MicroRNAs (miRNAs) have been identified as promising prognostic markers in non-small-cell lung cancer (NSCLC) since they play an important role in oncogenesis. The miR-34 family is composed of three miRNAs (miR-34a, miR-34b and miR-34c) that are part of the p53 network and whose expression is directly induced by p53 in response to DNA damage or oncogenic stress. We have analyzed the impact of miR-34 expression on relapse and overall survival in surgically resected NSCLC patients. For this purpose, we used stem-loop reverse transcription-polymerase chain reaction to analyze the expression of the miR-34 family in paired tumor and normal tissue from 70 surgically resected NSCLC patients who received no postsurgical treatment until relapse. In addition, in patients with sufficient tumor tissue, we assessed p53 mutations and the methylation status of the MIRN34A gene promoter region and correlated these findings with miR-34a expression. Molecular findings were correlated with relapse and overall survival. The miR-34 family was downregulated in tumor compared with normal tissue, and low levels of miR-34a expression were correlated with a high probability of relapse (P = 0.04). A relation was also found between MIRN34A methylation and miR-34a expression (P = 0.008). Patients with both p53 mutations and low miR-34a levels had the highest probability of relapse (P = 0.001). In the multivariate analysis, miR-34a expression emerged as an independent prognostic marker for relapse. In summary, we have identified miR-34a as a novel prognostic marker in NSCLC patients, providing a potential mechanism for estimating a patient's risk of disease recurrence and a useful tool to help guide treatment decisions.

Background/Aims: MicroRNAs (miRNAs) play a role during mouse embryonic development and are also important in carcinogenesis. In order to investigate whether there are similar patterns of miRNA expression levels in pseudoglandular human embryonic lung and in human lung tumors, we have analyzed 18 miRNAs (the let-7 family, the miR-17–92 cluster, miR-221 and miR-222) in human embryonic lung samples and in paired lung tumor and normal lung tissue samples and correlated the results with clinicopathological characteristics. Methods: RNA was obtained from 12 human embryonic lung samples, 33 lung tumor samples and 33 paired normal lung samples. miRNAs were assessed by quantitative real-time PCR. Results: Members of the let-7 family were downregulated and members of the miR-17–92 cluster and miR-221 were overexpressed both in embryonic lung tissue and in lung tumors. Low levels of let-7c were associated with absence of metastases (p = 0.015), early-stage non-small cell lung cancer (NSCLC, p = 0.05), and smokers (p = 0.009). High levels of miR-106a were associated with small-cell lung cancer (p = 0.031), and high levels of miR-19a with advanced NSCLC (p = 0.008). Conclusion: Our study lends support to the model of cancer as an alteration of normal development, as many miRNAs were similarly expressed in early human lung development and stage I-II of lung cancer development.

To define better the syndrome of diffuse alveolar hemorrhage (DAH), we conducted a postmortem study in 77 patients who died of pulmonary complications, distributed into three groups. Group A included 47 patients with hematologic diseases treated with allogeneic bone marrow transplant (BMT); Group B, 20 patients with hematologic diseases treated with conventional chemotherapy; and Group C, 10 patients without hematologic diseases. The diagnosis of DAH was established when there was blood in at least 30% of the lung tissue evaluated without evidence of infection or any other pathologic change that could account for its presence. The presence of an associated pulmonary complication was considered only when there was normal lung parenchyma between both blood and the specific lesions. Diffuse alveolar hemorrhage was shown in 11 patients in Group A (23%) compared with 1 patient in Group B (5%) (p < 0.05). Of the 11 patients with DAH in Group A, 10 had some associated pulmonary complication: 7 presented with diffuse alveolar damage (DAD), 2 with associated bacterial pneumonia and 1 with invasive aspergillosis, 2 others had an associated cytomegalovirus (CMV) pneumonitis, and the remaining patients had an associated herpes pneumonia. There were no clinical differences between patients with and without DAH. Of 8 patients with confirmed DAH in Group A, who had been submitted to a bronchoscopic examination within 1 wk of death, 4 had normal BAL fluid; by contrast, 7 of 13 patients without DAH had hemorrhagic BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Irritable bowel syndrome is the most frequently diagnosed disorder in gastroenterology. It has been demonstrated with specialized motility studies that these patients compared to healthy subjects show changes in rectoanal electrical and mechanical activity and in rectoanal sensitivity. However, until now no report has been published on morphological alterations in the rectum or the internal anal sphincter. Twenty-five consecutive patients with irritable bowel syndrome (mean age 32, range 17-47 years; 24 females) were evaluated prospectively by transrectal ultrasonography, rectal sensitivity studies, and recordings of both electrical and mechanical activity of the distal rectum and internal anal sphincter during a 2-h inter-digestive period. Ten healthy volunteers (mean age 34.5, range 19-50 years) served as a control group. Paired and non-paired Student's two-tailed t test and linear regression analysis were used. It was shown that muscle thickness of the rectum during rest (4.7 +/- 0.1 mm) was correlated neither with its rectal spike amplitude (0.73 +/- 0.1 mV) nor with rectal spike frequency (17.06 +/- 3.6 spike/2 h). In addition, the diameter of the internal anal sphincter (1.2 +/- 0.1 mm) was correlated neither with its resting pressure, nor with frequency (17.1 +/- 3.2/2 h), duration (14.9 +/- 1.5 s), or amplitude (14.1 +/- 1.9 mmHg), of inhibition of the spontaneous rectoanal inhibitory reflex. No correlation was found between ultrasonographic parameters and rectal distension variables (r = 0.03). This study demonstrates for the first time morphological anorectal changes in patients with irritable bowel syndrome compared to healthy subjects, in addition to showing that morphological changes are independent of physiological ones. Therefore both transrectal ultrasonography to determine anorectal morphology and electromanometry to assess anorectal function are important measures in the evaluation of patients with irritable bowel syndrome.