Article
Biochemistry & Molecular Biology
Ivan S. Alferiev, David T. Guerrero, Peng Guan, Ferro Nguyen, Venkatadri Kolla, Danielle Soberman, Benjamin B. Pressly, Ilia Fishbein, Garrett M. Brodeur, Michael Chorny
Summary: High-risk solid tumors with multidrug resistance are a major challenge in therapy. This study evaluated a structurally enhanced macromolecular prodrug to combat chemoresistance in high-risk neuroblastoma. The results showed that this prodrug effectively inhibited tumor growth and led to prolonged survival in the models.
Article
Biochemistry & Molecular Biology
Kyung-Hwa Jeon, Seojeong Park, Hae Jin Jang, Soo-Yeon Hwang, Aarajana Shrestha, Eung-Seok Lee, Youngjoo Kwon
Summary: The study revealed that AK-I-190, a novel topoisomerase II inhibitor, exerts potent inhibitory activity by intercalating into DNA without stabilizing the DNA-enzyme cleavage complex, resulting in less DNA toxicity compared to etoposide. AK-I-190 induces G1 arrest and effectively inhibits cell proliferation and colony formation in an androgen receptor-negative CRPC cell line, indicating the potential clinical relevance of topoisomerase II catalytic inhibitors in treating this type of prostate cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dawei Li, Xiyu Chen, Rumeng Yan, Zeshan Jiang, Bing Zhou, Bei Lv
Summary: It was found that oligodeoxynucleotides (ODNs) containing G-quadruplexes can efficiently inhibit the activity of DNA topoisomerase I. Among them, the parallel propeller-type G-quadruplex is the most effective inhibitor. Combining G-quadruplexes with duplexes to form hybrids can enhance the inhibition efficiency. Moreover, a circular ODN with a G-quadruplex motif and DNA topoisomerase I binding site showed high inhibitory efficiency.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Chemistry, Medicinal
Xuemei Deng, Tian Luo, Xi Zhang, Yuehua Li, Liming Xie, Weifan Jiang, Linyi Liu, Zhen Wang
Summary: Through the redesign of 3-aryl isoquinoline alkaloids, we discovered compound 7 with excellent activity and research depth, which exhibits dual inhibitory effects on topoisomerase I and II, and shows potential in inhibiting cell proliferation and inducing apoptosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiaoling Hu, Junfang Li, Honghua Zhang, Quanwei Yu, Yuying Wang, Xuelin Li, Lin Long, Weifan Jiang, Zhen Wang
Summary: A series of novel tolfenamic acid derivatives were designed and synthesized, among which W10 was identified as a potent dual-target inhibitor with improved solubility and exhibiting promising antitumor effects and pro-apoptosis activity, making it a potential chemotherapeutic candidate for colon cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Francesco Madeddu, Jessica Di Martino, Michele Pieroni, Davide Del Buono, Paolo Bottoni, Lorenzo Botta, Tiziana Castrignano, Raffaele Saladino
Summary: This study used computational methods to analyze the interaction between two new antitumor drug molecules and hTop1p enzyme. The results showed that these two compounds have a similar inhibitory mechanism to CPT and may have potential antitumor activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Amany E. Nofal, Elshaymaa I. Elmongy, Engy Abo Hassan, Ehab Tousson, Abdullah A. S. Ahmed, Ibrahim El Tantawy El Sayed, Reem Binsuwaidan, Manar Sakr
Summary: This study evaluated the antitumor efficacy of APAN and its protective effect against etoposide-triggered hepatic disorders in Ehrlich solid tumor (EST)-bearing female mice. APAN showed ameliorative activity against EST and hepatic toxicity. The combined treatment of APAN with etoposide had the greatest improvement.
Article
Infectious Diseases
Jose Manuel Tirado-Velez, David Carreno, David Sevillano, Luis Alou, Jose Yuste, Adela G. de la Campa
Summary: This study evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I, in mice infected with a serotype 8-resistant strain of Streptococcus pneumoniae. Seconeolitsine showed promising therapeutic effects, providing 70% protection and efficient reduction of bacteremia, especially against strains with high fluoroquinolone resistance levels. Levofloxacin had higher serum levels but seconeolitsine exhibited prolonged time to peak concentration and elimination half-life due to its higher plasma protein binding.
Review
Pharmacology & Pharmacy
Emma Baglini, Silvia Salerno, Elisabetta Barresi, Marco Robello, Federico Settimo, Sabrina Taliani, Anna Maria Marini
Summary: DNA topoisomerases are crucial enzymes involved in DNA topology regulation, with inhibitors targeting TopoI and TopoII showing broad-spectrum antitumor activities and potential to reduce drug resistance and side effects in cancer treatment. Targeting both enzymes simultaneously could provide more efficient and safe drugs for clinical usage.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Oncology
Kevin Chih-Yang Huang, Shu-Fen Chiang, Pei-Chen Yang, Tao-Wei Ke, Tsung-Wei Chen, Ching-Han Hu, Yi-Wen Huang, Hsin-Yu Chang, William Tzu-Liang Chen, K. S. Clifford Chao
Summary: The study evaluates the induction of immunogenic cell death (ICD) by the novel topoisomerase I inhibitor lipotecan for anticancer immunity. Lipotecan significantly increases tumor immunogenicity and promotes therapeutic efficacy of radiotherapy compared to conventional chemoradiotherapy in vivo. These results suggest potential therapeutic strategies to improve the efficacy of chemoradiotherapy in colorectal cancer patients, particularly those with locally advanced rectal cancer.
Article
Medicine, Research & Experimental
Zhongke Wang, Ruxin Xie, Xiaolin Yang, Huachun Yin, Xin Li, Tianyao Liu, Yuanyuan Ma, Junwei Gao, Zhenle Zang, Ruotong Ruan, Yang Li, Kaixuan Huang, Qingbo Chen, Kaifeng Shen, Shengqing Lv, Chunqing Zhang, Hui Yang, Maragret Warner, Jan-Ake Gustafsson, Shiyong Liu, Xiaotang Fan
Summary: The study found that the expression of estrogen receptor beta is decreased in female temporal lobe epilepsy, and its deletion exacerbates seizure susceptibility and imbalance in synaptic excitation/inhibition. ER beta may regulate synaptic E/I through the GLUL gene, providing a potential therapeutic target for female temporal lobe epilepsy patients.
Article
Oncology
Linping Lei, Xuqin Xie, Long He, Keling Chen, Zhaoying Lv, Bin Zhou, Yuan Li, Wenjun Hu, Zongguang Zhou
Summary: Camptothecin and its derivatives are potent anticancer drugs, but have associated side effects. Combining BET inhibitor JQ1 with Camptothecin can effectively reduce side effects and exhibit antitumor effects.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Cell & Tissue Engineering
Hanan Aljohani, Joseph P. Stains, Sunipa Majumdar, Deepa Srinivasan, Linda Senbanjo, Meenakshi A. Chellaiah
Summary: Inhibitory LPL peptide injection in aging mice increases trabecular bone density, reduces osteoclast function, and has no effect on osteoblast function, suggesting its potential as a therapeutic agent for treating osteoporosis.
Article
Biochemistry & Molecular Biology
Ahmed Seddek, Christian Madeira, Thirunavukkarasu Annamalai, Christopher Mederos, Purushottam B. Tiwari, Aaron Z. Welch, Yuk-Ching Tse-Dinh
Summary: This study establishes a yeast-based screening system that can identify human TOP1 poisons with anticancer efficacy and TOP1 suppressors that inhibit TOP1 DNA binding or cleavage activity.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2022)
Article
Endocrinology & Metabolism
Ling Cui, Chunlu Tan, Lili Huang, Weihao Wang, Zhengxiang Huang, Fang Geng, Mengjun Wu, Xiaolin Chen, Michael Cowley, Ferdinand Roelfsema, Chen Chen
Summary: Obese women often have reproductive dysfunction leading to infertility, and dapagliflozin may improve fertility in obese patients through modulation of hormone levels and gene expression.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Oncology
Alessio Giubellino, Andrew C. Nelson, Yuyu He, Sarah A. Munro, Kyu Young Song, Isabella C. Glitza Oliva, Carlos Torres-Cabala
Summary: Tumor heterogeneity is a characteristic of melanoma due to high mutation burden and immunogenicity. Understanding this can aid in developing predictive biomarkers and targeted therapies. In a case of melanoma, a dual phenotype was observed with shared mutations but distinct gene expression between different histologies.
PIGMENT CELL & MELANOMA RESEARCH
(2022)
Article
Genetics & Heredity
Yan Zhou, Andrew C. Nelson, Yuyu He, Sarah A. Munro, Kyu Young Song, Evidio Domingo-Musibay, Alessio Giubellino
Summary: BAP-1 inactivated melanocytic lesions exhibit distinct gene expression and mutational profiles, with genes involved in receptor protein kinase pathways gradually upregulated from nevus to melanoma. These lesions also show a gene enrichment in response to UV radiation, as well as upregulation of MAPK pathway-related genes and transcription factors related to melanomagenesis.
Article
Physiology
Lubica Cibickova, Katerina Langova, Jan Schovanek, Dominika Macakova, Ondrej Krystynik, David Karasek
Summary: The development of gestational diabetes mellitus affects lipid metabolism during pregnancy, but the extent of changes in lipid parameters is unclear. The patterns of these changes may also vary depending on the criteria used for diagnosing GDM.
PHYSIOLOGICAL RESEARCH
(2022)
Article
Medicine, General & Internal
David Karasek, Ondrej Krystynik, Veronika Kucerova, Dominika Macakova, Lubica Cibickova, Jan Schovanek, Martin Haluzik
Summary: This study compared the levels of adiponectin, A-FABP, and FGF-19 in women with early diagnosed GDM to healthy controls and examined their changes after early intervention. The results showed that women with GDM had lower adiponectin and higher A-FABP levels compared to controls, while FGF-19 levels were similar. Early intervention improved glucose control and restored impaired adiponectin production.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Madison Ernst, Alessio Giubellino
Summary: Malignant melanoma is the leading cause of death among cutaneous malignancies. The introduction of immunotherapies and targeted therapies have contributed to a small decrease in mortality rate. However, toxicity and resistance remain critical challenges in the field.
Review
Dermatology
Madison Ernst, Alessio Giubellino
Summary: CADR is common in clinical settings and can be life-threatening, with MDE being the most common clinical manifestation. Histopathologic features of MDE include epidermal spongiosis, lymphocytic infiltrate, and interface change at the DEJ. Biopsy may improve diagnostic accuracy by identifying common features of MDE and excluding other causes of maculopapular eruption.
Meeting Abstract
Rheumatology
V. Kaskova, A. Petrackova, J. Schovanek, M. Karhanova, J. Savara, E. Kriegova
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Ophthalmology
Marta Karhanova, Jana Kalitova, Radim Kovar, Jan Schovanek, David Karasek, Jakub Civrny, Petra Hubnerova, Petr Mlcak, Martin Sin
Summary: This study found that elevated intraocular pressure (TOP) in patients with thyroid-associated orbitopathy (TAO) in the active stage is positively correlated with the severity of extraocular muscle involvement, but not with the extent of exophthalmos. Patients with elevated TOP are more likely to require strabismus surgery and orbital decompression.
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2022)
Article
Biology
Kristyna Sloupenska, Barbora Koubkova, Pavel Horak, Beata Hutyrova, Mojmir Racansky, Jan Mares, Martina Miklusova, Jan Schovanek, Jana Zapletalova, Milan Raska, Michal Krupka
Summary: In this study, the presence of myositis-specific and myositis-associated autoantibodies was analyzed in patients with Lyme disease and post-treatment Lyme disease syndrome (PTLDS). The study found that PTLDS patients had a higher presence of these autoantibodies compared to control subjects, suggesting their involvement in the pathogenesis of this syndrome.
Article
Veterinary Sciences
Karen Koo, Arno Wuenschmann, Aaron Rendahl, Kyu Young Song, Colleen Forster, Amber Wolf-Ringwall, Antonella Borgatti, Alessio Giubellino
Summary: Analysis of canine melanoma tissue samples showed that MET receptor tyrosine kinase is expressed in these tumors, with a potential role in metastasis. However, further research is needed to fully understand its association with prognosis and treatment strategies in canine melanoma.
VETERINARY SCIENCES
(2023)
Article
Engineering, Biomedical
Vlastimil Novak, Lumir Hrabalek, Jan Schovanek, Zdenek Frysak, Racheal Temitope Ijisesan Perryova, Daniel Pohlodek
Summary: This study evaluated the results of surgical transnasal procedures in patients with functioning pituitary adenomas, showing that 58.6% of patients achieved normalization of hormonal excessive production after surgery. Drug therapy and radiotherapeutic methods were necessary for achieving hormonal remission in remaining cases.
BIOMEDICAL PAPERS-OLOMOUC
(2023)
Review
Cell Biology
Tiffany W. Cheng, Emily Hartsough, Alessio Giubellino
Summary: Assessment of sentinel lymph node status is crucial for melanoma patients' prognosis and therapeutic management, and pathologists play a vital role in this evaluation. Various methods have been used, including evaluating metastatic burden dimensions, determining tumor deposit locations within lymph nodes, and precise cell counting. However, no single method can independently predict prognosis. The management approach for sentinel lymph node-positive patients has also evolved, with a more conservative approach recognized for selected cases. This review provides an overview of past and current advancements in the field, along with potential future directions based on prior experiences and clinical trials.
Article
Oncology
Trevor F. Killeen, Ryan Shanley, Vidhyalakshmi Ramesh, Alessio Giubellino
Summary: Despite advancements in immunotherapy, melanoma remains the most deadly skin cancer. Immunocompromised patients have a higher risk of developing melanoma and experience more severe outcomes. This study characterizes melanoma in immunocompromised patients, highlighting histopathologic parameters and survival trends. The findings provide important insights for clinicians managing this unique patient population.
Article
Dermatology
Cody J. Rasner, Yan Zhou, Alessio Giubellino
Summary: The recurrent nevus phenomenon refers to the presence of a nevus within a scar from a previous biopsy site, with clinical and histologic features that often overlap with melanoma, making diagnosis challenging. This can also occur in nevi that have been traumatized recently or chronically, as well as in sclerosing nevi. Any type of nevus can be affected by this phenomenon. In this case report, a 42-year-old woman was found to have an atypical melanocytic proliferation within a keloidal scar. This highlights the importance of recognizing these melanocytic lesions as benign to avoid unnecessary treatment.
Article
Endocrinology & Metabolism
Milan Halenka, Hana Munteanu, Radko Obereigneru, Roman Dohnal, David Karasek, Jan Schovanek
Summary: The study evaluated the effectiveness of ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) in young patients. The results showed that US-PEIT had significant effects on cyst volume reduction and symptom improvement, making it a preferred treatment for young patients with thyroid cysts.
EUROPEAN THYROID JOURNAL
(2023)