This study characterized cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) cell lines, tumor specimens, and blood samples. The CD90+ cells, but not the CD90(-) cells, from HCC cell lines displayed tumorigenic capacity. All the tumor specimens and 91.6% of blood samples from liver cancer patients bore the CD45(-)CD90+ population, which could generate tumor nodules in immunodeficient mice. The CD90+CD44+ cells demonstrated a more aggressive phenotype than the CD90+CD44(-) counterpart and formed metastatic lesions in the lung of immunodeficient mice. CD44 blockade prevented the formation of local and metastatic tumor nodules by the CD90+ cells. Differential gene expression profiles were identified in the CD45(-)CD90+ and CD45(-)CD90(-) cells isolated from tissue and blood samples from liver cancer patients and controls.

Summary. The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course.Median survival times were 1´4 years, 3 months and 1´6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

The pharmacology and clinical application of traditional Chinese medicine has been extensively documented. We have used an in vitro model system, PC12 cells, to demonstrate the presence of neuroactive compounds in Ganoderma lucidum (lingzhi). Ganoderma extract induced the neuronal differentiation of PC12 cells and prevented nerve growth factor-dependent PC12 neurons from apoptosis. Moreover, these effects of ganoderma might be mediated via the ras/extracellular signalregulated kinase (Erk) and cAMP-response element binding protein (CREB) signaling pathways, as demonstrated by the phosphorylation of Erk1, Erk2 and CREB. Thus, our data not only present the first evidence of the presence of neuroactive compounds that mediate the neuronal differentiation and neuroprotection of the PC12 cells, but also reveal the potential signaling molecules involved in its action. ß

Summary:develop invasive fungal infections. [1][2][3][4] The diagnosis of fungal infections is particularly difficult in immunocompromised patients, and most patients are treated presumptively. Sixty-four adult patients (median age 43) with hematologic malignancies who were immunocompromised after Early institution of anti-fungal therapy is associated with better outcome, and withholding therapy until a definitive allogeneic (n = 23) or autologous (n = 9) blood/marrow transplantation, or chemotherapy (n = 32) received 68 diagnosis is made results in dissemination of the infection with a high mortality. 4 courses of amphotericin B lipid complex (ABLC, Abelcet) at the daily dose of 5 mg/kg for presumed Amphotericin B is the primary treatment for systemic fungal infections in immunocompromised patients because (n = 52) or proven (n = 16) fungal infection. The major indications for ABLC were failure of previous antifunof its broad spectrum of activity. 5,6 However, its use is limited by a variety of adverse effects including severe gal therapy and/or renal dysfunction. Fifty-three treatment courses in 49 patients comprising 4-58 doses systemic reactions such as fever, rigors, phlebitis and bronchospasm. 6 The major problem with amphotericin is (median 10) were considered evaluable. Fourteen courses administered for confirmed infections resulted its dose-related nephrotoxicity which compromises its efficacy in treating systemic fungal infections and restricts its in nine complete and one partial responses, and four failures (71% response). Thirty-nine empiric courses prophylactic use. 7 Drug-induced renal dysfunction is a major concern after blood or marrow transplantation resulted in 18 complete and six partial responses, and 14 failures (64% response). The overall response rate (BMT), 8,9 where the use of a less nephrotoxic formulation of amphotericin would be particularly attractive. 10 was 66%. Five of seven evaluable patients with aspergillus pneumonia responded. Response rates were compa-A number of lipid-based formulations of amphotericin have been developed to improve the tissue distribution of rable for chemotherapy, autograft and allograft recipients. The change in serum creatinine from the beginning amphotericin and to reduce the toxicity associated with conventional amphotericin. 10 Amphotericin B lipid comto the end of therapy was −284 to +277 mol/l (median +24). The creatinine doubled during seven evaluable plex (ABLC) is derived from a liposomal formulation of amphotericin B consisting of dimyristoyl-phosphatidylcourses of therapy, five of which were associated with concomitant nephrotoxic therapy. Nephrotoxicity was choline and dimyristoyl-phosphatidylglycerol in a 7:3 molar ratio. Unlike the original liposomal formulation, comparable for transplant and chemotherapy patients. Renal dysfunction necessitated discontinuation of ABLC has a ribbon-like appearance. 10 Here, we report our experience with the use of ABLC ABLC in only four patients. These data suggest that ABLC is effective in presumed or co...

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Summary We have previously shown that cimetidine, given concurrently for 2 weeks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydro‐xylamine metabolite of dapsone. The aim of the present study was to examine the effect of this combination on the benefit/toxic ratio of dapsone over a longer period. Eight patients (six dermatitis herpetiformis, one linear IgA disease, one folliculitis decalvans) on long‐term dapsone 50‐100 mg daily, took cimetidine 1·6g daily concurrently for 3 months. At 3‐weekly intervals, a clinical assessment was made, plasma dapsone and methaemoglobin were measured, and parameters of oxidative haemolysis were monitored. The dapsone level rose from 2298±849 ng/ml (mean+SD) at baseline to 3006±1131 ng/ml at week 3 of cimetidine (P<0·01). This rise in plasma dapsone was sustained during cimetidine administration, falling to 2446±954 ng/ml when cimetidine was stopped (P<0·02). The methaemoglobin fell from 5·5·2·2% (mean±SD) at baseline to 3·9±1·1% at week 3 (P<0·01). and remained low until week 12, when there was a return to baseline values (P<0·01). The haemoglobin did not change from the baseline of 12·7·0·3 g/dl (mean±SD), and other parameters of haemolysis were unaltered. There was a fall in the visual analogue score for headache (P<0·05), but this was not associated with any deterioration in control of the skin disorders. Hence, long‐term concurrent cimetidine results in increased plasma dapsone levels without increased haemolysis, and is accompanied by reduced methaemoglobinaemia for more than 2 months. Cimetidine thus improves the therapeutic/toxic ratio of dapsone. Such a therapeutic strategy may be appropriate for patients who require high‐dose dapsone, or those who are particularly susceptible to dapsone‐induced haemotoxicity.

SummaryA patient with homozygous sickle cell disease presented with sickle crisis complicated by hepatic and pulmonary sequestration and required intensive therapy. During the recovery phrase she developed a rapid rise of haemoglobin concentration, unrelated to blood transfusion, followed by hypertension, congestive cardiac failure and catastrophic intracerebral haemorrhage. This serious haemodynamic disturbance was considered to be caused by a reversal of the sequestration process. Careful monitoring ofa sickle cell patient's blood pressure, blood counts, haematocrits, haemoglobin S level and plasma viscocity, even after the end of a sequestration crisis, is recommended.