Autocrine/paracrine involvement of insulin‐like growth factor‐I and its receptor in chronic lymphocytic leukaemia

Schillaci, Roxana; Galeano, Adriana; Becú-Villalobos, Damasia; Spinelli, Olga; Sapia, Sandra; Bezares, Raimundo F.

doi:10.1111/j.1365-2141.2005.05579.x

Cited by 35 publications

(34 citation statements)

References 45 publications

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“…In addition, our evidence does not support the hypothesis that the unfavorable effects of serum IGF1 or IGF2 are limited to sex-hormone-related cancers (Schaffer et al 2007). The discrepancies between circulating IGF1 levels and those in the cellular microenvironment might be explained by the following theories: i) racial differences in socioeconomic and dietary influences and ii) paracrine or autocrine influences of IGFs on cancer cells (Schips et al 2004, Schillaci et al 2005, Serin et al 2008. The clinical significance of CA125 for cancer screening is limited, and thus, it is recommended as an adjunct in this clinical setting (Sturgeon et al 2008).…”

Section: Discussioncontrasting

confidence: 51%

Circulating IGF system and treatment outcome in epithelial ovarian cancer

Huang

Cheng

et al. 2013

Endocrine-Related Cancer

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Aggressive epithelial ovarian cancers (EOCs) frequently progress and become fatal, even when cytoreduction surgery plus platinum-based chemotherapy are performed. Thus, the early detection of high-risk subgroups is important in order to provide opportunities for better treatment outcomes, using alternative therapeutic strategies. This study aimed to explore the expression of circulating IGF system components and their relationship with treatment outcome in EOC. We included 228 patients with a median follow-up time of 44 months at two tertiary centers. There were 68 cancer deaths and 108 cases of cancer progression in the cohort. Preoperative serum levels of total IGF1, IGF2, IGF-binding protein 2 (IGFBP2), and IGFBP3 were analyzed using an ELISA and were then converted into an IGF1:IGFBP3 molar ratio. The risks of mortality and progression were estimated using Cox regression models in univariate and multivariate analyses. Our results showed that high IGF1, IGF2, and IGFBP3 levels were significantly associated with an early cancer stage, non-serous histology, and optimal cytoreduction. High IGFBP2 levels were associated with an advanced stage and serous histology. Overall and progression-free survival durations were significantly better among patients with high IGF1 (PZ0.003 and PZ0.001), IGF2 (PZ0.003 and PZ0.02), or IGFBP3 levels (PZ0.02 and PZ0.008). In multivariate analysis, serum IGFBP2 levels were significantly associated with increased risk of mortality (hazard ratioZ1.84, 95% CI: 1.07-3.18, PZ0.03), indicating that IGFBP2 could be used as an early predictor of EOCrelated mortality. The combination of elevated IGFBP2 and reduced IGF1 levels at diagnosis could further facilitate the identification of a patient subgroup with the worst prognosis. Key Words" insulin-like growth factor " insulin-like growth factor-binding protein " epithelial ovarian cancer " response to chemotherapy " prognosis

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Section: Discussioncontrasting

confidence: 51%

Circulating IGF system and treatment outcome in epithelial ovarian cancer

Huang

Cheng

et al. 2013

Endocrine-Related Cancer

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“…In our study, serum levels of IGF-1 and IGFBP-3 did not differ between two subgroups of IGF-1R overexpression with colocalised IGF-1 in the specimen sections. The possible hypothesis is that the IGF system may contribute to the regional influences in the battlefield, suggesting paracrine or autocrine function in agreement on prior suppositions (Bergmann et al, 1995;Schips et al, 2004;Schillaci et al, 2005). More candidates should be enroled in further studies to realise the differences of serum levels of IGF-1 between normal individuals, patients with precancer lesions and cervical cancer.…”

Section: Discussionmentioning

confidence: 71%

Clinical implications of insulin-like growth factor 1 system in early-stage cervical cancer

et al. 2008

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This study was aimed to identify the expression and the correlation of insulin-like growth factor-1 (IGF-1) system and their prognostic impacts in cervical cancer. Seventy-two patients with early-stage cervical cancer were eligible. We obtained the serum levels of total IGF-1 and IGF binding protein-3 (IGFBP-3) by enzyme-linked immunosorbent assay and the expression of IGF-1 receptor (IGF-1R) in cancerous tissue by immuno-fluorescent (IF) stains. The 5-year recurrence-free and overall survival rates were significantly lower (P ¼ 0.003 and P ¼ 0.01, respectively) among patients with high-grade expression of tissue IGF-1R, compared with those with low-grade expression. After adjustment for other factors, preoperative serum total IGF-1 or IGFBP-3 levels failed to predict cancer death and recurrence. High-grade expression of IGF-1R and elevated preoperative squamous cell carcinoma antigen level were independent predictors of both death and recurrence, and combination of both factors could further help identify the subgroup of patients at higher death risk. The IF staining indicates the colocalisation of IGF-1 and IGF-1R in the cancerous tissues, whereas the IGF-1R expression is not correlated with circulating levels of IGF-1 or IGFBP-3. In early-stage cervical cancer, IGF-1 system may have a paracrine or autocrine function and the adverse impacts on prognosis by IGF-1R overexpression are implicated.

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“…This suggests a proproliferative environment is located within bone marrow and lymph node, whereas CLL cells within blood are associated with long-term survival. CLL proliferation, survival, homing, and drug resistance (5)(6)(7)(8)(9)(10)(11)(12) have been attributed to numerous factors such as chemokines, cytokines, and direct cell-cell interactions mediated via adhesion molecules in the lymph node, spleen, and bone marrow microenvironment which suggests these factors may represent important therapeutic targets. For example, the Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, impairs B-cell receptor and chemokine-controlled retention of CLL cells in the marrow and lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

CD62L as a Therapeutic Target in Chronic Lymphocytic Leukemia

Burgess

Gill

Singhania

et al. 2013

Clinical Cancer Research

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Purpose: Despite advances in the treatment of chronic lymphocytic leukemia (CLL), the disease remains incurable with standard therapies and relapse is inevitable. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of CLL.Experimental Design: The expression of 71 cell surface molecules was examined on CLL peripheral blood mononuclear cells (PBMCs) over 3 weeks in culture. The most highly upregulated marker, CD62L, was examined further for expression on CD5 þ /CD19 þ CLL cells in vitro and in lymph node and bone marrow biopsies. The prosurvival role of CD62L was examined using a functional blocking antibody and therapeutic potential evaluated by comparison with current chemotherapy agents.Results: Blocking CD62L resulted in apoptosis of CLL cells but not PBMCs from healthy donors suggesting a novel role for CD62L in CLL cell survival. The beneficial effect of coculturing CLL cells with bone marrow stromal cells or endothelial cells does not protect CLL cells from anti-CD62L-related toxicity. Moreover, combining fludarabine or mafosfamide with the anti-CD62L in vitro produced an additive effect both with and without stromal cells.Conclusion: This is the first reported data showing that blocking the activation and homing marker, CD62L, regulates CLL cell survival in vitro. These data also suggest that therapeutic antibodies against CD62L may provide additional clinical benefit to patients with CLL receiving current standard chemotherapy protocols.

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Autocrine/paracrine involvement of insulin‐like growth factor‐I and its receptor in chronic lymphocytic leukaemia

Cited by 35 publications

References 45 publications

Circulating IGF system and treatment outcome in epithelial ovarian cancer

Circulating IGF system and treatment outcome in epithelial ovarian cancer

Clinical implications of insulin-like growth factor 1 system in early-stage cervical cancer

CD62L as a Therapeutic Target in Chronic Lymphocytic Leukemia

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