A new cytotoxic metabolite from a deep sea derived fungus, Phialocephala sp / 药学学报

A new sesquiterpene hydroquinone (1) was isolated from a deep sea sediment derived fungus, Phialocephala sp.. Its structure and stereochemistry were established on the basis of spectroscopic data and optical rotation. This compound was tested for cytotoxicity against P388 (murine leukemia cell) and K562 (human leukemia cell) cell lines, and displayed strong cytotoxic effects with IC50 value of 0.16 and 0.05 micromol x L(-1), separately.

A new erythrodiol triterpene fatty ester from Scorzonera mongolica / 药学学报

Two erythrodiol triterpene fatty esters, 3beta-dodecanoyl erythrodiol (1) and 3beta-tetradecanoyl erythrodiol (2), were isolated from Scorzonera mongolica. Their structures were elucidated on the basis of IR, MS and extensive 2D NMR spectroscopic analysis. Compound 1 was identified to be a new compound and 2 was confirmed to be a new natural compound. Their antitumor effects in vitro were evaluated with MTT and SRB assays, but compounds 1 and 2 only showed moderate cytotoxicities on A-549 cell line.

Effect of recipient mouse splenocytes taken orally by donor mouse on GVHD after splenocyte transplantation / 中国实验血液学杂志

This study was aimed to explore whether the GVHD in mice can be ameliorated and the GVL effect in mice can be reserved by transfusion of lymphocytes of donors fed with recipient splenocytes effect. Male (DBA-2) mice (H-2(d)) as donors were fed with BALB/c splenocytes, DBA-2 splenocytes, bovine serum albumin, or regular chow, every other day. Induction of tolerance was assessed by a mixed lymphocyte reaction (MLR). Female (BALB/c) mice (H-2(d)) as recipients received total body irradiation (TBI) of 6.0 Gy ((60)Cogamma-ray) followed by inoculation of 3 x 10(3) P388 mouse leukemia cells on the same day. Subsequently, tail vein injection of 2 x 10(7) splenocytes supplied by DBA-2 was undertaken. Control groups were fed identically without leukemia cell inoculation. The results showed that GVHD was significantly ameliorated and CD4(+)/CD8(+) ratio increased in recipient-mice transplanted with splenocytes of tolerated donors, compared with control animals. There was no significant difference in survival rate between different groups of recipients inoculated with leukemia cell. It is concluded that the peroral recipient-mouse splenocytes can ameliorate GVHD without hampering effect on GVL.

Selective elimination of alloreactive donor lymphocytes by using TBI and cyclophosphamide / 中国实验血液学杂志

This study was aimed to investigate a new method of avoiding graft-vs-host disease (GVHD) through selective elimination of alloreactive donor lymphocytes by using total body irradiation (TBI) and cyclophosphamide (Cy). Female (BALB/c x C57BL/6) F1 mice (H-2(d/b)) as recipients received (60)Co gamma-ray sublethal TBI of 4 Gy on day 0 followed by being inoculated with P388D1 leukemia cell line on day 1, injection of allogeneic splenocytes from C57BL/6 male mice (H-2(b)) was carried out for induction of graft-vs-leukemia (GVL) effect prior to stem cell transplantation (SCT), intraperitoneally injection of cyclophosphamide (Cy) (200 mg/kg) and TBI (9 Gy) was given on day 6. One day later, treated mice were rescued with bone marrow hematopoietic stem cells from (BALB/c x C57BL/6) F1 male mice (H-2(d/b)). The results showed that recipients had no occurrence of leukemia and GVHD through selective elimination of alloreactive donor lymphocytes by Cy and TBI, survived more than 210 days, the complete-donor chimerism occurred on day 21 after transplantation. The ratio of chimerism descended subsequently, but still displayed mixed-chimerism at 90 days. Control mice died of GVHD, leukemia or other death-related-transplantation within 20 to 36 days (P<0.01). It is concluded that to induce GVL effects by MHC mismatched splenocytes given before syngeneic bone marrow transplantation followed by selective elimination of alloreactive donor lymphocytes through TBI and Cy, graft-vs-host disease was thus avoided.

In vivo study on influence of a discrete nano-hydroxyapatite on leukemia P388 tissue in BALB/C mice / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the influence of a discrete nano-hydroxyapatite crystal (nano-HAp) on lymphatic leukemia P388 behavior by in vivo techniques.</p><p><b>METHODS</b>A nano-HAp was prepared by a neutralization reaction of 0.1 mol calcium hydroxide suspension and 0.06 mol phosphoric acid solutions at room temperature over pH7. The various doses of the nano-HAp only and the nano-HAp mixture with cyclophosphamide (CY) were injected into mice inoculated with solid tumor lymphatic leukemia P388 and dispersed into PRMI 1640 media harvested the leukemia P388 cells. Sixty P388 BALB/C mice were randomly grouped; 36 of them were used as nano-HAp treated groups and 24 mice as the control groups. The leukemia growth in the mice was examined morphologically, histopathologically and under a transmission electron microscope (TEM).</p><p><b>RESULTS</b>The nano-HAp was identified as a hydroxyapatite by an X-ray diffractometry (XRD) and a Fourier transform infrared spectroscopy (FTIR). The morphology and sizes were observed under a TEM. The tissue growth inhibition ratio (weight%) of solid lymphatic leukemia P388 bearing mice treated with nano-HAp at doses 35 mg/kg, 53 mg/kg and nano-HAp (53 mg/kg) combined with CY (35 mg/kg) in 3 consecutive days via intraperitineal injections were 14.95%, 32.67% and 60.45% respectively. Apoptosis of P388 cell cocultured with nano-HAp was confirmed by TEM.</p><p><b>CONCLUSIONS</b>The tissue growth restriction of solid tumor lymphatic leukemia P388 was greater after an injection of nano-HAp only or nano-HAp mixed with CY than that obtained after injection with physiological saline solution as a control (P < 0.01), and the tissue growth restriction of solid tumor after an injection of nano-HAp combined with CY was greater than that obtained after nano-HAp or CY injection only (P < 0.01).</p>

Effect of bone marrow mesenchymal stem cells on acute graft versus host disease and graft versus leukemia after allogeneic bone marrow transplantation / 中国实验血液学杂志

To investigate the effect of bone marrow mesenchymal stem cells (BMMSC) on acute graft versus host disease (aGVHD) and graft versus leukemia (GVL) after allogeneic bone marrow transplantation (allo-BMT), both bone marrow cells and BMMSC obtained after three to four weeks of culture from donor mice were transplanted into the recipient mice injected with acute lymphocytic leukemia cells 5 days before, the control group was injected with bone marrow cells alone. The survial time after allo-BMT was recorded; the general manifestation and pathological changes of aGVHD in recipient mice were observed; the effects of BMMSC on the quatity of CD4(+) and CD8(+) T cell in vivo after allo-BMT were evaluated by flow cytometry; chimerism was detected by sex chromosome. The results showed BMMSC could increase obviously the survival time, and delay onset of aGVHD, BMMSC could decrease the amount of CD4(+) T cell and increase CD8(+) T cell in vivo. It is concluded that cotransplantation of bone marrow cells with BMMSC from the same donor mice has GVL effect. BMMSC can alleviate aGVHD and maintain GVL effect after allo-BMT.

Pharmacodynamic tests of wulong kangai on transplantable tumors in mice / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the pharmacodynamic and side effects of Wulong Kangai, a new drug of Chinese traditional herbal medicine, on 4 strains of mice transplantable tumors.</p><p><b>METHOD</b>Mice transplantable tumors S180, H22, P388 and Lewis were used in the pharmacodynamic test on the granules of Wulong Kangai. The test on each tumor strain was repeated three times. In each test, 50 mice were used and divided into 5 groups. They were negative control group treated by physiological saline, cyclophosphamide control group and 3 test groups treated respectively with Wulong Kangai at deferent dosages of 10, 25, 40 g x kg(-1) x d(-1) in the treatment of Lewis and P388 and 15, 30, 50 g x kg(-1) x d(-1) in the treatment of S180 and H22.</p><p><b>RESULT</b>The tumor weight were inhibited at the rates of 90.1%, 30.8%, 49.8% and 52. 3% in the mice with tumors of Lewis, P388, S180, and H22 by high dosage of Wulong Kangai as compared with negative control group. The inhibitory rates in cyclophosphamide groups were 90.6%, 77.2%, 79.6% and 60.3% respectively. The mice body weights grew slower in high dose groups treated by Wulong Kangai granule.</p><p><b>CONCLUSION</b>Wulong Kangai was effective in treating mice transplantable tumors of Lewis, P388, S180 and H22 with a dose-dependent manner. The Lewis was the most sensitive strain to the drug among the 4 kinds of tested tumors. Side effects appeared during 9-11 days of uninterrupted treatment with high dose Wulong Kangai.</p>

Study on the anticancer activities of the Clematis manshrica saponins in vivo / 中国中药杂志

<p><b>OBJECTIVE</b>To study the anticancer activity of the Clematis manshrica saponins in vivo.</p><p><b>METHOD</b>Anticancer activities were tested in mice with experimental tumor (S180, HepA and P388) in vivo.</p><p><b>RESULT</b>The Clematis manshrica saponins showed a significant anticancer activities on Sarcoma-180, HepA and P388 implanted in mice. In S180 sarcoma, the average tumor inhibition rates were 42.78%, 52.06% and 58.25% (P < 0.05-0.01) respectively; The mean inhibition rates were 37.44%, 52.05% and 59.36% (P < 0.05-0.001) in Hep A tumor separately; while in P388 tumor, the mean inhibition rates were 34.50%, 46.78% and 54.39% (P < 0.05-0.01), respectively.</p><p><b>CONCLUSION</b>The results indicate that Clematis manshrica has obvious antitumor effects against various transplanted tumor in mice.</p>

Synthesis of 1-indole substituted beta-carboline alkaloid and its derivatives and evaluation of their preliminary antitumor activities / 药学学报

<p><b>AIM</b>To synthesize eudistomin U and its 6-OCH3/Br derivatives and 5'-Br derivatives as antitumor agents.</p><p><b>METHODS</b>Using tryptamine and indole-3-aldehyde as starting materials, through condensation, Pictet-Spengler cyclization and dehydrogenation three steps, the alkaloids and its derivatives were prepared.</p><p><b>RESULTS</b>The structures of the compounds were determined by 1HNMR, MS and HRMS. Antitumor activity in vitro was tested.</p><p><b>CONCLUSION</b>Eudistomin U and its derivatives were synthesized. The results showed that they all showed antitumor activities against mouse P388 strain.</p>

Relation between activation of NF-kappa B and chemotherapy induced apoptosis of leukemic cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the relation between activation of NF-kappa B and chemotherapy induced apoptosis of leukemic cells and the effect of vincristine (VCR) on them.</p><p><b>METHODS</b>Electrophoretic mobility shift assay (EMSA) was used to detect the activation of NF-kappa B and tunel DNA electrophoresis was adopted to observe the apoptosis induced by cytosine arabinoside (Ara-C) and etopside (Vp-16) in P388 leukemic cells.</p><p><b>RESULTS</b>The activation of NF-kappa B induced by Ara-C and Vp-16 was obviously correlated to apoptosis in P388 cells. VCR (0.1 micromol/L) could suppress activation of NF-kappa B by 52% and 63% and significantly increase the apoptosis by 89% and 123% as induced by Ara-C (100 micromol/L) and Vp-16 (100 micromol/L). The activity of NF-kappa B could be found in P388 cells before being exposed to chemotherapeutic agent.</p><p><b>CONCLUSION</b>Chemotherapeutic agents can induce apoptosis and activation of NF-kappa B of P388 cells. The mechanism of VCR potentiating chemotherapeutics induction of leukemia cell apoptosis may be related to its suppression of the NF-kappa B activity in the P388 cells.</p>

Studies on the chemical constituents of Lycianthes biflora / 药学学报

<p><b>AIM</b>To study the chemical constituents of Lycianthes biflora.</p><p><b>METHODS</b>Column chromatography was used to separate the chemical constituents. IR, MS, 1HNMR, 13CNMR and 2D-NMR technique were used to determine the structures of the isolated constituents.</p><p><b>RESULTS</b>Five compounds were isolated from this plant. Their structures were identified to be bifloride A (1), N-trans-cinnamoyltyramine (2), liquiritigenin (3), N-trans-p-coumaroyloctopamine (4), 1-O-beta-D-glucopyranosyl-2-N-2'-hydroxypalmitoyl-sphinga-4- trans-8-trans-dienine (5).</p><p><b>CONCLUSION</b>Compounds 1 and 2 are new compounds, the others were isolated from this plant for the first time. Compound 2 showed inhibitory effects on P-388.</p>

Screening of antimitotic portions from sea hare using conidia of Pyricularia Oryzae / 中国中药杂志

<p><b>OBJECTIVE</b>To apply conidia of Pyricularia Oryzae to the screening of antimitotic constituents from marine animal sea hare.</p><p><b>METHOD</b>To extract and fractionate active portions from sea hare through detecting deformation of mycelia germinated from conidia of P. Oryzae P-2b, in comparison with the cytotoxic test results in vitro.</p><p><b>RESULT</b>Two active portions, of which IC50 against P388 and HL-60 was 23.4, 18.6 and 19.4, 12.5 micrograms.ml-1, respectively, were screened from this animal.</p><p><b>CONCLUSION</b>This bioassay method was efficiently applied to the primary screening of antimitotic portions from marine animals for the first time. Being convenient, speedy and cheap, the screening model is suitable for the bioassay of active constituents from marine life.</p>

Effect of various microbial preparations on P-388 mouse lymphocytic leukemia

Four bacteria-derived immunopotentiators were tested for their protective effect on a P-388 mouse lymphocytic leukemia model. The microbial test products were prepared from the following bacterial strains: ATCC 35983 Staphylococcus epidermidis isolated from a patient with IV catheter; ATCC 31874, a patented strain listed as Staphylococcus epidermidis isolated from the urine of a cancer patient; ATCC 25615 Staphylococcus hominis obtained from a child with lymphocytic leukemia, and ATCC 25614 Staphylococcus warneri, an isolate from a patient with adenocarcinoma of the breast. A limited degree of protection and prolongation in survival time was observed in the animal group treated with the bacterial strain ATCC 31874

Methoxyphenyl maleamic acid augments the activity of cytotoxic drugs against murine tumours.

The anti-tumour effects of methoxyphenyl maleamic acid (MPMA) and cytotoxic drugs, in combination were investigated on P388 leukaemia and S180 (ascites) tumours. Simultaneous administration of MPMA with CTX or HN2 resulted in enhancement of anti-tumour activity. The increased activity was observed against P388 leukaemia, whereas S180 (ascites) tumour was not responsive to the combined treatment. The possible mechanism (s) of action, responsible for the modulation of activity of CTX and HN2 against P388 tumour have been postulated.

Actividad antitumoral del CCNU obtenido en Cuba / Antineoplasic activity of CCNU obtained in Cuba

El (1-[2-cloroetil] 1-nitroso, 3 ciclohexil urea) (CCNU) es una droga antitumoral que forma parte actualmente de múltiples esquemas de poliquimioterapia en el tratamienmto de diferentes localizaciones y su obtención en el país aumentará la disponibilidad de este producto. El presente trabajo evalúa la actividad, en comparación con el producto comercial usado actualmente en la clínica oncológica y por los resultados obtenidos en los tumores experimentales utilizados, ambos productos manifiestan semejante actividad antitumoral

Effects of cimetidine combination with cyclophosphamide in transplanted murine tumors.

Studies were carried out on the combination of Cimetidine (CMTD) with Cytoxan (CTX) in three murine tumors. While the combination significantly potentiated the anticancer effect of CTX in L1210 leukemia, the results with P388 leukemia were not significantly different. The results with Lewis Lung Carcinoma showed a consistent reduction in the number of metastases. However, there was no consistent concomitant prolongation in survival. The host strain, biology of the tumour and the drug used in combination with CMTD might be some of the factors responsible for the varied response.

Tamizaje antitumoral de plantas cubanas: II; estudio preliminar / Antitumorous screening of cuban plants: II; preliminary study

Los extractos etanólicos de 17 especies botánicas, fueron testados frente a los tumores experimentales leucemia P-388 y adenocarcinoma mamario 755. De estas especies, 16 pertenecen a la familia Rubiaceae y la restante a la familia Clusiaceae; 9 son endémicas. No se observó actividad antitumoralsignificativa de los extractos ensayados con las dosis administradas

Actividad antitumoral y principales efectos tóxicos del 1,3 biscloroetil nitrosourea (BCNU) sintetizado en Cuba / Antitumoregenic activity and main toxic effects of 1,3 bischloroethylnitrosourea (BCNU) synthetized in Cuba

Se estudió la actividad antitumoral del 1,3 biscloroetil nitrosourea (BCNU) sintetizado en Cuba en dos tumores transplantables de ratón, las leucemias L-1210 y P-388, así como la toxicidad de diferentes esquemas de administración del producto en ratas albinas. El producto aumentó notablemente la supervivencia de los animales tratados con respecto al control en los tumores experimentales usados y manifestó efectos tóxicos notables en el sistema hematopoyético y el hígado

Investigaciones sobre nuevas sustancias antitumorales: VI. Tamizaje alcaloidal y antitumoral de plantas cubanas / Researches on new antitumorigenic substances: VI. Antitumorigenic and alkaloidal screening of Cuban plants

Se estudia la actividad antitumoral de extractos etanólicos de plantas que crecen en Cuba en ratones con leucemia P-388 y leucemia 1210, se realiza un tamizaje alcaloidal para las mismas especies con el empleo de reactivos precipitantes y la cromatografía en placa delgada. Las plantas pertenecen a las familias Euphorbiaceae, Rubiaceae, Leguminoseae, Clusiaceae, Moraceae, Sapotaceae, Menispermeaceae y Sterculiaceae. Contienen alcaloides las especies Aleurites trisperma Blanco, Aleurites moluccana (L) Wiel, Pithecellobium dulce (Roxb) Benth, Tamarindus indica L., Chlorophora trinctoria L. Gaud e Hyperbaena racemosa Ukb. Tienen actividad antitumoral Chamaesyce buxifolia (Lam) Small, Andira inermis (Sw) H B K y Clusia rosea Jacq