Effect of IL‐1 on experimental bone/bone‐marrow metastases

Arguello, Francisco; Baggs, Raymond B.; Graves, Brian; Harwell, Shari E.; Cohen, Harvey J.; Frantz, Christopher N.

doi:10.1002/ijc.2910520522

Cited by 37 publications

(24 citation statements)

References 15 publications

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“…This finding may also suggest that some bone metastases are associated with bone marrow micrometastasis existing in the state of tumor dormancy. As factors activating this hematopoietic marrow metastasis, various cytokines, such as epithelial growth factor, vascular epithelial growth factor, interleukin-1, and tumor necrosis factor-a have been proposed in previous studies [26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Bone recurrence after curative resection of gastric cancer

Park

Song

et al. 2012

Gastric Cancer

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Background Standard follow up for bone recurrence has not yet been established for gastric cancer after surgical resection. The aim of this study was to investigate the incidence of and related risk factors for bone recurrence after surgical resection of gastric cancer. Methods A cohort of 3035 gastric cancer patients after curative resection was reviewed. We analyzed the patients who had bone scintigraphy before the surgery as well as during the follow-up period. The incidence of and the risk factors for bone recurrence after surgical resection of gastric cancer were investigated. Results In a total of 1683 patients analyzed, bone recurrence was detected in 30 patients (1.8 %). The incidence of bone recurrence was significantly higher in advanced gastric cancers than in early lesions (3.5 vs. 0.4 %, p \ 0.01). The most common recurrence site was the spine, followed by pelvic bone and rib. Most patients had multiple bone metastases. The median time for recurrence was 28 months (range 4-111) from the surgery. In univariate analysis, the recurrence rate was higher in the tumors with large size, undifferentiated pathology, location in the body, and advanced stage. In multivariate analysis, lymph node metastasis (N2/N3 vs. N0/N0I) was the most predictable risk factor for bone recurrence [hazard ratio [HR] 1.44 (95% confidence interval [CI] 1.217-1.694)] and depth of invasion (T2-4 vs. T1) was also independently associated with bone recurrence. Conclusions The incidence of bone recurrence was low after curative surgery in patients with gastric cancer. Intensive follow up with bone scintigraphy seems to be unnecessary in these patients.

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Section: Discussionmentioning

confidence: 99%

Bone recurrence after curative resection of gastric cancer

Park

Song

et al. 2012

Gastric Cancer

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“…21,22 These cytokines have been shown to increase the metastatic potential of tumor cells. [23][24][25][26] dThdPase is induced in tumor cells at the primary xenograft site by these inflammatory cytokines and growth factors and makes the tumor cells more susceptible to 5Ј-deoxy-5-fluorouridine, which is the major metabolite of capecitabine. 27 5Ј-deoxy-5-fluorouridine also inhibited spontaneous pulmonary metastasis selectively by the upregulation of dThdPase, the expression of which was induced by intrinsic cytokines in tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

Anti‐metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum

Ninomiya

Terada

Yoshizumi

et al. 2004

Intl Journal of Cancer

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Key words: capecitabine; lymph node metastasis; lung metastasis; thymidine phosphorylase; rectal xenograft modelGastrointestinal cancer is one of the most common internal malignancies and is one of the leading causes of cancer-related morbidity and mortality in the world. The primary definitive treatment modality is surgical excision. Adjuvant therapies subsequent to surgery have been studied extensively in recent years because of the high incidence of postoperative recurrences. More than 40 years after its development, 5-FU remains the chemotherapeutic mainstay for the management of patients with many types of cancer. In recent years, several new approaches to the treatment of cancer have undergone examination. These include the introduction of 2 novel cytotoxic compounds. Another strategy that has received attention has been the development of several oral forms of fluoropyrimidine, offering an alternative route of administration to intravenous 5-FU 1 . Capecitabine (N 4 -pentyloxycarbonyl-5Ј-deoxy-5-fluorocytidine) is a new fluoropyrimidine carbamate, which is designed to be activated to 5-FU by 3 sequential steps of enzyme reactions. 1 In humans, it is sequentially converted first to 5Ј-deoxy-5-fluorocytidine by carboxylesterase located in the liver, then to 5Ј-deoxy-5-fluorouridine by cytidine deaminase also with high activity in the liver and in various solid tumors and finally to 5-FU by thymidine phosphorylase (dThdPase) with high activity in many types of tumors. [1][2][3] This oral fluoropyrimidine has an advantage over parental therapy with 5-FU in its potential for affording patients greater convenience and comfort. 4 -6 Randomized clinical trials that compared capecitabine with parenteral 5-FU/leucovorin against metastatic colorectal cancer demonstrated that capecitabine provides at least equivalence, a favorable benefit-risk ratio and greater patient preference making it an acceptable replacement for 5-FU/leucovorin. 4,5,7 Our interest focused on the possibility of capecitabine usage in the prevention of metastasis. Neoadjuvant or adjuvant chemotherapy to inhibit spontaneous metastasis or suppress occult micrometastasis may reduce the incidence of postoperative distant metastasis and improve survival. To confirm this possibility, large randomized clinical trials should be needed. These clinical trials are expensive and time consuming. Animal experiments may take their place to examine the efficacy of new therapeutic modalities. Here, we develop an animal model of gastrointestinal cancer by the intrarectal injection of tumor cells, which resulted in the formation of local tumors with lymph node and lung metastasis consistent with the progression of gastrointestinal cancer in humans.In our study, we examined the efficacy of capecitabine for the inhibition of metastasis and its mechanism for doing so by using a mouse metastasis model. MATERIAL AND METHODS AnimalsMale BALB/c-nu/nu mice aged 5 weeks were obtained from Charles River Japan, Inc. (Kanagawa, Japan). After at least 1 week of observation, th...

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“…Evidence from animal studies and more recently of human studies supports the concept that the rate of bone remodeling is directly related to the occurrence and progression of bone metastases (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 90%

Interference with the Microenvironmental Support Impairs the De novo Formation of Bone Metastases In vivo

Pluijm

Que²,

Sijmons³

et al. 2005

Cancer Research

119

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Interference with the microenvironmental growth support is an attractive therapeutic strategy for repressing metastatic tumor growth. Bone is a highly dynamic tissue that is continuously remodeled by bone resorption and subsequent bone formation. Growth factors supporting bone metastatic growth are released especially during bone resorption. Differently from most other tissues, drugs that can limit local turnover, such as bisphosphonates, are available for bone. In the present study, we tested the hypothesis that inhibition of bone turnover can affect development and growth progression of experimental bone metastasis. Whole-body bioluminescent reporter imaging was used for the detection, monitoring, and quantification in vivo of the growth progression of bone metastases induced by intracardiac or intraosseous injection of luciferase-transfected breast cancer cells (MDA-231-B/luc + ) to nude mice. Suppression of bone turnover by bisphosphonates, before bone colonization by cancer cells, inhibited by a great extent the number of developing bone metastasis. Tumor growth in the few, but still developing, bone metastases was affected only transiently. Reduction of bone turnover had no effect on growth progression of bone metastases, which were already established when bisphosphonate treatment was initiated, despite a substantial reduction in osteolysis. Therefore, cancer cells metastatic to bone, after an initial growth phase that depends on the interaction with the local stroma, become independent of microenvironmental growth factor support and progress autonomously. Inhibition of bone turnover may represent a useful adjuvant therapy especially for cancer patients at risk to develop bone metastasis. IntroductionMicrometastases, persisting in various tissues of cancer patients after removal of the primary tumor, represent the pathophysiologic basis for cancer relapse as overt metastases. Preferential colonization of certain tissues by cancer cells and their subsequent growth are determined by interaction with the tissue-specific microenvironment (1, 2). Therefore, pharmacologic interference with the microenvironmental growth support is becoming an attractive therapeutic strategy for repressing metastatic tumor growth (3).Bone metastases are common in breast and prostate cancer and cause considerable morbidity (4-9). Evidence from animal studies and more recently of human studies supports the concept that the rate of bone remodeling is directly related to the occurrence and progression of bone metastases (10-15).The skeleton is a highly dynamic tissue that is continuously renewed through the process of bone remodeling. This occurs at multiple sites in the skeleton by temporary structures called basic multicellular units (BMU; refs. 16,17). The number and the activity of these BMUs determine the rate of bone turnover (18). During bone remodeling, osteoblasts and osteoclasts, the cellular components of the BMU, secrete paracrine factors that induce chemotaxis and cell adhesion, support cell survival and growth,...

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Effect of IL‐1 on experimental bone/bone‐marrow metastases

Cited by 37 publications

References 15 publications

Bone recurrence after curative resection of gastric cancer

Bone recurrence after curative resection of gastric cancer

Anti‐metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum

Interference with the Microenvironmental Support Impairs the De novo Formation of Bone Metastases In vivo

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