Hasegawa Takuya, Kawahara Kohichi, Sato Koji, Asano Yoshihisa, Maeda Takehiko
Department of Pharmacology, Faculty of Pharmacy, Niigata University of Pharmacy and Medical and Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata 956-8603, Japan.
Department of Bio-Analytical Chemistry, Faculty of Pharmacy, Niigata University of Pharmacy and Medical and Life Sciences, 265-1 Higashijima, Akiha-ku, Niigata 956-8603, Japan.
Curr Issues Mol Biol. 2024 Nov 23;46(12):13364-13382. doi: 10.3390/cimb46120797.
Cancer cachexia is a debilitating syndrome characterized by progressive weight loss, muscle wasting, and systemic inflammation. Despite the prevalence and severe consequences of cancer cachexia, effective treatments for this syndrome remain elusive. Therefore, there is a greater need for well-characterized animal models to identify novel therapeutic targets. Certain manifestations of cachexia, such as pain and depression, have been extensively studied using animal models of cancer-induced bone pain (CIBP). In contrast, other aspects of cachexia have received less attention in these models. To address this issue, we established the CIBP model by injecting Lewis lung carcinoma into the intramedullary cavity of the femur, observed cachexia-related symptoms, and demonstrated the utility of this model as a preclinical platform to study cancer cachexia. This model accurately recapitulates key features of cancer cachexia, including weight loss, muscle atrophy, adipose tissue depletion, CIBP, and anxiety. These findings suggest that psychological factors, in addition to physiological and metabolic factors, play significant roles in cancer cachexia development. Our model offers a valuable resource for investigating the underlying mechanisms of cancer cachexia and for developing innovative therapeutic strategies that target physical and psychological components.
癌症恶病质是一种使人衰弱的综合征，其特征为进行性体重减轻、肌肉消耗和全身炎症。尽管癌症恶病质普遍存在且后果严重，但针对该综合征的有效治疗方法仍然难以捉摸。因此，更需要特征明确的动物模型来确定新的治疗靶点。恶病质的某些表现，如疼痛和抑郁，已通过癌症诱导的骨痛（CIBP）动物模型进行了广泛研究。相比之下，恶病质的其他方面在这些模型中受到的关注较少。为了解决这个问题，我们通过将Lewis肺癌注射到股骨骨髓腔内建立了CIBP模型，观察了恶病质相关症状，并证明了该模型作为研究癌症恶病质的临床前平台的实用性。该模型准确地概括了癌症恶病质的关键特征，包括体重减轻、肌肉萎缩、脂肪组织消耗、CIBP和焦虑。这些发现表明，除了生理和代谢因素外，心理因素在癌症恶病质的发展中也起着重要作用。我们的模型为研究癌症恶病质的潜在机制以及开发针对身体和心理成分的创新治疗策略提供了宝贵资源。
