Article
Oncology
Rafah Alnafakh, Gabriele Saretzki, Angela Midgley, James Flynn, Areege M. Kamal, Lucy Dobson, Purushothaman Natarajan, Helen Stringfellow, Pierre Martin-Hirsch, Shandya B. DeCruze, Sarah E. Coupland, Dharani K. Hapangama
Summary: The study found that dyskerin levels are significantly lower in endometrial cancer and are linked to the survival of women. Experimental results suggest that dyskerin may be a regulator of endometrial cancer cell proliferation, and may be a potential target for developing new therapies.
Article
Endocrinology & Metabolism
Huiyang Yuan, Xin Qin, Qingya Yang, Li Liu, Zhiqing Fang, Yidong Fan, Dawei Xu
Summary: In clear cell renal cell carcinoma (ccRCC) patients, high expression of DKC1 is associated with shorter disease progression-free survival (PFS) in female but not male patients. In ccRCC patients treated with Sunitinib, female patients in the DKC1-high group have lower response rates and shorter PFS. DKC1 serves as an independent female-specific predictor for survival and Sunitinib efficacy.
BIOLOGY OF SEX DIFFERENCES
(2023)
Article
Multidisciplinary Sciences
Zhongqiu Xie, Pawel L. Janczyk, Xinrui Shi, Qiong Wang, Sandeep Singh, Robert Cornelison, Jingjing Xu, James W. Mandell, Frederic G. Barr, Hui Li
Summary: Research has found that the gene fusion MARS-AVIL is critical for tumorigenesis in RMS cells. Dysregulation of the AVIL gene is associated with the development of RMS and it functions upstream of the PAX3-FOXO1 and RAS oncogenic pathways. Overexpression of AVIL is correlated with clinical outcomes in sarcoma cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Rebecca S. Hesterberg, Min Liu, Aya G. Elmarsafawi, John M. Koomen, Eric A. Welsh, Stephen G. Hesterberg, Sujeewa Ranatunga, Chunying Yang, Weimin Li, Harshani R. Lawrence, Paulo C. Rodriguez, Anders E. Berglund, John L. Cleveland
Summary: Chronic T-cell receptor (TCR) signaling in the tumor microenvironment leads to T-cell dysfunction, and poorly immunogenic tumors compromise T cells by impairing their metabolism. Increasing lymphoma burden significantly affects CD4(+) T-cell function and promotes regulatory T cell (Treg) and Th1-cell differentiation. Early reprogramming and impairment of CD4(+) T-cell metabolism, glucose uptake, and mitochondrial function precede changes in T-cell fate. In contrast, B-cell lymphoma metabolism remains robust during tumor progression. Furthermore, mitochondrial functions are impaired in CD4(+) and CD8(+) T cells in lymphoma-transplanted OT-II and OT-I transgenic mice respectively. These findings support a model where early, TCR-independent, metabolic interactions with developing lymphomas limit T cell-mediated immune surveillance.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Information Science & Library Science
I-Cheng Chang, Chuang-Chun Liu
Summary: The popularity of social networking sites has increased rapidly and become a key part of many people's daily lives globally. This research empirically explored how different forms of capital (structural, relational, and cognitive) influence stickiness and addiction behavior among SNS users. It also introduced privacy concerns and perceived security as key moderators in this relationship. By using survey data and structural equation modeling, the proposed model was evaluated. This study contributes to a deeper understanding of SNS addiction behavior and has implications for both research and practice.
JOURNAL OF GLOBAL INFORMATION MANAGEMENT
(2023)
Article
Biology
Satyaprakash Pandey, Mona Hajikazemi, Theresa Zacheja, Stephanie Schalbetter, Jonathan Baxter, Victor Guryev, Andreas Hofmann, Dieter W. Heermann, Stefan A. Juranek, Katrin Paeschke
Summary: The study found that the catalytic subunit of telomerase (Est2) in budding yeast binds to multiple guanine-rich genomic loci, known as non-telomeric binding sites (NTBS). Est2 binds to NTBS in G1 and G2 phase independently of Est1 and Est3. The absence of Est1 and Est3 renders telomerase inactive at NTBS.
Article
Oncology
Dong Wang, Bethany Veo, Angela Pierce, Susan Fosmire, Krishna Madhavan, Ilango Balakrishnan, Andrew Donson, Irina Alimova, Kelly D. Sullivan, Molishree Joshi, Mark Erlander, Maya Ridinger, Nicholas K. Foreman, Sujatha Venkataraman, Rajeev Vibhakar
Summary: PLK1 is overexpressed in Group 3 MB, and Onvansertib shows efficacy in reducing colony formation, cell proliferation, inducing G2/M arrest, and enhancing DNA damage and apoptosis in combination with radiation therapy in vitro and in xenografts, suggesting its potential as an effective strategy for MB treatment.
Review
Biochemistry & Molecular Biology
Leila Jahangiri, Perla Pucci, Tala Ishola, Ricky M. Trigg, John A. Williams, Joao Pereira, Megan L. Cavanagh, Suzanne D. Turner, Georgios Gkoutos, Loukia Tsaprouni
Summary: MYC is a key player in the Wnt signaling pathway, influencing various cellular and developmental processes hijacked in cancers, and frequently amplified in cancer genomes. This review delves into MYC gene networks in solid cancers, its interaction with long non-coding RNAs (lncRNAs), and its role in inducing changes to cellular processes like autophagy. Exploring these networks presents unexplored opportunities for therapeutic gain in MYC-driven malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Ajay Kumar, Emily L. Yarosz, Anthony Andren, Li Zhang, Costas A. Lyssiotis, Cheong-Hee Chang
Summary: Natural killer T (NKT) cells have distinct metabolic programming from CD4 T cells, with a strict requirement for glutamine. Glutamine metabolism is critical for NKT cell homeostasis and mitochondrial functions, and is controlled by AMP-activated protein kinase (AMPK)-mammalian target of rapamycin complex 1 (mTORC1) signaling.
Article
Health Care Sciences & Services
Orhan Kocak, Ilayda Yilmaz, Mustafa Z. Younis
Summary: The study found a significant relationship between the level of internet addiction among university students and factors such as age, self-esteem, gender, and daily internet usage. Age and self-esteem were identified to play a mediation role in the impact of internet addiction, while social networks, gender, and location were determined to moderate the effect of self-esteem on internet addiction. Increasing self-esteem among young people can potentially reduce internet addiction as they grow older.
Review
Oncology
Yihui Chen, Ricardo A. Leon-Letelier, Ali Hussein Abdel Sater, Jody Vykoukal, Jennifer B. Dennison, Samir Hanash, Johannes F. Fahrmann
Summary: This review focuses on the dysregulation of MYC signaling in ovarian cancer progression and the challenges in directly targeting MYC for treatment. An alternative approach is proposed, targeting the downstream polyamine metabolism pathway of MYC. The review discusses the metabolism of polyamine, the regulation of polyamine metabolism by MYC signaling, the use of polyamine as therapeutic targets and cancer biomarkers. The amplification and overexpression of c-MYC and its paralogues MYCN and MYCL in ovarian cancer are also highlighted. Targeting the polyamine pathway through small molecule inhibitors has emerged as a potential therapeutic strategy. The potential of targeting c-MYC-driven polyamine metabolism and the utility of polyamine signatures in biofluids for early detection are discussed as well.
Article
Oncology
Tiantian Jing, Xiaoli Xu, Chengsi Wu, Dianhui Wei, Lili Yuan, Yiwen Huang, Yizhen Liu, Boshi Wang
Summary: This study reveals the regulatory role of deubiquitinase POH1 in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. POH1 stabilizes the MYC protein, promoting acinar-to-ductal metaplasia (ADM) and PDAC. Clinical evidence shows high expression of POH1 in PDAC samples and a correlation with poor prognosis. Targeting POH1 with a specific small-molecule inhibitor significantly reduces pancreatic tumor formation, offering a promising therapeutic strategy for PDAC treatment.
Article
Biochemistry & Molecular Biology
James W. Conrad, Mark L. Sowers, Dianne Y. Yap, Ellie Cherryhomes, B. Montgomery Pettitt, Kamil Khanipov, Lawrence C. Sowers
Summary: The increased expression of hTERT in tumors can promote tumor cell survival and decrease patient survival. C-to-T transition mutations in the hTERT promoter can enhance transcription by creating binding sites for transcription factors. The G-rich strand of the hTERT promoter can form G-quadruplex structures, while the C-rich strand can form an i-motif, which may promote cytosine deamination and C-to-T mutations.
Article
Biochemistry & Molecular Biology
Gautam Adhikary, Suruchi Shrestha, Warren Naselsky, John J. Newland, Xi Chen, Wen Xu, Ashkan Emadi, Joseph S. Friedberg, Richard L. Eckert
Summary: Restricting glutamine intake or conversion can significantly reduce mesothelioma cell proliferation, spheroid formation, invasion, and migration. Inhibition of the SLC1A5 glutamine transporter can also significantly reduce mesothelioma tumor growth. Furthermore, glutamine restriction can reduce the activity of the YAP1/TEAD signaling pathway, thereby decreasing survival and proliferation of mesothelioma.
MOLECULAR CARCINOGENESIS
(2023)
Article
Medicine, Research & Experimental
Pavlos Missios, Edroaldo Lummertz da Rocha, Daniel S. Pearson, Julia Philipp, Maria M. Aleman, Mehdi Pirouz, Dorian Farache, Joseph W. Franses, Caroline Kubaczka, Kaloyan M. Tsanov, Deepak K. Jha, Brian Pepe-Mooney, John T. Powers, Richard Gregory, Amy S. Y. Lee, Daniel Dominguez, David T. Ting, George Q. Daley
Summary: High expression of LIN28B is associated with aggressive malignancy and poor survival. LIN28B couples the MYCN-driven transcriptional program to enhanced ribosomal translation, thereby implicating LIN28B as a posttranscriptional driver of the metastatic phenotype.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Pharmacology & Pharmacy
Pouya Dehghankelishadi, Michelle F. Maritz, Parisa Badiee, Benjamin Thierry
Summary: This study demonstrates the potential of using high-density lipoprotein nanoparticles as a delivery system for radio-sensitising RNA in head and neck cancer cells. The results show enhanced radiation effects and increased apoptosis when miR34a is delivered by HDL nanoparticles.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Oncology
Janith A. Seneviratne, Daniel R. Carter, Rituparna Mittra, Andrew Gifford, Patrick Y. Kim, Jie-Si Luo, Chelsea Mayoh, Alice Salib, Aldwin S. Rahmanto, Jayne Murray, Ngan C. Cheng, Zsuzsanna Nagy, Qian Wang, Ane Kleynhans, Owen Tan, Selina K. Sutton, Chengyuan Xue, Sylvia A. Chung, Yizhuo Zhang, Chengtao Sun, Li Zhang, Michelle Haber, Murray D. Norris, Jamie I. Fletcher, Tao Liu, Pierre J. Dilda, Philip J. Hogg, Belamy B. Cheung, Glenn M. Marshall
Summary: High expression of mitochondrial adenine nucleotide translocase 2 (SLC25A5/ANT2) predicts poor prognosis and a more malignant phenotype in neuroblastoma. Inhibiting this transporter reduces cell viability in neuroblastoma cells. The histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) is the most effective drug against mutant TP53 neuroblastoma cells. SAHA and PENAO together delay tumor progression in neuroblastoma mouse models.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Mandy L. Ballinger, Swetansu Pattnaik, Piyushkumar A. Mundra, Milita Zaheed, Emma Rath, Peter Priestley, Jonathan Baber, Isabelle Ray-Coquard, Nicholas Isambert, Sylvain Causeret, Winette T. A. van der Graaf, Ajay Puri, Florence Duffaud, Axel Le Cesne, Beatrice Seddon, Coonoor Chandrasekar, Joshua D. Schiffman, Andrew S. Brohl, Paul A. James, Jean-Emmanuel Kurtz, Nicolas Penel, Ola Myklebost, Leonardo A. Meza-Zepeda, Hilda Pickett, Maya Kansara, Nicola Waddell, Olga Kondrashova, John Pearson, Andrew P. Barbour, Shuai Li, Tuong L. Nguyen, Diane Fatkin, Robert M. Graham, Eleni Giannoulatou, Melissa J. Green, Warren Kaplan, Shyamsundar Ravishankar, Joseph Copty, Joseph E. Powell, Edwin Cuppen, Kristel van Eijk, Jan Veldink, Jin-Hee Ahn, Jeong Eun Kim, R. Lor Randall, Kathy Tucker, Ian Judson, Rajiv Sarin, Thomas Ludwig, Emmanuelle Genin, Jean-Francois Deleuze, Michelle Haber, Glenn Marshall, Murray J. Cairns, Jean-Yves Blay, David M. Thomas
Summary: Cancer genetics has focused on epithelial malignancies, but this study explores specific pathways related to sarcomas, rare malignancies derived from embryonic mesoderm. Germline sequencing of sporadic cases and healthy controls reveals two sarcoma-specific pathways involved in mitotic and telomere functions. Centrosome gene variants are linked to specific tumors, while heritable defects in the shelterin complex increase susceptibility to sarcomas, melanomas, and thyroid cancers. These findings highlight the role of heritable defects in mitotic and telomere biology in sarcoma risk.
Article
Oncology
Claire Xin Sun, Paul Daniel, Gabrielle Bradshaw, Hui Shi, Melissa Loi, Nicole Chew, Sarah Parackal, Vanessa Tsui, Yuqing Liang, Mateusz Koptyra, Shazia Adjumain, Christie Sun, Wai Chin Chong, Dasun Fernando, Caroline Drinkwater, Motahhareh Tourchi, Dilru Habarakada, Dhanya Sooraj, Diana Carvalho, Phillip B. Storm, Valerie Baubet, Leanne C. Sayles, Elisabet Fernandez, Thy Nguyen, Mia Poerksen, Anh Doan, Duncan E. Crombie, Monty Panday, Nataliya Zhukova, Matthew D. Dun, Louise E. Ludlow, Bryan Day, Brett W. Stringer, Naama Neeman, Jeffrey A. Rubens, Eric H. Raabe, Maria Vinci, Vanessa Tyrrell, Jamie I. Fletcher, Paul G. Ekert, Biljana Dumevska, David S. Ziegler, Maria Tsoli, Nur Farhana Syed Sulaiman, Amos Hong Pheng Loh, Sharon Yin Yee Low, E. Alejandro Sweet-Cordero, Michelle Monje, Adam Resnick, Chris Jones, Peter Downie, Bryan Williams, Joseph Rosenbluh, Daniel Gough, Jason E. Cain, Ron Firestein
Summary: The study establishes a pediatric cancer model resource with 261 cell lines, including 224 representing childhood tumor types. Through multi-omics analysis and genetic screening, specific treatment opportunities and biomarkers in pediatric tumor classes are identified. The findings are of great significance in improving the clinical relevance of pediatric cancer treatment.
Article
Cell Biology
Ernest Moles, Christopher B. Howard, Pie Huda, Mawar Karsa, Hannah McCalmont, Kathleen Kimpton, Alastair Duly, Yongjuan Chen, Yizhou Huang, Melinda L. Tursky, David Ma, Sonia Bustamante, Russell Pickford, Patrick Connerty, Sofia Omari, Christopher J. Jolly, Swapna Joshi, Sylvie Shen, John E. Pimanda, Alla Dolnikov, Laurence C. Cheung, Rishi S. Kotecha, Murray D. Norris, Michelle Haber, Charles E. de Bock, Klaartje Somers, Richard B. Lock, Kristofer J. Thurecht, Maria Kavallaris
Summary: High-risk childhood leukemia has a poor prognosis due to treatment failure and toxic side effects. Encapsulation of drugs in liposomal nanocarriers improves biodistribution and tolerability, but lacks selectivity for cancer cells. In this study, bispecific antibodies were generated to target PEGylated liposomal drugs to leukemic cells. These antibodies improved targeting and cytotoxic activity, with minimal harm to normal cells. Targeted delivery using bispecific antibodies enhanced leukemia suppression and extended overall survival, representing a promising platform for improved treatment of high-risk leukemia.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Pamela Ajuyah, Chelsea Mayoh, Loretta M. S. Lau, Paulette Barahona, Marie Wong, Hazel Chambers, Fatima Valdes-Mora, Akanksha Senapati, Andrew J. Gifford, Colleen D'Arcy, Jordan R. Hansford, Neevika Manoharan, Wayne Nicholls, Molly M. Williams, Paul J. Wood, Mark J. Cowley, Vanessa Tyrrell, Michelle Haber, Paul G. Ekert, David S. Ziegler, Dong-Anh Khuong-Quang
Summary: This study reports a new subtype of midline gliomas with similar features to DMG but lacking the H3K27M mutation. These tumors have recurrent mutations in ACVR1 or EGFR and high expression of EZHIP. They have a poor prognosis similar to H3K27M DMG and exhibit distinct transcriptome and methylome profiles. The study provides new insights into the mechanism and pathway regulation of these tumors, potentially opening new therapeutic avenues.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Chelsea Mayoh, Andrew J. Gifford, Rachael Terry, Loretta M. S. Lau, Marie Wong, Padmashree Rao, Tyler Shai-Hee, Federica Saletta, Dong-Anh Khuong-Quang, Vicky Qin, Marion K. Mateos, Deborah Meyran, Katherine E. Miller, Aysen Yuksel, Emily V. A. Mould, Rachel Bowen-James, Dinisha Govender, Akanksha Senapati, Nataliya Zhukova, Natacha Omer, Hetal Dholaria, Frank Alvaro, Heather Tapp, Yonatan Diamond, Luciano Dalla Pozza, Andrew S. Moore, Wayne Nicholls, Nicholas G. Gottardo, Geoffrey McCowage, Jordan R. Hansford, Seong-Lin Khaw, Paul J. Wood, Daniel Catchpoole, Catherine E. Cottrell, Elaine R. Mardis, Glenn M. Marshall, Vanessa Tyrrell, Michelle Haber, David S. Ziegler, Orazio Vittorio, Joseph A. Trapani, Mark J. Cowley, Paul J. Neeson, Paul G. Ekert
Summary: By combining immunohistochemistry, RNA sequencing, and whole-genome sequencing, we identified a novel 15-gene immune signature, IPASS, associated with CD8(+) T-cell infiltration in high-risk paediatric cancers. Using this signature, we estimated that up to 31% of high-risk cancers exhibit infiltrating T-cells. Furthermore, we found that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression, and neoantigen load and TMB are not predictive of T-cell infiltration in paediatric cancers.
Article
Multidisciplinary Sciences
Jordan F. Hastings, Sharissa L. Latham, Alvin Kamili, Madeleine S. Wheatley, Jeremy Z. R. Han, Marie Wong-Erasmus, Monica Phimmachanh, Max Nobis, Chiara Pantarelli, Antonia L. Cadell, Yolande E. I. O'Donnell, King Ho Leong, Sophie Lynn, Fan-Suo Geng, Lujing Cui, Sabrina Yan, Joanna Achinger-Kawecka, Clare Stirzaker, Murray D. Norris, Michelle Haber, Toby N. Trahair, Frank Speleman, Katleen De Preter, Mark J. Cowley, Ozren Bogdanovic, Paul Timpson, Thomas R. Cox, Walter Kolch, Jamie I. Fletcher, Dirk Fey, David R. Croucher
Summary: Gene expression noise promotes stochastic drug resistance in rare cancer cells. However, when integrated across multiple components of an apoptotic signaling network, the influence of noise leads to a higher frequency of chemoresistant neuroblastoma cells. These cells are characterized by JNK impairment and retain a memory of their resistant state even after chemotherapy treatment.
Article
Oncology
Claire E. Wakefield, Kate Hetherington, Eden G. Robertson, Mark W. Donoghoe, Jacqueline D. Hunter, Janine Vetsch, Jonathan M. Marron, Katherine M. Tucker, Glenn M. Marshall, Alexander Broom, Michelle Haber, Vanessa Tyrrell, David Malkin, Loretta Lau, Marion K. Mateos, Tracey A. O'Brien, David S. Ziegler
Summary: Parents and patients rarely regretted participating in a childhood cancer precision medicine trial, even when their hopes were not fulfilled. Most participants found the trial beneficial and expressed high satisfaction.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Chelsea Mayoh, Jie Mao, Jinhan Xie, Gabor Tax, Shu-Oi Chow, Roxanne Cadiz, Karina Pazaky, Paulette Barahona, Pamela Ajuyah, Peter Trebilcock, Angela Malquori, Kate Gunther, Anica Avila, Doo Young Yun, Stephanie Alfred, Anjana Gopalakrishnan, Alvin Kamili, Marie Wong, Mark J. Cowley, Sophie Jessop, Loretta M. S. Lau, Toby N. Trahair, David S. Ziegler, Jamie I. Fletcher, Andrew J. Gifford, Maria Tsoli, Glenn M. Marshall, Michelle Haber, Vanessa Tyrrell, Timothy W. Failes, Greg M. Arndt, Richard B. Lock, Paul G. Ekert, M. Emmy M. Dolman
Summary: One-third of pediatric cancer patients enrolled in precision medicine programs do not receive therapeutic recommendations from molecular profiling. In order to find potential strategies for treating high-risk pediatric patients, a study conducted in vitro screening of 125 patient-derived samples against a library of 126 anticancer drugs. The results showed that high-throughput drug screening (HTS) can identify effective biomarker-driven therapeutic strategies for high-risk pediatric cancers.
Article
Biochemistry & Molecular Biology
Lei Zhai, Anushree Balachandran, Rebecca Larkin, Janith A. Seneviratne, Sylvia A. Chung, Amit Lalwani, Shoma Tsubota, Dominik Beck, Kenji Kadomatsu, Anneleen Beckers, Kaat Durink, Katleen De Preter, Frank Speleman, Michelle Haber, Murray D. Norris, Alexander Swarbrick, Belamy B. Cheung, Glenn M. Marshall, Daniel R. Carter
Summary: Mitotic dysregulation is identified as a hallmark of tumor initiation in neuroblastoma and can be targeted by a combination therapy of antimitotic and pro-apoptotic compounds, leading to selective cell death in MYCN-driven neuroblastoma cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Health Care Sciences & Services
Rebecca Daly, Kate Hetherington, Emily Hazell, Bethany R. Wadling, Vanessa Tyrrell, Katherine M. Tucker, Glenn M. Marshall, David S. Ziegler, Loretta Lau, Toby N. Trahair, Tracey A. O'Brien, Kiri Collins, Andrew J. Gifford, Michelle Haber, Mark Pinese, David Malkin, Mark J. Cowley, Jonathan Karpelowsky, Donna Drew, Chris Jacobs, Claire E. Wakefield
Summary: Precision medicine programs aim to identify personalized treatments for children with cancer, but the various professional groups involved in delivering these programs are understudied. This study explored the experiences of professionals involved in Australia's first precision medicine trial for children with poor-prognosis cancer. The professionals expressed both complexity in their roles and positive views about the impact of precision medicine on their profession.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Meeting Abstract
Oncology
Nadine Azzam, Nicole Melong, Lissandra Tuzi, Lisa Pinto, Jamie I. Fletcher, Alvin Kamili, Biljana Dumevska, Loretta Lau, Jennifer A. Chan, Donna L. Senger, Stephanie A. Grover, Michelle Haber, David Malkin, Jason N. Berman