Drug resistance to existing anticancer agents is a growing clinical concern, with many first line treatments showing poor efficacy in treatment plans of some cancers. Resistance to platinum agents, such as cisplatin, is particularly prevalent in the treatment of ovarian cancer, one of the most common cancers amongst women in the developing world. Therefore, there is an urgent need to develop next generation of anticancer agents which can overcome resistance to existing therapies. We report a new series of organoruthenium(II) complexes bearing structurally modified pyrithione ligands with extended aromatic scaffold, which overcome platinum and adriamycin resistance in human ovarian cancer cells. The mechanism of action of such complexes appears to be unique from that of cisplatin, involving G cell cycle arrest without generation of cellular ROS, as is typically associated with similar ruthenium complexes. The complexes inhibit the enzyme thioredoxin reductase (TrxR) in a model system and reduce cell motility towards wound healing. Importantly, this work highlights further development in our understanding of the multi-targeting mechanism of action exhibited by transition metal complexes.
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http://dx.doi.org/10.3390/cancers13102493 | DOI Listing |
Sci Adv
January 2025
MRC Laboratory of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK.
Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells.
View Article and Find Full Text PDFJ Assist Reprod Genet
January 2025
Department of Gynaecology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning Province, Shenyang, 110001, The People's Republic of China.
Background: The "Healthy China" initiative, along with advancements in technology for cancer diagnosis and treatment, has significantly enhanced outcomes for patients with gynecologic tumors. The trends of late marriage and delayed childbirth have led to an increasing number of women diagnosed with gynecologic cancers who are seeking fertility preservation in China. This issue is critical yet often overlooked in clinical practice.
View Article and Find Full Text PDFGinekol Pol
January 2025
Faculty of Medicine, Lazarski University, Warsaw, Poland, Poland.
In women after hematopoietic stem cell transplantation (HSCT), complications associated with the original disease and therapies used both before and after transplantation often occur, which significantly affects their quality of life. The most common gynaecological complications include secondary cancers, premature ovarian insufficiency (POI), infertility and chronic graft-versus-host disease (cGVHD). Cervical cancer is the most common secondary genital cancer in patients after HSCT.
View Article and Find Full Text PDFInt J Gynaecol Obstet
January 2025
Department of Obstetrics and Gynecology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Histopathology
January 2025
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Aims: Classification and risk stratification of endometrial carcinoma (EC) has transitioned from histopathological features to molecular classification, e.g. the ProMisE classifier, identifying four prognostic subtypes: POLE mutant (POLEmut) with almost no recurrence or disease-specific death events, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP), with intermediate outcome and p53 abnormal (p53abn) with poor outcomes.
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