Role of folate receptor genes in reproduction and related cancers

Elnakat, Hala; Ratnam, Manohar

doi:10.2741/1815

Cited by 88 publications

(56 citation statements)

References 108 publications

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“…For example, FRA distributed on the proximal tubules of the kidney is thought to scavenge filtered folates and recycle them into the circulation so they are not lost into the urine [24,25]. Similarly, FRA expression on bronchiolar epithelium is thought to have anti-bacterial activity by sequestering folates away from colonizing bacteria [26][27][28].…”

Section: Normal Tissue Staining Distribution For Mab 26b3mentioning

confidence: 99%

Folate Receptor Alpha Expression in Lung Cancer: Diagnostic and Prognostic Significance

et al. 2012

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ABSTRACT:With the advent of targeted therapies directed towards folate receptor alpha, with several such agents in late stage clinical development, the sensitive and robust detection of folate receptor alpha in tissues is of importance relative to patient selection and perhaps prognosis and prediction of response. The goal of the present study was to evaluate the expression of folate receptor alpha in non-small cell lung cancer specimens to determine its frequency of expression and its potential for prognosis. The distribution of folate receptor alpha expression in normal tissues as well as its expression and relationship to non-small cell lung cancer subtypes was assessed by immunohistochemistry using tissue microarrays and fine needle aspirates and an optimized manual staining method using the recently developed monoclonal antibody 26B3. The association between folate receptor alpha expression and clinical outcome was also evaluated on a tissue microarray created from formalin fixed paraffin embedded specimens from patients with surgically resected lung adenocarcinoma. Folate receptor alpha expression was shown to have a high discriminatory capacity for lung adenocarcinomas versus squamous cell carcinomas. While 74% of adenocarcinomas were positive for folate receptor alpha expression, our results found that only 13% of squamous cell carcinomas were FRA positive (p<0.0001). In patients with adenocarcinoma that underwent surgical resection, increased folate receptor alpha expression was associated with improved overall survival (Hazard Ratio 0.39, 95% CI 0.18-0.85). These data demonstrate the diagnostic relevance of folate receptor alpha expression in non-small cell lung cancer as determined by immunohistochemistry and suggest that determination of folate receptor alpha expression provides prognostic information in patients with lung adenocarcinoma.

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Section: Normal Tissue Staining Distribution For Mab 26b3mentioning

confidence: 99%

Folate Receptor Alpha Expression in Lung Cancer: Diagnostic and Prognostic Significance

et al. 2012

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“…The folate receptor alpha (FRα) is a glycosylphosphatidyl-inositol-linked protein that is overexpressed in several epithelial malignancies, including ovarian, renal, lung, and breast cancers [1]. While the function of FRα in tumors is unclear, in the kidney it serves as a highaffinity salvage receptor that retrieves folate from the filtrate and returns it via transcytosis to the blood [2]; in the brain, it likely concentrates folate in cerebrospinal fluid [3].…”

Section: Introductionmentioning

confidence: 99%

Folate receptor alpha as a tumor target in epithelial ovarian cancer

Kalli¹,

Oberg²,

Keeney³

et al. 2008

Gynecologic Oncology

383

271

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Objectives-Folate receptor α (FRα) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FRα expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease.Methods-FRα expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FRα staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death.Results-FRα expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FRα status detected at diagnosis. Metastatic foci were similar to primary tumors in FRα staining. FRα status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses.Conclusion-FRα expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FRα expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer.

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“…This is highly desirable for biological applications, because it reduces their nonspecific uptake by cells within the reticuloendothelial system, which diminishes their phagocytosis, thus leading to prolonged circulation time in blood. 54 PEGylation of SWCNTs does not disrupt the π network of SWCNTs, thus preserving their physical properties, which are promising for multiple biomedical applications, including imagining.…”

Section: Introductionmentioning

confidence: 99%

Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy

Jeyamohan¹,

Hasumura²,

Nagaoka³

et al. 2013

IJN

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Abstract:The photothermal effect of single-walled carbon nanotubes (SWCNTs) in combination with the anticancer drug doxorubicin (DOX) for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX) binds at physiological pH (pH 7.4) and is released only at a lower pH, ie, lysosomal pH (pH 4.0), which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR) region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light-heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy.

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Role of folate receptor genes in reproduction and related cancers

Cited by 88 publications

References 108 publications

Folate Receptor Alpha Expression in Lung Cancer: Diagnostic and Prognostic Significance

Folate Receptor Alpha Expression in Lung Cancer: Diagnostic and Prognostic Significance

Folate receptor alpha as a tumor target in epithelial ovarian cancer

Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy

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