Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I.

Cancer cachexia is a multifactorial metabolic syndrome that affects ∼50%-80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg-1per day, for 30 days) significantly ameliorated the reduction in body weight and atrophy of muscle, fat, spleen, and thymus in mice with spleen deficiency and cachexia. The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms.

Colon carcinoma treated with oxaliplatin and capecitabine in a 12-year-old child.

BACKGROUND: XELOX (oxaliplatin 130 mg/m(2) iv, capecitabine 1000 mg/m(2) bid oral d1-14, q3w) chemotherapy has never been used in children. In this report, we present a case of a 12-year-old girl with colon adenocarcinoma, treated with surgery and XELOX chemotherapy. METHODS: On admission, the girl complained of abdominal pain and intestinal obstruction. Physical examination revealed a distended abdomen with tenderness on the left upper quadrant. Barium enema revealed a stenotic lesion at the distal end of the transverse colon, and abdominal computed tomography showed acute obstruction and a colonic mass. Laparotomy was performed after the failure of conservative treatment. RESULTS: The mass was originated from the transverse colon. Frozen sections of the specimens revealed an adenocarcinoma. Transverse colectomy was performed and regional lymph nodes were removed. Pathological examination confirmed that the mass was a poorly differentiated adenocarcinoma, and XELOX chemotherapy was used. No evidence of recurrent or metastatic tumor was found after 18 months. CONCLUSION: Although complete resection is the most effective treatment, XELOX chemotherapy is beneficial to the improvement of clinical outcome of patients with colon adenocarcinoma.

Gypenosides improve cognitive impairment induced by chronic cerebral hypoperfusion in rats by suppressing oxidative stress and astrocytic activation.

Gypenosides (GP), the saponin extract derived from the Gynostemma pentaphyllum Makino, a widely reputed medicinal plant in China, has been reported to have some neuroprotective effects. We used a rat model of chronic cerebral hypoperfusion to investigate the protective effects of GP on the cortex and hippocampal CA1 region and the underlying mechanisms for its inhibition of cognitive decline. Daily doses of 100 and 200 mg/kg GP were orally administered to adult male Sprague-Dawley rats for 61 days after inducing cerebral hypoperfusion experimentally, and spatial learning and memory were assessed using the Morris water maze. Antioxidative capability was measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine, respectively. Activated astrocytes were assessed by immunohistochemical staining and western blotting with GFAP antibodies. Rats receiving 200 mg/kg GP had better spatial learning and memory than saline-treated rats. GP 200 mg/kg/day were found to markedly enhance antioxidant abilities, decrease lipid peroxide products and oxidative DNA damage, and reduce the activation of inflammatory astrocytes. However, GP 100 mg/kg had no significant effects. GP may have therapeutic potential for the treatment of dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted.

Gypenosides protects dopaminergic neurons in primary culture against MPP(+)-induced oxidative injury.

Oxidative injury has been implicated in the etiology of Parkinson's disease (PD). Gypenosides (GPs), the saponins extract derived from the Gynostemma pentaphyllum, has various bioactivities. In this study, GPs was investigated for its neuroprotective effects on the 1-methyl-4-phenylpyridinium ion (MPP(+))-induced oxidative injury of dopaminergic neurons in primary nigral culture. It was found that GPs pretreatment, cotreatment or posttreatment significantly and dose-dependently attenuated MPP(+)-induced oxidative damage, reduction of dopamine uptake, loss of tyrosine hydrolase (TH)-immunopositive neurons and degeneration of TH-immunopositive neurites. However, the preventive effect of GPs was more potential than its therapeutical effect. Most importantly, the neuroprotective effect of GPs may be attributed to GPs-induced strengthened antioxidation as manifested by significantly increased glutathione content and enhanced activity of glutathione peroxidase, catalyze and superoxide dismutase in nigral culture. The neuroprotective effects of GPs are specific for dopaminergic neurons and it may have therapeutic potential in the treatment of PD.

[Adhesion, proliferation and osteodifferentiation of bone mesenchymal stem cells on PLGA-[ASP-PEG] tri-bolck polymer scaffolds].

OBJECTIVE: To explore the adhesion,proliferation and osteodifferentiation of bone mesenchymal stem cells (BMSCs)on the prepared lactic acid/glycolic acid/asparagic acid-co-polyethylene glycol(PLGA-[ASP-PEG])tri-block polymer scaffolds. METHODS: Modified PLGA with polyethylene glycol (PEG) and asparagic acid(ASP)that has many liga nds,and then the synthesis PLGA-[ASP-PEG] tri-block polymer material was prepared. BMSCs were cultured in PLGA-[ASP-PEG] polymer material and poly lactic acid-co-glycolic acid(PLGA)were used as control group. Precipitation method, MUT assay and total cellular protein detection were used to test the adhersion and proliferation of BMSCs. After the third generation of BMSCs was cultured on PLGA-[ASP-PEG] tri-block polymer scaffolds for 14 day and 28 day with osteogenic supplements,the osteodifferentiation of MSCs were observed through alkaline phosphatase(ALP) staining and calcium tubercle staining. RESULTS: BMSCs grew adherent to the surface of PLGA-[ASP-PEG] polymer scaffolds and the number of BMSCs was much higher than that of PLGA. The precipitation method suggested that adhesion and proliferation of BMSCs on the surface of PLGA-[ASP-PEG] was much higher than the control group (P < 0.05). MTU assay showed that after BMSCs were cultured for 20 days,the absorbance A of PLGA-[ASP-PEG] polymer scaffolds and PLGA were 1.336 and 0.780 respectively. Total cellular protein could image the adhersion and proliferation of BMSCs indirectly. After BMSCs were cultured for 12 days,the total cellular protein of PLGA-[ASP-PEG] and PLGA were 66.44 microg/pore and 41.23 microg/pore respectively. PLGA-[ASP-PEG] polymer scaffolds had well biocompatibility and cell adhersion. The positive results with ALP staining and calcium tubercle staining in both groups indicated tri-block polymer scaffold and its degradations had no effect on osteodifferentiation. CONCLUSION: PLGA-[ASP-PEG]could improve the adhesion and proliferation of seed cells on bone-matrixmaterial, maintain the morphous of seed cells and had no obvious effect on cell osteodifferentiation.

[Effect of Xiaotan Sanjie Recipe on growth of transplanted tumor and expressions of proliferating cell nuclear antigen and epidermal growth factor receptor in tissue of gastric carcinoma of nude mice].

OBJECTIVE: To observe the influence of Xiaotan Sanjie Recipe on growth of the transplanted tumor and expressions of proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGFR) in tissue of the gastric carcinoma of nude mice, and to explore the mechanism of Xiaotan Sanjie Recipe in restraining the multiplication of the stomach cancer. METHODS: MKN-45 gastric carcinoma model in nude mice was established. Forty-five nude mice were randomly divided into control group, Xiaotan Sanjie group and 5-fluorouracil (5-FU) group. Drugs were given on the next day of inoculation. Mice in the control group were given normal saline, and mice in the Xiaotan Sanjie group were given Xiaotan Sanjie Recipe. Intraperitoneal injection of 5-FU was administered in the 5-FU group. The expressions of PCNA and EGFR were examined by using streptavidin peroxidase (SP) conjugate technique, and the tumor weight and pathological characteristics were also observed. RESULTS: Compared with the control group, Xiaotan Sanjie Recipe significantly restrained the growth of the transplanted tumor, and reduced the expressions of PCNA and EGFR in tissue of the gastric carcinoma of nude mice (P<0.05). CONCLUSION: Xiaotan Sanjie Recipe can disturb the synthesis of DNA and reduce the proliferous activity of cancer cells by decreasing the expressions of PCNA and EGFR.