Pretranslational regulation of albumin synthesis in tumor-bearing mice

Andersson, Carina; Lönnroth, Ivar; Gelin, Lindor; Moldawer, Lyle L.; Lundholm, Kent

doi:10.1016/0016-5085(91)90267-o

Cited by 18 publications

(6 citation statements)

References 29 publications

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“…Albumin is an important endogenous antioxidant that can help facilitate the transport of substances and maintain osmotic pressure in the blood vessels. Hypoproteinemia may be associated with cancer, which inhibits the synthesis of albumin by the liver and allows it to reside in pleural and peritoneal effusions . Tumor cells in cancer patients are characterized by rapid cell proliferation, which accelerates cell metabolism, consumes albumin, and severely reduces its storage capacity.…”

Section: Discussionmentioning

confidence: 99%

Potential prognostic factors for predicting the chemotherapeutic outcomes and prognosis of patients with metastatic colorectal cancer

Zhang

Wang

et al. 2019

Clinical Laboratory Analysis

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ObjectivesThe purpose of this study was to explore whether pretreatment potential prognostic factors are related to chemotherapeutic outcomes and the prognosis of inpatients with metastatic colorectal cancer (mCRC) undergoing chemotherapy.Materials and methodsData from 71 patients with mCRC were analyzed retrospectively. The relationship between the potential prognostic factors before first‐line chemotherapy and the clinicopathological characteristics and chemotherapy response of the patients was calculated using Fisher's exact test and the chi‐square test. The prognostic factors were analyzed using univariate and multivariate analyses. We analyzed the subgroups using the Mann‐Whitney U test.ResultsFour factors were eventually used as prognostic factors, namely the albumin‐to‐globulin ratio (AGR), the fibrinogen‐to‐albumin ratio (FAR), the prealbumin‐to‐globulin ratio (PGR), and the fibrinogen‐to‐prealbumin ratio (FPR); the cutoff values of the four potential prognostic factors were 1.40, 10.63, 5.44, and 18.49, respectively. The high AGR and PGR groups had a higher response rate than that of the low groups. Patients in the low FAR and FPR groups showed a higher objective response rate than the high FAR and FPR groups. Patients with low FPR were associated with a higher disease control rate than patients with high FPR. Higher progression‐free survival (PFS) was observed in the high AGR and PGR and low FAR and FPR groups. The AGR, FAR, PGR, and FPR were considered reliable prognostic factors for PFS in a univariate analysis.ConclusionsThe prechemotherapy AGR, FAR, PGR, and FPR were good prognostic factors to predict the chemotherapy response and PFS in patients with mCRC.

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Section: Discussionmentioning

confidence: 99%

Potential prognostic factors for predicting the chemotherapeutic outcomes and prognosis of patients with metastatic colorectal cancer

Zhang

Wang

et al. 2019

Clinical Laboratory Analysis

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“…In addition, evaluation of serum half‐life revealed that conjugation with this anti‐albumin anti‐TNF VHH protein substantially prolonged the half‐life of the relatively small bivalent molecules TR2‐TR2 (54 minutes versus 2.2 days) and MT1‐MT1 (47 minutes versus 1.9 days). This increased half‐life most likely correlates with the half‐life of serum albumin, which is 1.07–1.6 days for murine serum albumin and ∼19 days for human serum albumin (35–38).…”

Section: Discussionmentioning

confidence: 99%

Formatted anti–tumor necrosis factor α VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen‐induced arthritis

Coppieters

Dreier

Silence

et al. 2006

Arthritis & Rheumatism

262

220

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Objective. The advent of tumor necrosis factor (TNF)-blocking drugs has provided rheumatologists with an effective, but highly expensive, treatment for the management of established rheumatoid arthritis (RA). Our aim was to explore preclinically the application of camelid anti-TNF VHH proteins, which are singledomain antigen binding (VHH) proteins homologous to human immunoglobulin V H domains, as TNF antagonists in a mouse model of RA.Methods. Llamas were immunized with human and mouse TNF, and antagonistic anti-TNF VHH proteins were isolated and cloned for bacterial production. The resulting anti-TNF VHH proteins were recombinantly linked to yield bivalent mouse and human TNFspecific molecules. To increase the serum half-life and targeting properties, an anti-serum albumin anti-TNF VHH domain was incorporated into the bivalent molecules. The TNF-neutralizing potential was analyzed in vitro. Mouse TNF-specific molecules were tested in a therapeutic protocol in murine collagen-induced arthritis (CIA). Disease progression was evaluated by clinical scoring and histologic evaluation. Targeting properties were evaluated by 99m Tc labeling and gamma camera imaging.Results. The bivalent molecules were up to 500 times more potent than the monovalent molecules. The antagonistic potency of the anti-human TNF VHH proteins exceeded even that of the anti-TNF antibodies infliximab and adalimumab that are used clinically in RA. Incorporation of binding affinity for albumin into the anti-TNF VHH protein significantly prolonged its serum half-life and promoted its targeting to inflamed joints in the murine CIA model of RA. This might explain the excellent therapeutic efficacy observed in vivo.Conclusion. These data suggest that because of the flexibility of their format, camelid anti-TNF VHH proteins can be converted into potent therapeutic agents that can be produced and purified cost-effectively.Tumor necrosis factor (TNF)-blocking drugs are widely considered to be among the most efficient treatments available for rheumatoid arthritis (RA). TNF blockade is also highly therapeutic for several other chronic inflammatory diseases, such as spondylarthropathies, psoriasis, and inflammatory bowel disease (1-3).

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“…Moreover, there was direct evidence to show that tumor-bearing animals became hypoalbuminemic, which was reported to be resulted from depressed albumin synthesis and increased albumin degradation. [ 8 ] According to these findings, we hypothesize serum albumin may be a potential prognostic biomarker for glioma, with low level predicting poor survival. This hypothesis had been confirmed in the study of Han et al [ 9 ] and Wang et al [ 10 ] However, there were also some contradictory conclusions, showing no significant associations between serum albumin level and OS in patients with glioma.…”

Section: Introductionmentioning

confidence: 93%

Prognostic significance of preoperative serum albumin, albumin-to-globulin ratio, and prognostic nutritional index for patients with glioma

Liu¹,

Wang²

2020

Medicine

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Background: The serum albumin, albumin-to-globulin ratio (AGR), and prognostic nutritional index (PNI) have been recommended to represent the nutritional and inflammatory status. Thus, they may be potential prognostic biomarkers for cancer. However, contradictory results were reported in different studies on glioma. The goal of this study was to perform a meta-analysis to re-evaluate their prognostic potential for glioma. Methods: Databases of PubMed, EMBASE, and Cochrane Library were systematically searched to enroll all the studies investigating the prognostic significance of albumin, AGR, and PNI for glioma. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using STATA 13.0 software to indicate the intensity of association. Results: Eleven studies with 2928 cases were included. Overall meta-analysis showed that the prognostic values of albumin, AGR, and PNI were limited for glioma ( P > .05). However, subgroup analysis demonstrated a high preoperative serum albumin was significantly related with excellent OS of patients with GBM (HR = 0.95, 95% CI: 0.91–0.99, P = .018), while high PNI (HR = 0.56, 95% CI: 0.43–0.73, P < .001) and AGR (HR = 0.57, 95% CI: 0.34–0.96, P = .034) may be a protective factor of favorable OS for patients with high-grade gliomas. Furthermore, integration of all studies with multivariate analysis and clear cut-off also proved reduced preoperative serum albumin, AGR, and PNI were predictors of poor prognosis for patients with gliomas. Conclusion: Preoperative serum albumin, AGR, and PNI may represent promising biomarkers to predict the prognosis in patients with glioma, especially for high-grade.

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Pretranslational regulation of albumin synthesis in tumor-bearing mice

Cited by 18 publications

References 29 publications

Potential prognostic factors for predicting the chemotherapeutic outcomes and prognosis of patients with metastatic colorectal cancer

Potential prognostic factors for predicting the chemotherapeutic outcomes and prognosis of patients with metastatic colorectal cancer

Formatted anti–tumor necrosis factor α VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen‐induced arthritis

Prognostic significance of preoperative serum albumin, albumin-to-globulin ratio, and prognostic nutritional index for patients with glioma

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