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REVIEW
Anna Markowska, Zbigniew Kojs, Damian Twardawa, Joanna Pietras, Janina Markowska
Despite advances in surgical treatment techniques and chemotherapy-including anti-angiogenic and immune poly (ADP-ribose) polymerase inhibitors, the 5-year survival rate in ovarian cancer (OC) remains low. The reasons for this are the diagnosis of cancer in advanced clinical stages, chemoresistance and cancer recurrence. New therapeutic approaches are being developed, including the search for new biomarkers that are also targets for targeted therapy. The present review describes new molecular markers with relevance to targeted therapy, which to date have been studied only in experimental research...
May 2024: Experimental and Therapeutic Medicine
#22
JOURNAL ARTICLE
Yan Zhao, Yangyang Yu, Xiangmin Li, Ayao Guo
BACKGROUND: Chemoresistance and immunosuppression are two major obstacles in the current anti-cancer treatments. This study investigates the involvements of a CCAAT enhancer binding protein delta (CEBPD)/vesicle associated membrane protein 3 (VAMP3) axis in paclitaxel (PTX) resistance and immune evasion in triple-negative breast cancer (TNBC). METHODS: PTX resistance-related genes were screened by bioinformatics. CEBPD and VAMP3 expression in clinical TNBC samples was examined by immunohistochemistry...
April 16, 2024: Journal of Experimental & Clinical Cancer Research: CR
#23
JOURNAL ARTICLE
Eric James Panther, Hannah Lyons, Andrew Jacob Shychuk
A man in his 60s presented to an outside hospital with persistent groin pain and a scrotal mass which was thought to be a recurrent hernia. Three months after initial presentation, the patient was found to have dedifferentiated liposarcoma (LPS) of the spermatic cord. LPS of the spermatic cord is a rare entity; however, clinicians should have LPS on the differential diagnosis especially in men with recurrent scrotal pain and mass. If unrecognised, LPS is associated with a high degree of morbidity and mortality...
April 16, 2024: BMJ Case Reports
#24
REVIEW
Elena Rainero
Macropinocytosis (MP), the actin-dependent bulk uptake of extracellular fluids, plays a central role in nutrient scavenging, allowing cancer cells to sustain their growth in the hypoxic and nutrient-deprived microenvironment often found in solid tumours. The lack of soluble nutrients and several oncogenic signalling pathways, with RAS being the most studied, push MP-dependent internalisation of extracellular proteins, which are then digested in the lysosomes, replenishing the intracellular nutrient pools. This review will highlight recent advances in understanding how MP is regulated in hypoxic cancers, how it impinges on chemoresistance, and how different MP cargos facilitate tumour growth...
April 15, 2024: Current Opinion in Cell Biology
#25
JOURNAL ARTICLE
Neelima Anup, Anuradha Gadeval, Shubham Ramdas Mule, Tanisha Gupta, Rakesh Kumar Tekade
The development of chemoresistance is a major obstacle in post-surgical adjuvant therapy of cancer, leading to cancer cell survival, recurrence, and metastasis. This study reports a 3D-printed plasmonic implant developed for the post-surgical adjuvant therapy of cisplatin-resistant cancer cells to prevent relapse. The implant was printed using optimized biomaterial ink containing biodegradable polymers [poly(L-lactide) and hydroxypropyl methylcellulose] blended suitably with laser-responsive graphene and chemo drug (Cisplatin)...
April 13, 2024: International Journal of Pharmaceutics
#26
REVIEW
Elliot Lopez-Vince, Claire Wilhelm, Teresa Simon-Yarza
As the conversion rate of preclinical studies for cancer treatment is low, user-friendly models that mimic the pathological microenvironment and drug intake with high throughput are scarce. Animal models are key, but an alternative to reduce their use would be valuable. Vascularized tumor-on-chip models combine great versatility with scalable throughput and are easy to use. Several strategies to integrate both tumor and vascular compartments have been developed, but few have been used to assess drug delivery...
April 15, 2024: Drug Delivery and Translational Research
#27
REVIEW
Doha El-Sayed Ellakwa, Nadia Mushtaq, Sahrish Khan, Abdul Jabbar, Mohamed Ahmed Abdelmalek, Al-Hassan Soliman Wadan, Takwa E Ellakwa, Ali Raza
MiRNAs (microRNAs) constitute a group of diminutive molecules of non-coding RNA intricately involved in regulating gene expression. This regulation is primarily accomplished through the binding of miRNAs to complementary sequences situated in the 3'-UTR of the messenger RNA (mRNA) target; as a result, they are degraded or repressed. The multifaceted biogenesis of miRNAs is characterized by a meticulously orchestrated sequence of events encompassing transcription, processing, transportation, and decay. Colorectal cancer stands as a pervasive and formidable ailment, afflicting millions across the globe...
April 15, 2024: Naunyn-Schmiedeberg's Archives of Pharmacology
#28
JOURNAL ARTICLE
Tobias Suske, Helena Sorger, Gabriele Manhart, Frank Ruge, Nicole Prutsch, Mark W Zimmerman, Thomas Eder, Diaaeldin I Abdallah, Barbara Maurer, Christina Wagner, Susann Schönefeldt, Katrin Spirk, Alexander Pichler, Tea Pemovska, Carmen Schweicker, Daniel Pölöske, Emina Hubanic, Dennis Jungherz, Tony Andreas Müller, Myint Myat Khine Aung, Anna Orlova, Ha Thi Thanh Pham, Kerstin Zimmel, Thomas Krausgruber, Christoph Bock, Mathias Müller, Maik Dahlhoff, Auke Boersma, Thomas Rülicke, Roman Fleck, Elvin Dominic de Araujo, Patrick Thomas Gunning, Tero Aittokallio, Satu Mustjoki, Takaomi Sanda, Sylvia Hartmann, Florian Grebien, Gregor Hoermann, Torsten Haferlach, Philipp Bernhard Staber, Heidi Anne Neubauer, Alfred Thomas Look, Marco Herling, Richard Moriggl
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor-ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, even in absence of surface TCR...
April 15, 2024: Journal of Clinical Investigation
#29
JOURNAL ARTICLE
Longjiang Zhou, Haitao Xiang, Susu Liu, Honglin Chen, Yuanwei Yang, Jianyong Zhang, Wei Cai
PURPOSE: Hypoxia is often associated with glioma chemoresistance, and alleviating hypoxia is also crucial for improving treatment efficacy. However, although there are already some methods that can improve efficacy by alleviating hypoxia, real-time monitoring that can truly achieve hypoxia relief and efficacy feedback still needs to be explored. METHODS: AQ4N/Gd@PDA-FA nanoparticles (AGPF NPs) were synthesized using a one-pot method and were characterized. The effects of AGPF NPs on cell viability, cellular uptake, and apoptosis were investigated using the U87 cell line...
2024: International Journal of Nanomedicine
#30
JOURNAL ARTICLE
Keting Li, Wentao Hao, Jiwei Wu, Xianben Liu, Wenqun Xing, Yan Zheng
BACKGROUND: Neoadjuvant chemotherapy (nCT) combined with surgery is one of the main strategies for the treatment of resectable locally advanced esophageal squamous cell carcinoma (ESCC). However, nearly 40% of patients did not benefit from nCT, and the detection rate of NOTCH1 missense mutation was significantly increased in patients who did not respond to chemotherapy, suggesting that the missense mutation may be related to tumor chemoresistance. We aim to explore the effect of a NOTCH1 missense mutation on cell phenotype, to interpret the biofunctional changes in cell lines with a NOTCH1 missense mutation and to analyze the effect of a NOTCH1 missense mutation on drug resistance in ESCC cell lines...
March 29, 2024: Journal of Thoracic Disease
#31
JOURNAL ARTICLE
Tolulope Peter Saliu, Nirwani Natasha Seneviratne, Mishal Faizan, Umapriyatharshini Rajagopalan, Damith Chathuranga Perera, Achyut Adhikari, Kanishka Sithira Senathilake, Prasanna Galhena, Kamani Hemamala Tennekoon, Sameera Ranganath Samarakoon
Cancer stem cells (CSCs) play a vital role in metastasis, recurrence and chemoresistance in breast cancer. β-catenin, which is a frequently over activated protein in CSCs, binds to T-cell factor/lymphoid enhancer factor (Tcf/Lef) family transcription factors leading to ectopic expression of Wnt pathway responsive genes necessary for the maintenance and action of CSCs. With the aim of identifying a small molecules that can effectively eliminate CSCs, molecular docking studies were performed against the Tcf/Lef binding hotspot on β-catenin using a library of 100 natural or synthetic small molecules...
2024: In Silico Pharmacology
#32
JOURNAL ARTICLE
Xin Li, Wencai Guan, Huiqiang Liu, Jia Yuan, Fanchen Wang, Bin Guan, Junyu Chen, Qi Lu, Guoxiong Xu, Lingyun Zhang
Our previous study showed that pyridoxine 5'-phosphate oxidase (PNPO) is a tissue biomarker of ovarian cancer (OC) and has a prognostic implication but detailed mechanisms remain unclear. The current study focused on PNPO-regulated lysosome/autophagy-mediated cellular processes and the potential role of PNPO in chemoresistance. We found that PNPO was overexpressed in OC cells and was a prognostic factor in OC patients. PNPO significantly promoted cell proliferation via the regulation of cyclin B1 and phosphorylated CDK1 and shortened the G2M phase in a cell cycle...
April 13, 2024: Apoptosis: An International Journal on Programmed Cell Death
#33
REVIEW
Jiawei Fan, Jianshu Zhu, He Zhu, Hong Xu
In the tumor microenvironment (TME), myeloid cells play a pivotal role. Myeloid-derived immunosuppressive cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), are central components in shaping the immunosuppressive milieu of the tumor. Within the TME, a majority of TAMs assume an M2 phenotype, characterized by their pro-tumoral activity. These cells promote tumor cell growth, angiogenesis, invasion, and migration. In contrast, M1 macrophages, under appropriate activation conditions, exhibit cytotoxic capabilities against cancer cells...
April 11, 2024: Critical Reviews in Oncology/hematology
#34
JOURNAL ARTICLE
Yuhan Sun, Tiangui Wu, Jianguo Gu
Chemoresistance poses a significant obstacle in the effective treatment of cancer, limiting the success of chemotherapy regimens. N-glycosylation, the most important post-translational modification (PTM), plays multifaceted roles in the intricate landscape of cancer progression, particularly drug resistance in cancer cells. This review explores the complex relationship between N-glycosylation and chemoresistance in cancer. Altered glycosylation patterns have been proven to impact drug efflux mechanisms in cancer cells, which can further influence the intracellular concentration of chemotherapy drugs...
April 9, 2024: Carbohydrate Research
#35
JOURNAL ARTICLE
Yicheng Liang, Mei Liang, Tao Yan, Xiangzhi Meng, Boxuan Zhou, Yushun Gao
Drug resistance is the major difficulty in treatment of lung squamous cell carcinoma (LUSC). This study aims to explore drug response-related miRNAs (DRmiRNAs) based on multi-omics research. We identified DRmiRNAs of LUSC with a multi-omics integrated system that combines expression data of microRNA, lncRNA, mRNA, methylation levels, somatic mutations. After identifying DRmiRNAs, we screened and validated of the target mRNAs of DRmiRNAs through Targetscan and the miRDB database. Then, Real-time PCR and Western blot assays were used to estimate the expression of DRmiRNAs and target protein, and the dual-luciferase assays were used to confirm the interaction of DRmiRNAs and target mRNA...
April 13, 2024: Biochemical Genetics
#36
JOURNAL ARTICLE
Yoshiki Shinomiya, Yusuke Kouchi, Sakurako Harada-Kagitani, Takayuki Ishige, Shigetsugu Takano, Masayuki Ohtsuka, Jun-Ichiro Ikeda, Takashi Kishimoto
Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. Neoadjuvant chemotherapy is an effective PDAC treatment option, but chemotherapy causes unfavorable side effects. Glucocorticoids (e.g., dexamethasone [DEX]) are administered to reduce side effects of chemotherapy for solid tumors, including pancreatic cancer. Glucocorticoids have both beneficial and detrimental effects, however. We investigated the functional changes and gene-expression profile alterations induced by DEX in PDAC cells. PDAC cells were treated with DEX, and the cell proliferation, migration, invasion, and chemosensitivity to gemcitabine (GEM) were evaluated...
April 13, 2024: Cancer Science
#37
JOURNAL ARTICLE
Juan Pablo Rigalli, Anna Gagliardi, Klara Diester, Gzona Bajraktari-Sylejmani, Antje Blank, Jürgen Burhenne, Alexander Lenard, Lars Werntz, Andrea Huppertz, Lena Münch, Janica Margrit Wendt, Max Sauter, Walter Emil Haefeli, Johanna Weiss
Drug efflux transporters of the ATP-binding-cassette superfamily play a major role in the availability and concentration of drugs at their site of action. ABCC2 (MRP2) and ABCG2 (BCRP) are among the most important drug transporters that determine the pharmacokinetics of many drugs and whose overexpression is associated with cancer chemoresistance. ABCC2 and ABCG2 expression is frequently altered during treatment, thus influencing efficacy and toxicity. Currently, there are no routine approaches available to closely monitor transporter expression...
April 8, 2024: International Journal of Molecular Sciences
#38
REVIEW
Mariam Ahmed Galal, Mohammed Al-Rimawi, Abdurrahman Hajeer, Huda Dahman, Samhar Alouch, Ahmad Aljada
Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation...
April 6, 2024: International Journal of Molecular Sciences
#39
JOURNAL ARTICLE
Rina Fujiwara-Tani, Takamitsu Sasaki, Ujjal Kumar Bhawal, Shiori Mori, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Shingo Kishi, Kiyomu Fujii, Hitoshi Ohmori, Masayuki Sho, Hiroki Kuniyasu
Pancreatic ductal adenocarcinoma (PDAC) is highly malignant, with a 5-year survival rate of less than 10%. Furthermore, the acquisition of anticancer drug resistance makes PDAC treatment difficult. We established MIA-GEM cells, a PDAC cell line resistant to gemcitabine (GEM), a first-line anticancer drug, using the human PDAC cell line-MIA-PaCa-2. Microtubule-associated serine/threonine kinase-4 ( MAST4 ) expression was increased in MIA-GEM cells compared with the parent cell line. Through inhibitor screening, dysregulated AKT signaling was identified in MIA-GEM cells with overexpression of AKT3...
April 5, 2024: International Journal of Molecular Sciences
#40
JOURNAL ARTICLE
Shih-Ho Wang, Cheng-Hsi Yeh, Chia-Wei Wu, Chia-Yi Hsu, Eing-Mei Tsai, Chao-Ming Hung, Yi-Wen Wang, Tsung-Hua Hsieh
Breast cancer is the most common malignancy and its incidence is increasing. It is currently mainly treated by clinical chemotherapy, but chemoresistance remains poorly understood. Prefolded proteins 4 (PFDN4) are molecular chaperone complexes that bind to newly synthesized polypeptides and allow them to fold correctly to stabilize protein formation. This study aimed to investigate the role of PFDN4 in chemotherapy resistance in breast cancer. Our study found that PFDN4 was highly expressed in breast cancer compared to normal tissues and was statistically significantly associated with stage, nodal status, subclasses (luminal, HER2 positive and triple negative), triple-negative subtype and disease-specific survival by TCGA database analysis...
March 31, 2024: International Journal of Molecular Sciences
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