Establishment and Characterization of a Human Ovarian Serous Cystadenocarcinoma Cell Line That Produces the Tumor Markers CA-125 and Tissue Polypeptide Antigen

Imai, Shunsuke; Kiyozuka, Yasuhiko; Maeda, Hiroko; Noda, Tsuneo; Hosick, Howard L.

doi:10.1159/000226813

Cited by 54 publications

(46 citation statements)

References 6 publications

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“…12 KOC-2S cells were derived from a primary ovarian serous adenocarcinoma that was clinically refractory to the adjuvant chemotherapy with cisplatin. 14 It is noteworthy that SU6668 exerted an antitumor effect against these cells.…”

Section: Discussionmentioning

confidence: 99%

“…The human ovarian serous adenocarcinoma cell lines SHIN-3 (VEGF-hypersecretory), 12,13 provided by Dr. Y. Kiyozuka (Kurume University of Medicine, Japan), and KOC-2S 13,14 provided by Dr. A. Kataoka (Kurume University of Medicine, Japan), were maintained as reported. These xenografts grow in the peritoneal cavity of nude mice, producing ascites and dissemination.…”

Section: Cell Linesmentioning

confidence: 99%

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Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU‐68)

Machida

Saga

Takei

et al. 2004

Intl Journal of Cancer

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SU6668 (TSU-68) is a small-molecule synthetic inhibitor of the angiogenic related receptor tyrosine kinases Flk-1/KDR, PDGFR␤, and FGFR1. Using a mouse model of peritoneally disseminated ovarian cancer, we investigated whether SU6668 inhibits peritoneal dissemination and prolongs survival time. BALB/c nude mice were intraperitoneally (i.p.) inoculated with SHIN-3 (VEGF-hypersecretory) or KOC-2S (PDGF-hypersecretory) ovarian serous adenocarcinoma cells with marked peritoneal dissemination ability. From the day after i.p. inoculation of tumor cells, SU6668 was orally administered 6 times weekly at a daily dose of 100 mg/kg or 400 mg/kg. The SU6668-administered group and the vehicle-administered control group were compared for the number of tumor vascular endothelial cells, weight of peritoneally disseminated tumors, amount of ascitic fluid and survival time. As a result, these 3 parameters were significantly smaller in the SHIN-3-inoculated, SU6668-administered mice than in the control group (p ‫؍‬ 0.03, p ‫؍‬ 0.002, and p ‫؍‬ 0.02, respectively). The mean survival time was significantly longer, at 58.1 ؎ 11.2 days, in the SU6668-administered mice than that (34.5 ؎ 8.8 days) in the control group (p ‫؍‬ 0.002). Similarly, in the KOC-2S-inoculated mice, the oral administration of SU6668 significantly reduced these 3 parameters (p ‫؍‬ 0.04, p ‫؍‬ 0.04, and p ‫؍‬ 0.03, respectively), and significantly prolonged survival (16.6 ؎ 1.7 days vs. 11.0 ؎ 0.7 days, p ‫؍‬ 0.008). Thus, the oral administration of SU6668 inhibited angiogenesis and peritoneal dissemination and prolonged survival in mice with peritoneally disseminated ovarian cancer. These effects were observed with both the VEGF-and PDGF-hypersecretory cell lines. Our results suggest that molecular targeting with oral SU6668 will become a new therapeutic strategy targeting peritoneally disseminated ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Linesmentioning

confidence: 99%

Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU‐68)

Machida

Saga

Takei

et al. 2004

Intl Journal of Cancer

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“…Pao was prepared in DMSO and diluted with sterile water. Carboplatin (Sigma, St. Louis, MO) was prepared in sterile water and stock at À20 C. Human ovarian cancer cell lines OVCAR-5 and OVCAR-8 were obtained from the American Type Culture Collection (Manassas, VA), SHIN-3 was donated by Dr. Perter Eck at the National Institutes of Health (Imai et al, 1990). Immortalized human epithelial cells MRC-5 was provided by Dr. Sittampalam at the University of Kansas Medical Center.…”

Section: Study Materials Cell Lines and Viability Assaymentioning

confidence: 99%

The plant extract ofPao pereirapotentiates carboplatin effects against ovarian cancer

Yu¹,

Chen²

2013

Pharmaceutical Biology

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Context: Herbal preparation of Pao pereira [Geissospermum vellosii Allem (Apocynaceae)] has long been used by oncologic patients and Integrative Medicine practitioners in South America. However, its anticancer activities have not been systematically studied. Objective: To investigate the anticancer effects of b-carboline alkaloids-enriched extract from Pao pereira (Pao), either alone or in combination with carboplatin, in preclinical ovarian cancer models. Materials and methods: Cytotoxicity of Pao (0-800 mg/ml) against different ovarian cancer cell lines and an immortalized epithelial cell line was detected by flow cytometry, MTT assay and colony formation in soft agar. Combination of Pao and carboplatin, a primary chemotherapeutic drug for ovarian cancer, was evaluated using Chou-Talalay's methods. Mice bearing intraperitoneally spread ovarian cancer were treated with 20 or 50 mg/kg/day Pao by i.p. injection. Carboplatin at 15 mg/kg/week i.p. was compared and combined to Pao treatments. Results: Pao selectively inhibited ovarian cancer cell growth with IC 50 values of 180-235 mg/ml, compared to 537 mg/ml in normal cells. Pao induced apoptosis dose-and time-dependently and completely inhibited colony formation of tumor cells in soft agar at 400 mg/ml. Pao greatly enhanced carboplatin cytotoxicity, with dose reduction (DRIs) for carboplatin at 1.2-10 fold. In vivo, Pao alone suppressed tumor growth by 79% and decreased volume of ascites by 55%. When Pao was combined with carboplatin, tumor inhibition reached 97% and ascites was completely eradicated. Discussion and conclusion: Pao possess potent antitumor activity and could enhance carboplatin effect, and therefore holds therapeutic potential in the treatment of ovarian cancer.

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“…An established ovarian cancer cell line, SHIN3 (15), was used for in vitro fluorescence microscopy, flow cytometry, and in vivo optical imaging for i.p. disseminated cancer implants.…”

Section: Cell Culturementioning

confidence: 99%

A Self-Quenched Galactosamine-Serum Albumin-RhodamineX Conjugate: A “Smart” Fluorescent Molecular Imaging Probe Synthesized with Clinically Applicable Material for Detecting Peritoneal Ovarian Cancer Metastases

Hama

Urano²,

Koyama³

et al. 2007

Clinical Cancer Research

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Purpose: Fluorophore activation after cellular internalization of a targeted fluorescently labeled conjugate is an effective molecular imaging strategy to increase target-to-background ratios. The D-galactose receptor on ovarian cancer cells has been used to target self-quenched avidinrhodamineX conjugates in which the avidin component binds to D-galactose receptor and the rhodamines are optically activated by dequenching only after cellular internalization. As a nonimmunogenic alternative of avidin, galactosamine-conjugated serum albumin (GmSA) targets the D-galactose receptor with higher binding affinity and has more conjugation sites available for rhodamineX than avidin. Experimental Design: GmSA was conjugated with 20 rhodamineX molecules (GmSA-20ROX) to create a self-quenching complex, which was compared with a conjugate consisting of GmSA and a single rhodamineX (GmSA-1ROX) in ex vivo chemical activation characteristics, intracellular activation, and in vivo molecular imaging for detecting peritoneal micrometastases of SHIN3 ovarian cancer. Results: GmSA-20ROX was five times brighter than GmSA-1ROX when incubated with SHIN3 ovarian cancer cells for 3 h. Submillimeter SHIN3 ovarian cancer implants in the peritoneal cavity were clearly visualized in vivo with spectral fluorescence imaging due to the high tumorto-background ratio. The sensitivity and specificity of GmSA-20ROX for implant detection were determined by colocalization of the rhodamineX emission with red fluorescent protein expressed constitutively in the SHIN3 tumor implants. Among 336 lesions, sensitivity and specificity were 99%/99%, respectively, for GmSA-20ROX, whereas the results for GmSA-1ROX were only 24%/100% (n = 388), respectively, for lesions f0.8 mm or greater in diameter. Conclusion: Self-quenched GmSA-20ROX is more efficient than previous D-galactoset argeted fluorescent conjugates.Improving the detection of ovarian cancer peritoneal metastases during surgical resection could lead to better cancer outcomes. Optical fluorescence imaging has been proposed as means of guiding surgical resections because of its high sensitivity, its low cost, its compatibility with the operating room environment, and its absence of ionizing radiation (1). Several approaches have been proposed for enhancing the detection of cancer foci, including somatostatin receptor-targeted probes (2), folate receptor-targeted agents (3), D-galactose (asialo) receptor-targeted agents (1, 4 -8), tumor-associated protease activatable agents (9 -11), and hybrid viral particles (12). To achieve high sensitivity, the signal from the target tissue must greatly surpass the signal from the background and the extent to which the target-to-background ratio is maximized determines the ultimate sensitivity of the complex.A common approach to optimize target-to-background ratios is to use fluorophore activation wherein the fluorophore emits minimal light in the unactivated state but increases its emission several fold in the activated state. For instance, Weissleder et al...

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Establishment and Characterization of a Human Ovarian Serous Cystadenocarcinoma Cell Line That Produces the Tumor Markers CA-125 and Tissue Polypeptide Antigen

Cited by 54 publications

References 6 publications

Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU‐68)

Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU‐68)

The plant extract ofPao pereirapotentiates carboplatin effects against ovarian cancer

A Self-Quenched Galactosamine-Serum Albumin-RhodamineX Conjugate: A “Smart” Fluorescent Molecular Imaging Probe Synthesized with Clinically Applicable Material for Detecting Peritoneal Ovarian Cancer Metastases

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