A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis

BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(-) and HCO(3)(-), in mediating prostate HCO(3)(-) secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli)-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II), along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3)(-) content (>50 mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3)(-) on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3)(-) secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3)(-) secretion may be up-regulated in prostatitis as a host defense mechanism

Complete spontaneous remission of non-small-cell lung cancer: a case report

Spontaneous remission (SR) of cancer is a rare event, particularly in Lung cancer. We report the case of a 68-year-old man, who came to our attention with a diagnosis of poorly differentiated pulmonary adenocarcinoma and, in absence of any active therapy, underwent a durable complete SR. Our case supports the rare occurrence of SR in non-small-cell lung cancer (NSCLC). (C) 2004 Elsevier Ireland Ltd. All rights reserved

Management of malignant pleural effusions

Malignant pleural effusions (MPEs) represent a common complication of advanced malignancies. However, adequate palliation of this highly symptomatic accompaniment to cancer can be achieved in most patients by adopting the appropriate therapy. Several options are available for the treatment of MPE. Systemic therapy may control the effusion in patients whose underlying malignancy is sensitive to anticancer agents. Repeated thoracocentesis can be appropriate for patients with limited life expectancy or slowly recurrent effusions. In the majority of the remaining cases the treatment of choice is pleurodesis with sclerosing agents administered via tube thoracostomy. Controversy still exists as to which drug produces the best results: talc and bleomycin appear to be among the most cost-effective agents. The debate over the best agent to be used for pleurodesis refers to the difficulty in comparing results of studies using different eligibility criteria, response assessment and end-points. This article describes the various treatments which have been reported in the literature to play a role in the management of MPEs. It is also aimed at providing guidelines in allocating patients to appropriate treatments

Inadequacy of the new Response Evaluation Criteria in Solid Tumors (RECIST) in patients with malignant pleural mesothelioma: report of four cases

Unidimensional. Response Evaluation Criteria in Solid Tumor (RECIST) has been recently proposed in the attempt to simplify the standardized bidimensional World Health Organization (WHO) criteria. The complete accord between these two measurement systems was established in a large comparative study [J. NatL Cancer Inst. 92(3) (2000) 205] that demonstrated the validity and the good performance of RECIST criteria. We report four cases of inadequacy of RECIST criteria in the evaluation of response to chemotherapy in patients with malignant pleural mesothelioma. These four patients were enrolled in two consecutive multicenter phase II clinical trials investigating the activity of a novel chemotherapy regimen in advanced pleural mesothelioma. They were judged as having an objective response to chemotherapy according to WHO criteria. Reassessed according to both methods, we found that results obtained with RECIST criteria do not correspond to WHO underestimating response to chemotherapy. Our data raise doubts about the applicability of unidimensional RECIST response criteria to mesothelioma and, possibly, to any tumor involving the chest wall. (C) 2003 Published by Elsevier Ireland Ltd

Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer

BACKGROUND. The authors assessed the predictive and prognostic role of decline in the serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) during chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. Changes in serum levels of CEA and CYFRA 21-1 during first-line, conventional chemotherapy were studied prospectively with an immunometric assay at baseline and every 2 courses in 117 patients with advanced NSCLC. Data were correlated with radiologic objective response (OR) and survival. RESULTS. One hundred seven patients were evaluable for radiologic and serologic response assessment after 2 chemotherapy courses. The radiologic OR rate was 44% overall. The CEA and CYFRA 21-1 responses (≥20% reduction over baseline level; assessed after the second course of chemotherapy) were 38% and 61%, respectively. Statistically significant correlations were observed between CEA and CYFRA 21-1 responses and OR (P = .01 and P = .004, respectively). The median survival from response assessment (landmark analysis) was 9 months. In a univariate analysis, disease stage, performance status, baseline lactate dehydrogenase level (LDH), OR, CEA response, and CYFRA 21-1 response were correlated significantly with survival. In particular, the median survival was 13 months for patients who had a CEA response and 11 months for patients who had a CYFRA 21-1 response compared with 8 months and 6 months for patients who did not respond, respectively, In a multivariate analysis, performance status (P = .005), baseline LDH level (P = .02), CEA response (P = .03) and CYFRA 21-1 response (P = .01) were confirmed as independent prognostic factors for survival. CONCLUSIONS. CEA and CYFRA 21-1 responses appeared to be reliable surrogate markers of chemotherapy efficacy in patients with advanced NSCLC. © 2006 American Cancer Society

Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer

BACKGROUND. The authors assessed the predictive and prognostic role of decline in the serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) during chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. Changes in serum levels of CEA and CYFRA 21-1 during first-line, conventional chemotherapy were studied prospectively with an immunometric assay at baseline and every 2 courses in 117 patients with advanced NSCLC. Data were correlated with radiologic objective response (OR) and survival. RESULTS. One hundred seven patients were evaluable for radiologic and serologic response assessment after 2 chemotherapy courses. The radiologic OR rate was 44% overall. The CEA and CYFRA 21-1 responses (>= 20% reduction over baseline level; assessed after the second course of chemotherapy) were 38% and 61%, respectively. Statistically significant correlations were observed between CEA and CYFRA 21-1 responses and OR (P = .01 and P = .004, respectively). The median survival from response assessment (landmark analysis) was 9 months. In a univariate analysis, disease stage, performance status, baseline lactate dehydrogenase level (LDH), OR, CEA response, and CYFRA 21-1 response were correlated significantly with survival. In particular, the median survival was 13 months for patients who had a CEA response and 11 months for patients who had a CYFRA 21-1 response compared with 8 months and 6 months for patients who did not respond, respectively. In a multivariate analysis, performance status (P = .005), baseline LDH level (P = .02), CEA response (P = .03) and CYFRA 21-1 response (P = .01) were confirmed as independent prognostic factors for survival. CONCLUSIONS. CEA and CYFRA 21-1 responses appeared to be reliable surrogate markers of chemotherapy efficacy in patients with advanced NSCLC

Predictive and prognostic significance of neuron-specific enolase (NSE) in non-small cell lung cancer

Background: The Predictive and prognostic role of neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC) is still under debate. Patients and Methods: To study these aspects, serum NSE was prospectively measured at baseline of first-line chemotherapy treatment and tested for correlation with clinical outcome in 129 advanced NSCLC patients. Results: An objective response was achieved in 2 7 out of 65 (41.5%) patients with NSE = 8.6 ng/ml (p = 0.05). Logistic analysis confirmed the positive association between objective response and NSE values >= 8.6 ng/ml (odds ratio=1.69; 95% confidence interval: 1.09-2.63; p=0.02). Overall median survival was 10.8 months. A statistically significant prognostic effect on survival was found for performance status, stage and response to treatment, but not for baseline NSE value. Conclusion: Based on these data, baseline circulating tumor NSE levels appear to have a weak predictive role, but not a prognostic significance in patients with advanced NSCLC submitted to standard chemotherapy

Predictive and prognostic significance of neuron-specific enolase (NSE) in non-small cell lung cancer.

Background: The predictive and prognostic role of neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC) is still under debate. Patients and Methods: To study these aspects, serum NSE was prospectively measured at baseline of first-line chemotherapy treatment and tested for correlation with clinical outcome in 129 advanced NSCLC patients. Results: An objective response was achieved in 27 out of 65 (41.5%) patients with NSE <8.6 ng/ml and in 38 out of 64 (59.4%) patients with NSE ≥8.6 ng/ml (p=0.05). Logistic analysis confirmed the positive association between objective response and NSE values ≥8.6 ng/ml (odds ratio=1.69; 95% confidence interval: 1.09-2.63; p=0.02). Overall median survival was 10.8 months. A statistically significant prognostic effect on survival was found for performance status, stage and response to treatment, but not for baseline NSE value. Conclusion: Based on these data, baseline circulating tumor NSE levels appear to have a weak predictive role, but not a prognostic significance in patients with advanced NSCLC submitted to standard chemotherapy

Induction chemotherapy with carboplatin-paclitaxel followed by standard radiotherapy with concurrent daily low-dose cisplatin plus weekly paclitaxel for inoperable non-small-cell lung cancer

Both induction chemotherapy and concurrent platinating agents have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase 11 study investigated activity and feasibility of a novel chemoradiation regimen, including platinum and paclitaxel, both as induction chemotherapy and concurrently with thoracic radiotherapy. Previously untreated patients with histologically/cytologically proven unresectable stage I-III NSCLC were eligible. Induction chemotherapy consisted of 2 courses of 200 mg/m(2) paclitaxel and carboplatin at AUC of 6 mg/mL/min every 3 weeks. From day 43, continuous thoracic irradiation (60 Gy in 30 fractions radiotherapy for 6 weeks) was given concurrently with daily cisplatin at a dose of 5 mg/m(2) intravenously and weekly paclitaxel at a dose of 45 mg/m(2) for 6 weeks. Fifteen patients were accrued in the first stage of the trial. According to the previous statistical considerations, accrual at the second stage of the study was halted as a result of the achievement an insufficient number of successes. Major toxicity of combined chemoradiation was grade III-IV esophagitis requiring hospitalization for artificial nutrition, which occurred in 58% of patients. Other toxicities included grade II-IV fatigue in 75% of patients and grade I-IV neuromuscular toxicity in 67%. Only 7 patients completed the treatment program as scheduled. Eight patients (53.3%; 95% confidence interval, 26.5-78.7%) had a major response (5 partial response, 3 complete response), 2 patients had disease progression, and I was stable at the end of treatment. Four patients died early. With a median follow up of 38 months, the median survival was 12 months. A combined chemoradiation program, including platinum and paclitaxel, appears difficult to deliver at full dose as a result of toxicity, mainly esophagitis. More active and less toxic combined modality treatments need to be developed for inoperable NSCLC