Synthesis and antibacterial activity of some ester, amides, and hydrazides of 3-carboxyrifamycin S. Relationship between structure and activity of ansamycins.

Esters, amides, and hydrazides of 3-carboxyrifamycin S were synthesized by oxidizing the cyanohydrin of 3-formylrifamycin SV to 3-(cyanocarbonyl)rifamycin S, followed by treatment with alcohols, amines and hydrazines. The in vitro microbiological activity of the derivatives was quite low, especially toward Gram-negative bacteria. This poor activity was not shown to be due to the inadequate inhibiting action on the bacterial DNA-dependent RNA polymerase but to the poor penetration of the compounds through the bacterial cell wall. The microbiological activity was correlated to the chemical properties of the substituent on C3.

Synthesis and antibacterial activity of some derivatives of tolypomycinone. Relationship between structure and activity in ansamycins.

3-Aminotolypomycinoes and 3,16-diamino-16,17-dihydrotolypomycinones are formed by the addition of primary and secondary amines to tolypomycinone, obtained by mild hydrolysis of the antibiotic tolypomycin Y.3-Amino-16,17-dihydrotolypomycinones are formed by the addition of primary and secondary amines to 16,17-dihydrotolypomycinone. In vitro microbiological tests showed high antibacterial activity in compounds obtained by the addition of primary amines, which must be unbranched in the alpha position to the nitrogen atom to position 3 of the naphthoquinone ring. The relationship between structure and activity is described, and evidence is presented that hydrogen bonding between the amino NH bonded to C3 and the amide CO of tolypomycinone is very important for biological activity.

Squamous papilloma of the esophagus: long-term follow up.

BACKGROUND AND AIM: Squamous papilloma of the esophagus is a rare benign tumor; less than 200 cases have been reported in the literature. The prevalence of endoscopically diagnosed squamous papilloma of the esophagus has been reported in only a very few series, and varies from 0.01 to 0.43%. Clinical relevance and possible association with other pathological conditions, namely if it is a premalignant lesion, remain a matter of debate. The etiology is controversial, although a role of human papilloma virus has been recently proposed. The aim of this study was to try to determine the prevalence, clinical relevance, possible association with other pathological conditions of the upper digestive tract, and possible etiological role of human papilloma virus on our series of squamous esophageal papillomas. METHODS: Data from a total of 7618 upper gastrointestinal endoscopies consecutively performed in 4 years were obtained. A 4-year follow up was carried out. RESULTS: Squamous esophageal papilloma was found in nine patients (0.01%). The mean size of polyps was 4 mm and the mean distance from the dental ridge was 25 cm. Only one patient had more than one polyp. Two patients had liver cirrhosis and three had peptic ulcer disease. All squamous esophageal papillomas were removed and tested for human papilloma virus with commercial available kits for in situ hybridization, but none was found positive. CONCLUSION: Squamous papilloma of the esophagus is an uncommon disease that does not appear to predispose to esophageal cancer. No association was found with human papilloma virus.

[Flow cytometry in prostate cancer. Evaluation of its feasibility for biopsy specimens and correlation with grading]. / La citometria a flusso nel carcinoma della prostata. Valutazione della praticabilità su campioni bioptici e correlazione con il grading.

BACKGROUND: Pathologic staging and grading are the most important prognostic factors in prostatic cancer. Unfortunately, pathologic staging needs to be evaluated by surgical procedures; moreover, the proposed grading systems are largely based upon subjective histopathologic evaluations. In recent years, these problems have been approached with flow cytometry (FCM). The present study evaluates the significance of DNA ploidy of prostatic carcinoma assessed by FCM. MATERIALS AND METHODS: Microscopic slides from 132 core needle biopsies and 22 surgical specimens of prostatic carcinoma were reviewed and classified according to Gleason's score modified by Epstein et al. Formalin-fixed, paraffin-embedded tissue samples were prepared for FCM evaluation using standard techniques. Adequate histograms were obtained from 113 biopsies (85.6%) and from all the surgical specimens (100%). RESULTS: Among the 113 biopsy specimens, a statistically significant correlation was found between DNA ploidy and Epstein's grading, since high-grade neoplasms accounted for 40.38% of non-diploid cases and only for 21.33% of diploid cases (chi square = 5.8; p = 0.05). Moreover, tetraploid tumors were defined as a separate FCM category with an absolute prevalence (65.52%) of non-high grade neoplasms (chi square = 5.9; p = 0.05). Although not submitted to statistical analysis, data collected from surgical specimens showed similar distribution. CONCLUSIONS: DNA ploidy assessment by FCM is a viable procedure in the majority of needle biopsy tissue samples of prostatic carcinoma; it may produce prognostic parameters with greater objectivity than conventional histologic grading.

p53 mutations and DNA ploidy in colorectal adenocarcinomas.

The p53 tumour suppressor gene has an important role in the the maintenance of genome stability and its mutational inactivation may be at the origin of aneuploidy in cancer cells. The aim of this study was to determine whether p53 mutations were associated to DNA aneuploidy, as assessed by flow cytometry, in colorectal adenocarcinomas. Analysis of p53 mutations spectrum of the sorted nuclei was done by Denaturing Gradient Gel Electrophoresis (DGGE) and DNA sequencing. Overall, we studied 20 adenocarcinomas, the corresponding control mucosa, and 7 lymph node metastases. Five tumours (25%) were DNA diploid, while 15 tumours (75%) were composed of DNA aneuploid and diploid subpopulations. DNA diploid control mucosa and adenocarcinomas showed no p53 mutations, while 60% of the tumours with DNA aneuploidy had p53 mutations. Therefore, p53 mutations occurred significantly more often in DNA aneuploid than in DNA diploid tumours (p < 0.04, Fisher's exact test). Incidences of DNA aneuploidy and p53 mutations in lymph node metastases were 60 and 86%, respectively. In all tumours showing a p53 mutation, the wild-type allele was not or only bearly visible in DNA aneuploid cells suggesting that, in such cells, aneuploidy is accompanied by complete p53 functional inactivation. The present observations suggest that p53 mutations may have a role in the origin of aneuploidy at late stages of colorectal carcinogenesis.