The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in ovarian cancer and ovarian cysts

Orywal, Karolina; Jelski, Wojciech; Zdrodowski, Michał; Szmitkowski, Maciej

doi:10.2478/ams-2013-0012

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…Both the serum and tissue expression level of class I and total ADH were significantly increased in liver,27,28 colorectal,29,30 and brain cancers,31,32 while ALDH levels were not statistically significant different between cancer patients and healthy subjects. The upregulation trend of class I ADH between cancer and healthy tissue can also be found in cervical,33 ovarian,34 endometrial,35 and renal cell cancers,36 whereas the upregulation trend of class I ADH for cancer serum has been reported in bladder and esophageal cancers 37,38. However, the expression of class I ADH in breast cancer was significantly decreased compared to the tissue of healthy subjects, and the expression of ALDH was unchanged 39.…”

Section: Discussionmentioning

confidence: 94%

Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma

Liao¹,

Huang²,

Liu³

et al. 2017

OTT

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BackgroundAlcohol dehydrogenase (ADH) isoenzymes have been reported as a potential diagnostic marker for pancreatic cancer, but their prognostic value in pancreatic cancer remains unclear. The aim of this investigation was to identify the prognostic value of ADH genes in human patients with pancreatic adenocarcinoma (PAAD).Materials and methodsAn RNA sequencing dataset and corresponding survival profiles of PAAD were obtained from The Cancer Genome Atlas. Survival analysis and gene set enrichment analysis were used to investigate the prediction value and potential mechanism of ADH genes in PAAD prognosis.ResultsSurvival analysis of ADH genes suggests that a high expression of ADH1A (adjusted P=0.037, adjusted hazard ratio [HR] =0.627, 95% CI =0.404–0.972) and ADH6 (adjusted P=0.018, adjusted HR =0.588, 95% CI =0.378–0.914) were associated with a significantly decreased risk of death, while a high expression of ADH5 was associated with a significantly increased risk of death (adjusted P=0.043, adjusted HR =1.564, 95% CI =1.013–2.414). Joint effects analysis of three ADH gene prognostic markers suggests that the prognosis difference for any marker combination was more significant than that for any individual marker. The potential mechanism of ADH1A and ADH6 in PAAD prognosis was that a high expression of ADH1A and ADH6 was involved in the P450 pathway and biological processes, while high ADH5 expression was involved in transforming growth factor β regulation-related pathways and biological processes, Wnt, the cell cycle, ErbB, and mitogen-activated protein kinase signaling pathways.ConclusionOur data suggest that ADH1A, ADH5, and ADH6 expression may be potential prognostic markers of PAAD and in combination have a strong interaction and better predictive value for PAAD prognosis.

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Section: Discussionmentioning

confidence: 94%

Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma

Liao¹,

Huang²,

Liu³

et al. 2017

OTT

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“…It is considered to be both a serum biomarker and a therapeutic target for ovarian cancer [36] . Alcohol dehydrogenase 1 (ADH) participates in the metabolism of some biological substances, and its activity is typically increased in ovarian cancer, especially that of the class I isoenzyme, which may be a factor for the metabolic disturbances of important biological substances [37] . It has been reported that intertumor differences in glutathione S-transferase P (GSTP1) expression might influence the response to platinum-based chemotherapy in ovarian cancer patients [38] .…”

Section: Urine Proteome Changes In Nutu-19 Cell Intraperitoneal-injecmentioning

confidence: 99%

“…The increasing expression of platelet derived growth factor receptor alpha (PGFRA) is found to be associated with a significantly poorer overall survival of ovarian cancer patients [57] . The activity of alcohol dehydrogenase [NADP(+)] (AK1A1) might be an important factor for the disturbances in the metabolism of biological substances in ovarian cancer [37] . These urine proteins may indicate a metabolic disorder caused by bloody ascites in the advanced stages (III, IV) of ovarian cancer.…”

Section: Urine Proteome Changes In Nutu-19 Cell Intraperitoneal-injecmentioning

confidence: 99%

Dynamic changes in the urine proteome in two ovarian cancer rat models

Zhang

Meng

et al. 2019

Preprint

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Ovarian cancer is the most lethal gynecological malignancy in women, and it is likely to metastasize and has a poor prognosis. The early and reliable diagnosis and monitoring of ovarian cancer is very important. Without a homeostasis mechanism, urine can reflect early systemic changes in the body and has a great potential to be used for the early detection of cancer. This study tested whether early changes could be detected in two ovarian cancer rat models. Two rat models were established by either intraperitoneal (i.p.) or orthotopic (o.t.) injection of NuTu-19 ovarian cancer cells in female Fischer344 rats. Urine samples from ovarian cancer rats were collected at five time points during cancer development, and urinary proteins from the rats were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with pre-injection samples, 49 differential proteins that have human orthologues were significantly changed in the orthotopically injected model. Among them, 24 of the differential proteins have previously been reported to be associated with ovarian cancer, six of which were reported to be biomarkers of ovarian cancer. On the 7th day after orthotopic injection, four differential proteins (APOA1, OX2G, CHMP5, HEXB) were identified before obvious metastases appeared. In the intraperitoneal injection model, 76 differential proteins were changed during the course of ovarian cancer development. The results show that urine proteins could enable the early detection and monitoring of ovarian cancer progression and could lay a foundation for further exploration of the biomarkers of ovarian cancer. IntroductionOvarian cancer (OC) is the most lethal gynecological malignancy and it is the fifth leading cause of cancer death in women [1] , mainly because OC can spread to intraperitoneal tissues, such as the omentum in the peritoneal cavity, by the time of diagnosis [2] . The strongest risk factors for this disease are an advanced age and a family history of ovarian cancer. Epithelial ovarian cancer (EOC) is the most common ovarian malignancy and comprises 90% of all ovarian cancers [3] . More than 75% of affected women ovarian carcinomas are not diagnosed until a late stage (stage III or IV) because early-stage disease is not obvious and early symptoms, as well as symptoms of late-stage disease, are nonspecific.Pelvic or abdominal pain, a feeling of pelvic mass and abdominal swelling are the main clinical symptoms, but these are not specific to OC [4] . Currently, women who have symptoms consistent with ovarian cancer usually undergo a physical examination, transvaginal ultrasonography, and measurement of biomarkers such as CA125, but imaging and serum biomarkers tests are of limited 2 value in the early diagnosis of the ovarian carcinomas [5] . The treatment of ovarian cancer usually involves surgery and intraperitoneal and intravenous chemotherapy [6] . At present, patients are typically diagnosed at the advanced stage when the cancer has disseminated within the peritoneal cavity, and comp...

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“…In premenopausal women, alcohol consumption has been consistently, positively correlated with both total estrogen level and bioavailable estrogens, but postmenopausal alcoholics have elevated levels of serum estradiol and plasma levels of estrone sulfate [57, 58]. Similar to findings in the endometrial and cervical cancer, the activity of ADH (especially ADH class I) was significantly higher in ovarian cancer tissue than in ovarian cysts and healthy ovary, but the activity of ALDH was not changed [59]. This suggests increased ability to produce acetaldehyde by cancerous ovarian cells.…”

Section: Adh and Aldh In Malignant Diseasesmentioning

confidence: 99%

Alcohol dehydrogenase and aldehyde dehydrogenase in malignant neoplasms

Orywal

Szmitkowski

2016

Clin Exp Med

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According to International Agency for Research on Cancer, ethanol and acetaldehyde belong to group 1 of human carcinogens. The accurate mechanism by which alcohol consumption enhances carcinogenesis is still unexplained. Alcohol is oxidized primarily by alcohol dehydrogenase (ADH) to acetaldehyde, a substance capable of initiating carcinogenesis by forming adducts with proteins and DNA and causing mutations. Next, acetaldehyde is metabolized by aldehyde dehydrogenase (ALDH) to acetate. In tissues of many cancers, we can observe significantly higher activity of total alcohol dehydrogenase with any change in aldehyde dehydrogenase activity in comparison with healthy cells. Moreover, in malignant diseases of digestive system, significantly increased activity of ADH isoenzymes class I, III and IV was found. The gynecological, brain and renal cancers exhibit increased activity of class I ADH. ADH and ALDH can play also a crucial regulatory role in initiation and progression of malignant diseases by participation in retinoic acid synthesis and elimination of toxic acetaldehyde. Besides, changes of enzymes activities in tumor cells are reflected in serum of cancer patients, which create the possibilities of application ADH isoenzymes as cancer markers.

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The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in ovarian cancer and ovarian cysts

Cited by 14 publications

References 24 publications

Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma

Distinct prognostic values of alcohol dehydrogenase mRNA expression in pancreatic adenocarcinoma

Dynamic changes in the urine proteome in two ovarian cancer rat models

Alcohol dehydrogenase and aldehyde dehydrogenase in malignant neoplasms

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