Sarcomatoid renal cell carcinoma: Rapid dissemination detected on FDG PET‐CT

We present the FDG PET‐CT findings in a patient with persistent pain 7 weeks after a nephrectomy and lymph node dissection for a sarcomatoid renal cell carcinoma. Although conventional imaging was unable to detect evidence of metastatic spread outside the para‐aortic nodes, a PET‐CT scan showed unexpected extensive dissemination. Currently, there are no reports in the literature of the PET‐CT findings in sarcomatoid renal cell carcinomas.     

Diet and cancer prevention: the fiber first diet

Diet can play a major role in cancer prevention. The international differences in cancer incidence are largely accounted for by lifestyle practices that include nutrition, exercise, and alcohol and tobacco use. About 50% of cancer incidence and 35% of cancer mortality in the U.S., represented by cancers of the breast, prostate, pancreas, ovary, endometrium, and colon, are associated with Western dietary habits. Cancer of the stomach, currently a major disease in the Far East, relates to distinct, specific nutritional elements such as excessive salt intake. For these cancers, information is available on possible initiating genotoxic factors, promoting elements, and prophylactic agents. In general, the typical diet in the United States contains low levels of the potent carcinogenic agents, heterocyclic amines, formed during the cooking of meats. It provides only about half the potent appropriate fiber intake and is high in calories. About twice as many calories as would be desirable come from fat, certain kinds of which enhance the development of cancers. Other foods with functional properties, such as soy products and tea, can be beneficial. To achieve reduction in risk of certain cancers, diet must be optimized, primarily to reduce caloric intake and the fat component. The latter should be 20% or less of total caloric intake and fiber should be increased to 25- 35 g per day for adults. One approach to achieving these goals is the Fiber First Diet, a diet designed around adequate fiber intake from grains, especially cereals, vegetables, legumes, and fruits, which thereby reduces both calorie and fat intake. Such dietary improvements will not only reduce cancer and other chronic disease risks, but will contribute to a healthy life to an advanced age. A corollary benefit is a lower cost of medical care.      

菊叶三七生物碱成分的研究

从菊科蒂叶三七植物中分离出六个生物碱,对其中四个进行了鉴定。光谱数据证明:生物碱Ⅰ和Ⅱ分别为已知的千里光碱(senecionine,Ⅰ)和千里光菲灵碱(seneciphylline,Ⅱ),生物碱Ⅲ和Ⅳ为新成分,分别命名为菊三七碱甲(sineciphyllinine,Ⅲ)和菊三七碱乙[(E)-seneciphylline,Ⅳ]。     

Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-1 channel regulation and expression

Background and purpose:

Statins and fibrates can produce mild to life-threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC-1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin-treated rats. A high gCl, controlled by the Ca²⁺-dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl.

Experimental approach:

In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC-1 mRNA level by quantitative real time-polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC-1 channels expressed in human embryonic kidney (HEK) 293 cells.

Key results:

Chelerythrine, a PKC inhibitor, applied in vitro on muscle dissected from atorvastatin-treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin-treated rats but not in those from fenofibrate-treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC-1 channel mRNA was found in both fluvastatin-and fenofibrate-treated rat muscles. Fenofibric acid, the in vivo metabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells.

Conclusions and implications:

Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC-1 channel conductance. While statins promote Ca²⁺-mediated PKC activation, fenofibrate directly inhibits ClC-1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC-1.     

麦冬类中药组织切片计算机三维重建图鉴

利用计算机技术实现麦冬类中药组织连续切片三维重建与动态显示,为计算机辅助生药学鉴定和教学提供了新的三维图像技术和研究资料。     

Initiating activity of the anti-estrogen tamoxifen, but not toremifene in rat liver

A striking difference between two structurally related anti-estrogen medicines is that tamoxifen is strongly hepatocarcinogenic in the rat, whereas toremifene lacks such activity. To study the basis for this difference, the initiating potential of tamoxifen and toremifene were studied by measurement of rapid induction of hepatocellular altered foci (HAF) that express placental-type glutathione S-transferase in the livers of female Sprague-Dawley (S-D) rats and female Fischer 344 (F344) rats. Both agents were administered by gavage at equimolar doses up to a dose that produced marked weight gain suppression. In rats given the high dose of 40 mg/kg per day tamoxifen continuously for 36 weeks, 75% of S-D rats developed liver neoplasms, in contrast to only 10% of F344 rats. In the S-D strain, tamoxifen produced a tendency to increased HAF at 2 weeks at the dose of 40 mg/kg per day and by 12 weeks, a dose-related increase was evident. In contrast, toremifene induced no HAF even at the equimolar high dose of 42.4 mg/kg per day for 12 weeks. The induction of HAF by tamoxifen was less in the F344 rats. Neither agent elicited increases in hepatocellular proliferation in S-D or F344 rats. When phenobarbital was administered for 24 weeks as a promoting agent after the anti-estrogens, S-D rats given tamoxifen at 20 mg/kg per day for 12 weeks, developed liver neoplasms, but not F344 rats or rats of either strain given even a higher dose (42.4 mg/kg) of toremifene. Thus, tamoxifen has initiating activity in these rat strains whereas toremifene does not.      

Elevated expression and altered pattern of activity of DNA methyltransferase in liver tumors of rats fed methyl-deficient diets

DNA methyltransferase (MTase) activity in nuclear extracts from neoplastic and preneoplastic livers of rats fed a methyl-deficient diet (MDD) is elevated compared with that seen in the livers of control rats. Nuclear proteins were prepared in the presence of protease inhibitors including trans-epoxy succinyl-L-leucylamido-(4- guanido)butane and were fractionated by isoelectric focusing. In normal, control liver, two distinct MTase fractions were observed. In MDD-induced malignant liver, a third fraction, in addition to the previous two, was also seen. Both the DNA substrate and the cytosine site specificities of the third MTase fraction differ from those of the other two fractions. The distinct MTase activity in liver tumor has significantly more de novo MTase activity than do the MTase fractions of normal, control liver. Thus, normal and neoplastic rat livers differ in DNA MTase fractionation patterns and site specificities. The altered DNA MTase activity observed in rat liver tumors caused by MDDs may be one of the critical factors contributing to cancer formation through abnormal DNA methylation.      

Canthaxanthin induces apoptosis in human cancer cell lines

To investigate the possibility that canthaxanthin inhibits cancer cell growth by inducing apoptosis, human WiDr colon adenocarcinoma and SK- MEL-2 melanoma cells were treated with two different doses of the carotenoid for 48 h. Canthaxanthin was incorporated and/or associated to cells. The treatment with the carotenoid caused growth inhibition in both cell types. Concomitantly, apoptosis was induced. Increasing time of exposure and carotenoid concentration, this effect was more pronounced. At 48 h, the percentages of apoptotic cells were 13 and 15, using 1 microM canthaxanthin, and 18 and 20, using 10 microM canthaxanthin in WiDr and SK-MEL-2 cells, respectively. This study represents the first demonstration that canthaxanthin is able to induce apoptosis in tumour cells.      

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.