Article
Biochemistry & Molecular Biology
Zhiping Feng, Marisa E. Hom, Thomas E. Bearrood, Zachary C. Rosenthal, Daniel Fernandez, Alison E. Ondrus, Yuchao Gu, Aaron K. McCormick, Madeline G. Tomaske, Cody R. Marshall, Toni Kline, Che-Hong Chen, Daria Mochly-Rosen, Calvin J. Kuo, James K. Chen
Summary: Aldehyde dehydrogenases (ALDHs) are potential cancer drug targets, specifically certain isoforms essential for the survival of stem-like tumor cells. Selective inhibitors of ALDH1B1 have been identified, an enzyme essential for promoting colorectal and pancreatic cancer. Bicyclic imidazoliums and guanidines that target the ALDH1B1 active site have been described, with comparable molecular interactions and potencies. These inhibitors effectively suppress ALDH1B1 function in cells, with guanidines avoiding off-target mitochondrial toxicity observed with imidazoliums. A lead isoform-selective guanidinyl antagonist of ALDHs demonstrates proteome-wide target specificity and selectively hinders the growth of colon cancer spheroids and organoids. The ALDH1B1-dependent transcriptome, involving genes regulating mitochondrial metabolism and ribosomal function, has been elucidated through genetic and chemical perturbations. The importance of ALDH1B1 in colorectal cancer is supported, offering molecular probes for ALDH1B1 studies and potential leads for targeted therapies.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ethan Read, Jarod Milford, Jiechun Zhu, Lingyun Wu, Marc Bilodeau, Guangdong Yang
Summary: Disulfiram and hydrogen sulfide can sensitize liver cancer cells by inhibiting ALDH activity, and H2S can also inhibit the adhesion of liver cancer stem cells. The combination of DSF and H2S shows potential in inhibiting cancer cell growth and tumor development by targeting ALDH.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Oncology
Fei Liao, Jing Zhang, Yangyang Hu, Alireza Hassani Najafabadi, James J. Moon, Max S. Wicha, Bashir Kaspo, Joel Whitfield, Alfred E. Chang, Qiao Li
Summary: This study demonstrates the potential of targeting ALDH(high) CSCs using antigenic peptides derived from ALDH, and the enhanced efficacy achieved by combining the vaccine with anti-PD-L1 treatment.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Chemistry, Medicinal
Martin Loffelmann, Zdenek Skrott, Dusana Majera, Pavel Starha, Vladimir Krystof, Martin Mistrik
Summary: This study discovered that a class of DTCs-copper complexes target and aggregate NPL4 protein, leading to lethal proteotoxic stress in cancer cells. These findings have important implications for drug development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Oncology
Miao Ma, Wenyou He, Keyu Zhao, Linyuan Xue, Siyuan Xia, Baotong Zhang
Summary: Prostate cancer is the most common cancer in men in the United States, and a portion of cases progress to castration-resistant and metastatic disease. Aldehyde dehydrogenase (ALDH) plays an important role in prostate cancer, with its high expression associated with higher tumor stage and lymph node metastasis. Increased ALDH activity in prostate cancer cells enhances self-renewal and metastatic capabilities, while reducing sensitivity to treatment. Targeting ALDH may hold promise for eradicating prostate cancer, but challenges remain.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Victoria O. Hunsu, Caroline O. B. Facey, Jeremy Z. Fields, Bruce M. Boman
Summary: Retinoic acid (RA) agents show anti-tumor activity by inducing cellular differentiation, but have not yet been widely used for systemic treatment in most solid tumors. RA signaling is mediated through retinoic receptor subtypes, with mutations in these receptors offering opportunities for target discovery in personalized medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Xiaozhen Zhang, Xing Huang, Jian Xu, Enliang Li, Mengyi Lao, Tianyu Tang, Gang Zhang, Chengxiang Guo, Xiaoyu Zhang, Wen Chen, Dipesh Kumar Yadav, Xueli Bai, Tingbo Liang
Summary: The study reveals that NEK2 phosphorylates PD-L1 to maintain stability, impacting the efficacy of immunotherapy in pancreatic cancer, while NEK2 deficiency enhances lymphocyte infiltration and sensitivity to immunotherapy. Inhibiting NEK2 can enhance PD-L1 blockade, potentially improving the effectiveness of pancreatic cancer treatment.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Inorganic & Nuclear
Francesco Caruso, Gottumukkala Subbaraju, Modukuri Ramani, Marzia Gariboldi, Emanuela Marras, Carmen Kloer, Aron Sulovari, Sarjit Kaur, Miriam Rossi
Summary: This study synthesized three [(eta(6)-p-cymene)Ru(L)Cl] neutral complexes and evaluated their antiproliferative activity against lung cancer, colon cancer, and glioblastoma. The results showed that complexation significantly increased the antitumor activity of hispolon derivatives in glioblastoma, and the inhibitory ability towards aldehyde dehydrogenase was determined.
INORGANICA CHIMICA ACTA
(2022)
Review
Medicine, General & Internal
Michele Zanoni, Sara Bravaccini, Francesco Fabbri, Chiara Arienti
Summary: Aldehyde dehydrogenases (ALDHs) are detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. ALDHs have various functions in cancer stem cells and immune cells, playing a crucial role in cancer treatment.
FRONTIERS IN MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Sumbul Ahmad, Abdullah Arsalan, Amiruddin Hashmi, Masood Alam Khan, Waseem Ahmad Siddiqui, Hina Younus
Summary: This study reveals that phthalate plasticizers can inhibit human salivary aldehyde dehydrogenase (hsALDH), increasing the risk of aldehyde-induced toxicity and leading to structural changes in the enzyme.
Article
Immunology
Sabrina Patzelt, Manuela Pigors, Heiko Steenbock, Leonard Diel, Katharina Boch, Lenche Chakievska, Sven Kuenzel, Hauke Busch, Anke Faehnrich, Juergen Brinckmann, Enno Schmidt
Summary: Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by scarring lesions in the oral cavity and conjunctivae. In this study, increased collagen fibril density was observed in the skin and conjunctival lesions of MMP mice. However, a potential anti-fibrotic therapy using disulfiram did not improve ocular lesions in the experimental MMP model.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Nahla N. Kamel, Hanan F. Aly, Ghadha I. Fouad, Somaia S. Abd El-Karim, Manal M. Anwar, Yasmin M. Syam, Samia A. Elseginy, Kawkab A. Ahmed, Hoda F. Booles, Mohamed B. Shalaby, Wagdy K. B. Khalil, Rajat Sandhir, Sonam Deshwal, Maha Z. Rizk
Summary: New 2-oxo-chromene-7-oxymethylene acetohydrazide derivatives were synthesized and evaluated for their acetylcholinesterase inhibitory and antioxidant activities. Compound 4c showed promising inhibitory activity and scavenging ability. In vivo studies demonstrated that compound 4c had no adverse effects on blood profile, hepatic enzyme levels, or tissue architecture, and exhibited improvement in cognitive function and oxidative stress levels.
Review
Oncology
Olivia L. Walker, Margaret L. Dahn, Melanie R. Power Coombs, Paola Marcato
Summary: Cancer stem cells (CSCs) play a crucial role in cancer development, metastasis, and drug resistance. In breast cancer, there are two distinct CSC populations with similar properties but different signaling pathways. Understanding these CSC populations and their signaling pathways may lead to the development of novel therapeutic strategies for improving breast cancer patient outcomes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Katsutoshi Sato, Amol A. Padgaonkar, Stacey J. Baker, Stephen C. Cosenza, Olga Rechkoblit, D. R. C. Venkata Subbaiah, Josep Domingo-Domenech, Alison Bartkowski, Elisa R. Port, Aneel K. Aggarwal, M. V. Ramana Reddy, Hanna Y. Irie, E. Premkumar Reddy
Summary: Finding therapeutic strategies for aggressive triple negative breast cancer (TNBC) is an important challenge in clinical practice. Here, the authors identify a multi-kinase inhibitor with antitumor activity and able overcome chemotherapy resistance of TNBC in vivo.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Jukka Westermarck
Summary: Targeted therapies are commonly used in cancer treatment, but their effectiveness is limited by acquired drug resistance. Recent studies have highlighted the role of mitochondrial mechanisms in cancer cell sensitivity to targeted therapies, leading to the development of triplet therapies that target vulnerabilities in cancer cells, including the mitochondria. These triplet therapies show promising preclinical effects in overcoming drug resistance, but challenges in clinical translation need to be addressed.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Tereza Buchtova, Zdenek Skrott, Katarina Chroma, Jiri Rehulka, Petr Dzubak, Marian Hajduch, David Lukac, Stefanos Arampatzis, Jiri Bartek, Martin Mistrik
Summary: Disulfiram (DSF), a known alcohol-aversion drug, is being considered for repurposing in cancer treatment, but the presence of other drugs may interfere with its efficacy. Research has found that cannabidiol, a component of marijuana, could reduce the effectiveness of DSF in treating cancer, leading to inconsistent clinical outcomes.
MOLECULAR ONCOLOGY
(2022)
Article
Chemistry, Analytical
Sergii Okorochenkov, Zdenek Skrott, Dusana Majera, Martin Porubsky, Martin Mistrik, Jan Hlavac
Summary: A new fluorescent dye BODIPYAZD-1 is introduced in this study, able to selectively stain autolysosomes and distinguish them from lysosomes and autophagosomes. This compound has excellent fluorescent properties, is not phototoxic, and is compatible with live-cell and fixed-cell microscopy.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Anatomy & Morphology
Zuzana Sporikova, Rastislav Slavkovsky, Lucie Tuckova, Ondrej Kalita, Magdalena Megova Houdova, Jiri Ehrmann, Marian Hajduch, Lumir Hrabalek, Miroslav Vaverka
Summary: The study found that 25% of Czech diffuse astrocytic and oligodendroglial tumors (gliomas) patients below 55 years of age carry IDH1/IDH2 mutations. It is suggested to routinely combine IHC detection of the IDH1 R132H variant with MPS to improve the accuracy of detecting rare IDH1/2 variants in glioma patients below 55 years of age with negative IHC result of IDH R132H variant.
APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
(2022)
Article
Geriatrics & Gerontology
Marco Raffaele, Kristina Kovacovicova, Tommaso Biagini, Oriana Lo Re, Jan Frohlich, Sebastiano Giallongo, James D. Nhan, Antonino Giulio Giannone, Daniela Cabibi, Martin Ivanov, Anton B. Tonchev, Martin Mistrik, Matthew Lacey, Petr Dzubak, Sona Gurska, Marian Hajduch, Jiri Bartek, Tommaso Mazza, Vincenzo Micale, Sean P. Curran, Manlio Vinciguerra
Summary: The study identified MCOPB as a NOP ligand with tissue-specific senolytic effects, reducing the senescent cell burden in peripheral tissues but not affecting the central nervous system. Additionally, exposure to MCOPB led to changes in locomotion and lipid storage. Mechanistically, MCOPB treatment activated transcriptional networks involved in immune responses to external stressors, implicating Toll-like receptors (TLRs).
Article
Chemistry, Multidisciplinary
Klaudia Kvakova, Martin Ondra, Jiri Schimer, Milos Petrik, Zbynek Novy, Helena Raabova, Marian Hajduch, Petr Cigler
Summary: This study developed a sensitive approach using fluorescent nanodiamonds for visualizing tumor-draining sentinel lymph nodes. The results showed that the modified nanodiamonds have potential as a tracer for cancer diagnostics and fluorescence-guided surgery.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Biochemistry & Molecular Biology
Natalie Kudlova, Juan Bautista De Sanctis, Marian Hajduch
Summary: Cellular senescence is an irreversible cell cycle arrest associated with age-related pathologies, DNA damage, and tissue repair. However, there is contradictory research concerning its triggering mechanisms and detection. This review summarizes recent findings, presents commonly used senescence models, and briefly describes well-known anti-aging drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Tomas Ozdian, Jan Vodicka, Jiri Dostal, Dusan Holub, Jana Vaclavkova, Michal Jeseta, Barbora Hamernikova, Pavla Kourilova, Ondrej Malchar, Vladimir Dvorak, Pavel Hejtmanek, Katerina Sobkova, Pavel Ventruba, Radovan Pilka, Petr Dzubak, Marian Hajduch
Summary: This study focuses on the proteomic characterization of cervical mucus (CM), examining its potential as a source of non-invasive biomarkers and understanding the molecular physiology of the female genital tract. Proteomic analysis revealed 4370 proteins involved in processes such as neutrophil degranulation, cellular stress response, and hemostasis. The study also identified differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) and in vitro fertilization (IVF) cycles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dimitris C. Kanellis, Asimina Zisi, Zdenek Skrott, Bennie Lemmens, Jaime A. Espinoza, Martin Kosar, Andrea Bjorkman, Xuexin Li, Stefanos Arampatzis, Jirina Bartkova, Miguel Andujar-Sanchez, Oscar Fernandez-Capetillo, Martin Mistrik, Mikael S. Lindstrom, Jiri Bartek
Summary: Drug repurposing is a versatile strategy to improve current therapies. Disulfiram and its metabolite CuET have been found to target cancer cells by causing translational arrest, nucleolar stress, and trapping p53 in aggregates. The activation of pro-survival pathways suggests a potential feedback response to CuET treatment. These findings expand the mechanistic repertoire of CuET's anti-cancer activity and may lead to new clinical applications in oncology.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Biochemistry & Molecular Biology
Monika Vidlarova, Alona Rehulkova, Pavel Stejskal, Andrea Prokopova, Hanus Slavik, Marian Hajduch, Josef Srovnal
Summary: Circulating tumor cells (CTCs) are released from primary tumors and have been identified as a negative prognostic factor for survival in many types of cancer. They also provide valuable insights into tumor progression, cell senescence, and cancer dormancy. Various methods with different specificity, utility, costs, and sensitivity have been developed for isolating and characterizing CTCs, with novel techniques being developed to overcome limitations of existing methods. This literature review describes the current and emerging methods for enriching, detecting, isolating, and characterizing CTCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Tereza Buchtova, David Lukac, Zdenek Skrott, Katarina Chroma, Jiri Bartek, Martin Mistrik
Summary: CBD, a marijuana derivative, has a long history of medical use and is increasingly recognized for its potential anti-tumor properties. Besides its direct anti-cancer effects, CBD and other cannabinoids have shown promise in attenuating chemotherapy-induced adverse effects and enhancing the efficacy of anti-cancer drugs. However, CBD's interactions with other medications and therapeutic modalities can be unpredictable, raising concerns about its combined use. This review summarizes the current knowledge of CBD's interactions with selected anticancer chemotherapeutics, discusses the potential benefits and risks, and highlights the need for clinical trials to evaluate the impact of CBD combinations in oncology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Obstetrics & Gynecology
J. Vodicka, J. Dostal, D. Holub, R. Pilka, P. Dzubak, M. Hajduch, T. Ozdian
Summary: Cervical mucus is a viscous fluid that acts as a plug for the cervix. It contains products from the endometrial and cervical glands, as well as transudate from the fallopian tubes and proteins from the ovaries, peritoneum and distant tissues.
CESKA GYNEKOLOGIE-CZECH GYNAECOLOGY
(2023)
Article
Oncology
Lubomir Vecera, Petr Prasil, Josef Srovnal, Emil Berta, Monika Vidlarova, Tomas Gabrhelik, Pavla Kourilova, Martin Lovecek, Pavel Skalicky, Jozef Skarda, Zdenek Kala, Pavel Michalek, Marian Hajduch
Summary: Patients with pancreatic cancer who received morphine for postoperative analgesia had longer cancer-specific survival compared to those who received piritramide. Additionally, high expressions of cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) genes were associated with improved overall survival, while high expression of delta opioid receptor gene shortened survival.
Article
Biology
Martin Ondra, Lukas Lenart, Amanda Centorame, Daciana C. Dumut, Alexander He, Syeda Sadaf Zehra Zaidi, John W. Hanrahan, Juan Bautista De Sanctis, Danuta Radzioch, Marian Hajduch
Summary: This article describes the preparation and validation of a novel in vitro model system using CRISPR/Cas9 genome editing, which can tag the endogenously expressed WT-CFTR and detect CFTR in the plasma membrane of live cells. By inserting the HiBiT tag in WT-CFTR, a reporter luciferase with bright luminescence can be generated. Nine homozygous clones with the HiBiT knock-in were identified from the screened clones, and two clones were genetically and functionally validated. This work lays the foundation for developing unique cellular CF models by CRISPR-mediated insertion of CF-causing mutations.
LIFE SCIENCE ALLIANCE
(2023)
Review
Biochemistry & Molecular Biology
Jenny Valentina Garmendia, Alexis Hipolito Garcia, Claudia Valentina De Sanctis, Marian Hajduch, Juan Bautista De Sanctis
Summary: SARS-CoV-2 causes COVID-19, a complex respiratory illness that can also harm multiple organs and lead to long-lasting effects. While most individuals have mild symptoms or are asymptomatic, around 20% develop severe respiratory illness and organ failure. Compromised immune response, caused by immunodeficiency and autoimmunity, allows the virus to replicate and escape. Autoantibodies against various proteins have been reported, with their type and level depending on age and gender. Screening for immunodeficiency and autoimmunity is important in identifying risk factors for severe or prolonged COVID-19.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)