Article
Multidisciplinary Sciences
Robin M. Delaine-Smith, Eleni Maniati, Beatrice Malacrida, Sam Nichols, Reza Roozitalab, Roanne R. Jones, Laura S. M. Lecker, Oliver M. T. Pearce, Martin M. Knight, Frances R. Balkwill
Summary: In a multi-level deconstruction, a prognostic matrisome gene expression signature was identified in high-grade serous ovarian cancer and twelve other malignancies. The upregulation of six extracellular matrix molecules was found to be associated with TGF beta R activity and Hedgehog signaling. Using tri-culture models, it was demonstrated that activated omental fibroblasts produce more matrix than malignant cells and this production is directed by TGFbR and Hh signaling cross talk.
Article
Oncology
Guang-Ping Zou, Chun-Xia Yu, Sheng-Lan Shi, Qiu-Gen Li, Xiao-Hua Wang, Xin-Hui Qu, Zhang-Jian Yang, Wei-Rong Yao, Dan-Dan Yan, Li-Ping Jiang, Yu-Ying Wan, Xiao-Jian Han
Summary: The dynamics of mitochondria mediated by DRP1 and MFN2 play a crucial role in the development of cisplatin resistance in ovarian cancer cells. Modulating the expression of these proteins can impact cell migration capability and ATP levels.
Article
Oncology
Mario Cioce, Claudia Canino, Harvey Pass, Giovanni Blandino, Sabrina Strano, Vito Michele Fazio
Summary: Malignant pleural mesothelioma (MPM) is highly resistant to current treatment options and has a poor prognosis. Treatment-induced stress triggers an adaptive response involving complex rearrangement of the MPM secretome, mediated by the acquisition of a senescence-associated-secretory-phenotype (SASP). Arachidonic acid (AA) is identified as an early mediator of this adaptive response and is associated with chemoresistance in MPM.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Xinjian Huang, Dongni Shi, Xuxiazi Zou, Xuxia Wu, Shumei Huang, Lingzhi Kong, Muwen Yang, Yunyun Xiao, Boyu Chen, Xiangfu Chen, Ying Ouyang, Libing Song, Yunting Jian, Chuyong Lin
Summary: This study found that BAG2 is significantly upregulated in relapse breast cancer patient tissues, and its high expression is associated with a worse prognosis. BAG2 localizes in mutant p53 aggregates and interacts with misfolded p53 mutants. BAG2 exacerbates the formation of the aggregates and recruits HSP90 to promote their propagation and maintenance, leading to chemoresistance in breast cancer.
Review
Pharmacology & Pharmacy
Natalia Manzano-Leon, Patricia Garcia-Lopez
Summary: Ovarian cancer is often diagnosed in advanced stages with low survival rates, and chemotherapy is the primary treatment but is often compromised by chemoresistance. Statins have been suggested as an alternative for managing chemoresistant ovarian cancer, but their use is controversial. More research is needed to explore the potential benefits of using higher doses of statins in cancer treatment.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Reproductive Biology
Shuqing Li, Zhihui Yi, Mingqing Li, Zhiling Zhu
Summary: Baicalein improves the sensitivity of resistant ovarian cancer cells to cisplatin and inhibits cell proliferation, metastasis, and tumor growth.
JOURNAL OF OVARIAN RESEARCH
(2023)
Review
Cell Biology
MelissaR Pitman, Martin K. Oehler, Stuart M. Pitson
Summary: Ovarian cancer is a deadly gynaecological malignancy commonly diagnosed at an advanced stage, making treatment challenging. Novel strategies for early detection and therapeutics are urgently needed to improve patient survival, with the sphingolipid pathway showing promise as a potential therapeutic target against chemotherapy-resistant disease.
CELLULAR SIGNALLING
(2021)
Review
Biochemistry & Molecular Biology
Katarzyna M. Terlikowska, Bozena Dobrzycka, Slawomir J. Terlikowski
Summary: The advancement in our understanding of tumor biology has led to the development of targeted molecular therapies, such as CARs, which show potential in treating ovarian cancer. identification. CARs targeting overexpressed molecules in tumor cells causes high toxicity and reduces tumor burden with minimal side effects, inhibiting disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Nisha R. Pawar, Marguerite S. Buzza, Nadire Duru, Amando A. Strong, Toni M. Antalis
Summary: Metastatic spread of ovarian cancer is associated with the shedding and dissemination of multicellular spheroids. Overactive matriptase disrupts cell-cell contacts and promotes spheroid dissemination through the activation of PAR-2/PI3K/Akt/MMP9 signaling axis. Understanding this pathway provides potential therapeutic targets for aggressive metastatic ovarian cancer.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ryan P. Campbell, A. Carl Whittington, Diego A. R. Zorio, Brian G. Miller
Summary: The recruitment of promiscuous enzymes is a key step in metabolic pathway evolution. However, the factors determining the preferential recruitment of certain enzymes over others are not well understood. Through adaptive evolution of a glucokinase-deficient E. coli strain, it was found that the least active enzyme, AlsK, was preferentially recruited, while the more active enzymes, NagK and Mak, were not recruited, indicating that catalytic activity alone does not determine evolutionary outcomes.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Multidisciplinary Sciences
I-M Launonen, N. Lyytikainen, J. Casado, E. A. Anttila, A. Szabo, U-M Haltia, C. A. Jacobson, J. R. Lin, Z. Maliga, B. E. Howitt, K. C. Strickland, S. Santagata, K. Elias, A. D. D'Andrea, P. A. Konstantinopoulos, P. K. Sorger, A. Farkkila
Summary: In this study, the authors used highly multiplexed imaging to analyze the immune microenvironment of high-grade serous ovarian cancers (HGSOC) and identified phenotypic characteristics and spatial interactions associated with BRCA1/2 gene mutations. These findings have important implications for improving immunotherapeutic strategies and patient stratification.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Mikhail S. Chesnokov, Anil Yadav, Ilana Chefetz
Summary: Ovarian cancer is a highly aggressive and deadly form of gynecologic malignancy that is closely associated with the activity of the MEK/ERK signaling pathway. The study validated the performance of a multi-cancer gene signature in various experimental models and ovarian cancer samples. Several genes were found to be consistently responsive to MEK/ERK activity modulations and were significantly associated with pathway activity in human ovarian cancer cell lines and patient samples. The findings highlight the importance of validating gene expression signatures in specific cancer types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Hussein Chehade, Roslyn Tedja, Harry Ramos, Tejeshwar Singh Bawa, Nicholas Adzibolosu, Radhika Gogoi, Gil Mor, Ayesha B. Alvero
Summary: Adipocytes play a crucial role in the ovarian tumor microenvironment, as their secreted factors and direct interaction with ovarian cancer cells can support tumor progression. Elucidating the molecular pathways involved is vital in identifying relevant targets.
Article
Engineering, Biomedical
Filbert H. Juwono, W. K. Wong, Hui Ting Pek, Saaveethya Sivakumar, Donata D. Acula
Summary: This study proposes an optimal feature weighting/parameter optimization method for detecting ovarian cancer occurrence. By using adaptive differential evolution and LASSO regularization, features in the subset can be reduced and eliminated. The K-nearest neighbors and support vector machines algorithms achieve high accuracy.
BIOMEDICAL SIGNAL PROCESSING AND CONTROL
(2022)
Review
Cell Biology
Tamsin Wesley, Stuart Berzins, George Kannourakis, Nuzhat Ahmed
Summary: The plakin family of cytoskeletal proteins, particularly plectin, periplakin, and envoplakin, play crucial roles in disease-states and cancers, with a focus on ovarian cancer. They are involved in regulating cancer cell growth, survival, migration, invasion, and drug resistance, potentially impacting progression, chemoresistance, and recurrence. Abnormal expression of plakins may lead to the transition of benign ovarian tumors to carcinomas and contribute to the sustenance and progression of the disease.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Pharmacology & Pharmacy
Feng Deng, Maren Laasik, Liina Salminen, Lauri Lapatto, Kaisa Huhtinen, Yilin Li, Sampsa Hautaniemi, Johanna Hynninen, Mikko Niemi, Rainer Lehtonen
Summary: The study identified genetic variations in SLCO1B3, LIG3, GSTP1, ABCB1, and OPRM1 associated with risk of adverse effects, treatment response, and prognosis in patients receiving carboplatin-paclitaxel therapy for ovarian cancer.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Oncology
Alexandra Lahtinen, Kari Lavikka, Anni Virtanen, Yilin Li, Sanaz Jamalzadeh, Aikaterini Skorda, Anna Rossberg Lauridsen, Kaiyang Zhang, Giovanni Marchi, Veli-Matti Isoviita, Valeria Ariotta, Oskari Lehtonen, Taru A. Muranen, Kaisa Huhtinen, Olli Carpen, Sakari Hietanen, Wojciech Senkowski, Tuula Kallunki, Antti Hakkinen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Summary: Ovarian HGSC is often diagnosed at an advanced stage, with genetically diverse clones existing prior to treatment. This study analyzed whole-genome sequencing data from 510 samples of 148 HGSC patients, revealing three evolutionary states with distinct genomic features, pathways, and phenotypes, which showed significant association with treatment response. Pathway analysis suggested two potential evolutionary trajectories, and experiments with tumor organoids supported targeted therapy for tumors with enriched PI3K/AKT pathway. Heterogeneity analysis indicated more unique clones in samples from the site of origin compared to metastatic tumors or ascites. These findings highlight the importance of integrative tumor evolution analysis for identifying patient subtypes.
Article
Oncology
Sanna Pikkusaari, Manuela Tumiati, Anni Virtanen, Jaana Oikkonen, Yilin Li, Fernando Perez-Villatoro, Taru Muranen, Matilda Salko, Kaisa Huhtinen, Anna Kanerva, Heidi Koskela, Johanna Tapper, Riitta Koivisto-Korander, Titta Joutsiniemi, Ulla-Maija Haltia, Heini Lassus, Sampsa Hautaniemi, Anniina Farkkila, Johanna Hynninen, Sakari Hietanen, Olli Carpen, Liisa Kauppi
Summary: A clinically feasible assay was developed to identify HR-deficient tumors in high-grade serous ovarian cancers. The assay predicted clinical outcomes and helped determine which patients were most likely to benefit from platinum-based chemotherapy and PARP inhibitors.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Wojciech Senkowski, Laura Gall-Mas, Matias Marin Falco, Yilin Li, Kari Lavikka, Mette C. Kriegbaum, Jaana Oikkonen, Daria Bulanova, Elin J. Pietras, Karolin Vossgrone, Yan-Jun Chen, Erdogan Pekcan Erkan, Jun Dai, Anastasia Lundgren, Mia Kristine Gronning Hog, Ida Marie Larsen, Tarja Lamminen, Katja Kaipio, Jutta Huvila, Anni Virtanen, Lars Engelholm, Pernille Christiansen, Eric Santoni-Rugiu, Kaisa Huhtinen, Olli Carpen, Johanna Hynninen, Sampsa Hautaniemi, Anna Vaharautio, Krister Wennerberg
Summary: This article describes a method for culturing organoids from high-grade serous ovarian cancer (HGSC) with improved efficacy compared to previous reports (53% vs. 23%-38%). The organoids recapitulated genetic and phenotypic features of the original tumors. The organoid drug responses correlated with clinical treatment outcomes, but only in organoids maintained in human plasma-like medium. This resource facilitates the application of HGSC organoids in ovarian cancer research.
DEVELOPMENTAL CELL
(2023)
Article
Oncology
Jordi Gonzalez-Molina, Paula Hahn, Raul Maia Falcao, Okan Gultekin, Georgia Kokaraki, Valentina Zanfagnin, Tirzah Braz Petta, Kaisa Lehti, Joseph W. W. Carlson
Summary: This study explored the impact of fibrillar collagens on uterine leiomyosarcoma (uLMS) and found that uLMS tumors have low collagen density and increased expression of collagen-remodeling genes compared to uterine leiomyomas (LM).The overexpression of matrix metalloproteinase-14 (MMP14) in uLMS was found to support uLMS cell proliferation, and uLMS cells were found to be less sensitive to changes in collagen substrate stiffness. Additionally, enhanced basal yes-associated protein 1 (YAP) activity was observed in uLMS cells, which sustains their growth in low-stiffness substrates. These findings suggest that matrix remodeling and YAP may be potential therapeutic targets for uLMS.
MOLECULAR ONCOLOGY
(2023)
Article
Cell Biology
Emilia Piki, Alice Dini, Juuli Raivola, Kari Salokas, Kaiyang Zhang, Markku Varjosalo, Teijo Pellinen, Katja Valimaki, Kristina Tabor Veskimae, Synnove Staff, Sampsa Hautaniemi, Astrid Murumagi, Daniela Ungureanu
Summary: Dysregulation of the Wnt pathway, specifically the expression of the non-canonical receptor ROR1, is linked to ovarian cancer progression and drug resistance. ROR1 expression is enhanced by neoadjuvant chemotherapy, and its interaction with Wnt5a activates oncogenic signaling pathways in ovarian cancer cells. Furthermore, ROR1 and its downstream effector STAT3 are expressed at higher levels in stromal cells than in epithelial cancer cells in ovarian cancer tumors.
CELL DEATH DISCOVERY
(2023)
Meeting Abstract
Medicine, Research & Experimental
Valentina Zanfagnin, Okan Gultekin, Raul Maia Falcao, Kaisa Lehti, Tirzah Braz Petta, Joseph Carlson
LABORATORY INVESTIGATION
(2023)
Article
Obstetrics & Gynecology
Jenni M. Soederlund, Niina K. Hieta, Samu H. Kurki, Katri J. Orte, Paeivi Polo-Kantola, Sakari H. Hietanen, Marjut A. M. Haataja
Summary: This cross-sectional case-control study aimed to characterize the concurrent urogynecological and gastrointestinal disorders in female patients with lichen sclerosus (LS). The results showed that female patients with LS had an increased risk for gynecological cancers, pain syndromes, urinary incontinence, and gastrointestinal disorders. Therefore, increased awareness and timely treatment of these comorbidities are required.
JOURNAL OF LOWER GENITAL TRACT DISEASE
(2023)
Article
Biochemical Research Methods
Aikaterini Skorda, Anna Rossberg Lauridsen, Kaisa Huhtinen, Alexandra Lahtinen, Wojciech Senkowski, Jaana Oikkonen, Johanna Hynninen, Sampsa Hautaniemi, Tuula Kallunki
Summary: Patient-derived organoids (PDOs) are ideal ex vivo model systems for studying cancer progression and drug resistance mechanisms. This study presents a protocol for measuring drug efficacy in three-dimensional (3D) high-grade serous ovarian cancer PDO cultures through quantification of cytotoxicity and analyzing proliferation using the Ki67 biomarker.
Article
Oncology
Giovanni Marchi, Anna Rajavuori, Mai T. N. Nguyen, Kaisa Huhtinen, Sinikka Oksa, Sakari Hietanen, Sampsa Hautaniemi, Johanna Hynninen, Jaana Oikkonen
Summary: The study shows that ctDNA can adequately represent high-grade serous ovarian carcinoma (HGSC), and the mutations observed at relapse suggest personalized therapy options.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Medicine, Research & Experimental
Mai T. N. Nguyen, Anna Rajavuori, Kaisa Huhtinen, Sakari Hietanen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Summary: Circulating tumor DNA (ctDNA) analysis is a promising tool for detecting and profiling cancer genomics changes. However, copy-number analysis for treatment effect monitoring has received less attention compared to mutations. Our study shows that copy-number analysis using a sequencing panel can detect consistent profiles even in low-tumor content ctDNA samples. Longitudinal analysis reveals changes in copy-number profiles in high-tumor content plasma samples, suggesting a relationship between copy-number alterations and relapse. These findings highlight the importance of genomic profiling during treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)