The prognostic value of hTERT expression levels in advanced-stage colorectal cancer patients: a comparison between tissue and serum expression

AIM: Telomeres are regions of highly repetitive, non-coding DNA located at the termini of chromosomes whose principal function is to maintain the structural stability of these ends. In 90% of human tumours, telomere length is maintained by the expression and activation of telomerase reverse transcriptase. Various studies have demonstrated an increase in telomerase activity in tumour tissue, which suggests its possible prognostic value. The main objective of our study was to study the prognostic value of the expression level of telomerase catalytic component (hTERT) in patients with colorectal cancer (CRC). METHODS: We analysed the prognostic value of the ratio of telomerase expression in tumour tissue to telomerase expression in the adjacent healthy mucosa and the prognostic value of the expression level of hTERT in the serum of patients diagnosed with CRC. As secondary objectives of the study, we (1) analysed the correlation between telomerase expression in the serum and that in the tumour tissue and (2) analysed the relationship between telomerase expression and different clinical parameters. RESULTS: Peripheral blood and tissue samples taken from 48 patients with CRC were analysed. No significant differences were observed in disease-free survival (DFS) or overall survival time (OST) between the groups of patients categorised based on the ratio of telomerase expression between tumour tissue and healthy tissue. The correlation index (Pearson's coefficient) between telomerase levels in the serum and those in tissue was 0.32. Our study of the relationship between telomerase levels in the serum and different clinical variables, such as tumour size, ganglion affectation, preoperative carcinoembryonic antigen levels and stage, revealed a higher telomerase expression level in patients with stage IV CRC. There was no significant association between telomerase expression in tumour tissue and the clinical parameters analysed. CONCLUSIONS: The results obtained in our study do not allow us to propose that the level of telomerase expression be used as a prognostic factor in colorectal cancer. Thus, we cannot consider telomerase expression in the serum as a surrogate marker of its expression in tumour tissue (AU)

Phase II clinical trial with gemcitabine and paclitaxel sequential monotherapy as first-line treatment for advanced non-small-cell lung cancer (SLCG 01-04)

BACKGROUND: In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC. MATERIALS AND METHODS: Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m(2) of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m(2) of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m(2) of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate. RESULTS: The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival. CONCLUSIONS: Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival (AU)

Intrabronchial instillation of amphotericin B lipid complex: a case report.

OBJECTIVE: We sought to present our results of topical intrabronchial installation of amphotericin B lipid complex (AmpB lipid). PATIENT AND METHODS: A deposit of fungal material was observed in a bilateral lung transplant recipient who experienced stenosis of the left anastomosis and have been fitted with a double endobronchial prosthesis. The deposit was adherent to the prosthetic material, causing marked local laceration, risk of perforation, and exacerbation of the bronchial stenosis. Upon cultivation of a bronchial aspirate (BAS), we isolated Aspergillus fumigatus, Scedosporium prolificans, and Candida glabrata. Systemic antifungal treatment was begun with oral voriconazole (200 mg every 12 hours) and inhaled AmpB lipid (25 mg once daily). The fungal deposit on the prosthetic material was treated by topical instillation of a solution of 25 mg AmpB lipid before and after each therapeutic fibrobronchoscopy (FB), which was performed weekly at 5 consecutive examinations. Tolerance was excellent. RESULTS: The improvement obtained after the procedure made it possible to withdraw one of the displaced prostheses. Subsequent cultivation for the fungi found in the BAS was persistently negative over a follow-up of 2 years. CONCLUSION: Topical intrabronchial instillation of AmpB lipid has proven effective and well tolerated for the treatment of localized fungal colonies. This use could be extended by protocol to FB in the early postoperative period after lung transplantation for antifungal prophylaxis.

A comparision of several formats of amphotericin B as an inhaled antifungal prophylaxis.

OBJECTIVE: We sought compare the economic cost, ease of preparation and administration, and tolerance of the available alternatives of amphotericin B (AmpB) as an inhaled antifungal prophylaxis for lung transplant patients. MATERIALS AND METHODS: Doses administered and cost of the 3 formats: desoxycholate (desoxy; 50-mg vial); lipid complex (lipid; 100 mg/20 mL vial) and liposomal (lipos; 50-mg vial). The regimen for antifungal prophylaxis is as follows: AmpB desoxy (reconstituted and dilute): 5 mg/every 8 hours for 4 months and 5 mg/d in the following months; AmpB lipid (nonreconstituted): 25 mg/d for 7 days, 25 mg over 48 hours for days and 25 mg/wk; AmpB lipos (reconstituted): 24 mg 3 times weekly for 2 months, 24 mg/wk for 6 months and 24 mg every 2 weeks. We polled 8 nurses who prepare these drugs habitually. We also asked a random sample of treated patients regarding tolerance. RESULTS: Number of doses, vials per year per patient, and final cost for each type were: Desoxy, 609 doses, 72 vials, 607.90 euros; lipid, 63 doses, 15 vials, 1428 euros.15; and lipos, 57 doses, 57 vials, 7720.10 euros. Amp B lipid is considered to be the easiest to use, because it does not have to be reconstituted. The following cases of intolerance were recorded: AmpB desoxy 5 (45); AmpB lipid 1 (67); AmpB lipos 0 (4). CONCLUSIONS: AmpB desoxy is the most economical, but it requires greater care in handling, the highest number of doses, and has the worst tolerance. AmpB lipid has an intermediate price and is the easiest to prepare. AmpB lipos is the most expensive and it requires careful handling.

[Living with chronic renal insufficiency]. / Vivir con insuficiencia renal crónica.

In Spain today there are some 27,000 patients suffering from chronical renal insufficiency to such an extent that they require treatment which artificially performs their kidney functions or have had a kidney transplant. The basic artificial renal function therapies are hemodialysis and peritoneal dialysis. Both therapies, which are usually well-tolerated although not exempt from complications, allow patients to have an acceptable rehabilitation and quality of lifestyle. Theoretically, a kidney transplant is the ideal solution; however, the lack of donor organs, organ rejection and patients; particular circumstances place limits on this therapeutic option. Nevertheless, whatever therapy is chosen, patients must make adaptions in their life style to include following a diet, administering prescribed drugs, applying specific hygienic practices, and the like. All of these require the patient to have an appropriate educational support structure.