Gregory Loewen - Academia.edu (original) (raw)
Papers by Gregory Loewen
Journal of Clinical Oncology, Aug 15, 2004
The Annals of Thoracic Surgery, May 1, 2007
Cancer Epidemiology, Biomarkers & Prevention, May 1, 2008
Human Pathology, Jun 1, 2003
Clinical Pulmonary Medicine, Mar 1, 2004
Journal of Surgical Oncology, Nov 24, 2003
In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of ch... more In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.
![Research paper thumbnail of A Phase I Study of Light Dose for Photodynamic Therapy Using 2-[1-Hexyloxyethyl]-2 Devinyl Pyropheophorbide-a for the Treatment of Non–Small Cell Carcinoma In Situ or Non–Small Cell Microinvasive Bronchogenic Carcinoma: A Dose Ranging Study](https://attachments.academia-assets.com/115882798/thumbnails/1.jpg)
](Journal of Thoracic Oncology, Feb 1, 2016
Experimental Lung Research, 1988
We quantified the effects of continuous exposure to 100% O2 on the development of sublethal injur... more We quantified the effects of continuous exposure to 100% O2 on the development of sublethal injury to the pulmonary alveolar epithelium of rabbits. There was a progressive increase in alveolar permeability to solute after 48 h in O2, which coincided with the onset of damage to the pulmonary microvasculature. Rabbits that were exposed to 100% O2 for 64 h and returned to room air for 24 h had, in addition to increased permeability to solute, decreased phospholipid levels, decreased total lung capacity, pulmonary edema, high minimum surface tensions in their bronchoalveolar lavage, and moderate hypoxemia. Intratracheal instillation of calf lung surfactant (CLSE) significantly ameliorated the progression of hyperoxic injury by increasing alveolar phospholipid levels and thus preventing the inhibition of lung surfactant activity by plasma proteins and other high molecular weight components of alveolar edema. We concluded that the alveolar epithelium and the pulmonary microvasculature show similar sensitivity to hyperoxia and that clinical manifestations of hyperoxic lung injury may be due, at least in part, to surfactant dysfunction.
Journal of Applied Physiology, Mar 1, 1989
We have previously demonstrated that instillation of a calf lung surfactant extract (CLSE) in rab... more We have previously demonstrated that instillation of a calf lung surfactant extract (CLSE) in rabbits after exposure to 100% O2 for 64 h mitigates the progression of lung pathology after return to room air (J. Appl. Physiol. 62: 756-761, 1987). In the present study, we investigated whether we could prevent or reduce the onset and development of hyperoxic lung injury by sequential instillations of CLSE during the hyperoxic exposure. Rabbits were exposed to 100% O2. CLSE (125 mg, approximately 170 mumol of phospholipid) was suspended in 10 ml of sterile saline and instilled intratracheally into their lungs, starting at 24 h in O2, a time at which no physiological or biochemical injury was detected, and at 24-h intervals thereafter. Control rabbits breathed 100% O2 and received either equal volumes of saline or no instillations at all. CLSE-instilled rabbits had higher arterial PO2 (Pao2) values throughout the exposure period and survived longer when compared with saline controls [120 +/- 4 vs. 102 +/- 4 (SE) h; n greater than or equal to 10; P less than 0.05]. At 72 h in O2, CLSE-instilled rabbits had significantly higher lavageable alveolar phospholipid levels (12.5 +/- 1.5 vs. 5 +/- 1 mumol/kg) and total lung capacities (41 +/- 2 vs. 25 +/- 3.5 ml/kg) and lower levels of alveolar protein (24 +/- 3 vs. 52 +/- 8 mg/kg), minimum surface tension (2 +/- 1 vs. 26.1 dyn/cm), and lung wet-to-dry weights (5.9 +/- 0.2 vs. 6.5 +/- 0.3). After 72 h in O2, lungs from both CLSE- and saline-instilled rabbits showed evidence of diffuse hyperoxic injury. However, atelectasis was less prominent in the former. We concluded that instillation of CLSE limits the onset and development of hyperoxic lung injury to the alveolar epithelium of rabbits.
Journal of Hematology & Oncology, Dec 1, 2014
Journal of Cancer Therapy, 2012
American Journal of Industrial Medicine, Dec 27, 2021
BackgroundVermiculite ore from Libby, Montana contains on average 24% of a mixture of toxic and c... more BackgroundVermiculite ore from Libby, Montana contains on average 24% of a mixture of toxic and carcinogenic amphibole asbestiform fibers. These comprise primarily winchite (84%), with smaller quantities of richterite (11%) and tremolite (6%), which are together referred to as Libby amphibole (LA).Methods A total of 1883 individuals who were occupationally and/or environmentally exposed to LA and were diagnosed with asbestos‐related pleuropulmonary disease (ARPPD) following participation in communitywide screening programs supported by the Agency for Toxic Substances and Disease Registry (ATSDR) and followed up at the Center for Asbestos Related Disease (CARD) between 2000 and 2010. There were 203 deaths of patients with sufficient records and radiographs. Best clinical and radiologic evidence was used to determine the cause of death, which was compared with death certificates.ResultsAsbestos‐related mortality was 55% (n = 112) in this series of 203 patients. Of the 203 deaths, 34 (17%) were from asbestos‐related malignancy, 75 (37%) were from parenchymal asbestosis, often with pleural fibrosis, and 3 (1.5%) were from respiratory failure secondary to pleural thickening.ConclusionsAsbestos is the leading cause of mortality following both occupational and nonoccupational exposure to LA in those with asbestos‐related disease.
Journal of Bronchology, 2007
Cancer Chemotherapy and Pharmacology, Nov 25, 1997
To establish the maximum tolerated dose (MTD), dose-limiting and other major toxicities and the m... more To establish the maximum tolerated dose (MTD), dose-limiting and other major toxicities and the major pharmacokinetic parameters of a 10-day infusion of the nonclassical antifolate Thymitaq. The drug was given by 10-day infusion via a portable pump. The starting dose was 286 mg/m2 per day with escalation to 572 and 716 mg/m2 per day. Thymitaq in plasma was assayed by a validated isocratic reverse-phase HPLC assay with detection at 273 nm. The dose of 716 mg/m2 per day x 10 was considered too high as none of three patients completed a 10-day infusion and two of three developed grade IV myelotoxicity. At 572 mg/m2 per day three of four patients completed a 10-day infusion. Dose-limiting myelosuppression was seen in one of four but owing to a high incidence of thrombotic phenomena, no further patients were added. Continuous 10-day infusions of Thymitaq should be limited to low doses until further studies can be done.
Chest, Jun 1, 1988
Numerous dusts found commonly in the dental laboratory have been suggested as potential pulmonary... more Numerous dusts found commonly in the dental laboratory have been suggested as potential pulmonary hazards. We recently noted a case of severe interstitial pulmonary fibrosis with intraalveolar deposition of unique foreign body inclusions in an elderly dentist. The composition of these particles was shown to be consistent with that of alginate impression powder. This is in contrast to previously reported pneumoconioses in dental workers, which are usually induced by metallic alloys or silicates. Further studies are needed to identify the causes and prevalence of pneumoconiosis in the dental lab.
Background: More than 75% of lung cancer patients are diagnosed at an advanced stage, when the su... more Background: More than 75% of lung cancer patients are diagnosed at an advanced stage, when the survival rate is less than 15%. Sputum cytology, x-ray and CT scan have been evaluated as screening tools for early lung cancers, without much success. Auto-fluorescence bronchoscopy (AFB) has been recently shown to be effective in diagnosing central bronchial cancers. Combined surveillance with both spiral CT scan and AFB might help to increase the detection rate of the both central and peripheral lung cancers. Methods: The study included 205 patients who were enrolled in the High Risk Lung Cancer Surveillance Cohort at Roswell Park Cancer Institute (RPCI) with at least 2 of the following risk factors: (1) radiographically documented pulmonary asbestosis or; (2) a history of previously treated aero-digestive cancer or; (3) > 20 pack years smoking history or; (4) COPD with an FEV1 < 70% of predicted. Patients underwent spirometry testing, chest X-ray, sputum cytology, non-enhanced low dose spiral CT scan of the chest, and conventional white light/AF bronchoscopy with biopsy. Results: A total of 20 invasive cancers/CIS were diagnosed in the 205 patients. Seven were diagnosed at baseline, 4 within 1 year of enrollment and 9 on follow up of more than 1 year. Between them, AFB and CT scan diagnosed all baseline cancers. Only 3/7 cancers were detected on x-ray screening and only 1/7 patients demonstrated atypia on sputum cytology. Overall, 17 invasive cancers and 3 CIS were diagnosed during the surveillance study. All the 3 CIS were identified only on AFB. Of the 17 invasive cancers, CT scan detected 15 cancers (88%) and AFB detected 5 of these cancers (30%). CT scan showed a 67% relative increase in sensitivity for detecting prevalent cancers and 3 times greater sensitivity for incident and prevalent cancers compared to x-ray screening. CT scan and AFB detected 19 of the 20 CIS/cancers (95%), whereas x-ray and sputum cytology together detected only 5/20 CIS/cancers (25%). The sensitivity of CT scan and AFB in diagnosing pre-malignant lesions and cancers improved by almost two and half times relative to x-ray and sputum. Conclusion: The addition of AFB exam to yearly spiral CT scan of the chest could be a more efficient surveillance tool to identify early stage lung cancers, both in the central and peripheral lung. A greater efficiency and cost effectiveness can be achieved by limiting the use of the combination of AFB and CT scan in very high risk patients, selected based on their exposures and risk factors. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A21.
Journal of Clinical Oncology, Aug 15, 2004
The Annals of Thoracic Surgery, May 1, 2007
Cancer Epidemiology, Biomarkers & Prevention, May 1, 2008
Human Pathology, Jun 1, 2003
Clinical Pulmonary Medicine, Mar 1, 2004
Journal of Surgical Oncology, Nov 24, 2003
In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of ch... more In the 1970s, four trials failed to demonstrate any mortality reduction using a combination of chest X-ray (CXR) and/or sputum cytology. The recent early lung cancer action project (ELCAP) demonstrated that modern screening is capable of detecting Stage I lung cancers. Bronchial epithelial changes leading up to cancers are now being understood to include histologic changes and genetic alterations. Emerging molecular markers detected in sputum and serum show promise in the future of lung cancer screening.
Journal of Thoracic Oncology, Feb 1, 2016
Experimental Lung Research, 1988
We quantified the effects of continuous exposure to 100% O2 on the development of sublethal injur... more We quantified the effects of continuous exposure to 100% O2 on the development of sublethal injury to the pulmonary alveolar epithelium of rabbits. There was a progressive increase in alveolar permeability to solute after 48 h in O2, which coincided with the onset of damage to the pulmonary microvasculature. Rabbits that were exposed to 100% O2 for 64 h and returned to room air for 24 h had, in addition to increased permeability to solute, decreased phospholipid levels, decreased total lung capacity, pulmonary edema, high minimum surface tensions in their bronchoalveolar lavage, and moderate hypoxemia. Intratracheal instillation of calf lung surfactant (CLSE) significantly ameliorated the progression of hyperoxic injury by increasing alveolar phospholipid levels and thus preventing the inhibition of lung surfactant activity by plasma proteins and other high molecular weight components of alveolar edema. We concluded that the alveolar epithelium and the pulmonary microvasculature show similar sensitivity to hyperoxia and that clinical manifestations of hyperoxic lung injury may be due, at least in part, to surfactant dysfunction.
Journal of Applied Physiology, Mar 1, 1989
We have previously demonstrated that instillation of a calf lung surfactant extract (CLSE) in rab... more We have previously demonstrated that instillation of a calf lung surfactant extract (CLSE) in rabbits after exposure to 100% O2 for 64 h mitigates the progression of lung pathology after return to room air (J. Appl. Physiol. 62: 756-761, 1987). In the present study, we investigated whether we could prevent or reduce the onset and development of hyperoxic lung injury by sequential instillations of CLSE during the hyperoxic exposure. Rabbits were exposed to 100% O2. CLSE (125 mg, approximately 170 mumol of phospholipid) was suspended in 10 ml of sterile saline and instilled intratracheally into their lungs, starting at 24 h in O2, a time at which no physiological or biochemical injury was detected, and at 24-h intervals thereafter. Control rabbits breathed 100% O2 and received either equal volumes of saline or no instillations at all. CLSE-instilled rabbits had higher arterial PO2 (Pao2) values throughout the exposure period and survived longer when compared with saline controls [120 +/- 4 vs. 102 +/- 4 (SE) h; n greater than or equal to 10; P less than 0.05]. At 72 h in O2, CLSE-instilled rabbits had significantly higher lavageable alveolar phospholipid levels (12.5 +/- 1.5 vs. 5 +/- 1 mumol/kg) and total lung capacities (41 +/- 2 vs. 25 +/- 3.5 ml/kg) and lower levels of alveolar protein (24 +/- 3 vs. 52 +/- 8 mg/kg), minimum surface tension (2 +/- 1 vs. 26.1 dyn/cm), and lung wet-to-dry weights (5.9 +/- 0.2 vs. 6.5 +/- 0.3). After 72 h in O2, lungs from both CLSE- and saline-instilled rabbits showed evidence of diffuse hyperoxic injury. However, atelectasis was less prominent in the former. We concluded that instillation of CLSE limits the onset and development of hyperoxic lung injury to the alveolar epithelium of rabbits.
Journal of Hematology & Oncology, Dec 1, 2014
Journal of Cancer Therapy, 2012
American Journal of Industrial Medicine, Dec 27, 2021
BackgroundVermiculite ore from Libby, Montana contains on average 24% of a mixture of toxic and c... more BackgroundVermiculite ore from Libby, Montana contains on average 24% of a mixture of toxic and carcinogenic amphibole asbestiform fibers. These comprise primarily winchite (84%), with smaller quantities of richterite (11%) and tremolite (6%), which are together referred to as Libby amphibole (LA).Methods A total of 1883 individuals who were occupationally and/or environmentally exposed to LA and were diagnosed with asbestos‐related pleuropulmonary disease (ARPPD) following participation in communitywide screening programs supported by the Agency for Toxic Substances and Disease Registry (ATSDR) and followed up at the Center for Asbestos Related Disease (CARD) between 2000 and 2010. There were 203 deaths of patients with sufficient records and radiographs. Best clinical and radiologic evidence was used to determine the cause of death, which was compared with death certificates.ResultsAsbestos‐related mortality was 55% (n = 112) in this series of 203 patients. Of the 203 deaths, 34 (17%) were from asbestos‐related malignancy, 75 (37%) were from parenchymal asbestosis, often with pleural fibrosis, and 3 (1.5%) were from respiratory failure secondary to pleural thickening.ConclusionsAsbestos is the leading cause of mortality following both occupational and nonoccupational exposure to LA in those with asbestos‐related disease.
Journal of Bronchology, 2007
Cancer Chemotherapy and Pharmacology, Nov 25, 1997
To establish the maximum tolerated dose (MTD), dose-limiting and other major toxicities and the m... more To establish the maximum tolerated dose (MTD), dose-limiting and other major toxicities and the major pharmacokinetic parameters of a 10-day infusion of the nonclassical antifolate Thymitaq. The drug was given by 10-day infusion via a portable pump. The starting dose was 286 mg/m2 per day with escalation to 572 and 716 mg/m2 per day. Thymitaq in plasma was assayed by a validated isocratic reverse-phase HPLC assay with detection at 273 nm. The dose of 716 mg/m2 per day x 10 was considered too high as none of three patients completed a 10-day infusion and two of three developed grade IV myelotoxicity. At 572 mg/m2 per day three of four patients completed a 10-day infusion. Dose-limiting myelosuppression was seen in one of four but owing to a high incidence of thrombotic phenomena, no further patients were added. Continuous 10-day infusions of Thymitaq should be limited to low doses until further studies can be done.
Chest, Jun 1, 1988
Numerous dusts found commonly in the dental laboratory have been suggested as potential pulmonary... more Numerous dusts found commonly in the dental laboratory have been suggested as potential pulmonary hazards. We recently noted a case of severe interstitial pulmonary fibrosis with intraalveolar deposition of unique foreign body inclusions in an elderly dentist. The composition of these particles was shown to be consistent with that of alginate impression powder. This is in contrast to previously reported pneumoconioses in dental workers, which are usually induced by metallic alloys or silicates. Further studies are needed to identify the causes and prevalence of pneumoconiosis in the dental lab.
Background: More than 75% of lung cancer patients are diagnosed at an advanced stage, when the su... more Background: More than 75% of lung cancer patients are diagnosed at an advanced stage, when the survival rate is less than 15%. Sputum cytology, x-ray and CT scan have been evaluated as screening tools for early lung cancers, without much success. Auto-fluorescence bronchoscopy (AFB) has been recently shown to be effective in diagnosing central bronchial cancers. Combined surveillance with both spiral CT scan and AFB might help to increase the detection rate of the both central and peripheral lung cancers. Methods: The study included 205 patients who were enrolled in the High Risk Lung Cancer Surveillance Cohort at Roswell Park Cancer Institute (RPCI) with at least 2 of the following risk factors: (1) radiographically documented pulmonary asbestosis or; (2) a history of previously treated aero-digestive cancer or; (3) > 20 pack years smoking history or; (4) COPD with an FEV1 < 70% of predicted. Patients underwent spirometry testing, chest X-ray, sputum cytology, non-enhanced low dose spiral CT scan of the chest, and conventional white light/AF bronchoscopy with biopsy. Results: A total of 20 invasive cancers/CIS were diagnosed in the 205 patients. Seven were diagnosed at baseline, 4 within 1 year of enrollment and 9 on follow up of more than 1 year. Between them, AFB and CT scan diagnosed all baseline cancers. Only 3/7 cancers were detected on x-ray screening and only 1/7 patients demonstrated atypia on sputum cytology. Overall, 17 invasive cancers and 3 CIS were diagnosed during the surveillance study. All the 3 CIS were identified only on AFB. Of the 17 invasive cancers, CT scan detected 15 cancers (88%) and AFB detected 5 of these cancers (30%). CT scan showed a 67% relative increase in sensitivity for detecting prevalent cancers and 3 times greater sensitivity for incident and prevalent cancers compared to x-ray screening. CT scan and AFB detected 19 of the 20 CIS/cancers (95%), whereas x-ray and sputum cytology together detected only 5/20 CIS/cancers (25%). The sensitivity of CT scan and AFB in diagnosing pre-malignant lesions and cancers improved by almost two and half times relative to x-ray and sputum. Conclusion: The addition of AFB exam to yearly spiral CT scan of the chest could be a more efficient surveillance tool to identify early stage lung cancers, both in the central and peripheral lung. A greater efficiency and cost effectiveness can be achieved by limiting the use of the combination of AFB and CT scan in very high risk patients, selected based on their exposures and risk factors. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A21.