Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy in a model of hepatocellular carcinoma.

Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system combined with monocyte chemoattractant protein-1 (MCP-1) provides significant antitumor efficacy. The current study was designed to evaluate the antitumor immunity of a newly developed membrane-bound form of MCP-1 (mMCP-1) in an immunocompetent mouse model of hepatocellular carcinoma (HCC). A recombinant adenovirus vector (rAd) harboring the human MCP-1 gene and the membrane-spanning domain of the CX3CL1 gene was used. Large amounts of MCP-1 protein were expressed and accumulated on the tumor cell surface. The growth of subcutaneous tumors was markedly suppressed when tumors were treated with mMCP-1, as compared with soluble MCP-1, in combination with the HSV-tk/GCV system (P<0.01). The numbers of Mac-1-, CD4- and CD8a-positive cells were significantly higher in tumor tissues (P<0.05), and tumor necrosis factor (TNF) mRNA expression levels with mMCP-1 were almost five-fold higher than those with soluble MCP-1. These results indicate that the delivery of the mMCP-1 gene greatly enhanced antitumor effects following the apoptotic stimuli by promoting the recruitment and activation of macrophages and T lymphocytes, suggesting a novel strategy of immune-based gene therapy in the treatment of patients with HCC.

Monocyte chemoattractant protein-1 gene delivery enhances antitumor effects of herpes simplex virus thymidine kinase/ganciclovir system in a model of colon cancer.

Suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system is a well-characterized tool for cancer gene therapy; however, it does not yet exhibit sufficient efficacy to cure patients of malignancies. We have reported that adenovirally delivered monocyte chemoattractant protein (MCP)-1 augmented the antitumor effects of the HSV-tk/GCV system in an athymic nude mouse model. The current study, which uses an immunocompetent mouse model of colon cancer, was designed to evaluate the antitumor effects of MCP-1 gene delivery in conjunction with this suicide gene therapy system. Subcutaneous tumor foci were directly transduced with both recombinant adenoviruses (rAds) expressing an HSV-tk gene and either of the MCP-1, CD80 and LacZ genes, followed by GCV administration. The growth of tumors was markedly suppressed by codelivery of HSV-tk and MCP-1 genes, which was exclusively associated with the recruitment of monocytes/macrophages, T helper 1 (Th1) cytokine gene expression and cytotoxic activity of the splenocytes. Furthermore, the antitumor effects were more efficient than that obtained by the combination of HSV-tk and CD80 genes. These results suggest an immunomodulatory effect of MCP-1 in the context of suicide gene therapy of colon cancer via orchestration of innate and acquired immune responses.

[The usefulness of MR angiography (MBA) in the diagnosis of pulmonary thromboembolism].

We report a case of acute pulmonary thromboembolism (PTE) that was accurately diagnosed as PTE by magnetic resonance angiography (MRA). The patient was a 69-year-old woman who exhibited dyspnea. On chest radiography, neither infiltrative shadows nor tumor shadows were observed. Since the lung perfusion scintigram showed segmental defects in both lung fields, MRA was performed. On MRA, blockage of the artery and the perfusion defects in both upper lobes could be seen. We confirmed the diagnosis as PTE on the basis of these typical MRA findings. Our preliminary findings suggest that MRA shows promise as a safe, accurate imaging technique for the diagnosis of PTE.

[The usefulness of thoracic needle biopsy under computed tomographic fluoroscopy].

Computed tomographic (CT) fluoroscopy was utilized to perform percutaneous needle biopsies in 16 patients with abnormal thoracic shadows. Biopsies were successfully performed in 15 of the patients. A diagnosis was made in 13 cases (81%; 11 of 12 malignant and 2 of 4 benign lesions). The time required to perform a biopsy ranged from 16 to 45 minutes (26.6 minutes on average). Complications were observed in 4 patients; pneumothorax occurred in 3 and hemoptysis in 1. CT-fluoroscopic guidance was indicated when the tumor was small, located near blood vessels or in the mediastinum, or poorly visualized or invisible on conventional radiographs.

Synchronous primary adenocarcinoma of the lung and leiomyosarcoma of the small intestine.

The occurrence of synchronous epithelial cancer of the lung and leiomyosarcoma of the small intestine is rare. We report here the case of a 62-year-old man with adenocarcinoma of the lung in clinical stage IIIB (T4N0M0). After two courses of chemotherapy (cisplatin, 80 mg/m2 and mitomycin C, 8 mg/m2) the patient developed symptoms of a small bowel obstruction. Palliative surgical resection was performed and a leiomyosarcoma of the small intestine was found and defined by an immunohistological study. The resection ameliorated the patient's symptoms. The patient died of disseminated adenocarcinoma 26 months following chemotherapy.

Expression of DCC protein in colorectal tumors and its relationship to tumor progression and metastasis.

A loss of heterozygosity (LOH) at the DCC gene locus was detected in colorectal tumors, and this LOH might be related to metastasis. The aim of this study was to determine DCC protein expression in colorectal cancer and to evaluate its prognostic value. Allelic loss of the DCC locus was observed in 16 of the 23 patients (66.7%). In all 16 patients with LOH, DCC expression was decreased in the cancer tissue compared with the adjacent normal mucosa. All 23 colorectal tumors had decreased expression of this protein relative to the adjacent normal colonic mucosa in Western blot analysis. The levels of DCC protein were significantly lower in cancer tissues than in adenoma tissues. Decreased DCC protein expression was also observed by immunohistochemistry in the colorectal cancer cases. There were significant correlations between DCC protein expression and histologic type, venous invasion, and hematogenous metastasis. Patients with DCC-protein-negative tumors had a greater relative risk of recurrence compared with those whose tumors were DCC protein-positive. The 5-year survival rate was 91.0% in patients with DCC-protein-positive tumors, and 58.8% in those with DCC-protein-negative tumors; these differences between the two groups of patients were significant (p < 0.01). In multivariate analysis using the Cox regression model, DCC protein expression emerged as an independent prognostic indicator. These findings suggested that a decrease in DCC expression may have an important role in the progression of colorectal cancers and may be a biologic marker of prognostic significance.

[A case of stage IV (N4) esophageal cancer successfully treated with concurrent chemoradiotherapy].

A 71-year-old man with inoperable intrathoracic esophageal cancer was treated by concurrent chemoradiation. A dose of 48 Gy (neck) and 60.6 Gy (mediastinum) and four courses of 5-FU (500 mg/day)-CDDP (50 mg/week) were delivered. The esophageal tumor and metastatic lymph nodes of the neck showed a complete response (CR) to the treatment, whereas paraaortic lymph nodes evidenced no change (NC). The patient is doing well without symptoms at 13 months after treatment. The chemoradiotherapy produced effective improvement and quality of life in this patient.

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis.

BACKGROUND: Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. METHODS: ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. RESULTS: There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. CONCLUSIONS: The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

[Correlation between the tumor marker Pro-GRP and prognosis in patients with small-cell lung cancer].

We studied 90 patients with small-cell lung cancer in whom levels of Pro-GRP were abnormally high before therapy. Changes in the serum Pro-GRP level have been said to correlate strongly with therapeutic responses in patients with small-cell lung cancer. We found that changes in the serum Pro-GRP level (half-life > or = 30 vs < 30 days) were a significant prognostic factor. Multivariate analysis showed that in these patients the Pro-GRP level after therapy, Performance Status, and age were independent prognostic factors.

[Pulmonary alveolar proteinosis with coincidental thoracic injury. Successful bronchoalveolar lavage with a modified fiberoptic bronchoscope].

A 65-year-old laborer suffered thoracic injury in an accident. Ribs were fractured and chest X-ray films showed coincidental ground-glass, like opacities in both lung fields. CT indicated the possibility of pulmonary alveolar proteinosis, which was confirmed by histological examination of the specimen obtained during therapeutic bronchoalveolar lavage. A modified fiberoptic bronchoscope with a wedge device was used for segmental bronchoalveolar lavage. The wedge derice on a pediatric flexible fiberoptic bronchosiope allowed irrigation of six independent pulmonary segments, with no complication. Six months after discharge, the patient had no evidence of relapse.

Complete sternectomy for metastatic carcinoma with reconstruction using a latissimus dorsi musculocutaneous flap.

A 67-year-old man was hospitalized because of anterior chest pain and bulging. Histopathologic examination of a biopsy specimen revealed metastatic adenocarcinoma. For the metastatic sternal tumor a complete sternectomy was performed at all layers, following which the chest wall defect was reconstructed using no artificial materials but only a latissimus dorsi musculocutaneous flap. Postoperative respiratory function tests gave satisfactory results. This case suggests that, provided the organs within the thoracic cavity can be protected, solid or semi-solid stabilization achieved with artificial materials may not always be necessary, even in cases undergoing extensive sternectomy.

[Adherent surface treatment that improve the shear bond strength of calcium metaphosphate glass-ceramic (CMP)].

In this study we examined the shearing adhesive strength between a calcium metaphosphate glass-ceramic (CMP) and various luting materials. Two usual luting cement-zinc phosphate cement (Elite Cement 100), glass-ionomer cement (Fuji ionomer cement Type I) and three adhesive luting resin-Super Bond C & B, Panavia EX and a tentative luting resin were used as the material. We also examined the effect of three adherent surface treatments--50 microns Almina blasting, hydrofluoride etching, and sodium hydroxide etching--on the adhesive strength of the two adhesive resin, Panavia EX and the tentative luting resin, to CMP. The following conclusion were drawn: 1. The adhesive strength to CMP surface polished with #600 emery paper was higher in order of Super Bond C & B, a tentative luting resin, Panavia EX, Fuji ionomer cement Type I and Elite Cement 100. 2. Sodium hydroxide etching was the most effective for the adhesion between the adhesive luting resin and CMP among the above four adherent surface treatments. 3. Irrespective of the etching time, the stimulation of sodium hydroxide bath by supersonic waves gave an additional increase to the adhesive strength. 4. Under the stimulation by supersonic waves, increasing sodium hydroxide concentration tends to increase the adhesive strength, whereas it is little affected by the etching time within three minutes. The maximum was obtained with concentration in four or five normal (4 or 5 N) sodium hydroxide.