Heterogeneity of squamous cell carcinomas of the head and neck--analysis of tumor biologic factors and proliferation rates.

Specimens obtained from five different tumor regions in 12 patients who underwent surgery for squamous cell carcinoma (SCC) of the oropharynx were examined. The evaluation of each biopsy included quantitative DNA measurements based on image analysis, immunohistochemical assessment of proliferations markers (i.e., Ki67-MIB1, proliferating cell nuclear antigen [PCNA]), and morphological tumor-front grading. From single cell measurements, several DNA indices were derived which are known to reflect tumor aneuploidy. The results revealed a marked variation of proliferation and cellular differentiation in different regions of tumors and a wide intraindividual variation between particular tumors for all markers examined. There was good correlation between DNA data and proliferative cell fractions (Ki67 score, PCNA score). With the use of diagrams, three-dimensional distribution of proliferation rates and markers reflecting tumor aggressiveness within each tumor was obtained. The results confirmed previous clinical and histological observations that SCCs of the oropharynx are heterogeneous tumors. One might expect that the regions with increased proliferation and aggressiveness may predict the location of possible tumor recurrence.

[Examinations with DNA cytometry of mouth and oropharyngeal lavage fluid as a screening method in diagnosis of malignancies of the mouth cavity and oropharynx]. / DNA-zytometrische Untersuchungen von Mund- und Rachenspülflüssigkeit als Screening-Verfahren zur Diagnose von Malignomen der Mundhöhle und des Oropharynx.

BACKGROUND: Due to a high rate of false negative results, cytologic examinations of scrapings are currently not very common in diagnosing squamous cell carcinomas of the upper aerodigestive tract. The purpose of the present study was to determine whether cytometric and cytologic examinations are suitable in diagnosing squamous cell carcinomas of the oral cavity and oropharynx. METHODS: Cytologic and cytometric examinations of rinsing fluid from the mouth and throat were performed in 14 patients with histologically confirmed squamous cell carcinomas of the oral cavity and oropharynx. The patients were asked to rinse their mouth and throat with 10 ml of Ringer's solution. The rinsing fluid was centrifuged and fixed. The sediment was then smeared onto glass slides and stained according to the technique of Feulgen. Quantitative DNA measurements were then performed using a TV-based image analysis system. The DNA indices, 2 c DI, 5 c EE, and DNA entropy were determined from the single-cell measurements. RESULTS: The results of the carcinoma patient group were compared to those obtained in 19 patients without any evidence of cancer (control group). With this method, malignant and benign cells could be distinguished in all cases, i.e., all patients with a carcinoma could be identified as positive by this examination, whereas patients without evidence of cancer were identified as negative in all cases. CONCLUSIONS: The results of this pilot study show that quantitative DNA measurements might be a suitable tool for non-invasive screening of patients who are at high risk for developing a carcinoma in the upper aerodigestive tract and for follow-up of patients in order to detect tumor recurrence after successful initial treatment.

Electrogenic bicarbonate secretion in gallbladder: induction by barium via neuronal, possibly VIP-ergic pathways.

In guinea-pig gallbladder epithelium, cAMP converts electroneutral HCO3- secretion into an electrogenic process. The effects of blood side Ba2+ (5 mmol/l) on HCO3- transport were investigated in vitro, using pH-stat and voltage clamp techniques to determine unidirectional fluxes of HCO3- and transepithelial electrical characteristics. Serosal, not mucosal addition of Ba2+ elevated short-circuit current (Isc), transepithelial potential difference, and tissue conductance; it inhibited the absorptive HCO3- flux while leaving the secretory flux unchanged. The Isc effect of Ba2+ was inhibited or prevented by tetrodotoxin; D- and L-propranolol; the Cl- channel blocker 4-N-methyl-N-phenylaminothiophene-3-carboxylic acid; the intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)ocytl ester; noradrenaline, by a yohimbine-sensitive action; somatostatin; HCO3(-)-free solutions. Thus Ba2+ appeared to release a neurotransmitter that gives rise to cAMP synthesis sufficient to turn part of electroneutral HCO3- secretion electrogenic. In a search for the involved signalling pathways, the H1-receptor antagonist, cetirizine, largely and hexamethonium, atropine, atenolol, indomethacin, and trifluoperazine entirely failed to antagonize the Isc effect of Ba2+. Similarly, carbachol, dobutamine, salbutamol, and serotonin were unable to mimic the action of Ba2+ and Isc effects of histamine were small and short-lived. By contrast, vasoactive intestinal peptide (VIP; 3 x 10(-7) mol/l) completely transformed HCO3- secretion into an electrogenic process. The VIP receptor antagonist (4Cl-DPhe6, Leu17) VIP, delayed and reduced the Isc responses to Ba2+ and VIP. As guinea-pig gallbladder epithelial cells possess cAMP-coupled VIP receptors close to VIPergic neurons, Ba2+ is likely to act by releasing VIP from neural terminals.