The free β-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma

Hotakainen, Kristina; Ljungberg, Börje; Paju, Annukka; Rasmuson, Torgny; Alfthan, Henrik; Stenman, Ulf‐Håkan

doi:10.1038/sj.bjc.6600050

Cited by 61 publications

(36 citation statements)

References 25 publications

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“…In searching for intermediates of major metabolic pathways, an isoenzyme of pyruvate kinase has been suggested as a biomarker; however, enzymatic levels are variable and have a low sensitivity for nonmetastatic RCC (29 -31). Vinculin, human chorionic gonadotropin-␤, nuclear matrix proteins, metallothioneins, serum ferritin, matrix metalloproteinase activity, and many other proteins that are upregulated in tumor progression have also been suggested as [32][33][34][35][36][37]. These markers, however, have not proved useful in the clinical treatment of RCC patients because they lack specificity for RCC and/or require tissue.…”

Section: Discussionmentioning

confidence: 99%

Human Kidney Injury Molecule-1 Is a Tissue and Urinary Tumor Marker of Renal Cell Carcinoma

Han

Alinani

et al. 2005

Journal of the American Society of Nephrology

172

145

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Human kidney injury molecule-1 (hKIM-1) is a type 1 transmembrane protein that is not detectable in normal kidney tissue but is expressed at high levels in human and rodent kidneys with dedifferentiated proximal tubule epithelial cells after ischemic or toxic injury. Therefore, it was hypothesized that renal tumors express hKIM-1 and release this protein into the urine. Forty renal cell carcinoma (RCC) and 484 nonrenal tumors were analyzed by immunohistochemistry for expression of hKIM-1 (group 1). Urine samples before nephrectomy and nephrectomy tissue samples were collected from an additional 42 patients with renal tumors, from 30 normal control subjects, and also from 10 patients with prostate carcinoma (group 2). In five additional patients with RCC, urine was collected before and after nephrectomy (group 3). Tissue was examined for expression of hKIM-1, and cell-free urine supernatants were analyzed for hKIM-1 by ELISA. Urinary hKIM-1 was normalized to the urinary creatinine concentration (U Cr ). Expression of hKIM-1 was present in 32 tissue sections (91%) of 35 clear cell RCC (group 1). In group 2, the normalized urinary hKIM-1 levels were significantly higher in patients with clear cell RCC (0.39 ؎ 0.08 ng/mg U Cr ; n ‫؍‬ 21), compared with levels in patients with prostate carcinoma (0.12 ؎ 0.03 ng/mg U Cr ; P < 0.02; n ‫؍‬ 10), or normal control subjects (0.05 ؎ 0.01 ng/mg U Cr ; P < 0.005; n ‫؍‬ 30). Tissue sections from 28 (82%) of 34 primary RCC stained positively for the expression of hKIM-1. In all patients with a detectable prenephrectomy urinary hKIM-1 level, there was either complete disappearance or marked reduction after nephrectomy (group 3). In conclusion, the cleaved ectodomain of hKIM-1 can be detected in the urine of patients with RCC and may serve as a new biomarker for early detection of RCC.

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Section: Discussionmentioning

confidence: 99%

Human Kidney Injury Molecule-1 Is a Tissue and Urinary Tumor Marker of Renal Cell Carcinoma

Han

Alinani

et al. 2005

Journal of the American Society of Nephrology

172

145

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“…Purified B11-hCG␤ fusion protein was subjected to SDS-PAGE on 4 Preparation of Monocyte-Derived DCs. Peripheral blood mononuclear cells were suspended in RPMI 1640 medium (Invitrogen, Carlsbad, CA) supplemented with 10% fetal bovine serum, 40 g/ml gentamicin, and 50 M ␤-mercaptoethanol.…”

Section: Methodsmentioning

confidence: 99%

A Novel Human Cancer Vaccine Elicits Cellular Responses to the Tumor-Associated Antigen, Human Chorionic Gonadotropin β

He¹,

Ramakrishna²,

Connolly³

et al. 2004

Clinical Cancer Research

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Purpose: The oncofetal antigen, human chorionic gonadotropin ␤ subunit (hCG␤), is expressed by a number of carcinomas and is a prognostic indicator in renal, colorectal, bladder, and pancreatic cancers. We describe the development of a novel antibody-based dendritic cell (DC)-targeted cancer vaccine capable of eliciting cellular immune responses directed against hCG␤.Experimental Design: The tumor-associated antigen hCG␤ was coupled genetically to a human anti-DC antibody (B11). The resulting fusion protein (B11-hCG␤) was evaluated for its ability to promote tumor antigen-specific cellular immune responses in a human in vitro model. Monocytederived human DCs from normal donors were exposed to purified B11-hCG␤, activated with CD40 ligand, mixed with autologous lymphocytes, and tested for their ability to promote hCG␤-specific proliferative and cytotoxic T-lymphocyte responses.Results: B11-hCG␤ was found to be a soluble, welldefined, and readily purified product that specifically recognized the human mannose receptor via the B11 antibody portion of the fusion protein. B11-hCG␤ functionally promoted the uptake and processing of tumor antigen by DCs, which led to the generation of tumor-specific HLA class I and class II-restricted T-cell responses, including CTLs capable of killing human cancer cell lines expressing hCG␤.Conclusions: Although other hCG vaccines have been shown to be capable of eliciting antibody responses to hCG␤, this is the first time that cellular immune responses to hCG␤ have been induced by a vaccine in a human system. This DC-targeted hCG␤ vaccine holds promise for the management of a number of cancers and merits additional clinical development.

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“…We have previously shown that the preoperative serum concentration of hCG␤ is a prognostic indicator in RCC independent of stage and grade, 19 but the prognostic significance of hCG␤ tissue expression is not known. We have now developed a quantitative reverse transcriptionpolymerase chain reaction (RT-PCR) method for quantification of the mRNAs for the two groups of hCG␤ genes and compared the expression levels with clinicopathological data.…”

mentioning

confidence: 99%

Expression Of Human Chorionic Gonadotropin β-Subunit Type I Genes Predicts Adverse Outcome In Renal Cell Carcinoma

Hotakainen

Lintula

Ljungberg

et al. 2006

The Journal of Molecular Diagnostics

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Expression of the free ␤-subunit of human chorionic gonadotropin (hCG␤) in malignant tumors is frequently associated with aggressive disease. The pretreatment serum concentration of hCG␤ is an independent prognostic variable in renal cell carcinoma (RCC). The three so-called type II genes (hCG␤ 3/9, 5, and 8) have been shown to be up-regulated in relation to type I genes (hCG␤ 6/7) in some malignant tumors. We developed a reverse transcription-polymerase chain reaction method for quantification of relative levels of the mRNAs for the two types of hCG␤ genes and studied the association between the expression in RCC tissue (n ‫؍‬ 104) and clinical outcome. hCG␤ mRNA expression was detected in 40% (42 of 104) of the tumors, and in 40 of these (93%), this consisted of hCG␤ type I mRNA only, whereas type II hCG␤ mRNA was detected in two samples. hCG␤ mRNA expression was significantly associated with a shorter diseasespecific (log-rank P ‫؍‬ 0.023; median survival 1.4 versus 7.9 years) and overall survival (log-rank P ‫؍‬ 0.011). In a Cox regression model, stage (P < 0.0001) and hCG␤ mRNA expression (P < 0.0001) were independent prognostic variables. We conclude that expression of type I hCG␤ genes indicates adverse prognosis in

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The free β-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma

Cited by 61 publications

References 25 publications

Human Kidney Injury Molecule-1 Is a Tissue and Urinary Tumor Marker of Renal Cell Carcinoma

Human Kidney Injury Molecule-1 Is a Tissue and Urinary Tumor Marker of Renal Cell Carcinoma

A Novel Human Cancer Vaccine Elicits Cellular Responses to the Tumor-Associated Antigen, Human Chorionic Gonadotropin β

Expression Of Human Chorionic Gonadotropin β-Subunit Type I Genes Predicts Adverse Outcome In Renal Cell Carcinoma

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