Prostate adenocarcinoma is associated with the formation of osteoblastic metastases in bone. It is hypothesized that osteoclastogenesis is a critical component in the development of skeletal metastases. These findings, however, were generally noted in predominantly osteolytic lesions. The pathophysiology of osteoblastic lesions remains unknown but the type of bone lesion formed may be influenced by the cytokines produced by prostate tumors. To test this theory, we implanted PC-3 and LAPC-9 cells into the tibias of SCID mice. These mice were sacrificed at 1, 2,4, 6, and 8 weeks after implantation and histologic analysis was performed on these tibias. PCR analysis was also performed on bulk tumors. The results showed that the PC-3 implanted tibias developed pure osteolytic lesions while the LAPC-9 implanted tibias developed pure osteoblastic lesions on radiographs. Analysis of tibias after injection with PC-3 cells revealed progressive osteolytic lesions with abundant osteoclast activity at 2 weeks and destruction of the proximal tibia at 6 weeks after cell implantation. In contrast, the LAPC-9 cells formed osteoblastic lesions six weeks after cell injection. There were rare osteoclasts prior to the establishment of the osteoblastic lesions but greater osteoclast activity was noted with remodeling of the osteoblastic lesion 8 weeks after implantation of the tumor cells. PCR analysis revealed that PC-3 cells produced RANKL, IL-1, and TNF-a, which are associated with osteoclastogenesis. In contrast, LAPC-9 cells produced osteoprotegerin, which blocks osteoclast production and no detectable levels of RANKL or IL-1 and only minimal amounts of TNF-c( were noted. These cells secreted BMP-2, -4, -6, and IL-6, which are associated with bone formation. These results suggest that the role of the osteoclast in the development of a metastatic lesion is variable depending on the phenotype of the prostate cancer cells, and that tumor-induced osteolysis may not be required for osteoblastic metastases.
Purpose: Systemic lupus erythematosus (SLE) is a systemic disease and is commonly considered a contraindication for cardiac transplantation. Meanwhile, lupus myocarditis can present with severe left ventricular dysfunction which my progress to cardiogenic shock with a fatal outcome. Heart transplantation is rarely considered a treatment option, due to 1) multi-organ involvement, and 2) possibility of recurrence of lupus in the transplanted heart. We summarized published cases of cardiac transplantation in SLE. Methods: Two investigators independently searched PubMed, Ovid/Medline, and Google Scholar using terms "heart transplantation", "cardiac transplantation" AND "lupus", "systemic lupus erythematosus", and "lupus myocarditis" for papers published in English in 1988-2020. We then manually searched the references in relevant articles. We included all cases of adult patients where individual patient data were present. Results: We identified 11 cases, six males, and five females, mean age 28 +/-5.47 years. Six of the patients were male and five were female. While all patients had SLE, the most common indication for transplant was pulmonary hypertension (6), followed by lupus myocarditis (2), dilated cardiomyopathy (2), and infective endocarditis (1). In 6 patients there was a dual organ (heart/lung) transplantation, while in five the heart was the only transplanted organ. Two patients died within 2 months post transplant from bowel infarction, and one died in one year from rejection. Remaining eight patients were alive and well after a follow-up ranging nine months to four years, mean 26 +/-9.9 months. Recurrence of lupus was not reported in any patient, including six cases where it was specifically indicated that there was no recurrence. Conclusion: Based on reported cases, heart transplantation in SLE is a viable option, with good survival and no recurrence of lupus in the transplanted heart. In cases of intractable heart failure in patients with SLE, cardiac transplantation should be considered.
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