The localization of endothelin (ET)-1/big ET-1, ET-3/big ET-3, ET-A and ET-B receptor was immunohistochemically examined in human adrenal glands composed of 36 normal cases, nine hyperplasia, 70 adenomas and seven carcinomas of cortical cells. In normal adrenals, ET-1/big ET-1 and ET-B receptor were regularly detected in the cortical cells, especially in the zona fasciculata for ET-1 and zona glomerulosa for ET-B receptor but not in the medulla, while ET-A receptor localized occasionally in endothelial cells or rarely in cortical cells and ET-3/big ET-3 was very limited in the cortical cells. In hyperplasia, adenoma and carcinoma, ET-1/big ET-1 and ET-B receptor showed frequent localization, although focal distribution of the ET-B receptor was rather predominant in these groups. ET-A receptor and ET-3/big ET-3 were very infrequently expressed. Functioning versus non-functioning and hypertensive versus normotensive cases revealed no significant differences in the frequency of positive cells for ET-1/big ET-1, ET-3/big ET-3, ET-A receptor or ET-B receptor. Alternatively, the frequency of immunoreactivity to ET-1/big ET-1 or ET-B receptor significantly decreased in hyperplasia, adenoma and carcinoma, when compared with that of normal adrenal cortex. The present study, therefore, indicates that ET-1/big ET-1 and ET-B receptor are a prevalent ligand-receptor system in normal and hyperplastic/neoplastic adrenocortical cells, even with a malignant profile, and may contribute in maintaining adrenocortical cell function or cell viability but not cell growth or systemic hypertension.
The present study indicates that there is no therapeutic benefit of LND during RNU for UTUC, although pathologically positive LN status can predict poor prognosis.
Endothelin (ET) and its receptor system have been shown to exert various biological effects on different types of cells in addition to their well-known vasoconstrictor activity. Recently ET-1, ET-3 and the ETB receptor have been shown to play an important role in the development of neural crest-derived cells and, in this context, pheochromocytomas have been reported to harbor ET-1. Endothelin-3 or ET receptor subtypes, however, have not been examined in pheochromocytoma and paraganglioma so far. In the present study the immunohistochemical localization of ET-1/big ET-1, ET-3/big ET-3 and the ETA and ETB receptors were investigated to clarify the biological characteristics of these two tumors using 32 pheochromocytomas and 11 extra-adrenal paragangliomas. Endothelin-1/big ET-1 was detected in 19 pheochromocytomas (59%) and eight paragangliomas (72%), while ET-3/big ET-3 was detected in 10 pheochromocytomas (31%) and three paragangliomas (27%). The ETA receptor was found in 21 pheochromocytomas (66%) and in eight paragangliomas (73%), while the ETB receptor was found in 25 pheochromocytomas (78%) and in eight paragangliomas (73%). Normal adrenomedullary cells lacked each antigen examined. Endothelin-immunoreactive tumor cells were distributed focally or in a manner scattered, while receptor-immunostained tumor cells were distributed with a focal pattern for the ETA receptor and with a focal or diffuse pattern for the ETB receptor. Endothelin and its receptor coexisted in the same tumor in 21 of 28 ET-positive pheochromocytomas and in eight of 10 ET-positive paragangliomas. In addition, seven pheochromocytomas and two paragangliomas revealed positivity of the receptor(s) irrespective of the absence of ET-immunoreactivity. In conclusion, ET and its receptor are frequently and concomitantly expressed in the pheochromocytoma and paraganglioma. From the highly frequent expression of this system or the receptor(s), ET-receptor-mediated signal transduction of these tumors concerning growth and/or cell survival is expected, although definite biological significance of this ligand-receptor system in these tumors awaits further investigation.
Background
The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs.
Methods
We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center’s Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD.
Results
The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030–2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18,
P
< 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66,
P
< 0.001, respectively).
Conclusion
Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.
Electronic supplementary material
The online version of this article (10.1007/s10147-019-01426-w) contains supplementary material, which is available to authorized users.
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