Effect of moderate-to-severe chronic kidney disease on flow-mediated dilation and progenitor cells. Exp Biol Med Maywood. Epub Jul Soluble perlecan domain I enhances vascular endothelial growth factor activity and receptor phosphorylation in human bone marrow endothelial cells. BMC Biochem. Stat5 promotes metastatic behavior of human prostate cancer cells in vitro and in vivo. Endocr Relat Cancer. Print Jun. Quantitative modeling and analysis of the transforming growth factor beta signaling pathway.
Biophys J. Novel surface expression of reticulocalbin 1 on bone endothelial cells and human prostate cancer cells is regulated by TNF-alpha. J Cell Biochem. This compound is being tested again as a possible addition to the current standard of care, and it recently was shown to improve survival for children with osteosarcoma when combined with standard of care therapy.
No other therapies have shown any promise so far, although there are numerous ongoing clinical trials using compounds that activate the immune system TNF, FasL or targeted drugs Rapamycin. An example of one such trial was recently published Paoloni et al. Ongoing work supported by the AKC Canine Health Foundation, the National Institutes of Health, and other agencies is rapidly unraveling risk factors, causality, and potential new targets for therapy of bone cancer.
Reports from two groups Gavin et al from Minnesota Gavin et al. Further refinement of this work could lead to predictive tests that would allow owners to make educated decisions regarding treatment, based on the probability that their dog had a tumor that was likely to respond or not to conventional surgery plus adjuvant chemotherapy. The data from Gavin are complementary to published results by Thomas et al Thomas et al.
Innovative approaches using gene-based immunotherapy and targeted therapies also show promise to improve outcome for this disease. And finally, recently published as well as soon-to-be-published work from a long-term collaboration between our group and the Breen group, as well as others Selvarajah et al. These data will further validate the opportunities to develop new treatments that will simultaneously improve the health and wellbeing of our dogs and our kids. Comstock, K. Cooley, D.
Endogenous gonadal hormone exposure and bone sarcoma risk. Cancer Epidemiol Biomarkers Prev 11, Duval, D. Molecular markers of metastatic progression and chemotherapeutic resistance in canine osteosarcoma. Gavin, K. Kurzman, I. Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin. Clin Cancer Res 1, Paoloni, M.
Launching a novel preclinical infrastructure: comparative oncology trials consortium directed therapeutic targeting of TNFalpha to cancer vasculature. Phillips, J. Heritability and segregation analysis of osteosarcoma in the Scottish deerhound. Genomics 90, Ru, G.
Host related risk factors for canine osteosarcoma. Vet J , Selvarajah, G. Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times. Mol Cancer 8, Thomas, R. Influence of genetic background on tumor karyotypes: evidence for breed-associated cytogenetic aberrations in canine appendicular osteosarcoma.
Chromosome Res 17, Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases. Learn How to Help. Main Menu. Help Future Generations of Dogs Participate in canine health research by providing samples or by enrolling in a clinical trial.
Connect With Us:. Box , Raleigh, NC Similar to osteoporosis, osteolytic metastases are caused by osteoclast stimulation and not by the direct effects of tumor invasion into bone. Such increased bone resorption in the osseous microenvironment has the same mechanism as osteoporosis, and studies 10 , 22 , 23 have found that antiresorptive agents alleviated tumor burden in bone; in addition, bone resorption inhibitors, such as bisphosphonates, have been the standard of care for patients with bone lesions.
As such, patients with precancer osteoporosis presumably provide more fertile premetastatic niches compared with those without precancer osteoporosis because of the number of osteoclast-mobilizing factors. However, our study of a random sample of women with early-stage breast cancer found that those with precancer osteoporosis did not exhibit a greater risk of forming bone lesions.
We then examined whether precancer osteoporosis therapy would make any difference to the results and found that it was also not associated with a difference; those treated with nonbisphosphonate drugs had near-identical risks to those without any treatment, and the association for bisphosphonates use was nonsignificant as well. Age at cancer diagnosis was a significant risk factor for developing bone metastasis in our data, although other studies 24 - 26 have reported it as protective against several types of distant recurrences for breast cancer.
Although we treated age as a continuous variable, others 24 - 26 divided it into several age groups and included some covariates, which might have contributed to such different results. In our data, the proportions of patients with bone lesions increased with age, as did the percentages of patients with distant metastases and those who died eFigure 4 in the Supplement.
When we assessed the time it took for patients with breast cancer to develop bone metastasis among those in whom it developed, patients with precancer osteoporosis treated with either type of osteoporosis therapy did not have significant differences compared with those without precancer osteoporosis. However, those who never received osteoporosis therapy before the diagnosis of breast cancer developed bone lesions more quickly. In other words, untreated osteoporosis was associated with accelerated secondary bone lesions, and we suspect osteoporosis therapy only delayed tumor invasion into bone but did not prevent it.
Because anatomical structures in humans are presumably similar, it is unlikely that tumor cells from the primary site would travel to different first destinations. Our findings appear to contradict the seed-and-soil hypothesis of Paget, 1 which has been the predominant explanation of nonrandom metastatic patterns, but that hypothesis had little definitive proof from clinical observation or empirical studies. Had the hypothesis been true, cancers that affect large numbers of postmenopausal patients would have relapsed in bone, but ovarian cancer cells seldom metastasize outside the peritoneal cavity and the most common distant recurrence site for endometrial carcinoma is the lung.
This latter example indicates that the defected bone marrow did not attract more metastasis, but the progression of metastatic tumor was different from that in healthy controls after the metastasis developed, which is comparable to our finding. These results suggest that organ microenvironments interact with disseminated cancer mostly after the specific organ has been predetermined to be the designated location.realtours360.com/img/cewebeca/1516-localizar-un.php
Although we are not able to determine the organ selection mechanism for metastasis, we suggest 2 conclusions from the gathered evidence. First, each cancer type has its preferred secondary lesion sites, but not every patient followed this preference. Second, the preferred metastatic site is not dictated by the microenvironment of the selected organ. We therefore conceived a hypothesis that metastatic sites had been predetermined by an unknown mechanism we called the ecosystem of the body before the seed landed on the soil, then the microenvironment of the soil supported the growth of the seeds after their landing.
This study has some limitations. First, the data sets lack some clinical variables, including cancer subtypes and tumor size, although research indicates that rates of bone lesions were similar among different subtypes of breast cancer, and the poor prognosis of triple-negative type was attributable to the excess risk of visceral metastases. Third, the osteoporosis cohort lacks patients who had never developed osteoporosis throughout the study period.
Fourth, osteoporosis may be present for years before it is diagnosed; therefore, the associations might be underestimated. Our study found that osteoporosis that developed before breast cancer was not associated with the probability of forming secondary bone lesions, but untreated osteoporosis was associated with accelerated development of bone metastases should they occur; this finding suggests that organs of secondary lesions had been predetermined. Sites of distant metastases might be determined by the body rather than the organ microenvironments.
Because recurrences and metastases are major obstacles to cancer treatments, determining the organ preferences for metastases may be crucial to treating the disease. Published: March 8, Author Contributions: Ms. Chen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Critical revision of the manuscript for important intellectual content: All authors. Conflict of Interest Disclosures: None reported. Chen is supported by an Academia Sinica Student Grant. Home Issues Specialties For Authors.
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Download PDF Comment. View Large Download. Flow Diagrams of the Study Cohorts. Table 1. Definition of Osteoporosis Therapy eFigure 1. Age Distributions of the Studied Cohorts eFigure 2. The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev. PubMed Google Scholar. Metastasis of cancer: a conceptual history from antiquity to the s.
Bone Marrow Research
Nat Rev Cancer. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. J Natl Cancer Inst. Metastasis: from dissemination to organ-specific colonization. Metastasis to bone: causes, consequences and therapeutic opportunities. Mechanisms of bone metastasis. N Engl J Med. Cancer to bone: a fatal attraction. Bone metastasis: the importance of the neighbourhood. Association between nucleoside analogues and risk of hepatitis B virus—related hepatocellular carcinoma recurrence following liver resection.
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