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JOURNAL ARTICLE
Ge Li, Chengyu Liao, Jiangzhi Chen, Zuwei Wang, Shuncang Zhu, Jianlin Lai, Qiaowei Li, Yinhao Chen, Dihan Wu, Jianbo Li, Yi Huang, Yifeng Tian, Yanling Chen, Shi Chen
Induction of ferroptosis can inhibit cancer cells in vitro, however, the role of ferroptosis in treatment in vivo is controversial. The immunosuppressive cells activated by the ferroptotic tumor cells can promote the growth of residual tumor cells, hindering the application of ferroptosis stimulation in tumor treatment. In this study, a new strategy is aimed to be identified for effectively triggering immunogenic ferroptosis in pancreatic ductal adenocarcinoma (PDAC) and simultaneously stimulating antitumor immune responses...
April 9, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
#22
JOURNAL ARTICLE
Ramogohlo Diale, Phuti Ngoepe, Hasani Chauke, Joseph Moema, Maje Phasha
MnPt's exceptional stability and extremely high Néel temperature have generated a lot of interest in data storage applications. Previously, it was reported experimentally that the MnPt alloy shows ferromagnetic (FM) behavior at room temperature. In this study, the effects of partial substitution of Pt with Pd, Au, and Ag on magnetic properties is investigated using density functional theory. The stability of Mn50 Pt50-x Mx (M = Pd, Au, Ag, x = 6.25, 12.5, 18.75) alloys was assessed by determining their thermodynamic, magnetic, and mechanical properties...
January 23, 2024: Materials
#23
JOURNAL ARTICLE
Xingyuan Sun, Junli Chang, Chujie Zhou, Peng Zhao, Suxia Guo, Junjie Tong, Yongjun Wang, Yanping Yang
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Despite the development of new treatment plans in recent years, the prognosis for osteosarcoma patients has not significantly improved. Therefore, it is crucial to establish a robust preclinical model with high fidelity. The patient-derived xenograft (PDX) model faithfully preserves the genetic, epigenetic, and heterogeneous characteristics of human malignancies for each patient. Consequently, PDX models are considered authentic in vivo models for studying various cancers in transformation studies...
March 22, 2024: Journal of Visualized Experiments: JoVE
#24
JOURNAL ARTICLE
Gabriele Picco, Yanhua Rao, Angham Al Saedi, Yang Lee, Sara F Vieira, Shriram Bhosle, Kieron May, Carmen Herranz-Ors, Samantha J Walker, Raynold Shenje, Cansu Dincer, Freddy Gibson, Ruby Banerjee, Zoe Hewitson, Thilo Werner, Joshua E Cottom, Yang Peng, Nanhua Deng, Philip Landis, Daniela Conticelli, Katrina McCarten, Jacob Bush, Mamta Sharma, Howard Lightfoot, David House, Emma Milford, Emma K Grant, Michal P Glogowski, Craig D Wagner, Marcus Bantscheff, Anna Rutkowska-Klute, Cell Model Network Uk Group, Francesca Zappacosta, Jonathan Pettinger, Syd Barthorpe, H Christian Eberl, Brian T Jones, Jessica L Schneck, Dennis J Murphy, Emile E Voest, Joshua P Taygerly, Michael P DeMartino, Matthew A Coelho, Jonathan Houseley, Geeta Sharma, Benjamin J Schwartz, Mathew J Garnett
Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n-dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumours, and WRN inhibitors are in development. Here, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth In vitro and In vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage...
April 9, 2024: Cancer Discovery
#25
Chengfei Liu, Bo Chen, Pengfei Xu, Joy Yang, Christopher Nip, Leyi Wang, Yuqiu Shen, Shu Ning, Yufeng Shang, Eva Corey, Allen C Gao, Jason Gestwicki, Qiang Wei, Liangren Liu
Treatment-induced neuroendocrine prostate cancer (t-NEPC) often arises from adenocarcinoma via lineage plasticity in response to androgen receptor signaling inhibitors, such as enzalutamide. However, the specific regulators and targets involved in the transition to NEPC are not well understood. Plexin D1 (PLXND1) is a cellular receptor of the semaphorin (SEMA) family that plays important roles in modulating the cytoskeleton and cell adhesion. Here, we found that PLXND1 is highly expressed and positively correlated with neuroendocrine markers in patients with NEPC...
March 27, 2024: Research Square
#26
JOURNAL ARTICLE
Vivek Shukla, Haitao Wang, Lyuba Varticovski, Songjoon Baek, Ruihong Wang, Xinwei Wu, Frank Echtenkamp, Frank Villa Hernandez, Katherine P Prothro, Sudheer K Gara, Mary R Zhang, Stephanie Shiffka, Razi Raziuddin, Leonard M Neckers, W Marston Linehan, Haobin Chen, Gordon L Hager, David S Schrump
BACKGROUND: Recent insights regarding mechanisms mediating stemness, heterogeneity, and metastatic potential of lung cancers have yet to be fully translated to effective regimens for the treatment of these malignancies. This study sought to identify novel targets for lung cancer therapy. METHODS: Transcriptomes and DNA methylomes of 14 SCLC and 10 NSCLC lines were compared to normal human small airway epithelial cells (SAEC) and induced pluripotent stem cell (iPSC) clones derived from SAEC...
April 5, 2024: Journal of Thoracic Oncology
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JOURNAL ARTICLE
Nunki Hassan, Hangyu Yi, Bilal Malik, Lucie Charlotte Gaspard-Boulinc, Saumya E E Samaraweera, Debora A Casolari, Janith A Seneviratne, Anushree Balachandran, Tracy Chew, Alastair Duly, Daniel R R Carter, Belamy Cheung, Murray Norris, Michelle Haber, Maria Kavallaris, Glenn M Marshall, Xu Dong Zhang, Tao Liu, Jianlong Wang, Dan A Liebermann, Richard J J D'Andrea, Jenny Y Wang
The overall prognosis of acute myeloid leukemia (AML) remains dismal, largely due to the inability of current therapies to kill leukemia stem cells (LSCs) with intrinsic resistance. Loss of the stress sensor GADD45A is implicated in poor clinical outcomes but its role in LSCs and AML pathogenesis is unknown. Here we define GADD45A as a key downstream target of LGR4 oncogenic signaling and discover a regulatory role for GADD45A loss in promoting leukemia-initiating activity and oxidative resistance in LGR4/HOXA9-dependent AML, a poor prognosis subset of leukemia...
April 5, 2024: Blood
#28
JOURNAL ARTICLE
Cassandra L Moyer, Amanda Lanier, Jing Qian, Darian Coleman, Jamal Hill, Vidyasagar Vuligonda, Martin E Sanders, Abhijit Mazumdar, Powel H Brown
PURPOSE: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well-tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action. EXPERIMENTAL DESIGN: IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models and primary PDX tumors...
April 5, 2024: Clinical Cancer Research
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JOURNAL ARTICLE
Nicholas Choo, Shivakumar Keerthikumar, Susanne Ramm, Daisaku Ashikari, Linda Teng, Birunthi Niranjan, Shelley Hedwards, Laura H Porter, David L Goode, Kaylene J Simpson, Renea A Taylor, Gail P Risbridger, Mitchell G Lawrence
There are diverse phenotypes of castration-resistant prostate cancer, including neuroendocrine disease, that vary in their sensitivity to drug treatment. The efficacy of BET and CBP/p300 inhibitors in prostate cancer is attributed, at least in part, to their ability to decrease androgen receptor (AR) signalling. However, the activity of BET and CBP/p300 inhibitors in prostate cancers that lack the AR is unclear. In this study, we showed that BRD4, CBP, and p300 were co-expressed in AR-positive and AR-null prostate cancer...
April 5, 2024: Journal of Pathology
#30
JOURNAL ARTICLE
Chiao-Ping Chen, Shu-Fu Lin, Chun-Nan Yeh, Wen-Kuan Huang, Yi-Ru Pan, Yu-Tien Hsiao, Chih-Hong Lo, Chiao-En Wu
BACKGROUND: Anaplastic thyroid cancer (ATC), a rare and aggressive malignancy with a poor prognosis, has shown promise with the approved dabrafenib/trametinib combination for BRAFV600E mutation. Co-occurring PI3KCA mutations, identified as negative prognostic factors in lung cancer with BRAFV600E mutation, emphasize the need to target both pathways. Exploring trametinib and alpelisib combination becomes crucial for ATC. METHODS: A patient-derived xenograft (PDX) and primary cell line were obtained from an ATC patient with BRAF and PI3KCA co-mutation...
April 15, 2024: Heliyon
#31
JOURNAL ARTICLE
Esin Orhan, Carolina Velazquez, Imene Tabet, Lise Fenou, Geneviève Rodier, Béatrice Orsetti, William Jacot, Claude Sardet, Charles Theillet
One in three Triple Negative Breast Cancer (TNBC) is Homologous Recombination Deficient (HRD) and susceptible to respond to PARP inhibitor (PARPi), however, resistance resulting from functional HR restoration is frequent. Thus, pharmacologic approaches that induce HRD are of interest. We investigated the effectiveness of CDK-inhibition to induce HRD and increase PARPi sensitivity of TNBC cell lines and PDX models. Two CDK-inhibitors (CDKi), the broad range dinaciclib and the CDK12-specific SR-4835, strongly reduced the expression of key HR genes and impaired HR functionality, as illustrated by BRCA1 and RAD51 nuclear foci obliteration...
April 3, 2024: Cancer Letters
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JOURNAL ARTICLE
Linah Al-Alem, Jillian M Prendergast, Justin Clark, Bianca Zarrella, Dominique T Zarrella, Sarah J Hill, Whitfield B Growdon, Venkatesh Pooladanda, David R Spriggs, Daniel Cramer, Kevin M Elias, Rawan I Nazer, Steven J Skates, Jeff Behrens, Daniel T Dransfield, Bo R Rueda
BACKGROUND: Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies and markers to identify patients who would benefit from the new strategy. In this report, we sought to further validate applications for a novel humanized anti-Sialyl Tn antibody-drug conjugate (anti-STn-ADC) in ovarian cancer...
April 2, 2024: Journal of Ovarian Research
#33
JOURNAL ARTICLE
Shuo Zhang, Tinghe Fang, Yexuan He, Weichen Feng, Zhuoyang Yu, Yaoyao Zheng, Chi Zhang, Shuai Hu, Zhuojun Liu, Jia Liu, Jian Yu, Han Zhang, Anbang He, Yanqing Gong, Zhisong He, Kaiwei Yang, Zhijun Xi, Wei Yu, Liqun Zhou, Lin Yao, Shuhua Yue
BACKGROUND: Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. METHODS: Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling...
April 1, 2024: EBioMedicine
#34
JOURNAL ARTICLE
Remya Valsalakumari, Abhilash D Pandya, Lina Prasmickaite, Audun Kvalvaag, Anne Grethe Myrann, Andreas K O Åslund, Marianne Steinsvik Kjos, Cristina Fontecha-Cuenca, Hajira B Haroon, Ana R S Ribeiro, Jutta Horejs-Hoeck, S Moein Moghimi, Ýrr Mørch, Tore Skotland, Kirsten Sandvig, Gunhild Mari Mælandsmo, Tore Geir Iversen
BACKGROUND: Biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) are receiving increasing attention in anti-cancer nanomedicine development not only for targeted cancer chemotherapy, but also for modulation of the tumor microenvironment. We previously reported promising results with cabazitaxel (CBZ) loaded poly(2-ethylbutyl cyanoacrylate) NPs (PEBCA-CBZ NPs) in a patient derived xenograft (PDX) model of triple-negative breast cancer, and this was associated with a decrease in M2 macrophages...
2024: International Journal of Nanomedicine
#35
JOURNAL ARTICLE
Soundararajan Arvindh, Manashi Priyadarshini, Abdul Basit Baba, Veeran Veeravarmal, Rajakishore Mishra, Rupesh Dash, Siddavaram Nagini
BACKGROUND: A deregulated DNA damage response (DDR) network is implicated in cancer progression and therapy resistance. OBJECTIVE: The present study was designed to investigate whether nimbolide, an anticancer neem limonoid, targets key components of the DDR signalling pathway in cellular and animal models of oral squamous cell carcinoma (OSCC). METHODS: OSCC cells (SCC-4 and SCC-9), 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinoma model, chemoresistant OSCC patient-derived xenograft (PDX) model established in athymic nude mice, and tissue sections from patients with oral premalignant/malignant disease were used for the study...
March 28, 2024: Current Pharmaceutical Biotechnology
#36
JOURNAL ARTICLE
Vered Fuchs, Ariel Sobarzo, Maha Msamra, Yarden Kezerle, Liat Linde, Gur Sevillya, Alaa Anoze, Yael Refaely, Ahron Yehonatan Cohen, Israel Melamed, Amit Azriel, Rami Shoukrun, Yael Raviv, Angel Porgador, Nir Peled, Laila Catalina Roisman
PURPOSE: In the pursuit of creating personalized and more effective treatment strategies for lung cancer patients, Patient-Derived Xenografts (PDXs) have been introduced as preclinical platforms that can recapitulate the specific patient's tumor in an in vivo model. We investigated how well PDX models can preserve the tumor's clinical and molecular characteristics across different generations. METHODS: A Non-Small Cell Lung Cancer (NSCLC) PDX model was established in NSG-SGM3 mice and clinical and preclinical factors were assessed throughout subsequent passages...
March 29, 2024: Clinical & Translational Oncology
#37
JOURNAL ARTICLE
Tatjana Geukens, Marion Maetens, Jody E Hooper, Steffi Oesterreich, Adrian V Lee, Lori Miller, Jenny M Atkinson, Margaret Rosenzweig, Shannon Puhalla, Heather Thorne, Lisa Devereux, David Bowtell, Sherene Loi, Eliza R Bacon, Kena Ihle, Mihae Song, Lorna Rodriguez-Rodriguez, Alana L Welm, Lisa Gauchay, Rajmohan Murali, Pharto Chanda, Ali Karacay, Cristina Naceur-Lombardelli, Hayley Bridger, Charles Swanton, Mariam Jamal-Hanjani, Lori Kollath, Lawrence True, Colm Morrissey, Meagan Chambers, Arul M Chinnaiyan, Allecia Wilson, Rohit Mehra, Zachery Reichert, Lisa A Carey, Charles M Perou, Erin Kelly, Daichi Maeda, Akiteru Goto, Janina Kulka, Borbála Székely, A Marcell Szasz, Anna-Mária Tőkés, Wouter Van Den Bogaert, Giuseppe Floris, Christine Desmedt
While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research. Via an extensive questionnaire, we collected information on the study design, enrolment strategy, study conduct, sample and data management, and challenges and opportunities of research autopsy programmes in oncology worldwide...
March 29, 2024: Journal of Pathology
#38
JOURNAL ARTICLE
Maria Francesca Baietti, Eleonora Leucci
Patient-derived xenograft (PDX) models are the golden standard for preclinical oncology as they can recapitulate the genotypic and phenotypic complexity of human tumors, thus enabling the development of effective therapeutic strategies. PDX models are typically established in immunocompromised animals that allow efficient growth of the xenografted tumor. Given the recent success of immune therapies in different tumors however, the establishment of humanized PDX models is critical to evaluate immune oncology drugs and/or combinations thereof...
2024: Methods in Cell Biology
#39
JOURNAL ARTICLE
Menglin Chen, Huaizhi Li, Shanshan Zheng, Junyu Shen, Yuxuan Chen, Yaqi Li, Mengyun Yuan, Jian Wu, Qingmin Sun
BACKGROUND: Autophagy could sense metabolic conditions and safeguard cells against nutrient deprivation, ultimately supporting the survival of cancer cells. Nobiletin (NOB) is a kind of bioactive component of the traditional Chinese medicine Citri Reticulatae Pericarpium and has been proven to induce GC cell death by reducing de novo fatty acid synthesis in our previous study. Nevertheless, the precise mechanisms by which NOB induces cell death in GC cells still need further elucidation...
January 12, 2024: Phytomedicine
#40
JOURNAL ARTICLE
Tajhal D Patel, Sandra L Grimm, Rupa S Kanchi, Tanmay Gandhi, Amrit Koirala, Jason T Yustein, Cristian Coarfa
Osteosarcoma is the most prevalent bone tumor in pediatric patients. Neoadjuvant chemotherapy has improved osteosarcoma patient survival, however the 5-year survival rate for localized osteosarcoma is 75% with a 30-50% recurrence rate. We, therefore, sought to identify a prognostic gene signature which could predict poor prognosis in localized osteosarcoma patients. Using the TARGET osteosarcoma transcriptomic dataset, we identified a 13-hub gene signature associated with overall survival and time to death of localized osteosarcoma patients, with the high-risk group showing a 22% and the low-risk group showing 100% overall survival...
March 27, 2024: Scientific Reports
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