Illig K A, Maronian N, Peacock J L
Department of Surgery, University of Rochester Medical Center, New York 14642.
J Surg Res. 1992 Apr;52(4):353-8. doi: 10.1016/0022-4804(92)90115-g.
The cause of cancer cachexia is unclear. Tumors may be competing with the host for ingested nutrients or may be releasing some factor that actively inhibits energy utilization. To explore these questions, plasma was sterilely collected and pooled from 103 terminally cachectic Fischer 344 rats implanted with an experimental sarcoma. Control plasma was collected in similar fashion from 138 nontumor-bearing rats (NTBP). Plasma from tumor-bearing rats (TBP) or NTBP was continuously infused in a randomized, blinded fashion for 4 days into 20 normal rats. During infusion, food intake and nitrogen excretion were measured daily. At sacrifice, body weight and organ masses were determined. Rats receiving TBP demonstrated an immediate and profound anorexia compared with those receiving NTBP. Total food intake during treatment was 31.2 +/- 3.3 (g +/- SEM) in the TBP group versus 48.2 +/- 2.8 in the NTBP group (P less than 0.001 by t test). Likewise, the total decline in body weight was greater in the TBP group as compared with the NTBP group (-35.2 +/- 3.4 versus -14.6 +/- 4.0, P less than 0.001). Mean daily nitrogen balance during treatment was negative in the rats receiving TBP (-14.5 +/- 20.1 mg +/- SEM) while remaining highly positive in the rats receiving NTBP (110.7 +/- 19.3, P less than 0.002). Finally, cardiac and gastrocnemius muscle masses were decreased, while hepatic mass was unaffected. These data demonstrate that the syndrome of cancer-associated cachexia is transmissible in plasma and therefore may be mediated by a circulating molecule or molecules. Identification and purification of the molecule(s) responsible for this effect would have obvious clinical benefits.
癌症恶病质的病因尚不清楚。肿瘤可能与宿主争夺摄入的营养物质,或者可能释放某种能积极抑制能量利用的因子。为了探究这些问题,从103只植入实验性肉瘤的终末期恶病质Fischer 344大鼠中无菌采集并汇集血浆。以类似方式从138只无肿瘤大鼠(NTBP)中采集对照血浆。将荷瘤大鼠(TBP)或NTBP的血浆以随机、盲法连续4天输注到20只正常大鼠体内。在输注过程中,每天测量食物摄入量和氮排泄量。处死时,测定体重和器官质量。与接受NTBP血浆的大鼠相比,接受TBP血浆的大鼠立即出现明显的厌食症状。TBP组治疗期间的总食物摄入量为31.2±3.3(克±标准误),而NTBP组为48.2±2.8(P通过t检验小于0.001)。同样,与NTBP组相比,TBP组的体重总下降幅度更大(-35.2±3.4对-14.6±4.0,P小于0.001)。接受TBP血浆的大鼠治疗期间的平均每日氮平衡为负(-14.5±20.1毫克±标准误),而接受NTBP血浆的大鼠仍为高度正平衡(110.7±19.3,P小于0.002)。最后,心脏和腓肠肌质量下降,而肝脏质量未受影响。这些数据表明,癌症相关恶病质综合征在血浆中具有传染性,因此可能由一种或多种循环分子介导。鉴定和纯化负责这种效应的分子将具有明显的临床益处。