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J Godleski

Publications and source records attributed to J Godleski.

12 recordsLinked to original sources
PubMed2001

Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease.

OBJECTIVES: The aim of our study was to retrospectively compare the patient characteristics, the frequency and pattern of recurrent disease, and survival in patients with stage I bronchioloalveolar carcinoma and adenocarcinoma of the lung. METHODS: Patients with stage I bronchioloalveolar carcinoma or adenocarcinoma other than bronchioloalveolar carcinoma resected between 1984 and 1992 with adequate clinical follow-up were studied. The clinical characteristics of the patients, extent of initial surgical resection, sites of recurrent disease, and overall survival were examined and compared between the 2 groups. The median follow-up for patients with bronchioloalveolar carcinoma and adenocarcinoma was 6.2 years and 5.9 years, respectively. RESULTS: A total of 138 patients were identified. Thirty-three patients had bronchioloalveolar carcinoma and 105 patients had adenocarcinoma. Eleven (33%) of the patients with bronchioloalveolar carcinoma had never smoked cigarettes versus 9 (9%) of the patients with adenocarcinoma (P =.0036). There were no significant differences between patients with bronchioloalveolar carcinoma and adenocarcinoma in sex distribution and overall recurrence rate. Of the 12 patients with recurrent bronchioloalveolar carcinoma, 1 patient (8%) had extrathoracic disease develop at the site of first recurrence compared with 49% of patients with recurrent adenocarcinoma (P <.001). The 5-year survival in patients with bronchioloalveolar carcinoma and in those with adenocarcinoma was 83% and 63%, respectively (P =.04). CONCLUSIONS: Stage I bronchioloalveolar carcinoma is more likely to occur in nonsmokers. Survival is longer in patients with bronchioloalveolar carcinoma. Further research is warranted to define the etiology, clinical course, and molecular abnormalities in patients with bronchioloalveolar carcinoma to generate more effective therapeutic approaches.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1999

Cell motility as a prognostic factor in Stage I nonsmall cell lung carcinoma: the role of gelsolin expression.

BACKGROUND: Tumor cell motility is an important characteristic that facilitates the multistep process of tumor metastasis. Rac, ABP-280, and gelsolin are proteins that interact with actin and are important in cell motility. METHODS: The authors studied a cohort of 229 Stage I nonsmall cell lung carcinoma (NSCLC) patients who had a minimum of 3 years follow-up and had been previously analyzed for 22 clinical, pathologic, and molecular features, of which 9 had been found to provide significant prognostic information in a Cox proportional hazards model. Tumor sections were stained by the avidin-biotin complex method using monoclonal antibodies against rac, ABP-280, and gelsolin. RESULTS: In a pilot analysis of over 50 patients each, rac and ABP-280 were found to be moderately-to-highly expressed in the majority of tumors and to provide no prognostic information. Gelsolin expression was more variable and appeared to be negatively correlated with survival in the pilot population. In the larger 229-patient population, high focal gelsolin expression was seen in 32 tumors (14%) and conferred the highest relative risk (4.04) of cancer recurrence among all factors tested, compared with tumors that had no or low gelsolin expression. Moderate focal gelsolin expression, seen in 46 patients (20%), also conferred a significant risk of cancer recurrence, with a relative risk of 2.26 compared with tumors that had no or low gelsolin expression. Consideration of average gelsolin expression and of overall survival yielded similar results. CONCLUSIONS: Gelsolin expression appears to be a significant prognostic factor for cancer recurrence in cases of Stage I NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications.

PURPOSE: To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design a molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). METHODS: All patients with stage I NSCLC resected at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-up were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. RESULTS: Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge resection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection, tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. CONCLUSION: Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors for recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded Ia, with a 5-year CFS rate of 87%; those with three factors are graded Ib, with a 5-year CFS rate of 58%; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21%.

Adult↗
PubMed1995

Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines.

cdk4-mediated phosphorylation of the retinoblastoma susceptibility protein (Rb) is stimulated by cyclin D1, an oncogene, and inhibited by p16, a candidate tumor suppressor. We examined these proteins in non-small cell lung cancer (NSCLC), which is predominantly Rb positive, and small cell lung cancer (SCLC), which is Rb negative. Most NSCLC and SCLC resection specimens and cell lines overexpress cyclin D1 (indicating that cyclin D1 overexpression and Rb inactivation can coexist in SCLC). However, 9 of 9 Rb-positive NSCLC cell lines have absent or low p16, while an Rb-negative NSCLC line and 5 of 5 SCLC cell lines have high levels of p16. In primary resection specimens, p16 was undetectable in 18 of 27 NSCLC samples and abundant in 4 of 5 SCLC samples. Our data confirm the predicted reciprocity between Rb inactivation and p16 expression in a common human malignancy and define differential p16 expression as a fundamental distinction between NSCLC and SCLC.

Blotting, Southern↗
PubMed1995

Intracutaneous transport of orally administered fluconazole to the stratum corneum.

Fluconazole administered at 150 mg/week for 1-5 weeks is effective orally against dermatophytes and yeast in stratum corneum. Clinical and mycological cure rates approach 90%, but the precise distribution of the drug within various layers of skin is uncertain. We administered fluconazole at 150 mg/week for 2 weeks to 5 volunteers. Distribution of fluconazole in biopsies of skin was imaged by energy dispersive analysis of X-rays (EDX) and transmission electron microscopy, and in cells by electron energy-loss spectroscopy (EELS). Eight hours after a second dose, EDX showed fluconazole highest and homogeneously distributed in stratum corneum, lower in the rest of the epidermis, and lowest in dermis. The highest fluconazole levels detected by EELS were in cytoplasmic inclusions of sweat and sebaceous glands and less in keratinocytes and dermal collagen. We conclude that fluconazole delivered to stratum corneum by direct diffusion from capillaries and in sweat is also in all likelihood transported in sebum.

Administration, Oral↗
PubMed1994

In vivo evaluation of chemical biopersistence of nonfibrous inorganic particles.

The lung's response to deposited particles may depend upon the physical-chemical properties of the particles, the amount initially deposited, and the persistence of the particles. Clearance involves mucociliary transport as well as the action of phagocytic cells in nonciliated regions of the lung. Depending on the animal species studied, particle type, and particle load, inorganic materials are ingested by macrophages on alveolar surfaces with half-times of 0.6 to 7 hr. Particle-laden macrophages may migrate to airways, but we believe that an important mechanism of clearance is the dissolution of particles within alveolar macrophages and the subsequent translocation of dissolved materials to the blood. Particle dissolution in situ has long been recognized but was often thought to be carried out extracellularly in the alveolar lining layer, airway mucus, or interstitial fluid. However, many particles such as cobalt oxide or iron oxide which dissolve very little in simulated lung fluid, are solubilized more rapidly within alveolar macrophages. Clearance of particles from the lungs can be followed by a number of techniques, both invasive and noninvasive. The approaches vary in expense and resolution, and can be directed toward quantifying mechanical removal of particles versus their intracellular dissolution. Noninvasive methods permit repeated measurements of particle retention in the lungs of the same animal or human and thus allow replications and serial measurements. Greater precision with respect to the sites of retention and redistribution is achieved with quantitative morphometric methods that utilize fixation followed by physically dividing the respiratory tract into individual pieces.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1991

Drug-related pulmonary toxicity in non-Hodgkin's lymphoma. Comparative results with three different treatment regimens.

Pulmonary toxicity may complicate the treatment of non-Hodgkin's lymphoma (NHL). The possible drug-related cause of pulmonary toxicity was investigated retrospectively in 207 NHL patients treated between 1981 and 1988 with three regimens containing cyclophosphamide with and without methotrexate or bleomycin: methotrexate, calcium, leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) (n = 134); methotrexate, calcium, leucovorin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-ACOD) (n = 43); or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 30) chemotherapy. These regimens contained the same drugs and were administered in the same schedule; the regimens differed primarily in the addition of bleomycin or methotrexate. Pulmonary toxicity occurred in 24 of 134 (18%) m-BACOD-treated and in six of 43 (14%) m-ACOD-treated patients (P = 0.65). Chest radiography revealed diffuse pulmonary infiltrates in 16 (67%) and six (100%) of the m-BACOD-treated and m-ACOD-treated patients with pulmonary toxicity, respectively. None of the CHOP-treated patients had pulmonary toxicity. The clinical features of pulmonary toxicity and the amount of chemotherapy administered before it occurred did not differ in patients treated with m-BACOD or m-ACOD, although the toxicity tended to be more severe in the m-BACOD group. Open lung or transbronchial biopsies done in six (38%) of the m-BACOD-treated and three (50%) of the m-ACOD-treated patients with pulmonary infiltrates revealed nonspecific pneumonitis compatible with drug-related toxicity. In summary, these results showed that pulmonary toxicity during m-BACOD and m-ACOD therapy occurred with similar frequency and clinicopathologic features. This suggested that bleomycin was not responsible uniquely for the pulmonary toxicity in m-BACOD-treated patients. That pulmonary toxicity was not observed in patients treated with CHOP suggested that methotrexate may play an important role in the pathogenesis of the pulmonary toxicity.

Adult↗
PubMed1987

Sulfur-dioxide-induced bronchitis in dogs. Effects on airway responsiveness to inhaled and intravenously administered methacholine.

Chronic bronchitis was induced in 7 dogs of mixed breed by chronic exposure to SO2 gas. Within the first 2 to 4 wk of exposure, the dogs developed cough and mucous hypersecretion, chronic airway obstruction (increased pulmonary resistance), and persistent lung inflammation as demonstrated by an increase in the number of neutrophils recovered in the bronchoalveolar lavage (BAL) fluid. Airway responsiveness to methacholine aerosol decreased 2- to 3-fold within 8 wk of SO2 exposure. In contrast, airway responsiveness to intravenous administration of methacholine did not change. The data suggest that the decreased airway responsiveness observed during persistent pulmonary inflammation in SO2-exposed dogs is not due to an altered state of airway contractile elements but likely reflects expression of an inhibitory influence of the mucoepithelial barrier.

Airway Resistance↗
PubMed1976

Yellow pulmonary hyaline membranes.

Yellow pulmonary hyaline membranes were observed at autopsy in 16 newborn infants between 1972 and 1974 in four hospitals of Philadelphia, Pa., and Newark, N.J. Other pediatric pathologists in this country and in Spain have seen the same lesion within the last decade. Chemical analysis of affected lung tissue, histochemistry, and electron microscopy show the yellow color to be due to the presence of bilirubin. No substantial clues concerning the basic etiology or mechanism for the formation of these unique membranes emerge from a detailed review of clinical and postmortem data nor from comparison of these data with those for 68 control infants with the usual acidophilic pulmonary hyaline membranes. We are left, however, with the impression that prolongation of life, relatively elevated levels of serum bilirubin, and protracted assisted ventilation (with either CPAP or PEEP) are intimately related to their formation.

Bilirubin↗