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PubMed1989

Double-lung transplant for advanced chronic obstructive lung disease.

We have achieved repeated success with unilateral lung transplantation for pulmonary fibrosis and have developed an en bloc, double-lung transplant procedure for patients with advanced lung disease of an obstructive or infective nature. Six such procedures have now been performed for end-stage emphysema, and all recipients are alive and well 5 to 15 months later. A seventh transplant for primary pulmonary hypertension was unsuccessful. All recipients were judged to have a life expectancy of 12 to 18 months on the basis of the degree of disability and the documented rate of disease progression. We feel the double-lung procedure is more appropriate than the combined heart-lung transplant for patients requiring replacement of both lungs when right heart function is adequate or deemed recoverable. With this procedure, the recipient is able to retain his or her own heart, avoiding the liabilities associated with cardiac transplantation. Furthermore, the donor heart is available for a separate recipient, and this sharing of the heart and lungs greatly increases the supply of transplantable lungs for patients with end-stage lung disease. Ischemia of the donor airway has been a source of complication, including the one death to date, but this appears to be a surmountable problem.

Adult↗
PubMed2005

[Primary lung cancer incidentally diagnosed in lung biopsy for diffuse pulmonary disease].

UNLABELLED: We here presented 2 cases of interstitial pneumonia with lung adenocarcinoma incidentally diagnosed by partially resected lung for diffuse pulmonary disease. CASE 1: A 78-year-old female was admitted to the hospital complaining of productive cough and general fatigue. The chest computed tomography (CT) revealed diffuse honey comb pattern in bilateral lung field especially in the right lower lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as diffuse spreading well differentiated adenocarcinoma. CASE 2: A 59-year-old male was admitted to the hospital complaining of dyspnea and general fatigue. The chest X-ray revealed right pneumothorax and chest CT revealed diffuse honey comb pattern and bullae in bilateral lung field and fibrous tumor-like lesion in the right middle lung. Video-assisted thoracoscopic lung biopsy was performed and was diagnosed as pulmonary fibrosis with papillary adenocarcinoma. CONCLUSION: It is important to examine carefully the specimen obtained from thoracoscopic lung biopsy even if interstitial pneumonia is strongly suspected.

Adenocarcinoma↗
PubMed1989

Lung function after prolonged lung preservation.

Our previous study revealed significant improvement in lung preservation with a new solution, the UCLA formula, which contains verapamil and is based on a glucose-insulin-potassium solution. In this study, we extended the preservation time up to 12 hours and, using various parameters, compared lung function after 12 hours' preservation with that after 6 hours' preservation. The left lung of 15 dogs was perfused with 300 ml of the UCLA formula (4 degrees C) and preserved for 6 hours in eight dogs (group A) and for 12 hours in the other seven dogs (group B). The preserved left lung was then autotransplanted and pulmonary function was evaluated during the following 2 weeks. The oxygen tension was monitored at 2 and 12 hours postoperatively, then daily for 1 week, and on the fourteenth postoperative day. The right pulmonary artery was temporarily occluded to assess the function of the preserved left lung alone. Oxygen tension in group A was maintained within the normal range. By contrast, in group B transient deterioration in oxygen tension was observed from the third to the fourth postoperative day (p less than 0.01), improving toward the normal range by the seventh day. Pulmonary vascular resistance was significantly elevated after transplantation in group B, improving to the normal range by the fourteenth postoperative day. Lung compliance, according to the airway pressure-tidal volume curve, also deteriorated significantly in group B (p less than 0.01), improving to the normal range within 2 weeks. Lung perfusion scintigraphy with technetium-labeled macroaggregated albumin was performed on the fourth day after the operation. The ratio of left to right pulmonary flow on the fourth postoperative day was 57.1 +/- 8.5% in group A and 52.2% +/- 12.3% in group B (no significant difference). In conclusion, temporary deterioration of lung function was observed after 12 hours of lung preservation, manifested by impaired oxygen exchange and loss of compliance.

Animals↗
PubMed1987

Involvement of chromosome 7 in primary lung tumor and nonmalignant normal lung tissue.

By using the newly developed adhesive tumor cell culture system, we analyzed the chromosomal constitutions of primary lung tumor and nonmalignant normal lung tissue from 10 previously untreated patients with non-small cell lung cancer. Chromosomal analyses were successfully carried out in banded chromosome preparations from 10 tumor and 8 normal lung tissue samples. All analyzed tumor and normal lung tissue samples had a predominantly normal diploid chromosome number. However, there was at least one structural or numerical alteration in every tumor and lung tissue sample analyzed. Chromosomes 1, 3, 4, 6, 7, 8, 9, 12, 15, and 20 were more often involved in rearrangement. The most consistent finding was trisomy 7; 4 patients had trisomy 7 in both tumor and normal lung tissue, and another 2 had this anomaly in tumor tissue only. Of the 4 patients without trisomy 7, 2 had a homogeneously staining region in the short arm of chromosome 7 in tumor tissue. Phytohemagglutinin-stimulated peripheral blood lymphocytes from 7 patients, including 5 patients with trisomy 7 in tumor tissue, did not show trisomy 7. These cytogenetic data suggest that chromosome 7 may be associated with lung cancer development and that trisomy 7 may be the hallmark of premalignant changes, at least in a subgroup of patients with non-small cell lung cancer.

Aged↗
PubMedDate not supplied

Does the mode of donor death influence the early outcome of lung transplantation? A review of lung transplantation from donors involved in major trauma.

BACKGROUND: Pulmonary dysfunction, often delayed in presentation, is among the sequelae of major trauma. Transplantation of lungs from donors involved in major trauma therefore carries a risk of early graft dysfunction. This study was conducted to assess this risk. METHODS: A retrospective comparison of the outcome from 123 donors (57 donors resulting from major trauma, group T, and 66 donors with nontraumatic origin, group NT) in 125 consecutive technically successful lung or heart-lung transplantations. Variables analyzed included the following: clinical and bacteriologic details of donors and indexes of early graft dysfunction in the recipients. RESULTS: Group T donors were more likely to be younger and male (p < 0.05) and more likely to have had lung ventilation for over 48 hours (p < 0.05) than group NT donors. Microbial contamination of routine donor bronchial lavage (72 of 122, 61%) was no higher in group T (34 of 57, 60%), but, in this group, enteric gram-negative bacilli were more common (30% versus 7%; p < 0.05). Male patients were more likely to receive lungs from group T donors (35 male, 23 female), and female patients were more likely to receive lungs from group NT donors (27 male, 40 female). Mode of donor death did not affect the following indexes of early graft function: length of postoperative ventilation, ratio of arterial oxygen tension to fractional concentration of inspired oxygen at 1 or 24 hours after transplantation, or the incidence of diffuse alveolar damage in lung biopsy specimens at 7 days. Thirty-day mortality (28%) was no higher among recipients of group T lungs, but six recipient deaths were donor-related (donor-transmitted pneumonia in five and donor acquired fat embolism in one case). CONCLUSION: The use of donors involved in major trauma does not increase the risk of early complications after lung transplantation providing their specific characteristics are recognized.

Adult↗
PubMed1993

The donor lung: infectious and pathologic factors affecting outcome in lung transplantation.

The prevalence of posttransplantation pulmonary infection and the importance of this complication with respect to morbidity in patients undergoing lung transplantation is significant. Over a 1-year period, case histories of all patients undergoing lung transplantation at Barnes Hospital, Washington University, were reviewed to examine the importance of organisms isolated in the donor lung in the development of subsequent invasive infection in transplant recipients. Twenty-eight of 29 bronchial washings (97%) taken from donors before retrieval grew at least one organism. The most common organisms identified were Staphylococcus and Enterobacter. In 12 of these cases (43%), similar organisms were isolated from the tracheobronchial tree of the recipients, and 6 of these recipients (21%) subsequently had invasive pulmonary infections as a result of the organism originally isolated in the donor. We recommend that antibiotic coverage in transplant recipients should be initiated on the basis of Gram stain results and modified on the basis of cultures obtained from the donor lungs. Pathologic analysis of donor lung tissue taken before transplantation was available in 12 cases. Four donors had histologic evidence of established pneumonia in the donor lung, and infections then developed in the recipients. One other patient who received a lung that had widespread bone marrow emboli and subsequent infarction later had a complete anastomotic dehiscence. An additional patient had profound early donor lung dysfunction without any evidence of rejection or infection. Pathologic findings from the donor in this case demonstrated preexistent acute vasculitis with emboli. We suggest that as preservation techniques improve, the opportunities for closer scrutiny of donor lung tissue before implantation will become increasing desirable and feasible.

Hospitals, University↗
PubMed1993

Sevoflurane anaesthesia for one-lung ventilation with PEEP to the dependent lung in sheep: effects on right ventricular function and oxygenation.

This study was undertaken to examine the effect of sevoflurane on right ventricular function, the safety of sevoflurane for one-lung ventilation and the effects of PEEP (positive end-expiratory pressure) to the dependent lung in this model using 12 open-chest sheep. Haemodynamic variables, including cardiac output, mean arterial blood pressure, right ventricular pressure and pulmonary arterial pressure, and right ventricular segment shortening (sonomicrometry) were measured. First, animals received 2.0, 3.0 or 4.0% sevoflurane for 20 min each, respectively, during two-lung ventilation to measure the dose-dependent haemodynamic effects of sevoflurane. Then one-lung ventilation was performed with a randomized sequence of 0 (ZEEP), 5 and 10 cm H2O PEEP to the dependent lung under 2.0% sevoflurane anaesthesia after one-hour stabilization. A decrease in systolic segment shortening along with increases in both the end-diastolic and end-systolic lengths of the right ventricle were observed at 3.0 and 4.0% sevoflurane, while global right ventricular function remained substantially unchanged during two-lung ventilation. During one-lung ventilation the PaO2 was greater with 5 cm H2O PEEP 198 mmHg (+/- 25 SEM) than with ZEEP 138 mmHg (+/- 22) or with 10 cm H2O PEEP 153 mmHg (+/- 23) (P < 0.05). No differences in haemodynamic variables or segment shortening between ZEEP and PEEPs during one-lung ventilation were observed. We conclude that although sevoflurane causes a dose-dependent depression of right ventricular function, sevoflurane anaesthesia can be safely applied to one-lung ventilation, and that 5 cm H2O PEEP to the dependent lung can improve arterial oxygenation without causing changes in right ventricular function.

Anesthesia, Inhalation↗
PubMed2004

Facilitation of alternative one-lung and two-lung ventilation by use of an endotracheal tube exchanger for pediatric empyema during video-assisted thoracoscopy.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has emerged as an innovative and popular procedure for the management of postpneumonic empyema in children refractory to medical response. Alternative uses of two- and one-lung ventilations have been required during VATS. This study evaluated the efficacy of alternating one- and two-lung ventilation through intraoperatively through the same single-lumen endobronchial tube using a tube exchanger during a thoracoscopic procedure for pediatric empyema. METHODS: Between May 1995 and August 2001, 62 consecutive pediatric patients undergoing VATS for evacuation of the loculated empyema cavity were studied. The same single-lumen endobronchial tube was used, with an indwelling endotracheal tube exchanger in place for readjustment of the tube position to provide alternation of one- and two-lung ventilations in a thoracosopic procedure. Duration of operation, heart rate, mean arterial pressure, peak airway pressure, an partial pressure of oxygen (PaO(2)) and carbon dioxide (PaCO(2)) changes during one- and two-lung ventilations were recorded. The quality of lung deflation and inflation was rated by the surgeon using direct visualization as excellent, fair or poor. RESULTS: The mean operating time was 90 min (range, 50-120 min). No differences were found in heart rate, mean arterial pressure, or PaO(2) during one- and two-lung ventilations. Peak airway pressure and PaCO(2) during two-lung ventilation were significantly higher than during one-lung ventilation. The quality of lung deflation and inflation was judged excellent for all the patients. CONCLUSIONS: The VATS procedure can be performed safely and effectively in children using proper anesthetic technique. Retention of a tube exchanger within a single-lumen endobronchial tube an easily provide alternative one- and two-lung ventilations without inducing any significant airway flow obstruction during the operation.

Adolescent↗
PubMed1998

A new heparin-bonded dense membrane lung combined with minimal systemic heparinization prolonged extracorporeal lung assist in goats.

Heparin was covalently bonded to a new hollow-fiber dense membrane artificial lung and extracorporeal circuit using a silane coupling agent and polyethyleneimine. This study investigated whether prolonged, venoarterial bypass extracorporeal lung assist (V-A bypass ECLA) could be sustained in a goat by the combination of the new membrane lung and minimal systemic heparinization. We maintained ECLA with the hollow-fiber lungs (surface area, 0.8 m2) and circuits by titrating the activated clotting time (ACT) to below 150 s with minimal systemic heparinization in 5 goats. The outcome was assessed from the function of the artificial lung via macro and microscopic examinations after the experiments and the incidence of systemic complications. The 5 goats were maintained on ECLA for 6 to 27 days. The bypass flow rate, blood gases at the return and drainage sites, platelet counts, and platelet aggregation activity were well maintained. Although the hemoglobin concentration, hematocrit, and plasma protein at the start of the ECLA were significantly lower than the pre-ECLA values due to hemodilution, the values remained stable during ECLA. A cerebral infarction occurred in 1 goat. However, in the other 4 goats, no complications such as bleeding, thrombosis, or plasma leakage from the artificial lung were observed. Although several thrombi were observed in the stagnant area of the artificial lung, these local thrombi did not cause the function of the artificial lung to deteriorate. We found that this new type of highly biocompatible, dense membrane artificial lung, when combined with minimal systemic heparinization, prolonged ECLA without the deterioration of the artificial lung function and was suitable for prolonged ECLA.

Animals↗
PubMed2003

Lung-protective ventilation strategies in acute lung injury.

OBJECTIVES: To review the challenges of providing mechanical ventilatory support for respiratory failure while avoiding ventilator-associated lung injury in patients with acute lung injury. To review the results of several randomized clinical trials of lung-protective ventilation strategies using conventional mechanical ventilators. DATA SOURCES: Published reports of clinical trials comparing clinical outcomes of patients with acute lung injury, randomized to mechanical ventilation with either a lung-protective or a control, conventional, standard, or traditional approach. DATA EXTRACTION AND SYNTHESIS: Lung-protective mechanical ventilation strategies are designed to prevent injury from overdistention by using lower tidal volumes and lower inspiratory pressures (volume- and pressure-limited ventilation) or injury from ventilation with atelectasis and alveolar flooding at end-expiration (open-lung ventilation). In one trial, clinical outcomes were better in the study group that received combined volume- and pressure-limited and open-lung strategies compared with the study group that received a conventional approach. Of four trials focusing on volume- and pressure-limited ventilation alone, three did not demonstrate improvements in clinical outcomes, whereas one demonstrated a substantial reduction in mortality and an increase in ventilator-free days. The different results in these four trials may be attributable to differences in tidal volumes between the study groups, chance variation, or differences in the management of respiratory acidosis. CONCLUSIONS: Evidence supports the use of a volume- and pressure-limited approach to mechanical ventilation in patients with acute lung injury. It is not yet clear whether the open-lung approach will further reduce mortality in patients receiving volume- and pressure-limited ventilation support.

Humans↗
PubMed1994

Differential lung ventilation as an alternative to one-lung ventilation during thoracotomy. Report of three cases.

Investigation was carried out on three elderly patients undergoing thoracotomy. During one-lung ventilation using a Robertshaw double-lumen tube, the PaO2 decreased below 11.7 kPa despite ventilation of the dependent lung with 100% oxygen. Differential lung ventilation was then initiated by partial occlusion of the adapter limb to the nondependent lung, whilst maintaining unrestricted ventilation of the dependent lung. In the three patients, differential lung ventilation increased the PaO2 to 15-37.2 kPa. The increased PaO2 may be attributed to diffusion oxygenation via the partially inflated, nondependent lung. Differential lung ventilation can be used during thoracotomy whenever one-lung ventilation is followed by hypoxaemia, despite adequate ventilation of the dependent lung with 100% oxygen.

Adult↗
PubMed2005

Does sustained lung inflation at resuscitation reduce lung injury in the preterm infant?

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common outcome of preterm birth. Experimental animal work has shown that initial ventilation strategies injure the immature lung and may lead to BPD. Studies with asphyxiated babies have shown that, if tidal ventilation at birth is preceded by sustained lung inflation, larger inflation volumes can be achieved, which is thought to lead to clearance of lung fluid and formation of the functional residual capacity (FRC). OBJECTIVE: To see if sustained lung inflation at initial resuscitation of preterm babies would facilitate the removal of lung fluid, establish the FRC, and allow an even distribution of alveolar opening, permitting less aggressive ventilation, leading to a reduction in pulmonary inflammation and subsequent BPD. METHOD: The outcomes of 52 babies of less than 31 weeks gestation, resuscitated at birth using either a sustained lung inflation of five seconds or a conventional lung inflation of two seconds for the first assisted breath of resuscitation, were examined. Evidence of pulmonary inflammation was determined by quantification of interleukins 6, 10, and 1beta and tumour necrosis factor alpha in bronchoalveolar lavage fluid by enzyme linked immunosorbent assay. RESULTS: There were no significant differences in any of the cytokines. Death occurred in 3/26 babies in the conventional group and 6/26 babies in the sustained lung inflation group. Survival without BPD occurred in 13/26 and 14/26 respectively. CONCLUSION: The use of sustained lung inflation at resuscitation did not reduce lung injury, as measured by inflammatory markers.

Asphyxia Neonatorum↗
PubMed2005

Spontaneous breathing with airway pressure release ventilation favors ventilation in dependent lung regions and counters cyclic alveolar collapse in oleic-acid-induced lung injury: a randomized controlled computed tomography trial.

INTRODUCTION: Experimental and clinical studies have shown a reduction in intrapulmonary shunt with spontaneous breathing during airway pressure release ventilation (APRV) in acute lung injury. This reduction was related to reduced atelectasis and increased aeration. We hypothesized that spontaneous breathing will result in better ventilation and aeration of dependent lung areas and in less cyclic collapse during the tidal breath. METHODS: In this randomized controlled experimental trial, 22 pigs with oleic-acid-induced lung injury were randomly assigned to receive APRV with or without spontaneous breathing at comparable airway pressures. Four hours after randomization, dynamic computed tomography scans of the lung were obtained in an apical slice and in a juxtadiaphragmatic transverse slice. Analyses of regional attenuation were performed separately in nondependent and dependent halves of the lungs on end-expiratory scans and end-inspiratory scans. Tidal changes were assessed as differences between inspiration and expiration of the mechanical breaths. RESULTS: Whereas no differences were observed in the apical slices, spontaneous breathing resulted in improved tidal ventilation of dependent lung regions (P < 0.05) and less cyclic collapse (P < 0.05) in the juxtadiaphragmatic slices. In addition, with spontaneous breathing, the end-expiratory aeration increased and nonaerated tissue decreased in dependent lung regions close to the diaphragm (P < 0.05 for the interaction ventilator mode and lung region). CONCLUSION: Spontaneous breathing during APRV redistributes ventilation and aeration to dependent, usually well-perfused, lung regions close to the diaphragm, and may thereby contribute to improved arterial oxygenation. Spontaneous breathing also counters cyclic collapse, which is a risk factor for ventilation-associated lung injury.

Animals↗
PubMed2006

Biological markers of lung injury before and after the institution of positive pressure ventilation in patients with acute lung injury.

BACKGROUND: Several biological markers of lung injury are predictors of morbidity and mortality in patients with acute lung injury (ALI). The low tidal volume lung-protective ventilation strategy is associated with a significant decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy. The primary objective of this study was to test whether the institution of lung-protective positive pressure ventilation in spontaneously ventilating patients with ALI exacerbates pre-existing lung injury by using measurements of biomarkers of lung injury before and after intubation. MATERIALS AND METHODS: A prospective observational cohort study was conducted in the intensive care unit of a tertiary care university hospital. Twenty-five intubated, mechanically ventilated patients with ALI were enrolled. Physiologic data and serum samples were collected within 6 hours before intubation and at two different time points within the first 24 hours after intubation to measure the concentration of interleukin (IL)-6, IL-8, intercellular adhesion molecule 1 (ICAM-1), and von Willebrand factor (vWF). The differences in biomarker levels before and after intubation were analysed using repeated measures analysis of variance and a paired t test with correction for multiple comparisons. RESULTS: Before endotracheal intubation, all of the biological markers (IL-8, IL-6, ICAM-1, and vWF) were elevated in the spontaneously breathing patients with ALI. After intubation and the institution of positive pressure ventilation (tidal volume 7 to 8 ml/kg per ideal body weight), none of the biological markers was significantly increased at either an early (3 +/- 2 hours) or later (21 +/- 5 hours) time point. However, the levels of IL-8 were significantly decreased at the later time point (21 +/- 5 hours) after intubation. During the 24-hour period after intubation, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio significantly increased and the plateau airway pressure significantly decreased. CONCLUSION: Levels of IL-8, IL-6, vWF, and ICAM-1 are elevated in spontaneously ventilating patients with ALI prior to endotracheal intubation. The institution of a lung-protective ventilation strategy with positive pressure ventilation does not further increase the levels of biological markers of lung injury. The results suggest that the institution of a lung-protective positive pressure ventilation strategy does not worsen the pre-existing lung injury in most patients with ALI.

Adult↗
PubMed2000

Quality of life in patients awaiting lung transplant: cystic fibrosis versus other end-stage lung diseases.

The symptoms associated with chronic lung disease can impair quality of life and psychosocial functioning. The purpose of the present study was to provide a thorough baseline assessment of quality of life in patients with end-stage lung disease and being evaluated for transplant; and to assess potential differences in quality of life between patients with cystic fibrosis (CF) and those with other types of end-stage lung disease (e.g., chronic obstructive pulmonary disease (COPD), interstitial pulmonary fibrosis (IPF)). We evaluated 58 patients with CF and 52 patients with other types of end-stage lung disease who were recruited for this study during an assessment of their candidacy for lung transplant. Subjects completed a battery of questionnaires that assessed demographic factors (including work and educational status), the presence of psychological distress (anxiety and depression), availability of social support, coping styles, and physical functioning. Despite significant impairment in physical functioning in the areas of recreation, household activities, sleep, and ambulation, other indices of life quality suggested good adaptation in the majority of patients. Also, quality of life differed for patients with CF and for those with other types of end-stage lung disease. Patients with CF were more likely to be working, had lower levels of anxiety and higher levels of social support, and used more functional coping strategies than did patients with other end-stage lung disease. These results highlight the fact that patients with different types of lung disease may require different psychosocial services as they await transplant. These findings also raise the question of whether there is a difference in quality of life after transplant between patients with CF and those with other types of lung disease.

Adaptation, Psychological↗
PubMed2004

Nkx2.1 transcription factor in lung cells and a transforming growth factor-beta1 heterozygous mouse model of lung carcinogenesis.

The Nkx2.1 homeobox gene and transforming growth factor-beta1 (TGF-beta1) are essential for organogenesis and differentiation of the mouse lung. NKX2.1 is a marker of human lung carcinomas, but it is not known whether this gene participates in early tumorigenesis. Addition of TGF-beta1 to TGF-beta1-responsive nontumorigenic mouse lung cells cotransfected with a NKX2.1Luc luciferase reporter and either a Sp1 or Sp3 plasmid showed a significant increase or decrease, respectively, in NKX2.1Luc transcription. Cotransfection of Sp3 and dominant-negative TGF-beta type II receptor plasmids negated the effect of Sp1. Cotransfected Sp1 plasmid with either dominant-negative Smad2 or Smad3 or Smad4 plasmids significantly decreased NKX2.1Luc transcription. Electrophoretic mobility shift assays revealed binding of Sp1 and Smad4 to the NKX2.1 promoter. With a TGF-beta1 heterozygous mouse model, Nkx2.1 mRNA and protein in lungs of TGF-beta1 heterozygous mice were significantly lower compared to wildtype (WT) littermates. Competitive reverse transcription (RT)-polymerase chain reaction (PCR) and immunostaining showed that Nkx2.1 mRNA and protein decreased significantly in adenomas and adenocarcinomas compared to normal lung tissue. Our in vitro data showed that regulation of Nkx2.1 by TGF-beta1 occurs through TGF-beta type II receptor and Smad signaling, with Sp1 and Sp3 in lung cells. Our in vivo data showed reduced Nkx2.1 in lungs of TGF-beta1 heterozygous mice compared to WT mice, that is detectable in adenomas, and that is further reduced in carcinogenesis, and that correlates with reduction of Sp1, Sp3, and Smads in lung adenocarcinomas. Our findings suggest that reduced Nkx2.1 and TGF-beta1 signaling components may contribute to tumorigenesis in the lungs of TGF-beta1 heterozygous mice.

Animals↗
PubMed1996

Expression of cytochrome P 450 3A enzymes in human lung: a combined RT-PCR and immunohistochemical analysis of normal tissue and lung tumours.

We have previously demonstrated expression of cytochrome P 450 3A (CYP3A) protein in pulmonary carcinomas and surrounding normal tissue, using immunohistochemistry. These results suggested that different CYP3A enzymes may be expressed in normal and tumour tissue. Therefore, the aim of the present study was to identify specific CYP3A enzymes expressed in normal human lung and lung tumours. Both normal lung tissue and tumour tissue from eight patients was analyzed for CYP3A4, CYP3A5 and CYP3A7 mRNA using a specific RT-PCR (reverse transcriptase-polymerase chain reaction) method. Identical samples were subjected to immunohistochemical analysis of CYP3A protein. CYP3A5 was the major enzyme of the CYP3A subfamily present at the mRNA level in both normal human lung and lung tumours. CYP3A5 mRNA was detected in normal lung tissue in all eight cases and in tumour tissue in four cases. CYP3A7 mRNA was detected in five cases in normal tissue and in one tumour. Notably, no CYP3A4 mRNA was found in any of the samples. Immunohistochemical staining for CYP3A protein was found in normal lung tissue in each case. Interestingly, all pulmonary carcinomas showed immunostaining for CYP3A, while mRNA for CYP3A enzymes was found in only four cases. In summary, our study indicates a specific expression pattern of the members of the CYP3A subfamily in normal human lung and lung tumours. These findings have potential clinical significance, since it has been recently shown that CYP3A5 catalyzes the activation of the anticancer pro-drugs cyclophosphamide and ifosfamide. Thus, local activation of these agents may take place in pulmonary carcinomas and surrounding normal tissues.

Aged↗
PubMedDate not supplied

Growth stimulating activity of lung extract on lung-colonizing colon 26 clones and its partial characterization.

The effects of lung tissue extract on the cell growth of eight colon 26 tumor clones, four highly and four poorly lung-colonizing clones, were examined in vitro. Addition of lung extract to serum-free medium stimulated the growth of all four of the highly lung-colonizing clones and one of the poorly lung-colonizing clones, but it had minimal effect on the other three poorly lung-colonizing clones. These results indicate that the lung extract contains a growth stimulating activity; it selectively stimulated some of the colon 26 clones including highly lung-colonizing ones. The growth stimulating activity was not dialyzable, was partially destroyed by heating at 56 degrees C or 80 degrees C for 30 min and completely destroyed by trypsin. These results suggest that the activity resides in a protein. Gel filtration chromatography of lung extract on Sephacryl S-200 revealed that the active component was eluted in a molecular weight range of 90,000-120,000.

Animals↗