversely in this direction. In the adjacent bone, CF size and density do not change significantly with respect to the mature osteoid close to the mineralizing surface.     

Dose and volume as predictive factors of pulmonary toxicity

Dose and volume and their correlation with the development of pulmonary toxicity are among the most widely studied and validated factors in radiotherapy. Most common treatment planning systems allow prompt assessment of Vdose and Mean Lung Dose (MLD). The former represents the percentage of normal lung parenchyma receiving a dose equal to or higher than the established threshold dose; the latter corresponds to the mean dose delivered to the normal lung parenchyma. Most important studies reported on the subject and threhold values recommended for Vdose and MLD are analyzed. The monitoring system of late toxicity used by the authors is presented.     

DNA fragmentation and DNA repair synthesis induced in rat and human thyroid cells by four rat thyroid carcinogens

Four chemicals that are known to induce in rats thyroid follicular-cell adenomas and carcinomas were assayed for their ability to induce DNA damage and DNA repair synthesis in primary cultures of human thyroid cells. Significant dose-dependent increases in the frequency of DNA single-strand breaks and alkali-labile sites, as measures by the Comet assay, were obtained after a 20-h exposure to the following subtoxic concentrations of the four test compounds: 2,4-diaminoanisole (DAA) from 0.10 to 1.0 mM, 4,4'-methylene-bis(N,N-dimethyl)benzenamine (MDB) from 0.32 to 1.8 mM, propylthiouracil (PTU) from 1.8 to 5.6 mM, and 4,4'-thiodianiline (THA) from 0.032 to 0.18 mM. Under the same experimental conditions, DNA repair synthesis, as evaluated by quantitative autoradiography, was present in thyreocytes exposed to DAA but absent after treatment with MDB, PTU, and THA. Consistent with their thyroid-specific carcinogenic activity, all the four chemicals, administered p.o. in rats in a single dose corresponding to 1/2 LD50, induced a statistically significant degree of DNA fragmentation in the thyroid, whereas any substantial evidence of DNA lesions was absent in liver, kidney, and lung, which, with the exception of liver tumors caused by THA, are not targets of the carcinogenic activity of the four test compounds. These findings indicate that the DNA damage observed in thyroid cells was consistent with the carcinogenicity of the four test compounds, and suggest that DAA, MDB, PTU, and THA might be carcinogenic to thyroid in humans.