c-MYC and h-TERT co-expression in colon adenocarcinoma: a tissue microarray digitized image analysis.

PURPOSE: c-MYC oncogene is frequently deregulated by amplification in colon adenocarcinoma. c-MYC also activates telomerase by inducing expression of its catalytic subunit (h-TERT). Furthermore, telomerase activation plays a crucial role in tumorigenesis by sustaining cellular immortality. Our aim was to evaluate the significance of c-MYC and h-TERT co-expression in colon adenocarcinoma. METHODS: Sixty paraffin embedded primary colon adenocarcinomas were cored at 1.5 mm diameter and transferred to one microarray block. Immunohistochemistry was performed using anti-h-TERT, and c - MYC antibodies. A quantitative digitized macro was performed to evaluate their expression. RESULTS: c-MYC and h-TERT overexpression was observed in 27 (45%) and 28 (46.6%) cases, respectively. Co-over expression of those genes was observed in 17 (28.3%) cases and found to be statistically significant (p=0.001). The results also showed a strong association between c-MYC and grade of differentiation of the examined neoplasms (p=0.0217rpar;. CONCLUSION: Simultaneous c-MYC and h-TERT deregulation is a relatively frequent genetic event in colon adenocarcinoma. Because c-MYC overexpression is correlated with progressive disease - due to colon adenocarcinoma dedifferentiation - inhibition of its activity combined with h-TERT regulated expression is a new target for novel therapeutic regimens.

Randomized phase III trial of radiation treatment +/- amifostine in patients with advanced-stage lung cancer.

PURPOSE: This multicenter trial investigated whether daily pretreatment with amifostine (A) could reduce the incidence of acute and late lung toxicity and esophagitis without affecting antitumor efficacy of radiation in advanced lung cancer. PATIENTS AND METHODS: Radiotherapy (XRT) patients (n = 146) received a daily fraction of 2 Gy/5 days/week to a total of 55-60 Gy +/- amifostine 340 mg/m(2) administered daily 15 min before irradiation. Acute and late toxicities were graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer system. RESULTS: Ninety-seven patients were evaluated 2 months post-XRT for the incidence of pneumonitis; 43% (23/53) of patients in the XRT arm and 9% (4/44) in the A + XRT arm experienced > or = Grade 2 pneumonitis (p < 0.001) [corrected]. Forty-nine percent (26/53) of patients in the XRT arm and 16% (7/44) in the A+XRT arm demonstrated changes representative of > or = Grade 2 lung damage (p < 0.001). At 6 months, fibrosis was present in 53% (19/36) receiving XRT vs. 28% (9/32) receiving A+XRT (p < 0.05). Incidence of esophagitis > or = Grade 2 during Week 4 was 42% (31/73) in the XRT arm vs. 4% (3/73) in the A+XRT arm (p < 0.001). Among 97 patients evaluable for response 2 months after XRT, complete or partial response was present in 76% (40/53) of patients in the XRT arm and 75% (33/44) in the A+XRT arm (p = 1.0). CONCLUSION: Amifostine reduces the incidence of pneumonitis, lung fibrosis, and esophagitis in radiotherapy patients with lung cancer without compromising antitumor efficacy.

Sialolithiasis and salivary ductal stenosis: diagnostic accuracy of MR sialography with a three-dimensional extended-phase conjugate-symmetry rapid spin-echo sequence.

PURPOSE: To evaluate the accuracy of magnetic resonance (MR) sialography in detecting salivary glandular calculi and ductal stenoses. MATERIALS AND METHODS: In a prospective study, 64 salivary glands in 61 consecutive patients with acute or recurrent parotid or submandibular glandular swelling were examined by using three-dimensional (3D) extended-phase conjugate-symmetry rapid spin-echo (EXPRESS) MR imaging. Transverse and sagittal-oblique source images and maximum intensity projection images were obtained. All MR images were analyzed independently by two radiologists, without knowledge of the final diagnosis. The reference standard was conventional sialography, ultrasonography (US), and sialendoscopy with or without surgery in 31 glands and was conventional sialography and US in 33 glands. RESULTS: Final diagnoses included sialolithiasis (n = 23), sialolithiasis and stenosis (n = 9), stenosis without lithiasis (n = 11), early Sjögren syndrome without ductal stenosis (n = 2), ductal displacement (n = 3), and normal salivary glands (n = 16). The sensitivity, specificity, and positive and negative predictive values of MR sialography to detect calculi were 91%, 94%-97%, 93%-97%, and 91%, respectively. False-negative readings occurred due to calculi with a diameter of 2-3 mm in nondilated salivary ducts. Ductal stenosis was assessed, with a sensitivity of 100%, specificity of 93%-98%, positive predictive value of 87%-95%, and negative predictive value of 100%. Interobserver agreement was very good (kappa = 0.85-0.97). CONCLUSION: MR sialography with 3D EXPRESS imaging enables reliable prediction of salivary gland calculi and stenoses.

First report of Cryptococcus laurentii meningitis and a fatal case of Cryptococcus albidus cryptococcaemia in AIDS patients.

We report the first case of Cryptococcus laurentii meningitis and a rare case of Cryptococcus albidus cryptococcaemia in AIDS patients. Both infections were treated with amphotericin B and flucytosine. The C. laurentii meningitis was controlled after 2 weeks of treatment with no evidence of infection 20 months later. The patient with C. albidus cryptococcaemia, despite the amphotericin B/flucytosine combination therapy, died on the 14th day of treatment. The minimum inhibitory concentrations (MICs) for C. laurentii, as determined by Etest on RPMI 1640 agar, were 0.25 microg ml(-1) of amphotericin B, 1.25 microg ml(-1) flucytosine, 4 microg ml(-1) fluconazole, 0.50 microg ml(-1) itraconazole and 1.0 microg ml(-1) of ketoconazole. The MIC of amphotericin B for C. albidus was 0.5 microg ml(-1), flucytosine 1.25 microg ml(-1), fluzonazole 4 microg ml(-1), itraconazole 0.5 microg ml(-1) and ketonazole 0.25 microg ml(-1). The agreement of the amphotericin B MIC values obtained in antibiotic medium 3 by the broth microdilution method, with those obtained on casitone medium by Etest, was within a two-dilution range for both isolates. C. laurentii may cause meningitis and may also involve the lungs in AIDS patients.