Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Synergistic antiproliferative activity of quercetin and cisplatin on ovarian cancer cell growth

It has been demonstrated that the flavonoid quercetin (3,3',4',5-7-pentahydroxyflavone) (Q) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is mediated by a so-called type II estrogen binding site (type II EBS). We investigated the effects of quercetin and cisplatin (CDDP) alone and in combination on the proliferation of the ovarian cancer cell line OVCA 433. Both drugs exhibited a dose-related growth inhibition in a range of concentrations between 0.01 and 2.5 microM and 0.01 and 2.5 micrograms/ml for Q and CDDP respectively. The combination of the two drugs resulted in a synergistic antiproliferative activity. Two other flavonoids tested, i.e., rutin (3-rhamnosylglucoside of quercetin) and hesperidin [7-b rutinoside of hesperetin (3'-5-3-hydroxy-4-methoxyflavone)] were ineffective both alone and in combination with CDDP. Since both rutin and hesperidin do not bind to type II EBS it can be hypothesized that Q synergizes with CDDP by acting through an interaction with these binding sites.     

Food cravings in relation to body mass index, restraint and estradiol levels: a repeated measures study in healthy women.

The study considered the nature and extent of cravings in 108 healthy women between the ages of 20 and 37 who were tested at four time points over a 2-year period. There was substantial consistency over the four widely separated time points (3 months-1 year) in the types of foods craved, with chocolate and ice cream highest on the list, followed by fatty and spicy foods, and sweets. Women with a higher body mass index reported more consistent cravings for salty foods, especially those with high flavor intensity. There were no significant relationships between dietary restraint and the number, frequency or types of cravings. There were also no strong relationships between estradiol levels and the number, frequency or types of cravings women reported in the whole sample. The data suggest that women have a stable core of foods for which they experience cravings, relatively independent of estradiol levels, BMI or degree of dietary restraint.     

The significance of associated pre-invasive lesions in patients resected for primary lung neoplasms.

OBJECTIVE: To evaluate the prevalence and clinico/prognostic significance of the presence of pre-invasive lesions in patients resected for primary lung neoplasm. METHODS: From 1993 to 2002, 1090 patients received resection for primary lung carcinomas. Of these, 73 presented an associated pre-invasive lesion in the surgical specimen distant from the primary tumour. Classification of pre-invasive lesions included Atypical Adenomatous Hyperplasia (AAH); Carcinoma In Situ (CIS) either diffuse or at the bronchial resection margin; Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). Correlation between the presence of pre-invasive lesion and the following variables were calculated by logistic regression analysis: sex, age, median tumour size, histology, histologic differentiation, histologic evidence of invasiveness (vascular and perineural invasion), peritumoural lymphocytic infiltrate, pTNM, lobe location, history of previous malignancy. Survival rates were computed using Kaplan-Meier method and survival differences with the total patient population of resected lung carcinomas were tested using the log-rank method. RESULTS: There were 28 AAH, 42 CIS (5 at the bronchial resection margin) and 3 DIPNECH. Histology of the primary tumor included bronchioloalveolar carcinoma (9 patients), adenocarcinoma (19), squamous cell carcinoma (39), typical carcinoid tumour (3) and adenosquamous carcinoma (3). Overall prevalence of pre-invasive lesion was 6.7%. A strong correlation was found between the presence of AAH and the co-existence of either adenocarcinoma, bronchioloalveolar carcinoma or mixed adenocarcinoma-containing tumours (P = 0.00002) between CIS and squamous cell carcinoma (P = 0.009) and between DIPNECH and carcinoid tumours (P = 0.001). No significant correlation was found between the presence of any type of pre-invasive lesion and sex, age, median tumour size, histologic differentiation, histologic evidence of invasiveness, pTNM, lobe location and history of previous malignancy or the probability to develop a second primary lung carcinoma in the remaining lobe(s) after resection. Survival rates in the patients with AAH and CIS were not significantly different from those of patients without pre-invasive lesion (P = 0.3 and P = 0.1). CONCLUSIONS: Associated pre-invasive lesions in patients resected for primary lung neoplasms are not infrequent. AAH is associated with adenocarcinoma, CIS with squamous cell carcinoma, DIPNECH with typical carcinoid tumours. Our experience indicates that in these patients histology, stage distribution and survival do not differ from the total population of resected patients with lung tumors.     

Cathepsin D in primary squamous laryngeal tumors: correlation with clinico-pathological parameters and receptor status.

Using an immunoradiometric assay, Cathepsin D (Cath D) levels were measured in the cytosol of 23 normal and 39 neoplastic human laryngeal tissues. Scattered Cath D levels (from 2.2 to 17.8 pM/mg protein; median = 7.6) were found in normal mucosa specimens. Cath D concentrations range from 2.0 to 29.3 pM/mg protein (median = 8.5) in laryngeal tumors. When a comparison between Cath D levels in normal and neoplastic tissue specimens from the same patient was done, Cath D levels were significantly higher in laryngeal cancers than in their normal counterparts (P = 0.03). No correlation with clinico-pathological parameters and steroid hormone and epidermal growth factor receptor status was found. Further studies should investigate whether the production of Cath D by laryngeal tumors could have a clinical relevance for this neoplasia.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.