Prognostic factors relating to survival in uterine endometrioid carcinoma.

OBJECTIVE: Epidemiologic and clinicohistopathologic prognostic factors of uterine endometrioid carcinomas were analyzed. The association of estrogen related factors, focused on adenomyosis in the prognosis of endometrioid carcinomas was also examined. METHODS: Risk factors of surgically treated 286 patients with endometrioid carcinoma (Stage I-III) were statistically analyzed. RESULTS: Overall a recurrence-free 5-year survival rate was 81% (Stage I, 94%, Stage II, 71% and Stage III, 40%). Significant prognostic factors were lymph node metastases (P = 0.0035) and serosal/parametrial invasion (P = 0.014) by multivariate analysis. Endometrioid carcinomas with co-existing adenomyosis tend to be associated with endometrial hyperplasia (P = 0.04, Fisher's exact test), diagnosed in less invasive status (myometrial invasion, P = 0.004 and serosal/parametrial invasion, P = 0.006) and therefore have a favorable prognosis (P = 0.01, log rank test). CONCLUSIONS: A favorable prognosis of endometrioid carcinomas with co-existing estrogen related factors (adenomyosis and endometrial hyperplasia) was suggested.     

微透析技术在建立灵长类帕金森病模型中的应用

为了检测单侧注射ＭＰＴＰ制备的帕金森病恒河猴模型纹状体内多巴胺及其代谢产物的含量变化,本研究采用脑内微透析技术和高效液相色谱－ 电化学方法检测了双侧尾状核头部多巴胺及其代谢产物３,４－二羟基苯乙酸和高香草酸的含量。结果证明,ＭＰＴＰ注射侧与注射对侧相比,多巴胺、３,４－二羟基笨乙酸和高香草酸的含量分别降低８５．７％ , ９５．１％ 和６７．８％ 。这与动物呈现单侧帕金森病症状,核磁共振检查显示单侧黑质区域密度减低、面积缩小以及经抗酪氨酸羟化酶免疫组化方法显示脑切片单侧多巴胺能神经元明显减少等现象一致。以上结果表明,脑内微透析技术是活体检测脑内神经递质含量变化的有效方法,可以反映模型的病程变化,可用于评价帕金森病的治疗效果。     

T-Cell hyporesponsiveness induced by activated macrophages through nitric oxide production in mice infected with Mycobacterium tuberculosis.

In active tuberculosis, T-cell response to Mycobacterium tuberculosis is known to be reduced. In the course of Mycobacterium tuberculosis infection in mice, we observed that T-cell proliferation in response to M. tuberculosis purified protein derivative (PPD) reached the maximum level on day 7, then declined to the minimal level on day 14, and persisted at a low level through day 28 postinfection. The frequency of PPD-specific CD4 T cells in the spleen on day 28 decreased to one-sixth on day 7. To further investigate the mechanism of this T-cell hyporesponsiveness, we next analyzed the suppressive activity of spleen macrophages on T-cell function. The nonspecific proliferative response of naive T cells and the PPD-specific proliferative response of T cells were suppressed by day 28 macrophages, but not by day 7 macrophages or naive macrophages. This reduction of proliferative response was restored by addition of nitric oxide synthesis inhibitor, NG-monoethyl-L-arginine monoacetate, but not by monoclonal antibody against interleukin 10 or transforming growth factor beta. These data indicate that the macrophages from mice chronically infected with M. tuberculosis suppress T-cell response through production of nitric oxide, suggesting that nitric oxide-induced elimination mediated by activated macrophages may reduce the T-cell response and the number of mycobacterium-specific CD4 T cells in vivo.     

Effects of Endoscopic Variceal Ligation on Portal Hypertensive Gastropathy and Gastric Mucosal Blood Flow

Objective: Portal hypertensive gastropathy (PHG) has been recognized recently as a potential cause of upper gastrointestinal tract bleeding and is associated with a change in gastric hemodynamic indices in cirrhotic patients with portal hypertension. Endoscopic variceal ligation (EVL) is the treatment of choice for esophageal varices. We investigated the early effect of EVL on PHG and gastric mucosal blood flow (GMBF).
Methods: We examined 35 cirrhotic patients who were treated by EVL. PHG was evaluated endoscopically and GMBF was measured by laser Doppler flowmetry before and 1 or 2 wk after EVL.
Results: After EVL, only two patients (5.7%) developed severe PHG, 6 (17.1%) developed mild PHG, and 27 (77.1%) showed no change in endoscopic appearance of PHG. In those patients who developed PHG, EVL significantly decreased GMBF at the corpus (   p < .05  ). However, no significant changes of GMBF at the corpus were noted after EVL in those patients who had no worsening of endoscopic features. EVL had no effect on GMBF at the antrum in any patients.
Conclusions: Endoscopic variceal ligation is safe and does not lead, at least within 1–2 wk, to worsening of gastropathy in most cases. Our finding that gastropathy developed in the presence of reduced GMBF may suggest that PHG develops as a result of congestion caused by blockade of gastric blood drainage rather than by hyperemia.     

Squamous cell carcinoma of the nasal septum with Wegener''s granulomatosis treated with cyclophosphamide and corticosteroids

Well differentiated squamous cell carcinoma of the nasal septum developed in a 55-year old man with Wegener's granulomatosis. It is suggested that the malignancy was induced by immunosuppressive state from an increased and prolonged use of cyclophosphamide and corticosteroids. Although the efficacy of the therapeutic concept using cyclophosphamide and corticosteroids is well established, there have been some few reports that cyclophosphamide could be implicated in the genesis of malignancies. The pathophysiology of Wegener's granulomatosis should be better understood, and effective and less toxic alternative protocol should be established.     

Pulmonary paragonimiasis referred to the department of surgery.

We encountered seven cases of pulmonary paragonimiasis. All patients were adult males and 6 of 7 cases were over 50-year-old. Except for one case of chronic pleural empyema, 6 patients were referred to the department of surgery because of having a mass lesion on chest roentgenography which was indistinguishable from malignancy. Although 3 patients had mild hemoptysis, none of them showed classical rusty sputum. Only one patient had high level of eosinophilia, whereas others showed normal or marginal level of eosinophilia. Paragonimus eggs were detected in transbronchial lung biopsy specimens from 4 patients. All patients' sera were positive for Paragonimus-specific IgG antibody by immunodiagnosis. Surgical option was undergone only for one patient with chronic pleural empyema which was not cured by repeated chemotherapy. In the present series, we could avoid surgical options due to an erroneous diagnosis. When a pulmonary mass lesion or empyema is detected in patients who live in paragonimiasis endemic areas, paragonimiasis should always be included in the different diagnosis of lung diseases.     

Involvement of vascular endothelial growth factor and urokinase-type plasminogen activator receptor in microvessel invasion in human colorectal cancers

To evaluate the association among known angiogenic growth factors or factors related to the plasminogen activation system and clinicopathological factors in patients with colorectal cancer, we examined the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGF-α), urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PA-R) and plasminogen activator inhibitor-1 (PAI-1) in clinical specimens of colorectal cancers by Northern blot analysis. In comparison with the expression of these angiogenesis-related genes in 7 paired samples of colorectal cancers and the adjacent normal mucosa, VEGF mRNA level was significantly higher in the cancer tissues than in the adjacent normal mucosa (p < 0.05). We analyzed expression of these genes in 44 cases of primary colorectal cancers. Among the 3 angiogenic growth factors we examined, VEGF mRNA expression was significantly higher in the cancer tissues with blood vessel invasion or with lymphatic vessel invasion than in those without, respectively (p < 0.05). On the other hand, u-PA-R mRNA expression was significantly higher in the cancers with blood vessel invasion than in those without (p < 0.05). In addition, there was a correlation between the expression levels of VEGF and u-PA-R mRNA in the cancer tissues we have examined. Using immunohistochemistry, strong staining of VEGF or u-PA-R was observed in the cancer cells invading the microvessels. Our findings suggest that malignant transformation might accompany the upregulation of VEGF expression in colorectal cancers and that VEGF and u-PA-R might contribute cooperatively to increase angiogenesis around the tumor as well as the metastasis via microvessels. Int. J. Cancer (Pred. Oncol.) 79:179–186, 1998.© 1998 Wiley-Liss, Inc.     

DX-8951F,a water-soluble camptothecin analog,exhibits potent antitumor activity against a human lung cancer cell line and its SN-38-resistant variant

We previously reported that DX-8951f, a novel water-soluble camptothecin analog, significantly inhibits the growth of various human and murine tumors in vitro and in vivo. The antitumor effects and topoisomerase I inhibitory activity of DX-8951f are stronger than those of other current camptothecin analogs. In this study, we established an SN-38-resistant cell line, PC-6/SN2-5, from the human oat cell carcinoma PC-6 cell line by a stepwise selection system, investigated the mechanism of resistance of this cell line and then compared the antitumor activity of camptothecin analogs against the cell line. PC-6/SN2-5 cells were resistant to SN-38 (32-fold) and SK&F104864 (topotecan; 14-fold), but barely resistant to CPT-11 (3-fold) and DX-8951f (2-fold). Topoisomerase I protein levels and topoisomerase I activities of parental cells were similar to those of resistant cells. Determination of the cellular drug concentration by either flow cytometric analysis or the high-performance liquid chromatography method confirmed that the cellular accumulation of SN-38 and topotecan was significantly reduced in PC-6/SN2-5 cells, whereas that of DX-8951f was only slightly reduced. Furthermore, DX-895lf stabilized the cleavable complex formations in intact PC-6/SN2-5 cells as well as in parental cells, but SN-38 and topotecan did not in the resistant cells. Our data suggest that PC-6/SN2-5 cells may have acquired resistance to camptothecin analogs by a decrease in intracellular drug accumulation and that DX-8951f may have the potency to overcome such a type of resistance mechanism induced by camptothecin compounds. Int. J. Cancer 72:680–686, 1997. © 1997 Wiley-Liss, Inc.