Tumor products and the hypercalcemia of malignancy.
Tumor products and the hypercalcemia of malignancy.
复制标题
肿瘤产物和恶性肿瘤的高钙血症。
DOI：
10.1172/jci111984
复制
发表时间：
1985
期刊：
影响因子：
--
通讯作者：
D'Souza,SM
中科院分区：
文献类型：
--
作者：
Mundy,GR;Ibbotson,KJ;D'Souza,SM
在过去的五年里，我们对恶性肿瘤高钙血症机制的理解稳步推进。出现这种情况的部分原因是新兴的分子生物学技术在这一领域的应用。使用互补DNA（cDNA）探针检测基因表达和重组肿瘤产物在生物学检测中的可用性已经阐明了肿瘤影响骨细胞功能的一些机制。此外，研究人员已经认识到，了解肿瘤诱导的高钙血症的机制不仅可以增加我们对这一重要临床问题的认识，而且由于肿瘤产生这些因子可能代表正常生理机制的畸变，因此澄清它们的作用模式可能会导致对正常骨重建的新见解。与恶性高钙血症相关的肿瘤并不代表一个同质的组，也没有一个统一的机制可以解释所有的高钙血症病例。然而，类似的机制可能在类似类型的肿瘤中起作用（1）。在恶性血液病中（占总数的15-20%），局部骨吸收因素导致广泛的溶骨性骨破坏，高钙血症通常与肾小球滤过功能受损有关。在第二组中，实体瘤伴有晚期溶骨性转移，除非肿瘤广泛分布且存在广泛的局部骨破坏，否则很少发生高钙血症。这一组中最常见的例子是乳腺癌（约占总数的25%）。第三组由实体瘤组成，例如肺、头和颈的鳞状细胞癌，肾癌和卵巢癌，其中主要机制是由肿瘤分泌的一种或多种循环刺激物破骨细胞活性刺激物引起的骨吸收增加。这种综合征称为
Our understanding of the mechanisms of hypercalcemia of malignancy has advanced steadily over the last five years. This has occurred in part because of the application of the emerging techniques of molecular biology to this field. The use ofcomplementary DNA (cDNA) probes for detecting gene expression and the availability of recombinant tumor products for testing in biological assays have clarified some of the mechanisms by which tumors affect bone cell function. Moreover, investigators have realized that understanding the mech-anisms of tumor-induced hypercalcemia may not only lead to increasing our knowledge of this important clinical problem, but since production of these factors by tumors probably represents aberrations of normal physiological mechanisms, clarification of their mode of action may lead to new insights into normal bone remodeling. Tumors associated with hypercalcemia of malignancy do not represent a homogeneous group, and there is no single unifying mechanism that can explain all cases of hypercalcemia. However, it is likely that similar mechanisms are responsible in similar types of tumors (1). In the hematologic malignancies (" 15-20% ofthe total), local bone-resorbing factors are re-sponsible for extensive osteolytic bone destruction andhyper-calcemia usually occurs in association with impaired glomerular filtration. In a second group, the solid tumors associated with advanced osteolytic metastases, hypercalcemia rarely occurs unless the tumor is widespread and there is extensive local bone destruction. The most common example of this group is breast cancer (-25% of the total). A third group is comprised of solid tumors such as squamous cellcarcinoma of the lung, head, and neck, carcinoma of the kidney, and carcinoma of the ovaries, where the primary mechanism is increased bone resorption caused by tumor secretion of a circulating stimulator or stimulators of osteoclast activity. This syndrome is called