Pathophysiologic interactions in skeletal metastasis

Orr, F. W.; Lee, Joanne; Duivenvoorden, Wilhelmina; Singh, Gurmit

doi:10.1002/1097-0142(20000615)88:12+<2912::aid-cncr6>3.0.co;2-8

Cited by 76 publications

(39 citation statements)

References 56 publications

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“…PSA, bone sialoprotein (BSP), thymidine phosphorylase (TP) and bone morphogenetic protein-6 (BMP6) share a biochemical specificity towards bone, thereby predisposing Bisphosphonates use in prostate cancer P Rodrigues et al detached cells to land on fertile soil where metastasis can develop. [7][8][9][10] The release of local paracrine factors that promote the initial bone absorption is triggered by osteoclast activation, thereby initiating the lytic lesion. Factors that promote increased osteoblastic activity are subsequently released in anarchic patterns that allow excessive bone deposition over the initial lytic lesion.…”

Section: Discussionmentioning

confidence: 99%

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients

Rodrigues

Hering

Campagnari

2004

Prostate Cancer Prostatic Dis

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Introduction: Approximately 85% of patients who die from prostate cancer present the spread of bone metastases. Even though the radiological appearance of such metastases is osteoblastic, it is now known that these lesions coexist in their microenvironment with blastic and lytic lesions. The process always begins with bone lysis by osteoclast proliferation, paralleling nearby bone deposition. The treatment options are palliative and have poor clinical response with short-lived improvement. We have studied the clinical effect of bisphosphonates (clodronate) in the treatment of skeletal complications from prostate cancer. Materials and Methods:In an open prospective study, 58 patients with hormonerefractory prostate cancer with bone metastases were assessed from November 2000 to September 2003. The mean age was 70.3 y (range: 51-87 y). Bone scintigraphy, plain X-ray, assaying of prostate-specific antigen (PSA) and biochemical tests were requested before and following treatment. Patients were previously and subsequently assessed using the visual pain scale (0-10) and Karnofsky's index after the first and second intravenous (i.v.) infusions (administration of i.v. clodronate every 28 days) and every 4-6 months thereafter. Student's t-test was used for statistical analysis. Results: A total of 53 patients (91.4%) showed improvement after the first and/or second cycle, which persisted for at least 4 months (average 6.3 months). The averages on the visual pain scale improved from 7.4 (range: 2-8) to 2.4 (0-7) and on Karnofsky's index from 43 (32-58) to 73 (50-82). The radiological appearance of the metastases improved in 27 patients (46.5%) and there were few relapses (six patients; 10.3%). Conclusions: Clodronate was effective in the treatment of skeletal complications from prostate cancer. There was an objective response in 91.4% of treated patients, with a marked improvement in the subjective visual pain scale evaluation as well as on Karnofsky's index, with low side effects.

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Section: Discussionmentioning

confidence: 99%

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients

Rodrigues

Hering

Campagnari

2004

Prostate Cancer Prostatic Dis

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“…Essa interação tem sido alvo de muitos estudos, tendo sido descrito vários fatores humorais secretados pelas células do tumor, que são capazes de estimular ou inibir os osteoblastos ou osteoclastos, de modo que a atividade final dessas células determina o padrão lítico ou blástico das lesões (14).…”

Section: O D E S E N V O L V I M E N T O D E Metástases óSseas é Um Funclassified

Estudo da correlação entre o estadiamento clínico e as alterações esqueléticas das metástases ósseas do câncer da mama

Defino¹,

Garcia²,

Simionato³

et al. 2001

Acta ortop. bras.

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RESUMOForam estudadas 48 pacientes com câncer da mama e que apresentavam metástases ósseas, com o objetivo de avaliar-se a correlação entre o estadiamento clínico do tumor primário, de acordo com protocolo do Comitê Americano de Estadiamento do Câncer, e as manifestações esqueléticas das metástases ósseas, tendo sido utilizados como parâmetros para essa avaliação o período de seguimento, o número de metástases, o tipo de lesão, a sua localização e a região do osso acometida.Foi observado correlação entre o estadiamento da lesão primária e o tempo de seguimento, que diminuia à medida que o grau de estadiamento aumentava, não tendo sido observado correlação entre o estadiamento clínico do câncer de mama e os demais parâmetros estudados.Unitermos: Metástase óssea; Câncer de mama. SUMMARY Forty INTRODUÇÃOAs neoplasias são oriundas de distúrbios da regulação do crescimento das células, que resulta na sua proliferação anormal associada a lesões locais. As células neoplásicas possuem a capacidade de invadir os tecidos vizinhos, e também de destacar-se de seu local de origem, proliferando em tecidos e locais distantes do sítio primário, que são denominadas de metástases. (16) A susceptibilidade dos diferentes tecidos às metástases tumorais permanece ainda sem explicação, e observamos tecidos que apresentam alta porcentagem de metástases tumorais e raramente são acometidos por tumores primários, como ocorre com o tecido ósseo, contrastando com a mama e o cólon , que apresentam alta incidência de lesões tumorais primárias e raras lesões metastáticas. No pulmão observamos ainda padrão distinto, com alta incidência de lesões tumorais primárias e também de metástases. (16) Os estudos de autópsia tem demonstrado que as metástases ósseas são particularmente frequentes nos pacientes que evoluem para o óbito devido a neoplasia da mama, brônquios, próstata, rins e tireóide (5,6) e provavelmente os tumores da mama, brônquios e próstata são responsáveis por cerca de 80% das metástases do tecido ósseo. (7) O carcinoma da mama é o tumor de maior prevalência nas mulheres da Europa Ocidental e América do Norte, existindo no Reino Unido cerca de 24000 casos novos por ano, que são responsáveis por 15000 mortes anuais. (16) O carcinoma da mama é a neoplasia que apresenta a maior frequência de metástases ósseas, cujos relatos variam de 38,6 a 49,6% (8,12,15) , e esse fato, associado ao crescente número de pacientes que tem recebido tratamento ortopédico devido às metástases de carcinoma da mama, motivou a realização desse trabalho, que teve como principal objetivo a observação da possível correlação entre as características clínicas e radiológicas das lesões ósseas metastáticas com o estadiamento da lesão primária da mama , e a influência que o estadiamento da lesão primária da mama poderia apresentar na elaboração da abordagem diagnóstica ou terapêutica das lesões ósseas.

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“…Furthermore, the mitogenic activity of culture supernatants from resorbing bone on MDA-MB-231 cells was decreased by the addition of neutralizing antibodies to the IGF-I receptor . TFGβ has been shown to stimulate the proliferation of Walker 256 carcinosarcoma cells that metastasize to bone (Orr et al 1995).…”

Section: The Bone Microenvironmentmentioning

confidence: 99%

“…However, these models are extremely difficult to establish. Thus, few are available (Orr et al 1995) and there are no spontaneous models of breast cancer metastatic to bone.…”

Section: Experimental Approaches To the Study Of Breast Cancer Metastmentioning

confidence: 99%

“…There are several other animal models of bone metastasis (Orr et al 1995). These include the Walker 256 carcinosarcoma, which metastasizes spontaneously to bone after intramuscular inoculation (Kostenuik et al 1992), and the human PC3 prostate cancer, which metastasizes to vertebrae in nude mice following tail vein injection if the vena cava is compressed beforehand to force the flow of blood and the injected tumor cells into the vertebrae via Barton's vertebral venous complex (Shevrin et al 1988).…”

Section: Experimental Approaches To the Study Of Breast Cancer Metastmentioning

confidence: 99%

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Factors regulating the growth of metastatic cancer in bone.

Boyce¹,

Yoneda²,

Guise³

1999

Endocrine-Related Cancer

131

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Metastatic tumor cells can interfere directly with the function of bone cells involved in normal bone remodeling or indirectly by influencing the behavior of hematopoietic, stromal and other cells in bone marrow that interact with bone cells. Recent studies of metastatic cancer have revealed that tumor cells interact closely with vascular endothelial cells, basement membrane and bone marrow stromal cells through cell surface proteins or by releasing factors which affect the function of these cells. Bidirectional interaction between marrow cells and tumor cells can give the latter a selective advantage for growth in bone which can lead to the destruction of or to increased production of bone matrix. Understanding of the mechanisms involved in tumor metastasis and growth in bone has increased in recent years, and in this review we shall describe current knowledge of these mechanisms and of the predilection of certain types of cancers to metastasize to bone, their growth in the bone microenvironment and interactions between them and bone cells. Because metastatic breast cancer has been studied more than any other, we shall focus on it as a representative example, Endocrine-Related Cancer (1999) 6 333-347 although the general principles apply to other types of cancer and to myeloma.

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Pathophysiologic interactions in skeletal metastasis

Cited by 76 publications

References 56 publications

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients

Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients

Estudo da correlação entre o estadiamento clínico e as alterações esqueléticas das metástases ósseas do câncer da mama

Factors regulating the growth of metastatic cancer in bone.

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