Defective immunological functions associated with abnormal lymphokine-activated killer activity in patients with hepatocellular carcinoma

The in vitro lymphokine-activated killer (LAK) activity of peripheral blood mononuclear cells (PBMC) from 36 patients with hepatocellular carcinoma was investigated. The activity was greatly diminished in 13 patients and enhanced in seven patients. A flow cytometric study showed that the percentage of OKM1+, Leu-7+-11b+, and Leu-7-11b+ fractions in PBMC was decreased and the percentage of OKT8+ and Leu7+11- fractions was increased significantly in the 13 patients with lower LAK activity, compared with the values of the seven higher LAK activity patients. Furthermore, the response of PBMC to interleukin-2 (IL-2) was deficient in the lower activity group. However, there was no significant difference in IL-2 production by PBMC, IL-2 receptor (p55) expression of PBMC and mitogen (Con-A, PHA) response of PBMC between the two groups. These findings indicate the possibility that diminished LAK activity in hepatoma patients is due to a decreased number of LAK precursor cells and a defective response of LAK precursor cells to IL-2.     

Allogeneic Bone Marrow Transplantation for the Treatment of Acute Leukemia: The Kanazawa Experience

Twelve patients with acute leukemia (7 with nonlymphoblasticleukemia and 5 with lymphoblastic leukemia) were treated withhigh-dose cyclophosphamide and 1,000 rad total body irradiationfollowed by allogeneic bone marrow transplantation from theirHLA-identical sibling donors. Of eight patients given transplantsat relapse, only one patient has become a long-term survivor;he is alive in disease-free complete remission (CR) 4 yr afterthe transplantation. A cure is probable in this patient. Offour patients given transplants during remission, two have survivedin unmaintained CR for almost 1 yr or more. Recurrent leukemiawas observed in two patients whose disease was resistant toconventional therapy at the time of transplantation. Major causesof treatment failure were interstitial pneumonia, hepatic failuredue to veno-occlusive disease, severe infection and relapse.Transplantation-related complications were more frequent andserious in patients who received transplants at relapse thanin those receiving them during remission. The incidence of graft-versus-hostdisease was relatively high but the disease was neither primarynor leading cause of death. These preliminary but relativelyencouraging data suggest that transplantation during remissionmay reduce posttransplant morbidity and mortality. This approachwill contribute to producing long-term survival or cure in patientswith adult acute leukemia if a suitable donor is available.     

Haemophilus influenzae type D infection and JgG2 deficiency in a patient with chronic mucocutaneous candidiasis

A 14 year old boy with chronic mucocutaneous candidiasis and persistent pulmonary infection caused by Haemophylus influenzae and Streptococcus pneumoniae is reported. Initial bacterial culture studies showed H. influenzae type B and S. pneumoniae as causative agents. H. influenzae type D was constantly isolated from the patient's sputum. Abnormally low levels of serum immunoglobulin G2 (IgG2) found in the patient may have contributed to the pulmonary infection and H. influenzae type D may be an important causative agent in immunodeficient patients.     

Potential benefits of combining cytosine deaminase/5-fluorocytosine gene therapy and irradiation for prostate cancer: Experimental study

BACKGROUND: The purpose of this study was to investigate the potential of combining cytosine deaminase/5-fluorocytosine (CD/5-FC) gene therapy and radiation therapy (either external beam radiation or radioimmunotherapy [RIT]), for the treatment of prostate cancer. METHODS: Tumor xenografts of CD-transduced LNCaP cells grown in the testes of severe combined immunodeficiency (SCID) mice were used to evaluate antitumor effect. The mice were injected intraperitoneally with 500 mg/kg of 5-FC, or with 5, 15 or 30 mg/kg of 5-fluorouracil (5-FU), for 9 days. The tumors were treated with fractionated radiation at a dose of 1 or 3 Gy/day for 3 days, or I-131 labelled anti-prostate specific antigen (anti-PSA) monoclonal antibody (mAb) administration at a subtherapeutic dose of 20 or 80 micro Ci. Intratumoral and serum concentrations of 5-FU were measured using high performance liquid chromatography. RESULTS: Mice treated with CD/5-FC gene therapy presented a significant tumor growth inhibition comparable to that obtained with 15 mg/kg, 5-FU systemic administration without marked weight loss. Treatment with CD/5-FC gene therapy resulted in higher tumor but lower serum concentrations of 5-FU than treatment with systemic 5-FU chemotherapy. An additive antitumor effect was obtained when CD/5-FC therapy was combined with 1 Gy irradiation, which by itself did not produce a significant antitumor effect. However, the efficacy of CD/5-FC therapy was not enhanced when combined with RIT, probably due to poor accumulation of the mAb as the tumor/blood ratio never exceeded 1. CONCLUSION: These findings indicate that CD/5-FC gene therapy for prostate cancer may function with enhanced antitumor effect when combined with external beam radiation. However, combining CD/5-FC gene therapy and RIT using an anti-PSA mAb may not be effective because of insufficient accumulation of the mAb at the target tumors.     

Antitumor effect of reduction of 150-kDa oxygen-regulated protein expression on human prostate cancer cells

BACKGROUND: The 150-kDa oxygen-regulated protein ORP150, a new member of the heat shock protein family that functions as a molecular chaperone in the endoplasmic reticulum, was found to increase in infiltrating cancer cells. Since enhancement of ORP150 expression and the presence of vascular endothelial growth factor (VEGF) in human prostate cancer glands were immunohistochemically demonstrated, we examined whether transduced antisense ORP150 cDNA can reduce angiogenicity and tumorigenicity through suppression of VEGF secretion. METHODS: Human prostate cancer specimens were immunohistochemically stained with fluorescein isothiocyanate (FITC) for ORP150 or vascular endothelial growth factor (VEGF). An adenovirus vector (Ad) carrying antisense ORP150 cDNA (AdCA-Antisense ORP150) was constructed and infected to prostate cancer DU145 cells. Expression of ORP150 in the cells was analyzed with western blotting and secretion of VEGF into the supernatant with an enzyme-linked immunoabsorbent assay (ELISA). Angiogenicity was evaluated by chorioallantoic membrane (CAM) assay. A nude mouse xenograft model was used to examine tumorigenicity. RESULTS: Immunohistochemical study proved that the expression of ORP150 and VEGF was enhanced in the cytoplasm of prostate cancer cells. The Ad showed 100% transduction efficiency and minimum cytotoxicity when the cells were infected at a multiplicity of infection (MOI) of 20 for 24 h. Expression of ORP150 was substantially reduced by the antisense treatment. Secretion of VEGF into the culture supernatant was reduced to 30%. Consequently, the CAM assay showed relatively low angiogenicity, while marked suppression of tumor formation was observed in the xenograft model. CONCLUSION: Adenoviral-mediated antisense ORP150 cDNA transfer is well worth considering as an option for prostate cancer gene therapy.     

Electronic endoscopy: Its present and future

As its image sensor, the electronic endoscope incorporates the so-called charge-coupled device (CCD) at its tip. The device was developed by the high technology of microelectronics, and it has a quite new construction, different from fibre-optics. Two years after the electronic endoscope was produced first by Welch-Allyn from the USA, the first Japanese electronic endoscope model was developed in 1985, and now an upper gastrointestinal model, a duodenoscope model, and a colonoscope model are available commercially from four companies worldwide.     

Euthyroid Graves' disease showing no thyroid abnormalities except positive thyroid-stimulating antibody (TSAb): two case reports

Abstract. We report two cases of euthyroid Graves' disease in women who had ophthalmopathy without previous history of hyperthyroidism. Enlargement of extraocular muscles was observed by magnetic resonance imaging (MRI). The patients had no thyroid enlargement and their serum concentrations of free T₄, free T₃, and TSH were normal. The sera were negative for antithyroid microsomal and thyrogobulin antibodies, and anti-TSH receptor antibodies measured by radioreceptor assay. T₃ suppression test results were normal. Only thyroid-stimulating antibody (TSAb) measured by sensitive bioassay was positive. These findings indicate that sensitive TSAb is the most useful laboratory test in the diagnosis of euthyroid Graves' disease.     

IMMUNOHISTOCHEMICAL STUDY OF OVEREXPRESSION OF FIBROBLAST GROWTH FACTOR-1 (FGF-1), FGF-2, AND FGF RECEPTOR-1 IN HUMAN MALIGNANT SALIVARY GLAND TUMOURS

Fibroblast growth factor-1 (FGF-1) and FGF-2 are broad spectrum mitogens. The expression of FGF-1, FGF-2, and their receptor, FGF receptor-1 (FGFR-1), was examined in malignant salivary gland tumours and normal salivary glands, using immunohistochemical methods. In seven cases of adenoid cystic carcinoma (ACC), both duct-like cells and modified myoepithelial cells were apparently immunopositive for FGF-1, FGF-2, and FGFR-1. In five cases of mucoepidermoid carcinoma (MC), all three types of tumour cells including epidermoid cells, mucous cells, and intermediate cells expressed immunoreactive FGF-1, FGF-2, and FGFR-1. In these malignant salivary gland tumours, increased expression of FGFR-1 correlated with the intensity of both FGF-1 and FGF-2 immunoreactivity. In contrast to malignant salivary gland tumours, eight cases of normal salivary gland showed negative immunostaining for FGF-1, FGF-2, and FGFR-1 while four cases were weakly immunoreactive for FGF and its receptor. These results demonstrate that malignant salivary gland tumours overexpress FGF-1, FGF-2, and FGFR-1 compared with normal salivary glands and suggest that these growth factors may play an important role in facilitating neoplastic progression in human salivary glands.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The aim of this study was to investigate the efficacy and safety of high-dose chemotherapy (HDCT) for the treatment of patients with advanced testicular cancer. METHODS: Fourteen patients were treated with high-dose carboplatin, etoposide and cyclophosphamide (with or without THP-adriamycin) followed by peripheral blood stem cell transplantation. The treatment was used for two refractory cases, a second relapse, and for consolidation after the first relapse in one case each. It was also used for nine cases as part of the first-line treatment following primary conventional-dose chemotherapy, and for one case as the first salvage for a late recurrent tumor of teratoma with malignant transformation. RESULTS: The first two patients who received intensive pretreatment with cisplatin-based chemotherapy did not respond to HDCT. The two patients who were treated with HDCT as the first or second salvage therapy achieved successful outcomes. The results for the subsequent nine patients (consisting of two with stage IIIC, five with IIIB2, one with IIB, and one extragonadal seminoma) were two progressive disease, three no change and four partial remission. Only three are alive with NED following salvage surgery. Finally, a case of teratoma with malignant transformation did not respond well to two cycles of HDCT. There were no marked adverse reactions except one episode of severe neutropenic colitis. CONCLUSIONS: The results demonstrated the limited efficacy of HDCT even in cases with a good to intermediate risk rating according to classification by the International Germ Cell Cancer Collaborative Group. Because treatment for relapse after HDCT is extremely difficult, new HDCT regimens consisting of drugs that are not used in induction chemotherapy need to be established.     

EFFECTS OF NIFEDIPINE ON BLADDER OVERACTIVITY IN RATS WITH CEREBRAL INFARCTION

PURPOSE: Our objective was to evaluate the effect of the calcium (Ca2+) channel blocking agent nifedipine on bladder overactivity induced by middle cerebral artery (MCA) occlusion and determine its site of action. MATERIALS AND METHODS: Seven days after implantation of a bladder catheter, a cannula for intracerebroventricular and intrathecal administration was implanted and the left MCA was occluded with 4-0 monofilament nylon thread in male SD rats. Twenty-four hours after the induction of cerebral ischemia, saline was infused into the bladder at a constant rate (200 microL/min.) and cystometrogram was measured in conscious state. Nifedipine was administered intracerebroventricularly (5 microL) or intrathecally (20 microL) at graded doses (0.15 ng.-0.15 microg., 0.15 microg. -1.5 microg., respectively). RESULTS: Bladder capacity in conscious rats was significantly reduced after the left MCA occlusion. Intracerebroventricular administration of nifedipine significantly increased bladder capacity in cerebral infarcted rats but not in sham operated rats. Furthermore there was no significant difference in bladder capacity between before and after intrathecal administration of nifedipine in cerebral infarcted rats. CONCLUSION: These results show that Ca2+ channel blocking agents can operate especially on the supraspinal central nervous system rather than on the spinal system in rats with neurogenic bladder overactivity following cerebral infarction.