Juichiro Maeda

Local production and localization of transforming growth factor-beta in tuberculous pleurisy.

Transforming growth factor‐beta (TGF‐β) is one of the cytokines which play an immunosuppressive role in an inflammatory process. To investigate the local production of TGF‐β, we evaluated the levels of TGF‐β in tuberculous pleural effusions (TBPE) and non‐tuberculous benign pleural effusions (non‐TBPE) by the growth inhibition assay with MvILu mink lung epithelial cells. The mean level of TGF‐β in TBPE (46.1 ± 31.5 pM; mean ± s.d.) was higher than in non‐TBPE (21.7 ± 12.3 pM) (P<0.05). Although the level of interferon‐gamma (IFN‐γ) in TBPE measured by ELISA was significantly higher than in non‐TBPE. there was no significant difference in the levels of tumour necrosis factor‐alpha (TNF‐α) measured by ELISA between these two groups. Moreover, to elucidate localization of TGF‐β in tuberculous pleurisy, immunohistochemical studies of pleura, using the rabbit polyclonal antibody Ab39 against latent TGF‐β1 binding protein (LTBP) were performed. Results revealed that LTBP was localized in immature fibrotic areas where infiltrations of T lymphocytes and macrophages were absent. Importantly, the major sources of LTBP in these areas were thought to be mesothelial cells and fibroblasts. LTBP was not found in granulomas and mature fibrotic areas. Our data suggest that TGF‐β in tuberculous pleurisy may play important roles for regression of granulomatous inflammation and pleural fibrosis for tissue repair.

Potentiation of Metastatic Capacity by Transforming Growth Factor-β1 Gene Transfection

This study was designed to assess whether the excessive secretion of transforming growth factor‐β1 (TGF‐β1) by Chinese hamster ovary (CHO) cells transfected with TGF‐β1 gene may be linked to the development of a metastatic phenotype. We observed large numbers of metastatic colonies in the lungs of nude mice inoculated with the transfected CHO cells. The tumors derived from these transfected cells demonstrated marked angiogenesis. We postulate that the overproduction of TGF‐β1 by these tumors may participate in the metastatic progression following establishment of angiogenesis at the primary tumor site.

Transforming growth factor-beta 1 (TGF-β1)- and β2-like activities in malignant pleural effusions caused by malignant mesothelioma or primary lung cancer

We investigated the levels of TGF‐β in malignant pleural effusions (MPE) caused by malignant mesothelioma (MESO) or primary lung cancer. TGF‐β levels in MPE caused by MESO were 283.9 ± 219.2pM (mean plusmn; s.d.) and were three to six times higher than those due to primary lung cancers (P < 0.01 or P < 0.05). We also evaluated TGF‐β1‐ and β2‐like activities in MPE using specific polyclonal antibodies. Although TGF‐β1‐like activity could be detected in all cases, TGF‐β2‐like activities were detected in five of seven in MESO and in a few cases with primary lung cancer. These results demonstrate that the levels of total TGF‐β and TGF‐β2‐like activity may be clinically useful to differentiate MESO from primary lung cancer. Our data also suggest that TGF‐β may help further characterize the clinical features of MESO.

Chemotherapy of Malignant Pleural Mesothelioma.

悪性胸膜中皮腫の化学療法について検討を加えた. cisplatin+doxorubicin+vindesineによる多剤併用癌化学療法を行った5例の腫瘍縮小効果はNC4例, PD1例であった. また, cisplatin+VP-16, cyclophosphalnide+vincristine+aclacinomycinの症例は各々NCであった. 一方, tegafurまたはOK432の治療を行った4例は全てPDであった. 胸水に対しては多剤併用化学療法を行った7例に有効な結果が得られた. 以上より, 本疾患に対する今回用いた多剤併用化学療法は腫瘍縮小効果は得られなかったが, 胸水制御に関しては有効であると考えられた.