Anti-angiogenesis therapy:concepts and importance of dosing schedules in clinical trials

Mross, Klaus

doi:10.1054/drup.2000.0150

Cited by 24 publications

(13 citation statements)

References 74 publications

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“…Its significance was less important than serum Se (Lin et al, 2009). In this experiment the level of serum Cu was increased in bladder carcinoma which agreed with the previous studies (Huang et al, 1999;Hronek et al, 2000;McMillan et al, 2000;Mross, 2000;Valko et al, 2006). In many cancers, for example hepatoma and breast cancer, serum Cu/Zn also rises, which was same as that in this study (Marco et al, 2001;Zhai et al, 2003).…”

Section: Discussionsupporting

confidence: 92%

Variation of Urinary and Serum Trace Elements (Ca, Zn, Cu, Se) in Bladder Carcinoma in China

Guo¹,

Zhang²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Backgrounds: Deficiency or excess of trace elements can induce body metabolic disorders and cellular growth disturbance, even mutation and cancerization. Since there are few studies of the effect of trace elements in bladder carcinoma in China, the aim of this study was thus to assess variation using a case control approach. Methods: To determine this, 81 patients with bladder carcinoma chosen as a study group and 130 healthy persons chosen as a control group were all assayed for urinary and serum trace elements (calcium [Ca], zinc [Zn], copper [Cu], selenium [Se]) using an atomic absorption spectrophotometer, and the results were analyzed by independent sample t tests. The correlative factors on questionnaires answered by all persons were analyzed by logistic regression. Results: The results showed urinary Ca, Zn and serum Cu levels of the study group to be significantly higher (P<0.05) than those of he control group. Serum Ca and Se levels of study group were significantly lower (P<0.05) than those of control group. Conclusion: There were higher urinary Zn and serum Cu concentrations in bladder carcinoma cases. Bladder carcinoma may be associated with Ca metabolic disorder, leading to higher urinary Ca and lower serum Ca. Low serum Se and smoking appear to be other risk factors for bladder carcinoma in China.

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Section: Discussionsupporting

confidence: 92%

Variation of Urinary and Serum Trace Elements (Ca, Zn, Cu, Se) in Bladder Carcinoma in China

Guo¹,

Zhang²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Our finding is in agreement with most of the earlier studies suggesting that in the oesophageal cancer groups serum copper is higher [9][10][11]. Also, copper chelation by chelating agents has antiproliferative effects in many studies [12]. Brewer et al tested a drug known as tetrathiomolybdate, which binds up dietary copper in patients with different kinds of cancer.…”

Section: Discussionsupporting

confidence: 92%

Clinical study on magnesium, copper and chrome levels in patients with oesophageal squamous cell carcinoma

Sun¹,

Song²,

Zhang³

et al. 2011

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“…This metronomic dosing has been demonstrated to exhibit antitumor and anti-angiogenic effects. [23][24][25]37,39 However, in our model, treatment with continuous infusion 5-FU alone did not reduce tumor angiogenesis, and its addition to ATN-161 did not further decrease vessel density in the combination-therapy group either. However, the finding that metronomic therapy did not work in our model is not unique and has been reported by others.…”

Section: Discussionmentioning

confidence: 85%

Inhibition of integrin α₅β₁ function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice

Stoeltzing

Liu

Reinmuth

et al. 2003

Intl Journal of Cancer

206

150

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Integrin ␣ 5 ␤ 1 is expressed on activated endothelial cells and plays a critical role in tumor angiogenesis. We hypothesized that a novel integrin ␣ 5 ␤ 1 antagonist, ATN-161, would inhibit angiogenesis and growth of liver metastases in a murine model. We further hypothesized that combining ATN-161 with 5-fluorouracil (5-FU) chemotherapy would enhance the antineoplastic effect. Murine colon cancer cells (CT26) were injected into spleens of BALB/c mice to produce liver metastases. Four days thereafter, mice were given either ATN-161 (100 mg/kg, every 3rd day) or saline by intraperitoneal injection, with or without combination of continuousinfusion 5-FU (100 mg/kg/2 weeks), which was started on day 7. On day 20 after tumor cell inoculation, mice were killed and liver weights and number of liver metastases were determined. A follow-up study on survival was also conducted in which mice were randomized to receive ATN- Key words: angiogenesis; colon cancer; integrins; liver metastasesIntegrins are heterodimeric transmembrane glycoproteins that mediate their own function upon binding to components of the extracellular matrix such as fibronectin, vitronectin and collagen. Integrins are composed of various ␣-and ␤-subunits that form the receptor (reviewed in reference 1), and the unique dimer compositions determine the ability to bind to specific ligands.Integrins regulate cell adhesion and are expressed on the surface of many cell types, including tumor cells, ECs and numerous nonmalignant cell types. 2 In addition to their role in cell adhesion, integrins have been shown to affect intracellular signaling processes and thereby regulate cell survival and proliferation. 2-4 Recently, specific integrins have been identified as being crucial for mediating the angiogenic response of endothelial cells to angiogenic growth factors such as VEGF and bFGF. The integrins ␣ V ␤ 3 , ␣ V ␤ 5 and ␣ 5 ␤ 1 have been shown to play important roles in neoplastic and non-neoplastic angiogenesis by promoting EC migration, proliferation and survival. 5-8 Therefore, endothelial-specific integrins have become a promising target for anti-angiogenic approaches in antineoplastic regimens and in the treatment of nonmalignant angiogenic disorders. 9 -12 The integrin ␣ 5 ␤ 1 is of particular interest as a target since amounts of this integrin and its ligand fibronectin are significantly increased on tumor vessels of many solid malignancies. 13 In some types of cancer, integrin ␣ 5 ␤ 1 is also expressed on tumor cells and plays a direct role in tumor cell migration, invasion, and survival. 14,15 In colorectal cancers, ␣ 5 ␤ 1 overexpression has been associated with invasiveness and malignant progression. 14 However, only a few human colon cancer cell lines are known to express this integrin. 14,16,17 Recently, Livant et al. 15 demonstrated that a small peptide antagonist (amino-acid sequence PHSCN) to integrin ␣ 5 ␤ 1 significantly reduced neovascularization and formation of metastases in an animal model of prostate carcinoma that expresses integr...

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Anti-angiogenesis therapy:concepts and importance of dosing schedules in clinical trials

Cited by 24 publications

References 74 publications

Variation of Urinary and Serum Trace Elements (Ca, Zn, Cu, Se) in Bladder Carcinoma in China

Variation of Urinary and Serum Trace Elements (Ca, Zn, Cu, Se) in Bladder Carcinoma in China

Clinical study on magnesium, copper and chrome levels in patients with oesophageal squamous cell carcinoma

Inhibition of integrin α₅β₁ function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice

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Anti-angiogenesis therapy:concepts and importance of dosing schedules in clinical trials

Cited by 24 publications

References 74 publications

Variation of Urinary and Serum Trace Elements (Ca, Zn, Cu, Se) in Bladder Carcinoma in China

Variation of Urinary and Serum Trace Elements (Ca, Zn, Cu, Se) in Bladder Carcinoma in China

Clinical study on magnesium, copper and chrome levels in patients with oesophageal squamous cell carcinoma

Inhibition of integrin α5β1 function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice

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Inhibition of integrin α₅β₁ function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice