Preferential expression of hPGFS in primary SCCHN and tumour cell lines derived from respiratory and digestive organs

Li, S; Hanna, Ehab Y.; Breau, Randy; Ratanatharathorn, Vaneerat; Xia, Xueqing; Suen, James Y.

doi:10.1038/sj.bjc.6601636

Cited by 4 publications

(1 citation statement)

References 23 publications

(25 reference statements)

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“…Likewise, in the breast, AKR1C3 helps create pro-estrogenic state by enhancing the synthesis of 17β-estradiol and inactivating progesterone (Byrns et al, 2008); 2) by converting PGD 2 to 9α,11β-PGF 2 , AKR1C3 diverts the metabolism of the former from forming 15-deoxy-Δ 12,14 -PGJ 2 , thus depriving PPARγ receptor of its ligand and preventing terminal differentiation of myeloid leukemia cells (Desmond et al, 2003). PGF 2 and its isomers stimulate proliferation through F-prostanoid receptor (Chen et al, 1998;Sales et al, 2004); 3) AKR1C3 is overexpressed in several types of cancer (Stanbrough et al, 2006;Li et al, 2004).…”

Section: Iii) Inhibitorsmentioning

confidence: 99%

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

Barski

Tipparaju

Bhatnagar

2008

Drug Metabolism Reviews

417

328

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The Aldo-Keto Reductase (AKR) superfamily comprises of several enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism and detoxification. Substrates of the family include glucose, steroids, glycosylation end products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β/α) 8 barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the Phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.

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Section: Iii) Inhibitorsmentioning

confidence: 99%

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

Barski

Tipparaju

Bhatnagar

2008

Drug Metabolism Reviews

417

328

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An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3α-HSD, type 5 17β-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies

Byrns

Steckelbroeck

Penning

2008

Biochemical Pharmacology

121

141

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Aldo-keto reductase (AKR) 1C3 (type 2 3α-HSD, type 5 17β-HSD, and prostaglandin F synthase) regulates ligand access to steroid hormone and prostaglandin receptors and may stimulate proliferation of prostate and breast cancer cells. NSAIDs are known inhibitors of AKR1C enzymes. An NSAID analogue that inhibits AKR1C3 but is inactive against the cyclooxygenases and the other AKR1C family members would provide an important tool to examine the role of AKR1C3 in proliferative signaling. We tested NSAIDs and NSAID analogues for inhibition of the reduction of 9,10-phenanthrenequinone (PQ) catalyzed by AKR1C3 and the closely related isoforms AKR1C1 and AKR1C2. Two of the compounds initially screened, indomethacin and its methyl ester, were specific for AKR1C3 versus the other AKR1C isoforms. Based on these results and the crystal structure of AKR1C3, we predicted that N-(4-chlorobenzoyl)-melatonin (CBM), an indomethacin analogue that does not inhibit the cyclooxygenases, would selectively inhibit AKR1C3. CBM inhibited the reduction of PQ by AKR1C3, but did not significantly inhibit AKR1C1 or AKR1C2. Indomethacin and CBM also inhibited the AKR1C3-catalyzed reduction of Δ 4 -androstene-3,17-dione but did not significantly inhibit the reduction of steroid hormones catalyzed by AKR1C1 or AKR1C2. The pattern of inhibition of AKR1C3 by indomethacin and CBM was uncompetitive versus PQ, but competitive versus Δ 4 -androstene-3,17-dione, indicating that two different inhibitory complexes form during the ordered bi-bi reactions. The identification of CBM as a specific inhibitor of AKR1C3 will aid the investigation of its roles in steroid hormone and prostaglandin signaling and the resultant effects on cancer development.

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Thymoma and thymic carcinoma

Venuta

Anile

Diso

et al. 2010

European Journal of Cardio-Thoracic Surgery

179

149

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Thymoma and thymic carcinoma are an extremely heterogeneous group of neoplastic lesions with an exceedingly wide spectrum of morphologic appearances. They show different presentations with a variable and unpredictable evolution ranging from an indolent non-invasive attitude to a highly infiltrative and metastasising one. Prognosis can be predicted on the basis of a number of variables, mainly staging, the WHO histological pattern and diameter of the tumour. Complete surgical resection is certainly the gold standard to achieve cure. However, especially in patients with lesions at advanced stage, complete resection may be difficult and recurrence often occurs; at these stages, disease-free long-term survival may be difficult to be accomplished. Chemo- and radiotherapy protocols have been designed to complete surgical treatment and improve results in inoperable patients as well, based on the reported sensitivity of thymic tumours to these treatment modalities. The integration of clinical staging and histology, with the new histogenetic morphological classification, has contributed to design multimodality treatment protocols that help to improve prognosis. Induction therapy can now be applied before surgery in patients with tumours considered inoperable, improving resectability and outcome without adding morbidity and mortality to the surgical procedure. This newly developed approach helps to reduce the recurrence rate and to ameliorate disease-free survival. New therapies are now being evaluated as for many other tumours; however, they still need confirmation in prospective randomised studies. In the future, integrated treatment modality should be incorporated in a standardised approach that goes from a careful assessment of histology, staging and lymph node status, and a constructive and non-empirical co-operation between medical and radiation oncologists, pathologists and thoracic surgeons.

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Preferential expression of hPGFS in primary SCCHN and tumour cell lines derived from respiratory and digestive organs

Cited by 4 publications

References 23 publications

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3α-HSD, type 5 17β-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies

Thymoma and thymic carcinoma

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