Proteomic changes of alveolar lining fluid in illnesses associated with exposure to inhaled non-infectious microbial particles.

BACKGROUND: Hyperresponsiveness to inhaled non-infectious microbial particles (NIMPs) has been associated with illnesses in the airways. Hypersensitivity pneumonitis (HP) is considered to be the prototype for these NIMPs-related diseases; however, there is no consensus on the definitions or diagnostic criteria for HP and the spectrum of related illnesses. METHODS AND FINDINGS: In order to identify the possible diagnostic markers for illnesses associated with NIMPs in alveolar lining fluid, we performed a proteomic analysis using a two-dimensional difference gel electrophoresis on bronchoalveolar lavage (BAL) fluid from patients with exposure to NIMPs in the context of damp building-related illness (DBRI) or conditions on the borderline to acute HP, designated here as agricultural type of microbial exposure (AME). Samples from patients with HP and sarcoidosis (SARC) were included for reference. Results were compared to results of healthy subjects (CTR). Western blot was used for validation of potential marker proteins from BAL fluid and plasma. Protein expression patterns suggest a close similarity between AME and HP, while DBRI was similar to CTR. However, in DBRI the levels of the inflammation associated molecules galectin-3 and alpha-1-antitrypsin were increased. A novel finding emerging from this study was the increases of semenogelin levels in BAL fluid from patients with AME, HP and SARC. Histone 4 levels were increased in AME, HP and SARC. Elevated plasma levels of histone 2B were detected in HP and SARC, suggesting it to be a potential blood indicator for inflammatory diseases of the lungs. CONCLUSIONS: In this study, the proteomic changes in bronchoalveolar lavage of DBRI patients were distinct from other NIMP exposure associated lung diseases, while changes in AME overlapped those observed for HP patient samples. Some of the proteins identified in this study, semenogelin and histone 4, could function as diagnostic markers for differential diagnosis between DBRI and HP-like conditions.

Impact of Epoetin-beta on anemia and health-related quality of life in cancer patients: a prospective observational study using the generic 15D instrument.

AIM: Cancer-related anemia has a negative impact on the health-related quality of life (HRQoL). Our aim was to evaluate prospectively the effect of treatment of anemia with an erythropoietin on the hemoglobin level and HRQoL in cancer patients with anemia. PATIENTS AND METHODS: Consecutive patients (N=114) treated for the first time with epoetin (epoetin beta 30000 IU/wk, NeoRecormon®) for anemia during cancer treatment were eligible for study inclusion. Baseline characteristics were collected from patients' records. HRQoL was measured by the generic 15D instrument and fatigue by visual analogue scale (VAS) at baseline and four months from the start of the treatment with epoetin. The majority (87%) of patients had solid tumors; 69% with a metastatic disease and 89% disease with comorbidities. RESULTS: The mean hemoglobin concentration (SD) in blood increased from 96.6 (8.9) g/L to 112.9 (21.2) g/L, by 16.5 (20.6) g/L (p<0.0001). The mean 15D score rose from 0.72 to 0.77. The change was statistically significant (p=0.0047) and clinically important. The mean fatigue VAS score decreased by 16.0 points, or from 55.4 to 38.4 (+24.4) (p<0.0001). CONCLUSION: Correction of anemia increased the health-related quality of life in anemic cancer patients, as measured with the generic 15D instrument and the fatigue VAS.

[Fluid in the pleural space--from problem to therapy]. / Nestettä pleurassa--ongelmasta hoitoon.

Fluid may appear into the pleural space as a consequence of many diseases or mechanisms. If the patient's clinical picture does not explain the cause of pleural fluid accumulation, it is worthwhile to examine the fluid collected by pleural aspiration. The first question is: is the fluid transsudate or exudate? Secondly, if the fluid is exudate, does it result from malignant or benign disease? Pleural fluid samples are of limited diagnostic value, but provide good indication of the patient's disease. In some cases, however, it is necessary to adopt more invasive diagnostic measures.

Anaemia: a rare but neglected problem among Finnish patients receiving chemotherapy for solid tumours.

GOALS OF THE WORK: Anaemia is very frequently diagnosed among cancer patients. Use of erythropoietins has proved to be effective in reducing the need of transfusions and enhancing patients' quality of life, but may also have detrimental effects in treating nonanemic asymptomatic patients. We assessed the frequency of anaemia and the frequency with which it was diagnosed and treated in different types of solid tumours treated at outpatient chemotherapy policlinics. MATERIALS AND METHODS: During the study period, altogether 733 consecutive subjects received chemotherapy at the five Finnish University Hospitals. Their data were collected. The physician who was responsible for the chemotherapy treatment was unaware of the survey. The response to anaemia (treated or not, the modality of treatment) were established from patients records; 69% were females, mean age was 61 years (range, 24-92). RESULTS: The median haemoglobin level was 12.7 g/dL (range, 8.9-15.5 g/dL). About one third of the patients (200/733, 27%) had a value less than 12 g/dL. In only 15% of these cases was there any documentation of response or a possible treatment option for anaemia. On the other hand, only 12% of all patients (N=91) had a haemoglobin value less than 11 g/dL. However, in most of them anaemia had not been considered; in only 25% of cases was an active treatment option selected. CONCLUSIONS: According to our survey, anaemia was less common in our patients than in the European Cancer Anaemia Survey. Only a minority of chemotherapy patients receiving their treatments as outpatients would need active treatment for their anaemia.

[Bevacizumab in the treatment of non-small cell lung cancer]. / Bevasitsumabi ei-pienisoluisen keuhkosyövän hoidossa.

Treatment of advanced or metastatic non-small cell lung cancer with current cytotoxic agents is at its best able to only slow down the progression of the disease, while no curative treatment is known. Novel antiangiogenetic agents such as Bevacizumab have been expected to bring about a change in the treatment and prognosis of this disease. Two randomized studies have been conducted with Bevacizumab, whereby it was observed to make the therapeutic results more effective when combined with a cytotoxic platinum agent in a selected patient group. In our opinion the current scientific evidence does not yet support the use of Bevacizumab as the standard therapy for lung cancer.

Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study.

BACKGROUND: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study. METHODS: From January 2001, to December 2003, 173 evaluable patients with biopsy-verified malignant mesothelioma were included. Two patients were lost to follow-up, but all the others were followed for at least 4 years or until death. RESULTS: Toxicity was fairly low. There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some patients had their responses 4 to 6 months after last treatment. For 116 patients with epitheloid subtype, median survival was 17 months. A subgroup of these patients with good performance status, early stage, and age 70 years or less, showed a median survival of 22 months. CONCLUSION: The treatment yields good results with a high number of responses and long survival, and a low toxicity. The long survival of the epitheloid subgroup with good prognostic factors is as good as or even better than some studies on "radical" surgery or multimodal treatment, underlining the need of randomized studies to evaluate such treatment options.

Randomized phase II evaluation of aprinocarsen in combination with gemcitabine and cisplatin for patients with advanced/metastatic non-small cell lung cancer.

Aprinocarsen is a specific antisense oligonucleotide inhibitor of protein kinase C-alpha. This study aimed to evaluate the response rate to combination therapy with aprinocarsen, gemcitabine and cisplatin, in chemonaive patients with advanced/metastatic NSCLC. Secondary objectives included comparison of response rate, time to event efficacy parameters, and toxicities on the 2 treatment arms. Patients with stage IV, or stage IIIB disease (N3 and/or pleural/pericardial effusion), were randomized to either control or experimental arm. Patients on both arms received gemcitabine 1250 mg/m2 on days 1 and 8, and cisplatin 80 mg/m2 on day 1 of a 3-week cycle. Additionally, on the experimental arm, aprinocarsen was administered as 2 mg/kg continuous iv infusion on days 1-14, every 21 days. A total of 18 enrolled patients were randomized on the 2 arms. Further enrollment was terminated in March 2003 as a result of a phase III trial suggesting that aprinocarsen did not have an added survival benefit when combined with paclitaxel and carboplatin therapy in patients with NSCLC. Patients received a median of 4 cycles on control arm and 2.5 cycles on experimental arm. The response rate was 16.7% in the experimental arm and 44.4% in the control arm. Most frequent grade 3/4 toxicities were hematologic, with a higher incidence of thrombocytopenia in the experimental arm (87.5% vs. 33.3%). Despite the 14-day continuous infusion schedule, infection rate was not increased in the experimental arm. The present study did not show any advantage, in response rate or secondary endpoints, with aprinocarsen; however, the toxicity was not unduly increased, and aprinocarsen regimen was safely administered.

Tissue polypeptide antigen (TPA), hyaluronan and CA 125 as serum markers in malignant mesothelioma.

Mesothelioma is a rare disease with poor prognosis. Monitoring the effect of treatment is a problem and a serum marker might be of use for this purpose. We have studied three serum markers TPA, Hyaluronan and CA 125 in a limited material (11 patients) with the purpose of finding out if they might reflect treatment effect and/or indicate prognosis. The results in our material show that correspondence between initial TPA levels and survival seems to be better than corresponding data regarding Hyaluronan and CAI 25. Five patients show increasing serum levels of all three serum markers from first to last sample as the mesothelioma progressed according to consecutive CT scans. In three of these patients stable disease was followed by a decrease in the serum marker levels. Our results indicate that these three serum markers and mainly TPA might be useful as markers of disease progression and TPA for prediction of survival.