Therapeutic potential for cancer cachexia by modulating the tumor-host inflammatory interactions

在此之前，我们已经证明了肿瘤。宿主炎症相互作用在癌性恶病质的形成中起重要作用。我们还显示了肿瘤的顶部。宿主炎症相互作用是白介素1-白介素6级联反应。首先，我们评估了结直肠癌(CRC)患者癌症恶病质的状况。我们试图通过调节IL-1-IL-6级联反应来探讨IL-1受体拮抗剂(Ra)治疗恶病质的可能性。300例结直肠癌患者血清C反应蛋白(CRP)与血清白蛋白呈显著负相关。C组：CRP 0.5 mg/dl+白蛋白3.5g/dl；D组：CRP 0.5 mg/dl+白蛋白3.5g/dl。大约60%的IV期结直肠癌患者属于C或D组，这表明这些患者可能有恶病质前期或恶病质状态…更多。大约30%的III期CRC患者属于C或D组。即使在I期或II期CRC患者中，也有15%-30%属于这些组。这一癌症恶病质评分系统与接受根治性手术的结直肠癌患者的疾病复发有关。根据对癌组织和癌旁正常组织中IL-1β和IL-6的检测，D组患者这些促炎细胞因子的表达大约是其他组的4-5倍。实验上，IL-1ra抑制HT29结直肠癌细胞株中可溶性IL-6和可溶性糖蛋白130的表达。IL-1β促进可溶性IL-6和可溶性糖蛋白130的表达。同时给予IL-1ra和IL-1β，与对照组相比，这些表达略有增强。这些结果表明，基于血清CRP和白蛋白的癌症恶病质评分系统与结直肠癌的进展和肿瘤-宿主细胞因子失衡有关。控制IL-1-IL-6级联反应可能有助于改善结直肠癌癌性恶病质和肿瘤进展。较少

Previously, we demonstrated that the tumor. host inflammatory interactions play an important role in the formation of cancer cachexia. We also showed that the top of tumor. host inflammatory interactions is the Interleukin(IL)-1-IL-6 cascade. Firstly, we evaluated the status of cancer cachexia in patients with colorectal cancer(CRC). We sought to investigate the possibility of therapeutic potential of IL-1 receptor antagonist(ra) for of patients' cachexia by modulating IL-1-IL-6 cascade. In 300 patients with CRC, there is significantly negative correlation between serum C reactive protein(CRP) and serum albmin. We divided CRC patients into four groups ; group A : CRP<0.5 mg/dl and albumin> 3.5 g/dl, group B : CRP<0.5 mg/dl and albumin<3.5 g/dl, group C : CRP> 0.5 mg/dl and albumin> 3.5 g/dl, group D : CRP> 0.5 mg/dl and albumin<3.5 g/dl. Approximately 60% of patients with stage IV CRC belong to the group C or D, indicating that these patients may have the pre-cachexic or cachexic state … More . Approximately 30% of patients with stage III CRC belong to the group C or D. Even in patients with stage I or II CRC, 15-30% of them belong to these groups. This cancer cachexia scoring system is associated with disease recurrence of CRC patients with curative surgery. With regard to the measurement of IL-1 beta and IL-6 in both cancer and adjacent normal tissue, the expression of these pro-inflammatory cytokines in patients with group D is approximately four to five times higher than those with the other groups. Experimentally, IL-1ra inhibits the expressions of soluble IL-6 and soluble glycoprotein 130 in HT29 colorectal cancer cell line. IL-1 beta enhances the expressions of soluble IL-6 and soluble glycoprotein 130. The simultaneous administration of IL-1ra and IL-1 beta slightly enhances these expressions, compared with the control. These results suggest that the cancer cachexia scoring system based on the serum CRP and albumin is associated with colorectal cancer progression and the tumor-host cytokine imbalance. The control of IL-1-IL-6 cascade may contribute the improvement of cancer cachexia and cancer progression in colorectal cancer. Less