Article
Biochemistry & Molecular Biology
Hongqing Zhou, Tingting Zhang, Liang Chen, Fengzhen Cui, Chenxiang Xu, Jiaxi Peng, Weixiang Ma, Jirong Huang, Xia Sheng, Mingsheng Liu, Faming Zhao
Summary: Stress in the endoplasmic reticulum can activate the unfolded protein response and is associated with prostate cancer progression. This study found that ATF6 alpha, one of the UPR sensors, is correlated with prostate cancer development and its inhibition impairs the survival of castration-resistant prostate cancer cells. Transcriptomic analyses revealed the pathways regulated by ATF6 alpha, and gene expression differences were observed between ATF6 alpha knockdown and Ceapin-A7 treatment. Furthermore, analysis of human CRPC bulk RNA-seq and single-cell RNA-seq datasets confirmed that higher ATF6 alpha activity is associated with increased androgen receptor activity, proliferative and neuroendocrine phenotypes, and immunosuppressive features in CRPC tumors.
Article
Oncology
Judith Passildas-Jahanmohan, Jean-Christophe Eymard, Melanie Pouget, Fabrice Kwiatkowski, Isabelle Van Praagh, Laurent Savareux, Marc Atger, Xavier Durando, Catherine Abrial, Damien Richard, Angeline Ginzac Couve, Emilie Thivat, Brigitte Monange, Philippe Chollet, Hakim Mahammedi
Summary: Despite good compliance and verified absorption of curcumin, the study showed no significant difference in progression-free survival between the curcumin and placebo groups, as well as in the secondary endpoints such as PSA response rate, overall survival, and quality of life. Consequently, the study was discontinued due to lack of efficacy.
Article
Urology & Nephrology
Ravi A. Madan, Fatima H. Karzai, Munjid Al Harthy, Daniel P. Petrylak, Joseph W. Kim, Philip M. Arlen, Inger Rosner, Marc R. Theoret, Lisa Cordes, Marijo Bilusic, Cody J. Peer, Nancy A. Dawson, Anna Couvillon, Amy Hankin, Moniquea Williams, Guin Chun, Helen Owens, Jennifer L. Marte, Min-Jung Lee, Yusuke Tomita, Akira Yuno, Jane B. Trepel, Sunmin Lee, Seth M. Steinberg, James L. Gulley, William D. Figg, William L. Dahut
Summary: The study evaluated the safety and efficacy of cabozantinib combined with docetaxel in mCRPC patients. Cabozantinib was found to be safely added to docetaxel treatment with potential enhanced efficacy. However, due to limited patient accrual, the phase 2 study was terminated early.
Article
Chemistry, Medicinal
Yujie Huang, You Zhai, Meijia Wu, Chengdong Chang, Jindan Luo, Dongsheng Hong, Qingwei Zhao, Yao Dai, Jian Liu
Summary: This study investigated the role of mTORC2 signaling in docetaxel-resistant prostate cells to find potential methods for clinical treatment. The expression of mTORC2 is crucial for docetaxel drug resistance in prostate cells. The mTORC1/2 inhibitor AZD8055 disrupts mTORC2 kinase activity more significantly than the mTORC1 inhibitor Rapamycin, leading to decreased docetaxel-mediated resistance. Therefore, reversing docetaxel resistance may become a therapeutic option for the treatment of metastatic castration-resistant prostate cancer patients.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Biology
Kevin J. Tu, Sanjit K. Roy, Zachery Keepers, Manas R. Gartia, Hem D. Shukla, Nrusingh C. Biswal
Summary: The study investigates the effectiveness and molecular characteristics of the combination therapy of Docetaxel (DXL) and radiation in vitro. The results suggest that DXL sensitizes castration-resistant prostate cancer (CRPC) cells to radiation by downregulating CAV-1.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Article
Oncology
Wei Ning, Pengkang Chang, Ji Zheng, Fan He
Summary: This case report highlights the potential effectiveness and safety of a second docetaxel rechallenge as a later-line treatment strategy for patients with mCRPC who are concerned about the high costs of multigene molecular testing and PARP inhibitors, as well as repeated prostate needle biopsy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Atefeh Deris, Mahdi Sohrabi-Haghighat
Summary: Patients with mCRPC are classified into three groups based on their response to Abiraterone treatment: best responder, responder, and non-responder. Drug-resistant cells may hinder successful outcomes in the latter two groups. To overcome this challenge, a combination of Docetaxel and Abiraterone is proposed to control both the overall cancer cell population and the drug-resistant subpopulation. Evolutionary Game Theory (EGT) is used as a mathematical modeling approach to study the competition and evolution of mCRPC cancer phenotypes.
Article
Oncology
Xiang Cai, Xi Duan, Tielong Tang, Shu Cui, Tao Wu
Summary: This study investigated the mechanism of JMJD2A in regulating cytoskeleton remodeling in docetaxel-resistant castration-resistant prostate cancer cells. The results showed that JMJD2A regulates cytoskeleton remodeling through the miR-34a/STMN1/beta 3-Tubulin axis. Overexpression of miR-34a resulted in downregulation of STMN1 and upregulation of beta 3-Tubulin, leading to disruption of the microtubule network, inhibition of cancer cell proliferation, cell cycle arrest, and increased apoptosis.
Article
Urology & Nephrology
Kristine Kreis, Dirk Horenkamp-Sonntag, Udo Schneider, Jan Zeidler, Gerd Glaeske, Lothar Weissbach
Summary: This study examined real-world haematological toxicity, overall survival, and treatment characteristics of docetaxel and cabazitaxel chemotherapy in mCRPC patients. The findings suggest that cabazitaxel treatment poses higher risk of haematological toxicities and shorter survival time, emphasizing the importance of strict indications when using cabazitaxel in mCRPC patients.
Article
Cell Biology
Senmao Li, Jindong Sheng, Zhenhua Liu, Yu Fan, Cuijian Zhang, Tianjing Lv, Shuai Hu, Jie Jin, Wei Yu, Yi Song
Summary: Recent studies have shown that the novel mTOR inhibitor AZD2014 has significant antitumor effects in prostate cancer, especially in inhibiting cell proliferation, apoptosis, and invasion. This provides a solid theoretical basis for the clinical application of AZD2014 in treating prostate cancer.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Li-Wen Chang, Sheng-Chun Hung, Jian-Ri Li, Kun-Yuan Chiu, Cheng-Kuang Yang, Chuan-Shu Chen, Kevin Lu, Cheng-Che Chen, Shu-Chi Wang, Chia-Yen Lin, Chen-Li Cheng, Yen-Chuan Ou, Shun-Fa Yang, Chiann-Yi Hsu, Szu-Hang Ho, Shian-Shiang Wang
Summary: The study investigated the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in patients with metastatic Castration-resistant Prostate Cancer (mCRPC) receiving docetaxel as the first line of treatment. It was found that poor nutritional status, indicated by a GNRI <92, was associated with shorter progression free survival and overall survival. Additionally, metastatic volume and cumulative docetaxel dosage were identified as independent prognostic factors in overall survival.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Yuting Shan, Yingbo Huang, Adam M. Lee, Joshua Mentzer, Alexander Ling, R. Stephanie Huang
Summary: This study suggests that GAS5 expression may serve as a predictive biomarker for docetaxel response in castration-resistant prostate cancer (CRPC), although the exact mechanism behind this correlation remains to be elucidated. The findings also demonstrate that the change in GAS5 expression does not directly affect docetaxel response, and there is no significant relationship between GAS5 and ABCB1 expression that impacts docetaxel sensitivity.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yang Yu, Fu-han Yang, Wen-tao Zhang, Ya-dong Guo, Lin Ye, Xu-dong Yao
Summary: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion. The increase in CRPC cell autophagy induced by MSCs under docetaxel administration depends on MSCs secreting TGF-beta 1.
CELL AND BIOSCIENCE
(2021)
Article
Oncology
Lijun Mao, Haiyuan Yu, Sai Ma, Ziyang Xu, Fukun Wei, Chunhua Yang, Junnian Zheng
Summary: The combination therapy of oncolytic adenovirus ZD55-SATB1 and chemotherapy effectively inhibits the proliferation, migration, and invasion of prostate cancer cells, promoting apoptosis and showing superior therapeutic effects.
Review
Biochemistry & Molecular Biology
David Ka-Wai Leung, Peter Ka-Fung Chiu, Chi-Fai Ng, Jeremy Yuen-Chun Teoh
Summary: The management of castration-resistant prostate cancer has seen significant progress, with three novel hormonal agents showing survival benefits in non-metastatic patients and a wider range of management options being investigated for metastatic disease.
Article
Biochemistry & Molecular Biology
Namrata Khurana, Partha K. Chandra, Hogyoung Kim, Asim B. Abdel-Mageed, Debasis Mondal, Suresh C. Sikka
Article
Neurosciences
Partha K. Chandra, Ibolya Rutkai, Hogyoung Kim, Stephen E. Braun, Asim B. Abdel-Mageed, Debasis Mondal, David W. Busija
Summary: Damage to the cerebral vascular endothelium is a critical initiating event in the development of HIV-1-associated neurocognitive disorders. Exosomes isolated from HIV-infected cells accelerate dysfunction in brain microvascular endothelial cells by inducing mitochondrial hyperfusion and reducing nitric oxide synthase expression. These exosomes, containing viral proteins, reduce mitochondrial function and accelerate brain endothelial dysfunction.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Cell Biology
Mourad Zerfaoui, Titilope Modupe Dokunmu, Eman Ali Toraih, Bashir M. Rezk, Zakaria Y. Abd Elmageed, Emad Kandil
Summary: The link between melanoma and thyroid cancer may be due to specific gene mutations leading to tumor aggressiveness. Studies indicate an increased mutual risk between melanoma patients and thyroid cancer patients compared to healthy individuals.
Article
Multidisciplinary Sciences
Jacob W. Greenberg, Hogyoung Kim, Ahmed A. Moustafa, Amrita Datta, Pedro C. Barata, A. Hamid Boulares, Asim B. Abdel-Mageed, Louis S. Krane
Summary: Recent studies suggest that ketoconazole (KTZ) may impact clear cell renal cell carcinoma (ccRCC) by inhibiting exosome biogenesis and secretion, enhancing the efficacy of current therapies for RCC.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Rania Makboul, Islam F. Abdelkawi, Dalia M. Badary, Mahmoud R. A. Hussein, Johng S. Rhim, Eman A. Toraih, Mourad Zerfaoui, Zakaria Y. Abd Elmageed
Summary: TMTC4 expression was found to be significantly higher in PCa cells and tissues compared to BPH and normal cells, with strong cytoplasmic expressions in PCa cases. The protein showed high sensitivity and specificity in differentiating between PCa and BPH, indicating its potential for clinical application.
Article
Biochemistry & Molecular Biology
Sen Liu, Bing Zhang, Brian G. Rowan, S. Michal Jazwinski, Asim B. Abdel-Mageed, Chad Steele, Alun R. Wang, Oliver Sartor, Tianhua Niu, Qiuyang Zhang
Summary: The study investigated the impact of age on prostate cancer using an experimental model with Pten conditional knockout mice at different ages. Results showed that aged mice exhibited accelerated PI3K/AKT/mTOR signaling and increased prostate cancer onset and progression compared to young mice. This model could be useful for further research on cancer related to aging.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Oncology
Jacob W. Greenberg, Hogyoung Kim, Miae Ahn, Ahmed A. Moustafa, He Zhou, Pedro C. Barata, A. Hamid Boulares, Asim B. Abdel-Mageed, Louis S. Krane
Summary: Exosomes play a significant role in the resistance of metastatic renal cell carcinoma. The combination of Tipifarnib with standard therapy reduces tumor growth through an exosome-mediated mechanism. Tipifarnib also directly inhibits PD-L1 protein expression in chemo-sensitive and resistant cell lines.
Article
Oncology
Mourad Zerfaoui, Eman Toraih, Emmanuelle Ruiz, Youssef Errami, Abdallah S. Attia, Moroz Krzysztof, Zakaria Y. Abd Elmageed, Emad Kandil
Summary: This study investigates the role of nuclear BRAF(V600E) and its partner HMOX1 in melanoma aggressiveness and drug resistance. The findings provide valuable insights into the mechanisms of drug resistance and offer potential prognostic markers and therapeutic strategies for metastatic melanoma.
Article
Oncology
Hamdy E. A. Ali, Mohamed S. A. Gaballah, Rofaida Gaballa, Shahenda Mahgoub, Zeinab A. Hassan, Eman A. Toraih, Bettina F. Drake, Zakaria Y. Abd Elmageed
Summary: Novel sEV-associated miRs, including miR-6068 and miR-1915-3p, were found to be enriched in PCa patients, with miR-6716-5p and miR-3692-3p distinguishing between AA and CA men and low and high Gleason score. Among these miRs, miR-1915-3p emerged as an independent prognostic marker for longer recurrence-free survival.
Article
Biology
Naif E. Al Omairi, Ashraf Albrakati, Khalaf F. Alsharif, Abdulraheem S. Almalki, Walaa Alsanie, Zakaria Y. Abd Elmageed, Dalia Zaafar, Maha S. Lokman, Amira A. Bauomy, Saied K. Belal, Mohamed M. Abdel-Daim, Ahmed E. Abdel Moneim, Hussain Alyami, Rami B. Kassab
Summary: The study found that SeNPs-PDG has the potential to be an anticonvulsant agent. It delayed the onset of epileptic seizures and reduced their duration. It also protected against hippocampal cell loss, oxidative stress, and neuroinflammation. Additionally, SeNPs-PDG restored the balance between excitatory and inhibitory neurotransmitters and improved monoaminergic and cholinergic transmission.
Article
Oncology
Abu Bakar Siddique, Hassan Y. Ebrahim, Afsana Tajmim, Judy Ann King, Khaldoun S. Abdelwahed, Zakaria Y. Abd Elmageed, Khalid A. El Sayed
Summary: A compound called S-(-)-oleocanthal (OC), found in extra-virgin olive oil, can inhibit the growth and relapse of aggressive prostate cancer. OC works by suppressing an important enzyme called SMYD2, which is responsible for activating several proteins involved in prostate cancer. It has shown stronger anticancer activity in animal models compared to other SMYD2 inhibitors and is a potential natural compound for use in prostate cancer patients as a dietary supplement.
Article
Chemistry, Medicinal
Hoda A. Salem, Nehal Elsherbiny, Sharifa Alzahrani, Hanan M. Alshareef, Zakaria Y. Abd Elmageed, Sadeem M. Ajwah, Ahmed M. E. Hamdan, Yahia S. Abdou, Omneya O. Galal, Marwa K. A. El Azazy, Karema Abu-Elfotuh
Summary: Monosodium glutamate (MSG) is widely used in food, but it has been linked to protein malnutrition and various toxicities. This study explores the association between MSG, protein malnutrition, and brain injury similar to attention-deficit/hyperactivity disorder (ADHD). It also investigates the potential protective effects of morin hydrate (MH), a natural flavonoid. The findings suggest that MSG and/or protein malnutrition are associated with neuronal dysfunction, and MH may offer neuroprotection by targeting specific signaling pathways.
Article
Biochemistry & Molecular Biology
Emmanuelle M. Ruiz, Solomon A. Alhassan, Youssef Errami, Zakaria Y. Abd Elmageed, Jennifer S. Fang, Guangdi Wang, Margaret A. Brooks, Joe A. Abi-Rached, Emad Kandil, Mourad Zerfaoui
Summary: A 13-gene panel was identified to accurately predict resistance to BRAF/MEK inhibitor therapy in melanoma patients. Dysregulation of HMOX1, ICAM, MMP2, and SPARC defined a treatment-resistant landscape, and HMOX1-mediated mitochondrial stress response was identified as a potential key driver of resistance. These findings highlight the importance of these genes in predicting treatment outcomes and targeting underlying mechanisms to reduce resistance development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Khaldoun S. Abdelwahed, Abu Bakar Siddique, Hassan Y. Ebrahim, Mohammed H. Qusa, Ethar A. Mudhish, Ashkan H. Rad, Mourad Zerfaoui, Zakaria Y. Abd Elmageed, Khalid A. El Sayed
Summary: Metastatic castration-resistant prostate cancer (mCRPC) cells can synthesize their own cholesterol and overexpress proprotein convertase subtilisin/kexin type 9 (PCSK9). Knockdown of PCSK9 leads to reduced migration and colony formation in mCRPC cells. Higher expression of PCSK9 is associated with older age and early Gleason scores. The fermentation product pseurotin A (PS) suppresses PCSK9 expression and protein-protein interactions, as well as cancer recurrence. PS treatment inhibits migration and colony formation in mCRPC cells. In a mouse model, a high-fat diet increases tumor volume, metastasis, cholesterol, LDL-C, PSA, and PCSK9 levels, which can be prevented by daily oral PS treatment. PS-treated mice show reduced cholesterol, LDL-C, PCSK9, and PSA levels. These findings suggest that PS is a potential lead for suppressing mCRPC recurrence by targeting the PCSK9-LDLR axis.
Article
Biochemical Research Methods
Joshua A. Welsh, Bryce Killingsworth, Julia Kepley, Tim Traynor, Sean Cook, Jason Savage, Jenn Marte, Min-Jung Lee, Hoyoung M. Maeng, Michelle L. Pleet, Setty Magana, Andre Gorgens, Cecile L. Maire, Katrin Lamszus, Franz L. Ricklefs, Maria J. Merino, W. Marston Linehan, Tim Greten, Tomer Cooks, Curtis C. Harris, Andrea Apolo, Asim Abdel-Mageed, Alexander R. Ivanov, Jane B. Trepel, Matthew Roth, Mercedes Tkach, Aleksandar Milosavljevic, Clotilde Thery, Amy LeBlanc, Jay A. Berzofsky, Eytan Ruppin, Kenneth Aldape, Kevin Camphausen, James L. Gulley, Ionita Ghiran, Steve Jacobson, Jennifer C. Jones
Summary: Extracellular vesicles (EVs) carry various types of proteins and nucleic acids, and can provide a retrospective snapshot of cell state through liquid biopsies. Multiplex assays for high-parameter EV protein detection are still being developed. To facilitate EV repertoire studies, we developed MPAPASS software for stitched multiplex analysis, EV database-compatible reporting, and visualization of EV repertoires.
CELL REPORTS METHODS
(2022)