Clinical evaluations of a new ovarian cancer marker, COX‐1

Lee, G.; Ng, Han Seong

doi:10.1016/0020-7292(95)02406-3

Cited by 16 publications

(23 citation statements)

References 17 publications

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“…COX enzymes are required for ovarian function and many female reproductive processes, but overexpression of COX is associated with significant pathology. Increased expression of COX-2 is associated with manyepithelial carcinomas; however, COX-1 but not COX-2 overexpression has been shown to be associated with ovarian cancer [8,[21][22][23][24][25][26]. The laying hen provides an excellent model for studying normal ovarian functions, in particular ovulation [27,28].…”

Section: Discussionmentioning

confidence: 99%

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Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus)

Hales

Zhuge

Lagman

et al. 2008

Endocr

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Cyclooxygenase (COX) (PTGS) is the rate-limiting enzyme in the biosynthesis of prostaglandins. Two COX isoforms have been identified, COX-1 and COX-2, which show distinct cell-specific expression and regulation. Ovarian cancer is the most lethal gynecological malignancy and the © Humana Press Inc. 2008 Correspondence to: Dale Buchanan Hales, dbhale@uic.edu. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript disease is poorly understood due to the lack of suitable animal models. The laying hen spontaneously develops epithelial ovarian cancer with few or no symptoms until the cancer has progresses to a late stage, similar to the human disease. The purpose of this study was to examine the relative expression and distribution of COX-1 and COX-2 in the ovaries of normal hens and in hens with ovarian cancer. The results demonstrate that COX-1 was localized to the granulosa cell layer and cortical interstitium, ovarian surface epithelium (OSE) and postovulatory follicle (POF) of the normal ovary. In ovarian cancer, COX-1 mRNA was significantly increased and COX-1 protein was broadly distributed throughout the tumor stroma. COX-2 protein was localized to the granulosa cell layer in the follicle and the ovarian stroma. COX-2 mRNA expression did not change as a function of age or in ovarian cancer. There was significantly higher expression of COX-1 mRNA in the first POF (POF-1) compared to POF-2 and POF-3. COX-2 mRNA expression was not significantly different among POFs. There was no difference in COX-1 or COX-2 mRNA in the OSE isolated from individual follicles in the follicular hierarchy. The results confirm previous findings of the high expression of COX-1 in ovarian tumors further supporting the laying hen as a model for ovarian cancer, and demonstrate for the first time the high expression of COX-1 in POF-1 which is the source of prostaglandins needed for oviposition.

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Section: Discussionmentioning

confidence: 99%

“…In contrast to most malignancies, however, COX-2 expression is downregulated in ovarian cancer [20]. Instead, COX-1 expression has been shown to be elevated in ovarian cancer [8,[21][22][23][24][25][26]. Whereas considerable research has focused on the role of COX-2 in ovulation and normal ovarian function, much less is known about COX-1.…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus)

Hales

Zhuge

Lagman

et al. 2008

Endocr

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“…[1][2][3][4][5] CA215 was shown to be homologous to heavy chains of human immuoglobulins. RP215 monoclonal antibody was shown to react specifically with carbohydrate-associated epitope(s) located on the Fab region of cancer cell-expressed human immunoglobulins.…”

Section: Discussionmentioning

confidence: 99%

“…By enzyme immunoassays, serum levels of CA215 were elevated significantly among patients with various cancers, especially those of cervix and ovary. [1][2][3][4][5] Recently, it was also demonstrated from limited cases of immunohistochemical studies that RP215 reacts with a carbohydrate-associated epitope of CA215 in a variety of cancers including esophagus, stomach, colon, ovary, cervix, lung, breast and endometrium. 3 The molecular identity of CA215 was characterized by extensive biochemical, immunological as well as molecular biological studies.…”

Section: Introductionmentioning

confidence: 99%

Preclinical assessment of anti-cancer drugs by using RP215 monoclonal antibody

Lee¹,

Chu²,

Ting³

2009

Cancer Biology & Therapy

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RP215 monoclonal antibody was originally generated against OC-3-VGH ovarian cancer cells. It was shown to recognize specifically a carbohydrate-associated epitope(s) of cancer cell-expressed immunoglobulin heavy chains designated as CA215. Previous studies suggest that CA215 is expressed by all human cancer cell lines and tissues in both membrane bound and secreted forms. It may be an ideal target for therapeutic treatments of human cancers with humanized RP215-related antibodies. Based on the results of large scale immunohistochemical studies (50-100 cases each), the following types of cancers revealed high percentage(s) of positive staining with RP215: esophagus (76%), stomach (50%), colon (44%), ovary (64%), breast (32%), lung (31%), cervix (84%) and endometrium (78%). Nude mouse experiments were performed to determine if RP215 has any inhibitory effect on the growth of cancer cells in vivo. Following injections of a single dose (10 mg/kg) of I 131 -labeled RP215 (specific activity, 12.5 μCi/mg), the tumor size (OC-3-VGH ovarian cancer cells) was reduced to 30% of the untreated control within two weeks. By injecting the same dose, the unlabeled RP215 also reduced the tumor size to 50% of the control during the same period. The antibody treatments were found to have little effect on the body weight as well as apparent toxicity of these animals. To proceed with clinical trial studies of RP215-based anti-cancer drugs, chimeric form of this monoclonal antibody was generated and characterized. Through our effort, the "proof of concept" of anti-cancer drugs development was clearly established for the next stages of clinical trial studies.

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“…Therefore, the name of COX-1 was used during early studies of CA215 [4,27]. However, by use of MALDI-TOF MS analysis, it was clearly demonstrated that CA215 consists mainly of immunoglobulin heavy chains expressed by cancer cells [1,5,11,18].…”

Section: Applications Of Ca215 and Other Known Cancer Biomarkers In Rmentioning

confidence: 99%

CA215, A New Pan Cancer Biomarker, and its Clinical Applications

Lee¹

2015

CSROA

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The antigen recognized by RP215, CA215, can be detected in the shed media from a number of cultured cancer cells [2,5]. Therefore, Matrix-Assisted Laser Desorption/Ionization TimeOf-Flight Mass Spectrometry (MALDI-TOF MS) analysis was performed to determine the molecular identity of affinityisolated CA215 from the shed media of OC-3-VGH ovarian and C-33A cervical cancer cell lines [2,5]. Following tryptic digestion of CA215, the peptide fragments were subjected to analysis by MALDI-TOF MS. It was observed that as many as 50% of the peptide fragments derived from the shed media of cultured cancer cells were found to have a high degree of homology to antigen receptors, including immunoglobulins (42%) and T cell receptors (6%) expressed by cancer cells [5]. Many other different glycoproteins generally categorized as immunoglobulin superfamily proteins (IgSF) were also detected in such analyses [11].In view of the observation that the immunoactivity of the RP215-specific epitope in CA215 is destroyed by periodate treatments under mild conditions at neutral pH, it was assumed that the unique RP215 epitope is carbohydrate-associated [3]. Following extensive studies through glycopeptide mapping and glycosyl linkage analysis, it was suggested that the RP215-specific epitope may be associated with a simple O-linked glycan together with amino acid residues in the variable region of cancerous immunoglobulin heavy chains [12]. But this RP215-specific epitope is not found in immunoglobulins expressed by normal B cells [3].Since CA215 is cancer-associated, elevated levels of CA215 in the human circulation may indicate active growth/proliferation or metastasis of cancer cells in the human body [1,2,5,11,[13][14][15][16][17][18][19][20]. Immunoassays using RP215 as a unique substitute for antibodies against cancerous immunoglobulins have been established for the quantitative determination of serum levels of CA215 [1]. They have successfully been used to monitor CA215 levels in the human sera of patients confirmed or diagnosed with cancers of various tissue origins [21].Therefore, in this review, results of CA215 clinical evaluations are highlighted to demonstrate the potential applications of Abstract CA215 is a tumor-associated antigen which originated from the generation of a monoclonal antibody, RP215, against cultured ovarian cancer cell extract in 1987. To identify the molecular identity of CA215, MALDI-TOF MS studies were performed for affinity-isolated CA215 from shed medium of cultured OC-3-VGH ovarian cancer cells. RP215 was shown to react with a carbohydrate-associated epitope located mainly on the immunoglobulin heavy chains (designated in general as CA215) expressed by most cancer cells. By using RP215 as a probe, both sandwich and competitive immunoassays were formulated to determine the serum CA215 levels among patients diagnosed with known cancers of the lung, liver, colon, esophagus, ovary, breast, pancreas, cervix, and lymphocytes. When each of the other known cancer biomarkers, such as AFP, CEA, CA 125, CA 19-...

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Clinical evaluations of a new ovarian cancer marker, COX‐1

Cited by 16 publications

References 17 publications

Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus)

Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus)

Preclinical assessment of anti-cancer drugs by using RP215 monoclonal antibody

CA215, A New Pan Cancer Biomarker, and its Clinical Applications

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