Rapid response of hepatocyte growth factor in pulmonary ischemia in a rat model.

Hepatocyte growth factor (HGF) is a multifunctional factor implicated in tissue regeneration, wound healing, and angiogenesis. HGF was initially thought to be liver-specific, but it has become clear that HGF acts on alveolar type II cells and bronchial epithelial cells. This study was conducted to determine the role of HGF in pulmonary ischemia in a rat model. The first increase of the plasma HGF level was noted 30 min after pulmonary ischemia, and reached a peak at 12 h. Real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) revealed that the HGF messenger RNA (mRNA) expression in the injured left lung was markedly increased at 1, 6, and 12 h after pulmonary ischemia (P &#60; 0.05). The interleukin-1beta (IL-1beta) mRNA expression, one of the inflammatory cytokines which induces HGF expression, was markedly increased at 1 h in the injured left lung (P = 0.0007). Therefore, we considered that HGF might be mainly induced by paracrine mechanisms in pulmonary ischemia. In conclusion, we have shown that the expression of HGF was induced in pulmonary ischemia, and may be a useful biological marker for the early diagnosis.</p

Dry Small Pleural Dissemination of Adenocarcinoma of the Lung Preoperatively Detected by PET/CT: A Report of Two Cases

Dry pleural dissemination in non-small cell lung cancer, defined as solid pleural metastasis of lung cancer without pleural eff usion, is a condition occurring in T4 lung cancer. Positron emission tomography (PET) has been reported to be useful for the diagnosis and staging of lung cancer. It has been reported that positive findings on PET scans of indeterminate pleural abnormalities at computed tomography (CT) are sensitive to malignancy. We encountered two cases of dry small pleural dissemination of adenocarcinoma of the lung preoperatively detected by PET/CT. A 75-year-old man and a 66-year-old man underwent CT scan, which demonstrated solitary tumor in the lung, an enlarged mediastinal lymph node, and a small pleural nodule less than 10 mm in size, all of which were positive findings on the fluorine 18 fluorodeoxyglucose (FDG) PET portion of an integrated PET/CT. Both patients underwent thoracoscopic biopsy of the dry pleural nodule revealing dissemination of adenocarcinoma of the lung (T4). Whereas histological thoracoscopic diagnosis remains mandatory before planning treatment, our cases may suggest that PET/CT will be useful as a screening modality for dry pleural dissemination of lung cancer.</p

Prognostic significance of proliferating cell nuclear antigen (PCNA) expression in non-small cell lung cancer.

Formalin-fixed, paraffin-embedded tissue sections of resected tumors from 90 patients were immunohistochemically studied to assess the prognostic value of proliferating cell nuclear antigen (PCNA) expression in non-small cell lung cancer. The individual tumors were classified into groups of high, moderate or low proliferative grade, and 38 (42.2%) patients had a high grade of proliferation. No statistically significant correlations were observed between PCNA grade and TNM status, pathological stage, resectability, histological type, degree of histological differentiation. Only vascular invasion significantly correlated with proliferative grade (p &#60; 0.05). Survival analysis showed that patients with low proliferative grade tumors survived significantly longer (a 5-year survival rate of 83.3%) than those with high proliferative grade tumors (39.4%, p &#60; 0.005). Cox's multivariate analysis revealed that PCNA grade was a significant prognostic determinant of survival. These results suggest that PCNA expression provides an independent prognostic variable for patients with non-small cell lung cancer and that it may be useful to consider this factor in treatment planning.</p

Partial liquid ventilation does not affect BALF TNF-, MIP-2, CINC-1 concentrations, or CD11b cell surface expression, but does increase macrophage proportion among BALF cells in the acute phase of rat LPS-induced lung injury.

To elucidate the mechanism of anti-inflammatory effect of partial liquid ventilation (PLV), cytokine concentration, surface CD11b, and macrophage expression were investigated in BALF. The 30-minutes group was treated with gas ventilation (GV) for 30 minutes after intratracheal LPS administration. The GV group was prepared in the same manner as the 30-minutes group, then the GV was continued for the following 2 hours. The PLV group was treated in the same manner as the 30-minutes group, and then received PLV with perflubron for the following 2 hours. Animals were euthanized to receive BAL. The PLV group showed a tendency to have a higher concentration than the GV group of TNF-alpha, MIP-2, and CINC-1 as measured by ELISA, although there were no significant differences. The ratio of expressions of CD11b and macrophages to total leukocytes were determined by flow-cytometry. There were no significant differences in the ratio of CD11b-positive expression to acquired cells (GV: 63.6 +/- 8.4%, PLV: 60.5+/-5.4%, P=0.73). However, the proportion of macrophages was significantly increased (GV: 5.6 +/-1.5, PLV: 14.0+/-1.3, P=0.006). These results suggest that the anti-inflammatory effect of PLV is not caused by the change in CD11b expression, and that PLV affects the proportion of macrophage among BALF cells.</p

Intraatrial extension of thyroid cancer: a case report.

A 61-year-old man, who was diagnosed with superior vena cava syndrome by papillary thyroid carcinoma, was referred to our hospital. A bulky thyroid tumor with tracheal invasion extended from the left neck to the right atrium without distant metastases. The risk of sudden death due to airway occlusion, tumor embolism or obstruction of the tricuspid valve led us to elect surgery. Extended resection of thyroid cancer was performed with cardiopulmonary bypass. Peritoneal dissemination was found via laparotomy. A histological diagnosis of anaplastic carcinoma arising from transformation of papillary carcinoma was made. After the operation, bilateral ureteral occlusion by peritoneal dissemination and multiple lung metastases were detected. The patient died with acute renal failure on postoperative day 12. Intraatrial extension of thyroid cancer is rare, and only 12 cases have been reported in the literature. We present a case of thyroid cancer with intraatrial extension.</p

Experimental study on size matching in a canine living-donor lobar lung transplant model

AbstractObjective: In an effort to address the donor-shortage issue, living-donor lobar lung transplants have been performed with satisfactory results. The use of small grafts is potentially problematic because it could cause high pulmonary artery pressure, resulting in lung edema. The purpose of this study was to evaluate the effect of small grafts on early pulmonary function and to identify the predictor for acceptable size discrepancy. Methods: Seventeen pairs of mongrel dogs with various donor-recipient sizes were used. Body weight, height, chest circumference, and lung weight were measured as size parameters. Right middle, lower, and cardiac lobes were implanted as a right lung of the recipient and the left lower lobe was implanted as a left lung without use of cardiopulmonary bypass. Pulmonary function of the recipient was measured for 6 hours after reperfusion. Results: A significant negative correlation was found between donor/recipient body-weight ratio and mean pulmonary artery pressure at 1 hour (r = –0.594, P =.025). A significant correlation was found between donor/recipient body-weight ratio and PaO2 at 6 hours (r = 0.704; P =.007). There was no significant correlation between the other 3 size parameters and postoperative pulmonary function. All 8 recipients with a donor/recipient body-weight ratio of 1.2 or greater survived the 6-hour assessment period, and their PaO2 exceeded 500 mm Hg at 6 hours. Conclusions: Donor/recipient weight ratio is an important predictor of early pulmonary function in a canine living-donor lobar lung transplant model

Suppression Effects of Human Recombinant Tissue Inhibitor of Metalloproteinases-1(TIMP-1) on Tumor Proliferation Using in Vivo Treatment Model of Well-differentiated Colon Cancer Cell Line, HT29

To investigate the suppressive effect of human recombinant TIMP-1 (rh-TIMP-1) on tumor proliferation using an in vivo xenograft system, HT29 was suspended in 0.1 ml phosphate buffered saline (PBS) and then subcutaneously injected in the back of female mice (BALB/C nu/nu). The mice were divided into 2 groups an and the tumor diameter was measured after rh-TIMP-1 (2 mg/kg) (rh-TIMP-1 group) or PBS (control group) was administered injections according to the following schedules. Schedule 1 : Beginning 2 weeks after the subcutaneous injection of HT29, an intraperitoneal injection of rh-TIMP-1 or PBS were performed twice a day (every 12 h) for 14 consecutive days. Schedule 2 : Beginning 1 week after the subcutaneous injection of HT29, an intraperitoneal injection was performed twice a day for 14 consecutive days. Schedule 3 : Intraperitoneal injections were started simultaneously with the subcutaneous injection of HT29, and then performed twice a day for 21 consecutive days. The mice were sacrificed and the tumors extirpated for immunohistochemical investigation. In addition, gelatin zymography and a cell proliferation assay were performed. With Schedule 1, the changes in the tumor diameter in the rh-TIMP-1 group followed the same course as those in the control group, and no suppressive effect on tumor proliferation was observed. However, with Schedule 3, a remarkable suppressive effect was observed throughout the treatment period. In immunostaining, more cases negative for MMP-9 were observed in the rh-TIMP-1 group than in the control group. Cases negative for CD34 were significantly more observed in the rh-TIMP-1 group than in the control group with Schedule 3. All of the results were obtained through the suppressive effect of rh-TIMP-1 on angiogenesis

Enhancement of gene transduction efficiency in cancer cells using cationic liposome with hyperthermia.

We evaluated the effects of hyperthermia on the efficiency of gene transduction by using a cationic liposome to develop an efficient method for lipofection. We used Lewis lung carcinoma (LLC), NIH3T3, and A549 cell lines, with Lipofectamine reagent as the cationic liposome and the LacZ gene as the reporter gene. In LLC, co-incubation of the cationic liposome and plasmid DNA complex (lipoplex) with the cells for 2 h at 41 degrees C enhanced the efficiency of gene transduction approximately 1.4-fold compared to incubation for 2 h at 37 degrees C, as measured by X-gal staining and beta-galactosidase activity. In cell lines NIH3T3 and A549, the efficiency of gene transduction showed a tendency toward enhancement after 2 h co-incubation with lipoplex at 41 degrees C compared to that at 37 degrees C, as measured by X-gal staining. This is the first study to demonstrate the enhancement of gene transduction efficiency achieved by using a cationic liposome under conditions of hyperthermia. This method should prove useful for lipofection in other cancer cells.</p

Prognostic value of vascular endothelial growth factor expression in primary lung carcinoma.

To investigate whether an association exists between vascular endothelial growth factor (VEGF) expression and tumor prognosis in primary lung carcinoma, we used immunohistochemical techniques to analyze microvessel density and VEGF expression in lung carcinoma tissue from 98 patients. Tissue had been fresh-frozen at the time of operation and preserved for more than 5 years. The results indicated that VEGF expression was positive for 50 of the 98 patients (51.0%), with 27 (27.6%) being weakly positive and 23 (23.5%) being strongly positive. The microvessel density in tissue showing weakly positive and strongly positive VEGF expression was significantly higher than that in VEGF-negative tumor tissue (P &#60; 0.05: negative vs. weakly positive, P &#60; 0.01: negative vs. strongly positive), we showed demonstrating that VEGF expression was significantly associated with intratumoral microvessel density. The 5-year survival rates were 8.7% for strongly VEGF-positive patients, 43.9% for weakly VEGF-positive patients and 79.2% for VEGF-negative patients, respectively (P &#60; 0.01: negative vs. weakly positive or strongly positive). Furthermore, multivariate analysis employing multiple regression analysis indicated that VEGF expression correlates highly with the overall survival rates of patients with primary lung carcinoma. Two variables, N status and VEGF expression, were found to be significant prognostic factors (P &#60; 0.01). The results of this study suggest that VEGF expression is associated with intratumoral microvessel density. VEGF expression may constitute important independent prognostic evidence that can help us in predicting the outcomes of patients with primary lung carcinomas.</p

Changes in levels of arachidonic acid metabolites in blood and bronchoalveolar lavage fluid after warm ischemia-reperfusion of lung.

The purpose of this study was to evaluate the role of arachidonic acid metabolites in the reimplantation response after lung transplantation in mongrel dogs. The left lung was used and two groups were studied. Group I underwent hilar stripping, while Group II underwent hilar stripping plus warm ischemia for 60 min., achieved by clamping the left pulmonary artery and veins. We measured the lung wet to dry weight ratio (W/D ratio), total pulmonary vascular resistance (TPVR), and blood and bronchoalveolar lavage fluid (BALF) levels of leukotriene B4 and C4 (LTB4,C4) and thromboxane B2 (TXB2). These parameters were measured periodically for 7 days after reperfusion. In group II, the W/D ratio and TPVR were significantly increased in comparison with Group I. The blood LTC4 level was elevated immediately after reperfusion, and BALF level of LTC4 also rose subsequently. These levels changed concomitantly with the W/D ratio. The above results suggest that arachidonic acid metabolism plays an important role in the reimplantation response, especially in pulmonary edema.</p