Immunohistochemical localization of metallothionein in benign and malignant epithelial ovarian tumors

McCluggage, W Glenn; Strand, Kathryn; Abdulkadir, AY

doi:10.1136/ijgc-00009577-200201000-00010

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…The percentage of MT‐positively stained cells was significantly higher in borderline than in benign tumours, being more elevated in malignant mucinous ovarian ones 119 . McCluggage et al 116 . reported similar MT positivity in different types of ovarian malignant tumours (endometrioid, mucinous, serous neoplasms).…”

Section: Ovarian Neoplasiamentioning

confidence: 93%

“…MT content of tumours obtained from patients that had completed chemotherapy was not different from that from untreated ones. Additionally, the levels of MT were not influenced by age, stage, histology, tumour differentiation state or response to therapy in ovarian carcinoma patients 115–118 . Germain et al .…”

Section: Ovarian Neoplasiamentioning

confidence: 95%

“…reported similar MT positivity in different types of ovarian malignant tumours (endometrioid, mucinous, serous neoplasms). In mucinous and serous ovarian tumours an increasing percentage of MT expression was observed during the progression of malignancy 116,119–121 . MT expression either before or after chemotherapy was not associated with the survival of ovarian carcinoma patients, although postchemotherapy, an increasing trend to MT expression was found 122 .…”

Section: Ovarian Neoplasiamentioning

confidence: 96%

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Metallothionein expression in human neoplasia

et al. 2004

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The metallothionein family is a class of low-molecular-weight, cysteine-rich proteins with high affinity for metal ions. Four major isoforms (metallothionein-1, -2, -3, and -4) have been identified in mammals, involved in many pathophysiological processes, including metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, drug and radiotherapy resistance and several aspects of the carcinogenic process. In the present review we examine the expression of metallothionein in different human tumours and its correlation with histopathological variables, tumour cell proliferation or apoptosis, resistance to radiation or chemotherapy, patient survival and prognosis. A variable profile of metallothionein and its isoforms' expression has been observed in different cancer types. Although metallothionein expression has been implicated in carcinogenic evolution, its use as a marker of tumour differentiation, cell proliferation and prognosis predictor remains unclear. Detailed studies focused on the expression of metallothionein isoforms and isotypes in different tumour types could elucidate the role of this group of proteins in the carcinogenic process, delineating its possible clinical significance for the management of patients.

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Section: Ovarian Neoplasiamentioning

confidence: 93%

Section: Ovarian Neoplasiamentioning

confidence: 95%

Section: Ovarian Neoplasiamentioning

confidence: 96%

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Metallothionein expression in human neoplasia

et al. 2004

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Metallothionein isoforms as double agents – Their roles in carcinogenesis, cancer progression and chemoresistance

Rodrigo

Jimemez

Haddad

et al. 2020

Drug Resistance Updates

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Metallothioneins (MTs) are small cysteine-rich intracellular proteins with four major isoforms identified in mammals, designated MT-1 through MT-4. The best-known biological functions of MTs are their ability to bind and sequester metal ions and their active role in redox homeostasis. Despite these protective roles, numerous studies have demonstrated that changes in MT expression could be associated with the process of carcinogenesis and participation in cell differentiation, proliferation, migration, and angiogenesis. Hence, MTs have the role of double agents, i.e., working with and against cancer. In view of their rich biochemical properties, it is not surprising that MTs participate in the emergence of chemoresistance in tumor cells. Many studies have demonstrated that MT overexpression is involved in the acquisition of resistance to anticancer drugs, including cisplatin, anthracyclines, tyrosine kinase inhibitors and mitomycin. The evidence is slowly becoming available for a cellular switch in MT functions, showing that they indeed have two faces: protector and saboteur.Initially, MTs display anti-oncogenic and protective roles; however, once the oncogenetic process has started, MTs are utilized by cancer cells for progression, survival, and the coordination of chemoresistance. The duality of MTs can serve as a potential prognostic/diagnostic biomarker and can therefore open the door to new strategies in cancer treatment. Herein, we review and discuss MTs as tumor disease markers and describe their role in chemoresistance to distinct anticancer drugs.

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Application of Phi29 Motor pRNA for Targeted Therapeutic Delivery of siRNA Silencing Metallothionein-IIA and Survivin in Ovarian Cancers

et al. 2011

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Ovarian cancer is a highly metastatic and lethal disease, making it imperative to find treatments that target late-stage malignant tumors. The packaging RNA (pRNA) of bacteriophage phi29 DNA-packaging motor has been reported to function as a highly versatile vehicle to carry small interference RNA (siRNA) for silencing of survivin. In this article, we explore the potential of pRNA as a vehicle to carry siRNA specifically targeted to metallothionein-IIa (MT-IIA) messenger RNA (mRNA), and compare it to survivin targeting pRNA. These two anti-apoptotic cell survival factors promote tumor cell viability, and are overexpressed in recurrent tumors. We find that pRNA chimeras targeting MT-IIA are processed into double-stranded siRNA by dicer, are localized within the GW/P-bodies, and are more potent than siRNA alone in silencing MT-IIA expression. Moreover, knockdown of both survivin and MT-IIA expression simultaneously results in more potent effects on cell proliferation in the aggressive ovarian tumor cell lines than either alone, suggesting that therapeutic approaches that target multiple genes are essential for molecular therapy. The folate receptor-targeted delivery of siRNA by the folate-pRNA dimer emphasizes the cancer cell-specific aspect of this system. The pRNA system, which has the capability to assemble into multivalent nanoparticles, has immense promise as a highly potent therapeutic agent.

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Immunohistochemical localization of metallothionein in benign and malignant epithelial ovarian tumors

Cited by 4 publications

References 27 publications

Metallothionein expression in human neoplasia

Metallothionein expression in human neoplasia

Metallothionein isoforms as double agents – Their roles in carcinogenesis, cancer progression and chemoresistance

Application of Phi29 Motor pRNA for Targeted Therapeutic Delivery of siRNA Silencing Metallothionein-IIA and Survivin in Ovarian Cancers

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