Article
Medicine, Research & Experimental
Wen Bai, Jun-Song Ren, Min Xia, Ya Zhao, Jing-Juan Ding, Xi Chen, Qin Jiang
Summary: Fascin homologue 1 (FSCN1) plays a crucial role in ocular neovascularization and is highly expressed in oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV). NP-G2-044, an oral inhibitor of FSCN1, inhibits the sprouting, migration, and filopodia formation of endothelial cells. Oral NP-G2-044 effectively and safely blocks the development of OIR and CNV, and improves efficacy when combined with intravitreal aflibercept (Eylea) injection to overcome anti-VEGF resistance.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Xiangyu Zhang, Xinran Wang, Tianxiao Wu, Wenbo Yin, Jiangkun Yan, Yixiang Sun, Dongmei Zhao
Summary: This study provides an extensive review of LSD1 as an important histone demethylase in cancer and its potential applications. The aberrant overexpression of LSD1 in tumor cells is associated with tumor growth, invasion, and metastasis, making it a promising target for cancer therapy. The review summarizes recent advances in LSD1 inhibitors, including their structural characteristics, screening methods, and future directions for development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Chemistry, Medicinal
Nuria A. Tamayo, Matthew P. Bourbeau, Jennifer R. Allen, Kate S. Ashton, Jian Jeffrey Chen, Matthew R. Kaller, Thomas T. Nguyen, Nobuko Nishimura, Liping H. Pettus, Mary Walton, Brian Belmontes, Jodi Moriguchi, Kui Chen, John D. McCarter, Kelly Hanestad, Grace Chung, Maria Stefania S. Ninniri, Jan Sun, Leszek Poppe, Chris Spahr, John Hui, Lei Jia, Tian Wu, Upendra P. Dahal, Katheryne Z. Edson, Marc Payton
Summary: This study identifies a series of compounds that can serve as KIF18A inhibitors and demonstrates that compounds 23 and 24 can cause significant mitotic arrest and subsequent cell death. The study also reveals that these inhibitors bind at the interface of KIF18A and tubulin. This represents the first disclosure of KIF18A inhibitors with in vivo activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Cell Biology
Yi Xiao, Jixin Dong
Summary: This article discusses the role and therapeutic potential of Cyclin K in cancer. Studies have shown that Cyclin K plays important roles in various biological processes and is critical in cancer cell growth and therapeutic resistance. Additionally, the druggability of Cyclin K has been demonstrated, providing novel opportunities for cancer treatment.
Article
Pharmacology & Pharmacy
Elham Seidkhani, Fatemeh Moradi, Auob Rustamzadeh, Sara Simorgh, Sakine Shirvalilou, Mehdi Mehdizadeh, Hamed Dehghani, Zeinab Akbarnejad, Manijeh Motevalian, Enam Alhagh Charkhat Gorgich
Summary: This study aimed to evaluate the effects of sunitinib on GBM-bearing rats and compare the effects of different delivery methods on angiogenesis inhibition and hepatotoxicity. The results showed that intra-nasal delivery of sunitinib may be a potential non-hepatotoxic alternative for the treatment of GBM.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Oncology
Joseph A. Zundell, Takeshi Fukumoto, Jianhuang Lin, Nail Fatkhudinov, Timothy Nacarelli, Andrew Kossenkov, Qin Liu, Joel Cassel, Chih-Chi Andrew Hu, Shuai Wu, Rugang Zhang
Summary: The SWI/SNF chromatin-remodeling complex is frequently altered in human cancers, with the ARID1A mutation conferring sensitivity to inhibition of the IRE1 alpha-XBP1 pathway in ovarian clear cell carcinomas. Targeting the IRE1 alpha-XBP1 axis represents a promising therapeutic approach for ARID1A-mutant ovarian cancers, especially when combined with HDAC6 inhibition.
Article
Immunology
Xiaojie Chu, Du-San Baek, Wei Li, Taras Shyp, Brian Mooney, Margaret G. Hines, Gregg B. Morin, Poul H. Sorensen, Dimiter S. Dimitrov
Summary: ENPP1, a type II transmembrane glycoprotein, is highly expressed in various cancers and associated with poor prognosis. In this study, two high-affinity and specific anti-ENPP1 Fab antibodies, 17 and 3G12, were isolated and characterized. Antibody-drug conjugates, IgG-based bispecific T-cell engagers, and CAR T-cells were generated based on these antibodies, all demonstrating potent killing of ENPP1-expressing cells. These antibody-derived modalities hold promise as therapeutic candidates for cancers expressing human ENPP1.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Dustin J. Flanagan, Simon A. Woodcock, Caroline Phillips, Catherine Eagle, Owen J. Sansom
Summary: This review summarizes the contribution of Wnt pathway dysregulation to the development of gastrointestinal cancers, focusing on upstream pathway aberrations. Tumors with upstream aberrations depend on functional Wnt ligand and can be treated with Porcupine inhibitors.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Chemistry, Medicinal
Belal Almajali, Hamid Ali Nagi Al-Jamal, Wan Rohani Wan Taib, Imilia Ismail, Muhammad Farid Johan, Abd Almonem Doolaanea, Wisam Nabeel Ibrahim
Summary: Natural product thymoquinone (TQ) from Nigella sativa has shown promising anticancer activities through inhibiting cell proliferation, migration, and invasion in various human cancers. Its efficacy in inducing apoptosis and mechanisms on different cancer types are still not fully understood, but there is ongoing research on its potential as a future anticancer therapy nominee, especially in combination with other anticancer agents using nanotechnology.
Review
Cell Biology
Yan Yang, Guangming Zhu, Li Yang, Yun Yang
Summary: This article reviews the role of CD24 in tumorigenesis and cancer progression, its potential as a therapeutic target, and summarizes different therapeutic agents or strategies targeting CD24 in solid cancers.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Chemistry, Medicinal
Claudia Korzeniecki, Ronny Priefer
Summary: KRAS genes are commonly mutated in cancer, and targeting KRAS mutant cancers has proven difficult due to lack of success with direct inhibitors. Researchers are now focusing on targeting other areas of the MAPK signaling pathway to inhibit KRAS function.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Simin Zhao, Jian Li, Qingxin Xia, Kangdong Liu, Zigang Dong
Summary: Anaplastic lymphoma kinase (ALK), a member of the insulin receptor protein-tyrosine kinase superfamily, is associated with cancer initiation and progression. ALK alterations, including fusions, over-expression, and mutations, play a significant role in various types of cancer. Several ALK inhibitors have been developed and approved by the FDA, but resistance remains an issue. Monoclonal antibody screening and combination therapies may provide alternative treatments for ALK-positive tumors. This review discusses the structure and functions of wild-type ALK and fusion proteins, ALK target therapy, drug resistance, and future therapeutic directions.
Review
Biochemistry & Molecular Biology
Jaewang Lee, Jong-Lyel Roh
Summary: FSP1 is a critical protein in regulating ferroptosis and resistance to ferroptosis, operating independently from the canonical pathway. This review highlights the importance of FSP1 modulation and its potential as a therapeutic target in cancer treatment. Recent advances in developing FSP1 inhibitors and their implications for cancer therapy are also discussed.
Review
Pharmacology & Pharmacy
Kimberley M. Hanssen, Michelle Haber, Jamie Fletcher
Summary: The article discusses various therapeutic strategies targeting ABC transporters, including the development of small molecule inhibitors, exploiting collateral sensitivity to glutathione depletion and ferroptosis, gene silencing, and modulation of transporter activity by new molecules. These new approaches show promise beyond simple MDR reversal and provide exciting avenues for further research.
DRUG RESISTANCE UPDATES
(2021)
Review
Cell Biology
Timofey Lebedev, Rubina Kousar, Bbumba Patrick, Muhammad Usama, Meng-Kuei Lee, Ming Tan, Xing-Guo Li
Summary: Epigenetic remodeling and metabolic reprogramming are two highly intertwined cancer hallmarks. Recent studies have shown that the interplay between epigenetic regulation and metabolic rewiring can be targeted as a potential Achilles' heel in cancer. This review explores the immunomodulatory role of ARID1A and summarizes the advances in targeting ARID1A-deficient cancers to improve patient outcome by harnessing the immune-metabolic vulnerability.
Article
Peripheral Vascular Disease
Akinori Hayashi, Masayoshi Shichiri
Article
Medicine, General & Internal
Akinori Hayashi, Koji Takano, Yuko Kawakami, Mamiko Hitomi, Yasuhiro Ohata, Agena Suzuki, Yuji Kamata, Masayoshi Shichiri
Article
Gastroenterology & Hepatology
Chikatoshi Katada, Saeko Fukazawa, Mitsuhiro Sugawara, Yasutoshi Sakamoto, Kaoru Takahashi, Akiko Takahashi, Akinori Watanabe, Takuya Wada, Kenji Ishido, Yasuaki Furue, Hiroki Harada, Kei Hosoda, Keishi Yamashita, Naoki Hiki, Teruko Sato, Takafumi Ichikawa, Masayoshi Shichiri, Satoshi Tanabe, Wasaburo Koizumi
Summary: Nutritional support provided by an amino acid-rich elemental diet was ineffective for reducing the incidence of adverse events caused by DCF chemotherapy in patients with esophageal cancer, but tended to maintain certain indicators after chemotherapy.
Article
Multidisciplinary Sciences
Tomomi Taguchi, Yoshio Kodera, Kazuhito Oba, Tatsuya Saito, Yuzuru Nakagawa, Yusuke Kawashima, Masayoshi Shichiri
Summary: The study successfully identified three novel bioactive polypeptides derived from suprabasin in plasma using a novel strategy, demonstrating a new approach for discovering unknown bioactive peptides.
SCIENTIFIC REPORTS
(2021)
Article
Peripheral Vascular Disease
Kazumi Fujimoto, Sayuki Kawamura, Satoru Bando, Yuji Kamata, Yoshio Kodera, Masayoshi Shichiri
Summary: The study looked at the molecular forms of human plasma prorenin and developed an enzyme-linked immunosorbent assay to directly measure its concentration. It found that plasma prorenin concentrations are far higher than previously thought, with three major distinct components identified. Additionally, plasma prorenin concentrations were not affected by postural changes, indicating potential posttranslational modifications or albumin binding.
HYPERTENSION RESEARCH
(2021)
Article
Endocrinology & Metabolism
Akinori Hayashi, Naoya Shimizu, Agena Suzuki, Kenta Matoba, Akari Momozono, Tsuguto Masaki, Akifumi Ogawa, Ibuki Moriguchi, Koji Takano, Naoyuki Kobayashi, Masayoshi Shichiri
Summary: Despite the use of dialysate containing 100-150 mg/dL glucose, patients with diabetes undergoing HD experienced HD-related hypoglycemia frequently. SGL showed a sustained decrease during HD, reaching a nadir lower than the dialysate glucose concentration, regardless of the dialysate glucose concentration.
Article
Multidisciplinary Sciences
Tsuguto Masaki, Yoshio Kodera, Michishige Terasaki, Kazumi Fujimoto, Tsutomu Hirano, Masayoshi Shichiri
Summary: A new plasma peptidomic technique was used to identify a novel endogenous proatherogenic peptide, GIP_HUMAN[22-51], which accelerates atherosclerosis by modulating the cardiovascular system and inducing inflammatory responses.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Hiroaki Iwasaki, Masayoshi Shichiri
Summary: In Japanese patients with type 2 diabetes, the rs3745468 variant in the PRMT1 gene was associated with an increased incidence of proliferative diabetic retinopathy (PDR) and may be involved in the HIF-1-dependent hypoxic pathway through altered PRMT1 levels.
ACTA DIABETOLOGICA
(2022)
Article
Endocrinology & Metabolism
Naoya Shimizu, Akifumi Ogawa, Akinori Hayashi, Masayoshi Shichiri
Summary: This study shows that changes in HbA1c levels may not accurately reflect the glycemic improvements in patients treated with SGLT2 inhibitors. The study suggests that GA may be a more reliable biomarker for evaluating the glucose-lowering effect and glycemic fluctuations induced by SGLT2 inhibitors.
JOURNAL OF DIABETES AND ITS COMPLICATIONS
(2022)
Article
Peripheral Vascular Disease
Sayuki Kawamura, Kazumi Fujimoto, Akinori Hayashi, Yuji Kamata, Ibuki Moriguchi, Naoyuki Kobayashi, Masayoshi Shichiri
Summary: Although the measurement of plasma prorenin levels is still unavailable in clinical practice, this study found that utilizing a sandwich enzyme-linked immunosorbent assay that captures posttranslationally modified prorenins with their prosegment antibodies, plasma and serum prorenin concentrations can be measured in patients with diabetes mellitus, hypertension and/or renal disease. The results showed no significant difference compared to healthy controls, but were significantly higher than previously reported levels using conventional assay kits. Furthermore, the study found that plasma prorenin levels were negatively correlated with body weight, serum albumin levels, and serum creatinine levels, while the use of loop diuretics was associated with elevated plasma prorenin levels.
HYPERTENSION RESEARCH
(2022)
Article
Endocrinology & Metabolism
Sayaka Sasaki, Kazuhito Oba, Yoshio Kodera, Makoto Itakura, Masayoshi Shichiri
Summary: The discovery of bioactive peptides is important for understanding human diseases and drug discovery. In this study, a anorexigenic peptide ANGT_HUMAN[448-462] was identified and found to bind to the beta-subunit of ATP synthase. It was shown to suppress eating behavior in mice.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)
Article
Endocrinology & Metabolism
Naoya Shimizu, Akinori Hayashi, Shiori Ito, Agena Suzuki, Rei Fujishima, Kenta Matoba, Tatsuhiko Wada, Koji Takano, Masato Katagiri, Masayoshi Shichiri
Summary: This study investigated the accuracy of isCGM in COVID-19 patients during dexamethasone therapy. The results showed that isCGM correlated well with point-of-care measurements and had good reliability in COVID-19 patients with and without diabetes.
Article
Endocrinology & Metabolism
Naoya Shimizu, Akinori Hayashi, Shiori Ito, Agena Suzuki, Rei Fujishima, Kenta Matoba, Tatsuhiko Wada, Koji Takano, Masato Katagiri, Masayoshi Shichiri
Summary: The clinical utility of intermittently scanned continuous glucose monitoring (isCGM) in patients with coronavirus disease 2019 (COVID-19) during dexamethasone therapy was investigated. The accuracy of isCGM compared to point-of-care (POC) fingerstick glucose monitoring was evaluated in 16 patients with COVID-19, showing good correlation and reliability, especially for COVID-19 patients with and without diabetes. While isCGM may not be as accurate as traditional blood glucose monitoring, it demonstrated good reliability in this specific patient population.
Article
Endocrinology & Metabolism
Agena Suzuki, Yuji Kamata, Tomomi Taguchi, Koji Takano, Yuto Yamazaki, Hironobu Sasano, Masayoshi Shichiri
Summary: Advances in imaging technology have led to an increase in the number of identified patients with bilateral adrenal incidentalomas, but there is no consensus on the optimal management of these lesions. This study reports a clinically interesting case of a 59-year-old female with adrenocortical adenoma harboring a venous thrombus that mimicked adrenal malignancy, highlighting the difficulty in preoperatively diagnosing and differentiating between benign and malignant adrenal lesions.
Article
Endocrinology & Metabolism
Akari Momozono, Akinori Hayashi, Koji Takano, Masayoshi Shichiri
Summary: The study demonstrates that growth hormone replacement therapy significantly improves resting energy expenditure and body composition in patients with adult growth hormone deficiency. This therapy leads to an increase in lean body mass, improved lipid metabolism, and no change in body weight over the course of 12 months.