Meningitis associated with strongyloidiasis in an area endemic for strongyloidiasis and human T-lymphotropic virus-1: a single-center experience in Japan between 1990 and 2010.

Meningitis caused by enteric flora is a known complication of strongyloidiasis, and human T-lymphotropic virus-1 (HTLV-1) predisposes individuals to severe strongyloidiasis. We reviewed the clinical features of bacterial meningitis associated with strongyloidiasis seen at a single center in subtropical Japan, in an area endemic for both strongyloidiasis and HTLV-1. We found 33 episodes in 21 patients between 1990 and 2010. The results were remarkable for the high incidence of meningitis due to Gram-positive cocci (27.3 %), especially Streptococcus bovis, and culture-negative cases (42.4 %). Given the high incidence of Gram-positive meningitis, a modified approach to corticosteroid use would be advisable in areas where strongyloidiasis is endemic, due to the potentially adverse consequences of glucocorticoid therapy.

Comparative antitumor activity of 5-fluorouracil and its prodrugs in combination with hyperthermia in vitro.

We investigated the antitumor activities of 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5'-DFUR), 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207) in combination with hyperthermia in vitro. The antitumor effect of 5-FU (10(-4) M) was slightly enhanced by combination with hyperthermia (42 degrees C) for 2h, and the effect was determined to be additive. Synergistic enhancement of antitumor activity was obtained by the concurrent use of hyperthermia (42 degrees C, 2h) and 5'-DFUR (10(-4) M) or HCFU (10(-5) M). However, the antitumor effect of FT-207 (10(-4) M) in combination with hyperthermia was comparable that of hyperthermia alone. The synergistic enhancement of antitumor activity was not obtained for all drugs when the cells were preheated at 42 degrees C for 2h. On the other hand, when cells were pretreated with drugs before heat exposure, weak interactions were obtained after 5-FU and 5'-DFUR treatment, and a synergistic interaction was obtained after HCFU treatment. It is speculated that the metabolites of 5'-DFUR and HCFU enhance the cytotoxicity of 5-FU, or might change the threshold concentration for a cytotoxic effect of 5-FU in cancer cells.

Primary malignant lymphoma of the breast mimicking breast carcinoma: a case report.

A case of primary malignant lymphoma of the breast in a 52 year old woman is described herein. She presented with a painless tumor of the right breast, which was elastic-hard and measured 2 X 1 cm, although there was no lymphadenopathy noted in the axilla or any other regions. Both the biopsy carried out prior to surgery and frozen sections revealed evidence of malignancy, however, histologically, it was difficult to differentiate between malignant lymphoma and carcinoma until staining with the monoclonal antibody MB1 was performed. This allowed a diagnosis of B cell malignant lymphoma of the diffuse large-cell type to be made. The patient remains alive and well 24 months after her mastectomy.

A comparison of the antitumor effects of natural human tumor necrosis factors alpha and beta: the roles of arachidonic acid metabolism and intracellular cAMP.

We compared the antiproliferative efficacies of the natural human tumor necrosis factors alpha (nHuTNF-alpha) and beta (nHuTNF-beta). A phospholipase A2 inhibitor reduced the antitumor effects of both nHuTNF-alpha and nHuTNF-beta, but the inhibitory effect was more marked for nHuTNF-alpha than for nHuTNF-beta. Two other arachidonate metabolism pathways were also examined. A cyclo-oxygenase inhibitor moderately reduced nHuTNF-alpha-induced cell growth inhibition but did not affect nHuTNF-beta-induced growth inhibition, while a lipoxygenase inhibitor slightly reduced the antitumor effects of both types of nHuTNF. A third arachidonate metabolism pathway, cytochrome P450-dependent reductase inhibitor, did not affect nHuTNF-dependent growth inhibition. Exogenous cAMP and forskolin enhanced nHuTNF-alpha-induced growth inhibition but had no effect on nHuTNF-beta-induced growth inhibition. The stimulation of cancer cells by nHuTNF-alpha resulted in a significant elevation of intracellular cAMP concentrations, whereas nHuTNF-beta caused no such elevation. Additional studies demonstrated that combined nHuTNF-alpha and nHuTNF-beta (at similar unit concentrations, so that nHuTNF-beta was present at a molar concentration 1.4-fold greater than nHuTNF-alpha) showed an antitumor activity comparable to that of nHuTNF-alpha alone. These findings suggest the antiproliferative effect of nHuTNF-alpha to be both quantitatively and qualitatively distinguishable from that of nHuTNF-beta.

Synergistic antitumor effects of natural human tumor necrosis factor-alpha and natural human interferon-alpha or -gamma on human cancer cell lines.

This study was conducted to assess the enhanced antitumor effects of natural human tumor necrosis factor alpha (nHuTNF-alpha) and natural human interferon alpha or gamma (nHuIFN-alpha or -gamma), in combination, on ten human cancer cell lines. The cell lines tested were colon cancer (RPMI4788), lung cancer (PC10), gastric cancer (MKN-1 and MKN-28), nasopharyngeal cancer (KB), leukemia (K562), lymphoma (Daudi), Liver cancer (H-7) and breast cancer (ZR-75-30 and ZR-75-1). A mixture of nHuTNF-alpha and nHuIFN-alpha (1:1, by unit) showed cytotoxic effects on nHuTNF-alpha resistant cell lines such as RPMI4788, KB and Daudi or nHuIFN-alpha resistant cell lines such as KB, and ZR-75-1, as well as on nHuTNF-alpha or nHuIFN-alpha sensitive cells. A synergistic antitumor effect occurred in four cell lines (RPMI4788, PC10, Daudi and ZR-75-1) treated with a combination of nHuTNF-alpha and nHuIFN-alpha. Also, a combined treatment with nHuTNF-alpha and nHuIFN-gamma (1:1/100, by unit) showed cytotoxic effects on nHuTNF-alpha or nHuIFN-gamma resistant cell lines such as MKN-1, MKN-28, Daudi, H-7 and ZR-75-1. A synergistic antitumor effect occurred in eight cell lines (RPMI4788, PC10, MKN-1, MKN-28, KB, Daudi, H-7 and ZR-75-1). Thus, the combined treatment with nHuTNF-alpha and nHuIFN-alpha or -gamma expanded the spectrum of sensitive cells. These results indicate that the combined use of nHuTNF and nHuIFN may provide a certain approach to cancer treatment.

A mechanism for the potentiation of the cytotoxic effects of antimetabolites drugs (FT-207, 5FU) by hyperthermia.

This study demonstrates that the cytotoxicity of FT-207 was potentiated with elevated temperatures. This result leads us to the hypothesis that the heat-produced superoxide radicals could metabolize and degradate FT-207 to 5FU at membrane or cytoplasm.

Therapeutic potential of natural human tumor necrosis factor-alpha in combination with natural human interferon-alpha or -gamma on human cancer cells.

We assessed the antiproliferative effects of natural human tumor necrosis factor alpha (nHuTNF-alpha) and natural interferon alpha and gamma (nHuIFN-alpha and -gamma), either alone or in combination, on human lung, colon, breast cancer, leukemia and lymphoma cell lines (PC10, RPMI4788, ZR-75-1, K562 and Daudi). PC10 and ZR-75-1 were minimal sensitive (30-50% inhibition) to nHuTNF-alpha. PC10 and RPMI4788 were sensitive to both nHuIFN-alpha and -gamma. K562 and Daudi were resistant to nHuTNF-alpha and also to nHuIFN-alpha and -gamma at the concentration tested. The combination treatment with nHuTNF-alpha and nHuIFN-alpha or -gamma showed the marked antitumor effects in four cell lines (PC10, RPMI4788, ZR-75-1 and Daudi). Though further investigations using fresh tumors or in vivo experiments need to be conducted, our results may have therapeutic implications.