Serum soluble mesothelin-related peptide (SMRP): a potential diagnostic and monitoring marker for epithelial ovarian cancer

Wu, Xiaohua; Li, Dongxiu; Liu, Liping; Bo-jun, Liu; Liang, Hongxia; Yang, Bo

doi:10.1007/s00404-013-3128-x

Cited by 20 publications

(16 citation statements)

References 27 publications

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“…Many studies showed that serum mesothelin levels are related to the FIGO surgical pathological staging and pathological grade in EOC patients. Patients with advanced stage and low differentiation tumors showed higher levels of SMRP most recent study reported the expression of mesothelin in ovarian tissue correlated to chemotherapy resistance and poor prognosis suggesting a role for mesothelin in diagnosis and disease staging [32].…”

Section: Mesothelinmentioning

confidence: 99%

HE4 in the differential diagnosis of ovarian masses

Granato

Porpora

Longo

et al. 2015

Clinica Chimica Acta

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Ovarian masses, a common finding among pre- and post-menopausal women, can be benign or malignant. Ovarian cancer is the leading cause of death from gynecologic malignancy among women living in industrialized countries. According to the current guidelines, measurement of CA125 tumor marker remains the gold standard in the management of ovarian cancer. Recently, HE4 has been proposed as emerging biomarker in the differential diagnosis of adnexal masses and in the early diagnosis of ovarian cancer. Discrimination of benign and malignant ovarian tumors is very important for correct patient referral to institutions specialized in care and management of ovarian cancer. Tumor markers CA125 and HE4 are currently incorporated into the "Risk of Ovarian Malignancy Algorithm" (ROMA) with menopausal status for discerning malignant from benign pelvic masses. The availability of a good biomarker such as HE4, closely associated with the differential and early diagnosis of ovarian cancer, could reduce medical costs related to more expensive diagnostic procedures. Finally, it is important to note that HE4 identifies platinum non-responders thus enabling a switch to second line chemotherapy and improved survival.

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Section: Mesothelinmentioning

confidence: 99%

HE4 in the differential diagnosis of ovarian masses

Granato

Porpora

Longo

et al. 2015

Clinica Chimica Acta

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“…[30][31][32][33][34] The presence of SMRP can also alter the binding capacity of mesothelin-targeting therapeutic agents. 22,23 On the basis of these data, we used the serum of 21 patients with metastatic colon and pancreatic cancers in competition assays with selected Fabs.…”

Section: Competition Tests With Smrp In Patients' Serum and Cell Supementioning

confidence: 99%

A new anti-mesothelin antibody targets selectively the membrane-associated form

Asgarov

Balland

Tirole

et al. 2017

mAbs

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Mesothelin is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that shows promise as a target for antibody-directed cancer therapy. High levels of soluble forms of the antigen represent a barrier to directing therapy to cellular targets. The ability to develop antibodies that can selectively discriminate between membrane-bound and soluble conformations of a specific protein, and thus target only the membrane-associated antigen, is a substantive issue. We show that use of a tolerance protocol provides a route to such discrimination. Mice were tolerized with soluble mesothelin and a second round of immunizations was performed using mesothelin transfected P815 cells. RNA extracted from splenocytes was used in phage display to obtain mesothelin-specific antigen-binding fragments (Fabs) that were subsequently screened by flow cytometry and ELISA. This approach generated 147 different Fabs in 34 VH-CDR3 families. Utilizing competition assays with soluble protein and mesothelin-containing serum obtained from metastatic cancer patients, 10 of these 34 VH-CDR3 families were found to bind exclusively to the membrane-associated form of mesothelin. Epitope mapping performed for the 1H7 clone showed that it does not recognize GPI anchor. VH-CDR3 sequence analysis of all Fabs showed significant differences between Fabs selective for the membrane-associated form of the antigen and those that recognize both membrane bound and soluble forms. This work demonstrates the potential to generate an antibody specific to the membrane-bound form of mesothelin. 1H7 offers potential for therapeutic application against mesothelin-bearing tumors, which would be largely unaffected by the presence of the soluble antigen.

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“…Mesothelin, a membrane-bound peptide, is consistently present in normal mesothelial cells and overexpressed in many malignancies including mesothelioma, ovarian, colon, gastric, lung, triple-negative breast cancer, and pancreatico-biliary adenocarcinomas [5][6][7][8][9][10][11]. The mesothelin gene encodes a 69-71-kDa polypeptide anchored to the cell membrane by a glycosyl-phosphatidyl-inositol (GPI) linkage that can be processed to yield mesothelin, which remains attached to cell membrane, and another protein called MPF secreted into the blood [12][13][14].…”

Section: Smrpmentioning

confidence: 99%

Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma

Liu

Jiao

et al. 2015

Tumor Biol.

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Malignant pleural mesothelioma (MPM) is a highly aggressive tumor of the pleura closely related to asbestos exposure. Rare as it is, the incidence of MPM is predicted to increase mainly as a result of a lengthy latency period from the initial asbestos exposure, making it a public health concern for the next decades. Moreover, the patients with MPM have an extremely poor prognosis due to its high resistance to conventional oncologic treatments and delayed diagnosis. Although the result of current therapeutic modalities based on patient features and clinical stages is very frustrating, great advances have been shown in the knowledge of molecular biology of MPM in recent years. This is accompanied by dozens of putative prognostic biomarkers that are actively involved in tumor biological activities. These prognostic candidates can offer us a new insight into the biological characteristics of MPM, contributing to development of individualized therapeutic strategies directed against oncogenesis and tumor progression. Thus, personalized approaches based on the molecular biology of the patient's tissue or body fluid will potentially improve the present disappointing outcome, bringing new hope for patients with MPM. This article reviews the principal and several novel biomarkers that can have an influence on prognosis, in the hope that they can provide us with a more profound understanding of the biology of this lethal disease.

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Serum soluble mesothelin-related peptide (SMRP): a potential diagnostic and monitoring marker for epithelial ovarian cancer

Abstract: Serum SMRP is a promising marker for the diagnosis and monitoring of EOC, especially in combination with CA125.

Cited by 20 publications

References 27 publications

HE4 in the differential diagnosis of ovarian masses

HE4 in the differential diagnosis of ovarian masses

A new anti-mesothelin antibody targets selectively the membrane-associated form

Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma

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