Metastatic phenotype correlates with high expression of membrane-associated complete β-human chorionic gonadotropin in vivo

Acevedo, Hernan F.; Hartsock, Robert J.

doi:10.1002/(sici)1097-0142(19961201)78:11<2388::aid-cncr18>3.0.co;2-x

Cited by 39 publications

(25 citation statements)

References 32 publications

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“…18 -25 In studies on the hCG␤ subunit, no expression has been found in non-neoplastic mucosa of the rectosigmoid colon or in benign colorectal neoplasms. 4,26,27 According to several reports, hCG production is associated with more aggressive behavior in non-trophoblastic tumors. 18,28,29 Other studies indicate that hCG expression is of limited prognostic value.…”

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confidence: 99%

“…2,3 The presence of hCG in any of its forms is an in vivo phenotypic characteristic of human cancer cells. 4 Intact hCG appears to be the main form of hCG immunoreactivity (hCG-IR) during growth and local invasion of a tumor, whereas expression of the free ␤ subunit (hCG␤) correlates more closely with a metastatic phenotype. 4 hCG-IR has been detected in a wide variety of non-trophoblastic neoplasms in both tumor cells [5][6][7] and serum.…”

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confidence: 99%

“…4 Intact hCG appears to be the main form of hCG immunoreactivity (hCG-IR) during growth and local invasion of a tumor, whereas expression of the free ␤ subunit (hCG␤) correlates more closely with a metastatic phenotype. 4 hCG-IR has been detected in a wide variety of non-trophoblastic neoplasms in both tumor cells [5][6][7] and serum. 9 -14 In colorectal cancer, the reported rate of elevated serum hCG is between 2% and 41% 2,3,12,14 -17 and the rate of immunohistochemical tissue expression is between 17% and 52 %.…”

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confidence: 99%

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Tissue expression of human chorionic gonadotropin ? predicts outcome in colorectal cancer: A comparison with serum expression

et al. 2001

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Tissue expression of human chorionic gonadotropin ? predicts outcome in colorectal cancer: A comparison with serum expression

et al. 2001

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“…8 This work was performed using human tumors grown in nude mice. In addition, others have shown that cell membrane-associated HCG␤ identifies a subgroup of prostate adenocarcinoma patients with a poor prognosis, regardless of the histologic grade of the tumor.…”

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confidence: 99%

Human chorionic gonadotropin β (HCGβ) down‐regulates E‐cadherin and promotes human prostate carcinoma cell migration and invasion

Walker

2005

Cancer

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People are not equally disabled by combined anterior cruciate ligament (ACL)/medial collateral ligament (MCL) injuries, nor do they all develop osteoarthritis (OA). Although biological/biomechanical causes are not clear, some association presumably exists between joint instability and OA development. We hypothesized that degree of OA development following standardized complete ACL/MCL injuries will vary directly with the degree of biomechanical abnormality between individuals. Three groups of sheep were used to test the hypothesis: 17 normal, 9 ACL/MCL transected, and 7 sham animals. Normal joints were assessed morphologically while sham and experimental animals had gait assessment pre‐ and at 4 and 20 weeks post‐surgery, with cartilage and bone changes being mapped and graded at sacrifice at 20 weeks. Sham joints were morphologically normal and had only one minor kinematic change at 20 weeks. Although variable, ACL/MCL deficient animals showed significant kinematic abnormalities in 4/6 degrees of freedom (DOFs), as well as cartilage/bone damage by 20 weeks (p < 0.05). Linear regression analysis revealed that changes in medial–lateral (ML) translation were related to the current level of joint degradation as represented by total gross OA score (p = 0.0044, R2 = 0.71) in the ACL/MCL transected group. Even identical ACL/MCL injuries result in inter‐animal variations in instability and OA, however significant kinematic abnormalities in ML translation do relate to early OA in sheep. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:384–392, 2012

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“…For example, Acevedo et al 4,5 demonstrated that cultured human cancer cells expressed HCG on the cell mem-brane and suggested a direct correlation between the extent of membrane-associated HCG and the metastatic potential of the cells. Kellen et al 6 demonstrated that adenocarcinoma cells have significantly diminished tumorigenicity when inoculated into mice previously exposed to HCG conjugated to a tetanus toxoid intended to prophylactically stimulate an immune response against HCG-like substances.…”

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In vitro effects and clinical evaluation of a human chorionic gonadotrophin preparation in acute leukemia

et al. 1998

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Commercial human chorionic gonadotrophin (HCG) preparations decrease the tumorigenicity of human tumors in immunodeficient mice and induce apoptotic cell death in animal tumor models. Preliminary studies in humans have demonstrated tumor regression in patients with Kaposi's sarcoma given intralesional injections of HCG. To further evaluate HCG's antitumor activity we conducted in vitro and clinical evaluations of HCG in acute myeloid leukemia (AML). In HL-60 leukemic cell lines, a 20-40% inhibition of cell density was demonstrated by trypan blue exclusion method at low concentrations of an HCG preparation (2 ؋ 10 −3 -2 ؋ 10 −2 ). Similar concentrations also resulted in a reduction in the proportion of cells in G 2 M phase of the cell cycle, as well as enhanced differentiation compared to control cells. Fifteen patients with advanced AML with marrow blast counts Ͼ30%, and five with marrow blast counts between 10 and 26% were given daily subcutaneous injections of HCG 2-4 IU and oral levamisole 50 mg weekly. Five patients with absolute blast counts in the blood ranging from 0 to 3500/ l and percent blasts in the marrow ranging from 16 to 81% were observed to have no progressive increase in either marrow or peripheral blast counts for 70-121 days. One patient with a pretreatment blast count of 10% in the marrow, no circulating blasts and minor cytopenias had a decrease in marrow blasts to less than 5% which has persisted at 550 days. No significant improvement from baseline levels of neutrophils, hemoglobin or platelets were observed in any of the patients treated. Increases in apoptotic cell death were observed in over 50% of patients' cells with some demonstrating peak levels similar to experiences in patients treated with DNA-damaging chemotherapy. A decreased expression of bcl-2 was seen in the majority of patients ranging from 6 to 62%. These new observations suggest that HCG preparations may inhibit leukemic cell growth through enhancement of cell death mechanisms and could be used in judicious combinations with other approaches. The results confirm the pro-apoptotic effects of HCG preparations reported in patients with Kaposi's sarcoma. Identification of the active component of HCG preparations and further understanding of its growth modulatory action will be important in its development as a clinically useful agent.

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Metastatic phenotype correlates with high expression of membrane-associated complete β-human chorionic gonadotropin in vivo

Abstract: BACKGROUND. Investigations using living human cancer cells and the nude mouse

Cited by 39 publications

References 32 publications

Tissue expression of human chorionic gonadotropin ? predicts outcome in colorectal cancer: A comparison with serum expression

Tissue expression of human chorionic gonadotropin ? predicts outcome in colorectal cancer: A comparison with serum expression

Human chorionic gonadotropin β (HCGβ) down‐regulates E‐cadherin and promotes human prostate carcinoma cell migration and invasion

In vitro effects and clinical evaluation of a human chorionic gonadotrophin preparation in acute leukemia

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