Modulation of multidrug resistance in a cancer cell line by anti-multidrug resistance-associated protein (MRP) ribozyme.

Multidrug resistance-associated protein (MRP) is the major candidate molecule responsible for non-P-glycoprotein (PGp)-mediated multidrug resistance. We used a hammerhead anti-MRP ribozyme (alpha MRP-Rz) to inactivate MRP function in a multidrug resistant cancer cell line, KB8-5. The beta-actin promoter-driven alpha MRP-Rz sequence (pH beta/alpha MRP-Rz) was introduced into KB8-5 cells (KB8-5/alpha MRP-Rz) and we evaluated growth of the cell line. The gene expression of multidrug resistance-related molecules was estimated. Drug sensitivity was estimated by MTT assay in vitro. MRP mRNA expression was decreased in KB8-5/alpha MRP-Rz cells. The MTT assay showed increased IC50 values or resistance to doxorubicin (DOX), etoposide (VP-16) and cisplatin (CDDP) in KB8-5/alpha MRP-Rz cells. No significant differences were observed in expression of multidrug resistance gene (MDR1), thymidylate synthase, glutathione S-transferase pi or topoisomerase II alpha. The hammerhead ribozyme-mediated simple suppression of MRP mRNA expression was not sufficient to reverse multidrug resistance in the cancer cell line KB8-5.

Significant correlation between interleukin 10 expression and vascularization through angiopoietin/TIE2 networks in non-small cell lung cancer.

The expression of interleukin 10 (IL-10) is correlated with clinical prognosis in non-small cell lung cancer [NSCLC (H. Hatanaka et al., ANN: ONCOL:, 11: 815--819, 2000)]. However, the effects of IL-10 expression on vascularization in NSCLC are not apparent. We examined the gene expression of IL-10/IL-10 receptor and various angiogenic/angioinhibitory factors in 95 NSCLC samples to determine the correlation between IL-10 production and vascularization. Vascular endothelial growth factor, angiopoietin [Ang (Ang-1 and Ang-2)], thrombospondin, brain-specific angiogenesis inhibitor 1, vascular endothelial growth factor receptors (KDR and flt-1), and Ang receptor (TIE2) gene expression were evaluated by reverse transcription-PCR. The cellular localization of these factors and vascularity in the cancer stroma were examined immunohistochemically. Seventy-eight (82.1%) and 93 (97.9%) of these 95 NSCLCs were positive for IL-10 and IL-10 receptor, respectively. Ang-1, Ang-2, and TIE2 gene expression was seen in 76 (97.4%), 73 (93.6%), and 78 (100%) of 78 IL-10-positive NSCLCs, respectively, and was significantly correlated with IL-10 gene expression (P < 0.0088, <0.0008, and 0.0305, respectively; Fisher's exact method). The localizations of Ang-1, Ang-2, and TIE2 were confirmed within tumor cells immunohistochemically. Vascular number and measurement area were significantly higher in the IL-10-positive NSCLCs (33.500 +/- 9.299/microm(2) and 4.742 +/- 1.287%) as compared with IL-10-negative NSCLCs (10.611 +/- 2.839/microm(2) and 0.718 +/- 0.331%; Mann-Whitney U test, P = 0.0039). The IL-10 expression did not show any significant correlation with the expression of other factors. These results suggested that tumor-produced IL-10 promotes stromal vascularization through expression of Ang-1, Ang-2, and TIE2.

Interleukin-10 expression is correlated with growth fraction in human non-small cell lung cancer xenografts.

We examined IL-10 and IL-10 receptor (IL-10R) gene expression in 44 xenografts of human non-small cell lung cancer (NSCLC) by reverse transcription-polymerase chain reaction (RT-PCR) assay with human-specific primers. IL-10 gene expression was detected in 10 (22.7%) of 44 xenografts (0/11 adenocarcinomas, 6/19 squamous cell carcinomas, 4/14 large cell carcinomas) and IL-10R expression in 8 (18.2%) xenografts. The IL-10-positive xenografts immunohistochemically showed significantly increased growth fractions of neoplastic cells (471.0 +/- 112.2) relative to IL-10-negative xenografts (208.4 +/- 96.3) (p=0.009, Mann-Whitney U test), and showed significantly increased vascular number (p=0.008, Mann-Whitney U test). These results suggested that IL-10 expression is correlated with growth features in human NSCLC.

An uncommon case of simultaneous malignant tumors: bronchioloalveolar cancer and Ewing's sarcoma in a 17-year-old girl: report of a case.

This report describes a 17-year-old girl with a simultaneous occurrence of bronchioloalveolar cancer and Ewing's sarcoma of the femur, which is a previously unreported association. This case emphasizes the existence of multiple primary malignant neoplasms even in adolescents. Primary lung cancer should therefore be considered in patients under 19 years of age who present with abnormal pulmonary lesions.

Expression and prognostic value of the standard CD44 protein in pulmonary adenocarcinoma.

We examined immunohistochemically the expression of the standard form of CD44 (CD44S) tissue specimens from 164 patients with pulmonary adenocarcinoma. Of the 164 specimens, 79 (48%) expressed CD44S and the incidence of expression correlated with the tumor size. The prognosis for CD44S positive patients was poorer than that of CD44S negative patients. Our findings suggest that CD44S plays an important role in tumor progression and that CD44S expression is a useful prognostic marker for pulmonary adenocarcinomas.

Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma.

BACKGROUND: Angiogenesis in individuals with various solid tumors has provided useful information on tumor progression and prognosis, and many examples of mast cell (MC) accumulation coupled with angiogenesis can be found in the literature. METHODS: Utilizing monoclonal antibodies for tryptase that are specific markers for MC and for the endothelial surface marker CD34, the authors quantified MC infiltration in 180 patients with pulmonary adenocarcinoma who underwent curative tumor resection, to investigate the relation between mast cell density (MCD) and microvessel density (MVD), clinicopathologic factors, and prognosis. RESULTS: A significant association was found between MCD and MVD (P < 0.0001). The MC count was significantly related to tumor progression, involving N classification and stage (P = 0.0002 for N classification and P = 0. 0015 for stage). A significant difference in the rate of patient survival was detected between patients whose tumors had an MCD defined as high and those whose tumors had an MCD defined as low (P < 0.0001). Multivariate analysis also showed that MCD was significantly related to survival (P = 0.0378). CONCLUSIONS: These data indicate that MC infiltration may contribute to tumor angiogenesis and tumor progression, and that MCD is a useful prognostic marker in pulmonary adenocarcinoma.

The surgical approach for descending necrotizing mediastinitis: report of two cases.

Descending necrotizing mediastinitis (DNM) is a potentially life-threatening complication that can develop after an oropharyngeal infection. Patients with DNM are usually treated with mediastinal drainage through a cervical or transthoracic approach, as well as by the systemic administration of antibiotics. We report herein the cases of two patients we recently treated for DNM. In the first patient, the DNM was limited to the upper mediastinum, and cervicomediastinal drainage was performed. In the second patient, the mediastinitis spread below the tracheal bifurcation down into the lower mediastinum, and an abscess was drained through a thoracotomy approach. The principles of the surgical approach for DNM are discussed, with a brief review of the literature following these case reports.

Autocrine motility factor in pulmonary adenocarcinomas: results of an immunohistochemical study.

Autocrine motility factors (AMF) have been shown to play an important role in tumor cell migration and metastasis. We have detected AMF expression in tissue specimens from 119 patients with pulmonary adenocarcinoma and examined the relationship between AMF expression, clinicopathological factors and prognosis. AMF expression was correlated with lymph node metastasis and stage. The prognosis of AMF-positive patients was poorer than that of AMF-negative patients. The expression of AMF correlated with more tumor aggressiveness and worse prognosis in pulmonary adenocarcinomas.

[Acute exacerbation of subacute interstitial pneumonia after thoracoscopic lung biopsy].

A 55-year-old woman was admitted to our hospital with progressive dyspnea that had begun one month before. Chest rentogenogram revealed groundglass appearance and reticular shadows bilaterally. Pulmonary function tests showed both decreased vital capacity and diffusing capacity. Bronchoalveolar lavage fluid had a high lymphocyte fraction with a low CD4+/CD8+ ratio. Thoracoscopic lung biopsy revealed thick, fibro-edematous interstitium and diffuse infiltration of lymphocytes. We also observed an intra-alveolar exudate with infiltration of histiocytes and lymphocytes. The clinical features and pathological findings were consistent with subacute interstitial pneumonia, which was the entity proposed by Kawabata and colleagues. The patient developed acute respiratory failure four days after lung biopsy and died despite steroid pulse therapy. Although subacute interstitial pneumonia has been reported to respond to steroid therapy, and to have a good prognosis, we believe that subacute interstitial pneumonia could fatally worsen when associated with lung biopsy, infection, or some other stimulus.

Long-term survival after repeated resections of Askin tumor recurrences.

The case of a 16-year-old boy is reported who underwent surgery for the excision of an Askin tumor and has subsequently undergone six excisions of local Askin tumor recurrences, with follow-up postoperative chemo- and radiotherapy over a 7-year period. The patient continues to survive. As far as can be determined, this patient appears to be the first reported case of long-term survival after repeated resections of local Askin tumor recurrences. It thus may be that postoperative chemo- and radiotherapy after repeated excisions of these local Askin tumor recurrences plays a role in prolonging survival.

[Outcome from surgery of lung cancer invading the carina].

By 1995, 17 patients with lung cancer invading the carina underwent surgical resection and reconstruction of the carina. Procedures which applied to patients were two cases of wedge pneumonectomy, seven cases of sleeve pneumonectomy, four cases of carinal reconstruction with right upper lobectomy, and four cases of carinal resection and reconstruction. Overall survival for five years were 40.3% and 33.6% for ten years survival. Operative death occurred in 5 cases. Long term survival was achieved in localized diseases which showed no lymph node extension. As for N1 and N2 diseases, only one patient among 7 cases survives 12 months. Thus we conclude that selected cases which showed localized disease without lymph node extension are the candidate for carinal resection and reconstruction. Postoperative intensive care is mandated for these patients. Adjuvant therapy with surgery for these patients with lymph node progression is a future problem.

[Reconstruction of chest wall defects with autogenous ribs grafts].

Three methods of chest wall reconstruction using autogenous rib grafts were reported. Fresh non-vascularized autogenous rib graft, vascularized autogenous ribs with muscle-flap, and pasteurized autogenous rib grafts were the materials used in these techniques. They are less convenient than those with artificial materials but afterwards physiologically more natural chest wall will be reconstructed. The third method (pasteurized rib graft) was applied to 22-year-old female with large recurrent desmoid tumor. Six resected ribs were heated in the saline at 60 degrees C for 30 min. and three of them were returned to the former position. Though tumor cells and bacteria are killed under this condition, these heated bone can be revascularized and replaced by normal bone as early as fresh non-vascularized rib graft.