Expression of several cytokines in prostate cancer: Correlation with clinical variables of patients. Relationship with biochemical progression of the malignance

Torrealba, Norelia; Rodríguez-Berriguete, Gonzalo; Fraile, Benito; Olmedilla, Gabriel; Martínez-Onsurbe, Pilar; Guil-Cid, Manuel; Paniagua, Ricardo; Royuela, Mar

doi:10.1016/j.cyto.2016.08.008

Cited by 26 publications

(13 citation statements)

References 42 publications

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“…The percentage of tumor cells that indicated positive staining was further assessed semi-quantitatively. The histochemical score (H-score) of immunoreactivity was obtained by multiplying the intensity and the percentage of positive cells, which yielded a final score of 0–300 [ 34 ]. The median expression level was selected as a cut-off value in order to classify the samples as positive or negative.…”

Section: Methodsmentioning

confidence: 99%

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Xiong

Liu

et al. 2018

Biol Res

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BackgroundArsenic trioxide (As2O3), a drug that has been used in China for approximately two thousand years, induces cell death in a variety of cancer cell types, including neuroblastoma (NB). The tyrosine kinase receptor (Trk) family comprises three members, namely TrkA, TrkB and TrkC. Various studies have confirmed that TrkA and TrkC expression is associated with a good prognosis in NB, while TrkB overexpression can lead to tumor cell growth and invasive metastasis. Previous studies have shown that As2O3 can inhibit the growth and proliferation of a human NB cell line and can also affect the N-Myc mRNA expression. It remains unclear whether As2O3 regulates Trks for the purposes of treating NB.MethodsThe aim of the present study was to investigate the effect of As2O3 on Trk expression in NB cell lines and its potential therapeutic efficacy. SK-N-SH cells were grown with increasing doses of As2O3 at different time points. We cultured SK-N-SH cells, which were treated with increasing doses of As2O3 at different time points. Trk expression in the NB samples was quantified by immunohistochemistry, and the cell cycle was analyzed by flow cytometry. TrkA, TrkB and TrkC mRNA expression was evaluated by real-time PCR analysis.ResultsImmunohistochemical and real-time PCR analyses indicated that TrkA and TrkC were over-expressed in NB, and specifically during stages 1, 2 and 4S of the disease progression. TrkB expression was increased in stage 3 and 4 NB. As2O3 significantly arrested SK-N-SH cells in the G2/M phase. In addition, TrkA, TrkB and TrkC expression levels were significantly upregulated by higher concentrations of As2O3 treatment, notably in the 48-h treatment period. Our findings suggested that to achieve the maximum effect and appropriate regulation of Trk expression in NB stages 1, 2 and 4S, As2O3 treatment should be at relatively higher concentrations for longer delivery times;however, for NB stages 3 and 4, an appropriate concentration and infusion time for As2O3 must be carefully determined.ConclusionThe present findings suggested that As2O3 induced Trk expression in SK-N-SH cells to varying degrees and may be a promising adjuvant to current treatments for NB due to its apoptotic effects.

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Section: Methodsmentioning

confidence: 99%

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Xiong

Liu

et al. 2018

Biol Res

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“…Emerging data in a range of solid tumor types suggest that cytokine levels at treatment initiation, or changes during treatment, may be prognostic and/or predictive of outcomes with certain therapies . Additionally, elevated levels of cytokines, such as IL‐8 and TNF‐α, have been correlated with decreased survival in advanced PCa . Cytokine data in intermediate stages of the disease, such as in men with BCR treated with ADT, are comparatively sparse.…”

Section: Introductionmentioning

confidence: 99%

Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy

et al. 2020

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Background: Immunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets.Methods: Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36-parameter electrochemiluminescence assay. The Wilcoxon signed-rank sum test was used to compare observations between time points. Kaplan-Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median.Pearson's rank correlation coefficient was used to compare continuous variables.Results: Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively.Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-α (P = .002), IL-23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-α correlated with IL-23 (r = .72; P < .001) and IL-8 (r = .59; P < .001) from baseline to post ADT and to PSA progression. Neutrophil-to-lymphocyte ratio correlated with IL-27 (r = .57; P < .001) and MIP-3α (r = .56; P < .001). Patients with a detectable PSA after ADT had elevated levels of IL-6 (P = .049) and IL-8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-α levels above the median (P = .042).Conclusions: Several innate cytokines were associated with biochemically recurrent prostate cancer. K E Y W O R D S biochemical recurrence, IL-8, IL-23, TNF-α

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“…Mechanisms potentially involved in this process include the production of cytokines and other factors by inflammatory cells that promote epithelial proliferation, stimulate angiogenesis, and malignancy [67,69]. In this setting, some proinflammatory (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10) play an important role in prostate carcinogenesis through signaling pathways such as JAK-STAT, PI3k-AKT, and MAPk-ERK [70][71][72]. Elevated levels of TNF-α correlate with increased proliferation, mortality, and malignancy [73], while high levels of IL-6 are associated with metastases and progression to the hormone refractory stage [74].…”

Section: Discussionmentioning

confidence: 99%

Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats

et al. 2018

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Use of drug combinations that target different pathways involved in the development and progression of prostate cancer (PCa) has emerged as an alternative to overcome the resistance caused by drug monotherapies. The antiandrogen abiraterone acetate and the PI3K/Akt inhibitor NVP-BEZ235 (BEZ235) may be suitable options for the prevention of drug resistance and the inhibition of PCa progression. The aim of the present study was to evaluate whether abiraterone acetate and BEZ235 achieve superior therapeutic effects to either drug administered as monotherapy, in the early stages of PCa in an androgen-dependent system. Our study showed that each drug might impair tumor growth by reducing proliferation and increasing cell death when administered as monotherapy. However, tumor growth continued to progress with each drug monotherapy and some important side effects were related to BEZ. Conversely, when used in combination, the drugs impaired the inflammatory response, decreased hyperplastic lesions, and blocked tumor progression from premalignant to a malignant stage. Our data showed that the strategy to block the androgenic and PI3K/AKT/mTOR pathway is an effective therapeutic option and should be investigated including distinct PI3K pathway inhibitors.

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Expression of several cytokines in prostate cancer: Correlation with clinical variables of patients. Relationship with biochemical progression of the malignance

Cited by 26 publications

References 42 publications

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy

Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats

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