Article
Biochemistry & Molecular Biology
Zihan Cui, Dapeng Li, Jun Zhao, Kai Chen
Summary: This study demonstrates that the combination of Falnidamol (FLD) and cisplatin (DDP) effectively inhibits the progression of non-small-cell lung cancer (NSCLC). FLD enhances the cytotoxicity of DDP and reduces the proliferation of NSCLC cells. The combination treatment induces cell cycle arrest, DNA damage, and apoptosis through the generation of reactive oxygen species (ROS). Furthermore, it triggers ferroptosis and inhibits epithelial to mesenchymal transition (EMT) and epidermal growth factor receptor (EGFR) phosphorylation in NSCLC cells. Animal studies confirm the therapeutic efficacy of FLD/DDP in reducing tumor growth and lung metastasis.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Genetics & Heredity
Prerna Pandey, Geetika Suyal, Kiran Pasbola, Rinu Sharma
Summary: Esophageal cancer (EC) incidence is increasing globally, with unchanged recurrence and survival rates due to chemoresistance. This study reveals the involvement of miRNA dysregulation and its relation to dysregulated mRNAs in the development of cisplatin resistance in EC. Comparative profiling using NGS identified significant dysregulation of 261 miRNAs and 1892 genes in a cisplatin-resistant EC cell line. Pathway analysis indicated enrichment of EMT and several signaling pathways in the chemoresistant cells. Validation confirmed the dysregulation of specific miRNAs in the resistant cells. Further analysis highlighted the potential role of these miRNAs and their target genes in the regulation of chemoresistance in esophageal cancer.
FUNCTIONAL & INTEGRATIVE GENOMICS
(2023)
Article
Biochemistry & Molecular Biology
Linus Gohlke, Ahmad Alahdab, Angela Oberhofer, Karolina Worf, Stefan Holdenrieder, Martin Michaelis, Jindrich Cinatl Jr, Christoph A. Ritter
Summary: This study investigates the mechanistic role of key microRNAs in regulating epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). The study finds that miR-205-5p can partially reverse the EMT in drug-resistant cells by inhibiting ZEB1. The study also demonstrates the correlation between gene expression of EMT markers, transcription factors, and miRNAs during the adaptation of NSCLC cells to osimertinib. Additionally, the study suggests that treatment pauses could provide prolonged benefits for patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Zhi Xiong Chong, Swee Keong Yeap, Wan Yong Ho
Summary: Osteosarcoma, a prevalent primary bone tumor, has high metastatic potential and poor prognosis. MiRNAs play crucial roles in regulating the EMT process in osteosarcoma, which may offer insights for prognostic and therapeutic strategies.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Oncology
Asma Safi, Milad Bastami, Soheila Delghir, Khandan Ilkhani, Farhad Seif, Mohammad R. Alivand
Summary: Cisplatin is widely used for treating malignant tumors but resistance remains a major challenge. Recent studies highlight the importance of Cancer Stem Cell (CSC)-derived drug resistance, particularly in Breast Cancer Stem Cells (BCSCs) when it comes to cisplatin sensitivity. Understanding the role of miRNAs in regulating cisplatin resistance/sensitivity can lead to more effective personalized anti-cancer therapies.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jisu Jeong, Jiyeon Kim
Summary: EMT plays a crucial role in the development of lung cancer, and targeting EMT could inhibit cancer cell invasion and metastasis. This study found that combination treatment with erlotinib and cilengitide showed enhanced inhibitory effects on EMT in lung cancer cells, suggesting that cilengitide could improve the efficacy of anticancer drugs and contribute to improved treatment strategies for inhibiting EMT-based cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Oncology
Xiuning Le, Monique B. Nilsson, Jacqulyne P. Robichaux, John V. Heymach
Summary: The ARTEMIS study showed that combining the VEGF inhibitor bevacizumab with the EGFR inhibitor erlotinib can significantly improve progression-free survival in patients with EGFR mutant non-small-cell lung cancer, especially in those with brain metastases and the EGFR L858R mutation. This suggests the potential benefits of tailored use of VEGF/EGFR combinations in this patient population.
Article
Environmental Sciences
Yunxia Wang, Yijue Zhong, Kunyan Sun, Yong Fan, Jiping Liao, Guangfa Wang
Summary: Chronic exposure to PM2.5 induces bronchial epithelial cell atypical hyperplasia and EMT event in vivo, and leads to expression differences of exosome-miRNAs in vitro. The identified exosome-miRNAs may partially contribute to lung cancer tumorigenesis induced by chronic PM2.5 exposure.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biochemistry & Molecular Biology
Elaheh Mohammadnejadi, Nima Razzaghi-Asl
Summary: Non-small cell lung cancer (NSCLC) is the majority type of lung cancer, and its treatment remains a challenge. This study focused on targeting the epidermal-growth factor receptor (EGFR) to develop therapies for NSCLC. The research identified potential erlotinib analogues through computational servers and molecular docking. The aim was to find molecules that can overcome clinically frequent EGFR-TK mutants. The study provided insights into synthetically accessible small molecules with affinity for EGFR-TK mutants.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Oncology
Vivek Kumar, Sameer Gupta, Amrita Chaurasia, Manisha Sachan
Summary: Epithelial ovarian cancer (EOC) is a lethal gynecological malignancy, and early diagnosis is crucial for management. Aberrantly expressed miRNAs, particularly miR-205, miR-200c, and miR-141, show potential as minimally invasive biomarkers for early detection of EOC. The miRNA panel has high diagnostic potential with elevated AUC, sensitivity, and specificity, especially in early-stage serum samples.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yi Han, Jianquan Shi, Ziwei Xu, Yushan Zhang, Xiaoqing Cao, Jianhua Yu, Jie Li, Shaofa Xu
Summary: This study identified Solamargine as a potential sensitizer for DDP resistance in lung cancer. Mechanistically, Solamargine induced cell cycle arrest and apoptosis in DDP-resistant lung cancer cell lines by inhibiting the hedgehog pathway through direct binding to the SMO protein. Furthermore, Solamargine and DDP showed a synergistic effect in inhibiting DDP-resistant lung cancer cells.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Carminia Maria Della Corte, Vincenza Ciaramella, Kavya Ramkumar, Giovanni Vicidomini, Alfonso Fiorelli, Valerio Nardone, Salvatore Cappabianca, Immacolata Cozzolino, Federica Zito Marino, Gaetano Di Guida, Qi Wang, Robert Cardnell, Carl Michael Gay, Davide Ciardiello, Erika Martinelli, Teresa Troiani, Giulia Martini, Stefania Napolitano, Jing Wang, Lauren Averett Byers, Fortunato Ciardiello, Floriana Morgillo
Summary: The combined inhibition of MEK and PD-L1 shows significant synergistic effect in immune-dependent cancer cell death in non-small cell lung cancer (NSCLC), but may lead to the activation of the Ido-1 pathway as an escape mechanism.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Medicine, General & Internal
Minhan Yi, Zexi Liao, Langmei Deng, Li Xu, Yun Tan, Kun Liu, Ziliang Chen, Yuan Zhang
Summary: This study conducted a meta-analysis of 80 studies and identified several single miRNAs and combined groups with high diagnostic power for non-small cell lung carcinoma (NSCLC), indicating specific miRNAs as good biomarker candidates for NSCLC, further researches are needed.
ANNALS OF MEDICINE
(2021)
Article
Medicine, Research & Experimental
Hong-Wei Xia, Zhi-Qiang Zhang, Jun Yuan, Qing-Ling Niu
Summary: High levels of RECQL5 were found in major subtypes of NSCLC, LUAD and LUSC, and were associated with poor prognosis in LUAD. RECQL5 promoted NSCLC metastasis and hindered response to cisplatin therapy, suggesting its potential as a biomarker or clinical target for NSCLC.
Article
Cell Biology
Ke Mi, Lizhong Zeng, Yang Chen, Jingya Ning, Siyuan Zhang, Peilin Zhao, Shuanying Yang
Summary: In this study, the researchers explored the role of DHX38 in NSCLC and its underlying molecular mechanism. They found that DHX38 was overexpressed in NSCLC and patients with high DHX38 expression had poor prognosis. DHX38 promoted cell proliferation, migration, and invasion in NSCLC and activated the MAPK pathway. The researchers also identified G3BP1 as a target protein that interacted with DHX38 and showed that DHX38 regulated the expression of G3BP1. Silencing G3BP1 reversed the effects of DHX38 overexpression on tumor cell proliferation, migration, and invasion and inhibited the MAPK pathway activation.
CELLULAR SIGNALLING
(2024)
Article
Chemistry, Applied
Ibrahim S. Al Nasr, Markus Weise, Waleed S. Koko, Tariq A. Khan, Rainer Schobert, Bernhard Biersack
Summary: Gold(I) complexes with imidazole-2-ylidene and ferrocene substituents were synthesized and tested for their anti-parasitic activities against Leishmania major and Toxoplasma gondii. Certain complexes exhibited promising effects, showing high activities against the parasites with good selectivity.
APPLIED ORGANOMETALLIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Sofia Baer, Rohan Pradhan, Bernhard Biersack, Bianca Nitzsche, Michael Hoepfner, Rainer Schobert
Summary: Colorectal cancer is a major cause of cancer-related deaths, necessitating the development of new chemotherapeutic agents to combat high recurrence rates and resistance to established therapies. This study focuses on targeting the apoptosis-inhibiting protein survivin, which is specific to cancer cells. A combination of established anticancer agents was tested on colorectal cancer cells, revealing selective cytotoxicity, disruption of the microtubular cytoskeleton, and inhibition of survivin expression.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Natalie Oberhuber, Hindole Ghosh, Bianca Nitzsche, Prasad Dandawate, Michael Hoepfner, Rainer Schobert, Bernhard Biersack
Summary: New N-alkylindole-substituted 2-(pyrid-3-yl)-acrylonitriles and their (p-cymene)Ru(II) piano-stool complexes were synthesized and found to exhibit potent antiproliferative activity in various cancer models. Some of the derivatives showed lower IC50 values than clinically relevant multikinase inhibitors gefitinib and sorafenib, indicating their potential as novel therapeutic agents for cancer treatment. The investigation of drug mechanism in HCT-116 p53-knockout colon cancer cells revealed that the derivatives induced apoptotic caspase-3/7 activity, ROS formation, and anti-angiogenic properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ibrahim S. Al Nasr, Waleed S. S. Koko, Tariq A. A. Khan, Rainer Schobert, Bernhard Biersack
Summary: A series of fourteen pyrimido[1,2-a]benzimidazole compounds were synthesized using straightforward heterocyclic chemistry and oxidation methods. Among them, the new pyrimidobenzimidazole derivative 2a, with a 3-fluorophenyl substituent, exhibited excellent antiparasitic activity, showing high activity against Leishmania major parasites with EC50 values in the nanomolar concentration range. Compound 3b was less active against L. major but more active against Toxoplasma gondii, displaying considerable selectivity. Therefore, two promising and selective antiparasitic drug candidates, namely 2a and 3b, were identified for the treatment of two parasitic diseases, which can be prepared using green chemistry methods and simple one-pot reactions and oxidation procedures, respectively.
Editorial Material
Biochemistry & Molecular Biology
Bernhard Biersack
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Bianca Nitzsche, Michael Hoepfner, Bernhard Biersack
Summary: Heat shock protein 70 (Hsp70) and its interaction with Hsp90 play a significant role in cancer diseases. The Hsp70-Hsp40 axis, formed by the connection between Hsp70 and a smaller heat shock protein Hsp40, is a suitable target for designing anticancer drugs. This review discusses the current state and recent developments in the field of (semi-)synthetic small molecule inhibitors targeting Hsp70 and Hsp40, as well as their potential in medicinal chemistry and anticancer therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mohammad Aatif, Muhammad Asam Raza, Mohamed El Oirdi, Mohd Farhan, Muhammad Waseem Mumtaz, Muhammad Hamayun, Adnan Ashraf, Ghazala Muteeb
Summary: Bioassay-guided isolation of colchicine and caffeine from Camellia sinensis and Colchicum luteum, respectively, using a protease assay model. Structural validation was carried out using spectral techniques. Optimization of the purified compounds was performed using Gaussian software. Several global reactivity characteristics were determined to explain the diverse behavior of the compounds.
Review
Biochemistry & Molecular Biology
Mohd Farhan, Asim Rizvi, Mohammad Aatif, Aamir Ahmad
Summary: Cancer is a leading global cause of death, associated with genetic abnormalities, inflammation, bad eating habits, radiation exposure, work stress, and toxin consumption. Natural bioactive chemicals called polyphenols have been found to have anticancer capabilities, selectively targeting malignant cells without harming normal cells. Flavonoids, a type of polyphenol, possess antioxidant, antiviral, anticancer, and anti-inflammatory effects, whose biological actions are determined by their type, bioavailability, and mode of action. Recent research has focused on isolating, synthesizing, and studying the effects of flavonoids on human health, particularly their role in cancer.
Article
Oncology
Khaled Saleh, Mai Al Sakhen, Sana Kanaan, Salem Yasin, Michael Hoepfner, Lubna Tahtamouni, Bernhard Biersack
Summary: The compound Briva showed selective activity against BRAFV600E-mutant colorectal carcinoma cells by targeting VEGFR2 tyrosine kinase and reducing cell adhesion and metastasis formation.
INVESTIGATIONAL NEW DRUGS
(2023)
Article
Virology
Abhishek Asthana, Angela Corona, Woo-Jin Shin, Mi-Jeong Kwak, Christina Gaughan, Enzo Tramontano, Jae U. Jung, Rainer Schobert, Babal Kant Jha, Robert H. Silverman, Bernhard Biersack
Summary: Viral replication relies on RNA maturation and degradation processes catalyzed by viral ribonucleases, making them potential targets for antiviral drugs. A newly synthesized nitrocatechol compound (1c) and its analogs were found to strongly inhibit DEDD box viral ribonucleases, HIV-1 RNase H and SARS-CoV-2 nsp14 ExoN. Compound 1c inhibited SARS-CoV-2 replication without toxicity to human lung adenocarcinoma cells, making it a potential lead compound for the development of antiviral drugs targeting coronavirus nsp14 ExoN and other viral ribonucleases.
Article
Oncology
Sarah Eltahir, Aamir Ahmad
Editorial Material
Oncology
Shahab Uddin, Aamir Ahmad
Editorial Material
Oncology
Aayami Jaguri, Aamir Ahmad
Article
Pharmacology & Pharmacy
Hindole Ghosh, Sangita Bhattacharyya, Rainer Schobert, Prasad Dandawate, Bernhard Biersack
Summary: Pancreatic carcinoma is a highly fatal cancer disease, and there is a critical need for new and efficient treatments. Curcumin has shown potential effects in pancreatic cancer patients, but its limited efficacy and bioavailability hinder its clinical approval. In this study, a synthetic curcuminoid called EF24 was developed and found to have superior anticancer effects compared to curcumin. By modifying EF24 analogs with N-acrylation, particularly in compounds containing specific moieties, a significant increase in activity was achieved. These findings provide promising insights for the development of effective and superior curcuminoids as valuable treatment options for one of the most lethal cancer diseases.
Review
Chemistry, Physical
Doaa S. R. Khafaga, Mohamed G. Radwan, Ghazala Muteeb, Mohammad Aatif, Mohd Farhan
Summary: Nanobiocatalysts (NBCs) are a new class of biocatalysts that combine the advantages of enzymes and nanomaterials, improving stability, activity, and selectivity. They address the need for sustainable and environmentally friendly bioprocessing methods, providing a reusable platform for enzymes. The key challenge in NBCs development is enzyme immobilization, which protects enzymes and enables easy recovery and reuse. This review explores the effective role of NBCs in the pharmaceutical and biomedical fields.