ABSTRACT
BACKGROUND: With the recent development of minimal treatment for early stage gastric carcinoma, identifying specific indicators of the metastatic potential of primary tumors has become more important. Cathepsin B and cathepsin L, both lysosomal cysteine proteases, degrade the extracellular matrix during tumor progression. Although many studies have shown their relation to human cancer progression, little is known about their roles in the early stage. The clinicopathologic significance of cathepsins was therefore studied in early stage gastric carcinoma. METHODS: Expression of both cathepsins was studied immunohistochemically in 51 tissue specimens from gastric carcinomas that invaded the submucosal layer or muscularis propria. The relation between their expression and clinicopathologic factors was analyzed. RESULTS: Both cathepsins were expressed at higher levels in tumors that invaded the muscularis propria than in those within the submucosa (P < 0.05). In addition, tumors with lymphatic invasion showed higher cathepsin B expression than those without it (P < 0.05), whereas tumors with venous invasion showed higher cathepsin L expression than those without it (P < 0.05). No other clinicopathologic factors correlated with expression of either cathepsin. CONCLUSIONS: Tumors with overexpression of cathepsins have powerful potential for invasiveness in the early stage of gastric carcinoma. Moreover, the authors hypothesize that cathepsins may be one of the determinants of the metastatic route. To the authors' knowledge, this is the first report on specific proteases concerning the mode of metastasis, and the results of this study suggest that therapeutic strategies for early stage gastric carcinoma might need to be changed according to the status of cathepsins.
Subject(s)
Cathepsin B/metabolism , Cathepsins/metabolism , Endopeptidases , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma/metabolism , Carcinoma/pathology , Cathepsin L , Cysteine Endopeptidases , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm InvasivenessABSTRACT
A 54-year-old man was admitted for further investigation of multiple nodules disclosed by a chest roentgenogram. Adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome was diagnosed because serum ACTH and serum cortisol levels were elevated with a loss of diurnal rhythm. Because several extensive examinations, including inferior petrosal sinus sampling, did not detest ACTH-producing tumors, the patient was also given a diagnosis of occult ectopic ACTH syndrome. The nodules disclosed on chest roentgenograms increased gradually in size and number, and some were cavitary. Bronchial secretion samples obtained by fiberoptic bronchoscopy contained numerous Nocardia asteroides bacteria. After treatment with sulfamethoxazole-trimethoprim, the nodules gradually disappeared, leaving only scars. Although mitotane had been continuously administered to inhibit the synthesis of intrinsic corticosteroids, pulmonary nocardiosis relapsed in the patient following the termination of sulfamethoxazole-trimethoprim therapy.
Subject(s)
Cushing Syndrome/complications , Lung Diseases/etiology , Nocardia Infections/etiology , Nocardia asteroides , ACTH Syndrome, Ectopic/complications , Anti-Bacterial Agents/therapeutic use , Drug Combinations , Humans , Lung Diseases/drug therapy , Male , Middle Aged , Nocardia Infections/drug therapy , Sulfamethoxazole/analogs & derivatives , Sulfamethoxazole/therapeutic use , Trimethoprim/therapeutic useABSTRACT
To evaluate the incidence of abnormal gastroesophageal reflux in patients with bronchial asthma and the influence of drug therapy on the gastroesophageal reflux, we investigated the gastroesophageal reflux patterns using an ambulatory 24-hour esophageal monitoring in 25 healthy volunteers and 58 asthmatics. All the patients were stable conditions at the time of the study. Bronchodilator therapy was continued, if necessary along with steroid inhalation and xanthines. Compared with healthy volunteers, the asthmatics had significantly greater esophageal acid exposure time, more frequent reflux episode, and longer single reflux time. About 70% of asthmatics had abnormal gastroesophageal reflux. Asthma medications were not associated with the incidence of abnormal gastroesophageal reflux. However, asthmatics receiving beta(2)-stimulants therapy (n = 27) had significantly greater esophageal reflux exposure time than those not receiving (n = 31). Our study suggested that most asthmatics have abnormal gastroesophageal reflux unrelated to asthma attack or asthma medications and that beta(2)-stimulants used in asthmatics may worsen gastroesophageal reflux.