Article
Biochemistry & Molecular Biology
Zohreh Jahani, Jamshid Davoodi
Summary: Metformin, an anti-diabetic drug, has a dual effect on breast cancer cell lines by both upregulating and enhancing the degradation of certain proteins during mTORC1 inhibition.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Loka Raghu Kumar Penke, Jennifer Speth, Scott Wettlaufer, Christina Draijer, Marc Peters-Golden
Summary: This study evaluated the therapeutic efficacy of the proteasomal inhibitor bortezomib (BTZ) and found that it has antifibrotic actions in lung fibrosis. Surprisingly, these actions are independent of proteasome inhibition and instead mediated by the induction of dual-specificity protein phosphatase 1 (DUSP1).
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Oncology
Tian-Yi Jiang, Xiao-Fan Feng, Zheng Fang, Xiao-Wen Cui, Yun-Kai Lin, Yu-Fei Pan, Chun Yang, Zhi-Wen Ding, Yong-Jie Zhang, Ye-Xiong Tan, Hong-Yang Wang, Li-Wei Dong
Summary: This study identified frequent alterations of PTEN in GBC, showing correlation with poor prognosis, and indicated proteasome inhibitor bortezomib as a promising therapeutic agent. Knockdown of PTEN increased bortezomib efficacy, and further evaluation using PDXs supported the utilization of bortezomib in PTEN-deficient GBC. Mechanistically, PTEN inhibited proteasome activity and bortezomib sensitivity through ARE-dependent transcriptional regulation, with involvement of the BACH1 transcriptional suppressor.
Article
Medicine, Research & Experimental
Helen E. Burston, Oliver A. Kent, Laudine Communal, Molly L. Udaskin, Ren X. Sun, Kevin R. Brown, Euihye Jung, Kyle E. Francis, Jose La Rose, Joshua Lowitz, Ronny Drapkin, Anne-Marie Mes-Masson, Robert Rottapel
Summary: Relaxin and its associated GPCR RXFP1 form an autocrine signaling loop essential for ovarian cancer in vivo tumorigenesis, cell proliferation, and viability. Relaxin signaling activates expression of prooncogenic pathways, and inflammatory cytokines can activate Relaxin transcription.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Kyota Ishii, Mayuko Hido, Misaki Sakamura, Nantiga Virgona, Tomohiro Yano
Summary: This study demonstrated that T3, TOS, and T3E enhance the sensitivity of the proteasome inhibitor BTZ in solid cancers by modulating the activity of NFE2L1. Inactivation of NFE2L1 by T3, TOS, and T3E is essential to potentiate the cytotoxic effect of BTZ in solid cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Mingyu Chen, Sarun Juengpanich, Shijie Li, Win Topatana, Ziyi Lu, Qiang Zheng, Jiasheng Cao, Jiahao Hu, Esther Chan, Lidan Hou, Jiang Chen, Fang Chen, Yu Liu, Sukanda Jiansirisomboon, Zhen Gu, Suparat Tongpeng, Xiujun Cai
Summary: This study reports on a targeted therapy for gallbladder cancer using pH-responsive nanoparticles encapsulating bortezomib and mediated by estrogen-induced endocytosis. The treatment effectively inhibits proteasomes and induces apoptosis under tumor microenvironment and laser irradiation.
Article
Multidisciplinary Sciences
Mengmeng Dong, Jinna Zhang, Xiaoyan Han, Jingsong He, Gaofeng Zheng, Zhen Cai
Summary: This study retrospectively analyzed clinical data of 155 MM patients and found that baseline PN was age-related, leading to more severe BiPN during bortezomib induction therapy and worse PN outcome after induction therapy. MM patients with baseline PN also had worse PFS and OS.
SCIENTIFIC REPORTS
(2022)
Review
Oncology
Ramon Yarza, Mateo Bover, Maria Teresa Agullo-Ortuno, Lara Carmen Iglesias-Docampo
Summary: Nasopharyngeal carcinoma (NPC) is a molecularly paradigmatic tumor with complex environmental and host dependent factors, where Epstein Barr Virus (EBV) plays a key role in malignant transformation. The dysregulation of proteasome signaling is central in NPC pathogenesis and could be a potential therapeutic target. Studies have shown the efficacy of immunotherapy in NPC, with novel strategies aiming to reverse immune resistance and favor tumor recognition.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Hua Su, Fei Yang, Rao Fu, Xin Li, Randall French, Evangeline Mose, Xiaohong Pu, Brittney Trinh, Avi Kumar, Junlai Liu, Laura Antonucci, Jelena Todoric, Yuan Liu, Yinling Hu, Maria T. Diaz-Meco, Jorge Moscat, Christian M. Metallo, Andrew M. Lowy, Beicheng Sun, Michael Karin
Summary: Although many cancers rely on autophagy for nutrient acquisition, blocking autophagy alone does not effectively inhibit tumor growth. Research has shown that blocking autophagy can lead to pancreatic ductal adenocarcinoma (PDAC) upregulating an alternative nutrient pathway, macropinocytosis (MP), allowing tumor cells to extract nutrients from outside sources. This switch from autophagy to MP, driven by the activation of transcription factor NRF2, presents a potential therapeutic strategy for inhibiting tumor growth and regression.
Article
Chemistry, Medicinal
Markus Klein, Michael Busch, Manja Friese-Hamim, Stefano Crosignani, Thomas Fuchss, Djordje Musil, Felix Rohdich, Michael P. Sanderson, Jeyaprakashnarayanan Seenisamy, Gina Walter-Bausch, Ugo Zanelli, Philip Hewitt, Christina Esdar, Oliver Schadt
Summary: Proteasomes are essential components of the ubiquitin-dependent protein degradation pathway, with LMP7 being a subunit of the immunoproteasome. Current pan-proteasome inhibitors nonselectively target LMP7 and other subunits, limiting their therapeutic applicability. Novel amido boronic acids were discovered to selectively inhibit LMP7, leading to the identification of the highly potent and orally available inhibitor M3258, which showed strong antitumor activity in MM models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Philipp Klingler, Marius Niklaus, Juergen Koessler, Katja Weber, Angela Koessler, Markus Boeck, Anna Kobsar
Summary: In platelets incubated for 24 hours, bortezomib mediates a slight attenuation of inhibitory signaling, associated with facilitated platelet aggregation using threshold agonist concentrations and enhanced adhesion on agonist-coated surfaces.
VASCULAR PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Fujun Yang, Qingyu Ji, Rui Liao, Shumeng Li, Yuequan Wang, Xuanbo Zhang, Shenwu Zhang, Haotian Zhang, Qiming Kan, Jin Sun, Zhonggui He, Bingjun Sun, Cong Luo
Summary: This study presents a facile dual-drug nanoassembly that enhances the efficacy of photodynamic therapy by inhibiting the proteasome. The engineered nanoassembly demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment, and favorable stability and enrichment.
CHINESE CHEMICAL LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Jianhao Liu, Ruogang Zhao, Xiaowen Jiang, Zhaohuan Li, Bo Zhang
Summary: Bortezomib is a proteasome inhibitor that has been approved for the treatment of multiple myeloma and other hematological cancers. However, its limited specificity, poor permeability, and low bioavailability hinder its applications. Recent research has focused on the development of BTZ-based drug delivery systems.
Article
Cardiac & Cardiovascular Systems
Hericka Bruna Figueiredo Galvao, Quynh Nhu Dinh, Jordyn M. Thomas, Flavia Wassef, Henry Diep, Alex Bobik, Christopher G. Sobey, Grant R. Drummond, Antony Vinh
Summary: The effect of reducing antibody-secreting cells (ASCs) on angiotensin II-induced hypertension was tested using the proteasome inhibitor bortezomib. ASCs and antibody levels were decreased, but hypertension was not affected.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Oncology
Lijun Tan, Katelyn Tondo-Steele, Caroline Foster, Carrie McIlwain, Danielle E. Bolland, Howard C. Crawford, Andrew Sciallis, Karen McLean
Summary: This study demonstrates the crosstalk between cytokine signaling and estrogen signaling in high-grade serous ovarian cancer. Inhibiting cytokine signaling activates estrogen signaling, and blocking both pathways has a synergistic effect in inhibiting tumor cell growth. Combination therapy may be a potential new treatment approach for ovarian cancer patients.
Article
Oncology
Xing-Guo Tang, Ke Lin, Shun-Wen Guo, Yi Rong, Dan Chen, Zhe-Sheng Chen, Feng-Feng Ping, Jin-Quan Wang
Summary: This study confirmed that the increment-Ru1/Dox combination had a synergistic effect in inhibiting tumor growth in a mouse xenograft model. It was found that this combination treatment promoted tumor cell apoptosis and reduced cardiac fibrosis and iron accumulation caused by doxorubicin. Further investigation revealed that doxorubicin regulated iron accumulation via the ferroptosis pathway and the expression of lipid peroxidation-related proteins. Therefore, the increment-Ru1/Dox combination therapy shows promise in reducing the toxic side effects of doxorubicin, especially cardiac injury.
RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY
(2023)
Review
Pharmacology & Pharmacy
Jingyi Fan, Kenneth Kin Wah To, Zhe-Sheng Chen, Liwu Fu
Summary: Multidrug resistance (MDR) is when cancer cells become resistant to a wide range of unrelated drugs. This hinders cancer treatment and is a major cause of chemotherapy failure. ABC transporters are frequently overexpressed in MDR cancer cells, promoting drug efflux and reducing drug accumulation. Recent evidence suggests that ABC transporters also regulate the tumor immune microenvironment (TIME) by transporting cytokines, influencing anti-tumor immunity and drug sensitivity. Inhibition of ABC transporter expression or function can enhance the efficacy of immune checkpoint inhibitors by promoting an anticancer immune microenvironment. This review provides an update on current research progress in this field.
DRUG RESISTANCE UPDATES
(2023)
Review
Pharmacology & Pharmacy
Kun Pang, Zhen-Duo Shi, Liu-Ya Wei, Yang Dong, Yu-Yang Ma, Wei Wang, Guang-Yue Wang, Ming-Yang Cao, Jia-Jun Dong, Yu-Ang Chen, Peng Zhang, Lin Hao, Hao Xu, Deng Pan, Zhe-Sheng Chen, Cong-Hui Han
Summary: The PD-1/PD-L1 immune checkpoint plays a crucial role in tumor immune escape, but the main challenges of this therapy are low response rate and acquired resistance, thus further research is needed to improve the treatment outcome.
DRUG RESISTANCE UPDATES
(2023)
Article
Physics, Multidisciplinary
Jiuxiang Zhang, Zhesheng Chen, Jonathan Caillaux, Yannick Klein, Andrea Gauzzi, Azzedine Bendounan, Amina Taleb-Ibrahimi, Luca Perfetti, Evangelos Papalazarou, Marino Marsi
Summary: Time-resolved ARPES provides a method to investigate the band structure and dynamics of excited electronic states in solids. Understanding the orbital character of bands near the Fermi level is crucial for explaining exotic phenomena in quantum materials. By conducting polarization-dependent time-and angle-resolved photoemission spectroscopy and analyzing the photoelectron yield for different crystal orientations, we determine the orbital character of bands above and below the chemical potential in the Dirac semimetal BaNiS2. Our results demonstrate the significance of controlling and understanding matrix elements' effects in time-resolved photoemission spectroscopy for the study of quantum materials.
EUROPEAN PHYSICAL JOURNAL-SPECIAL TOPICS
(2023)
Article
Chemistry, Multidisciplinary
Jiuxiang Zhang, Thibault Daniel Pierre Sohier, Michele Casula, Zhesheng Chen, Jonathan Caillaux, Evangelos Papalazarou, Luca Perfetti, Luca Petaccia, Azzedine Bendounan, Amina Taleb-Ibrahimi, David Santos-Cottin, Yannick Klein, Andrea Gauzzi, Marino Marsi
Summary: In the Dirac semimetal BaNiS2, the Dirac nodes can be moved along the Gamma-M symmetry line in reciprocal space by varying the concentration of adsorbed K atoms. This peculiar feature offers a promising tool for engineering Dirac states at surfaces, interfaces, and heterostructures, as demonstrated by first-principles calculations considering the effect of charge transfer gap.
Article
Biochemistry & Molecular Biology
Gao-Jie Ye, Chao-Yun Cai, Zhuo-Xun Wu, Qiu-Xu Teng, Jing-Quan Wang, Zhe-Sheng Chen, Bo Wang
Summary: Three series of phenylurea indole derivatives were synthesized with potent inhibitory activities on ABCG2. Four phenylurea indole derivatives with extended 7C system showed the most potent ABCG2 inhibition and no inhibition on ABCB1. Further investigation on two compounds revealed that they increased the accumulation of mitoxantrone in ABCG2-overexpressing cells and stimulated the ATP hydrolysis of ABCG2 transporter.
BIOORGANIC CHEMISTRY
(2023)
Article
Oncology
Ruikun Lin, Lei Zhang, Biwei Ye, Yanan Wang, Yi-Dong Li, Hsu Jason, Wenzhen Liu, Ping Hu, Jincan Chen, Zhe-Sheng Chen, Zhuo Chen
Summary: Our study demonstrates a novel approach to treat multidrug resistance in cancer by targeting and inhibition of P-gp using a nanoparticle system. In vitro and in vivo experiments showed that this nanoparticle system significantly enhanced the efficacy of chemotherapy, reversed drug resistance, inhibited cell proliferation, induced apoptosis, and prevented cancer cell metastasis, with no apparent toxicity.
Review
Pharmacology & Pharmacy
Jia Fu, Wei Qin, Lu-Qi Cao, Zhe-Sheng Chen, Hui-Ling Cao
Summary: This review summarizes the applications and immobilization methods of receptor chromatography, which is widely used for high-throughput separation and accurate drug screening. The review focuses on screening active compounds in natural products, as well as the design and application of receptor chromatography in drug-receptor interactions.
DRUG DISCOVERY TODAY
(2023)
Review
Pharmacology & Pharmacy
Juan Jin, Yuhao Xie, Jin-Shi Zhang, Jing-Quan Wang, Shi-Jie Dai, Wen-fang He, Shou-Ye Li, Charles R. Ashby Jr, Zhe-Sheng Chen, Qiang He
Summary: Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer, and targeted therapy with Sunitinib has become the main treatment option due to the lack of efficacy in radiation therapy and chemotherapy. However, many patients develop resistance to Sunitinib within months of therapy. In this review, we discuss the molecular mechanisms of Sunitinib resistance, strategies to overcome it, and potential predictive biomarkers.
DRUG RESISTANCE UPDATES
(2023)
Article
Oncology
Ruixiang Guo, Huiru Dai, Fuweijian Liu, Minling Liu, Xueying Li, Tingwei Li, Jiehao Liao, Zhe-Sheng Chen, Yuchen Liu, Shuo Fang
Summary: LEF1 has been found to be significantly associated with high histological grade in hepatocellular carcinoma (HCC) and its overexpression is correlated with poor prognosis. LEF1 may regulate the cell cycle, WNT signaling pathway, and NOTCH signaling pathway in HCC. It could serve as a potential drug target for HCC.
RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY
(2023)
Article
Pharmacology & Pharmacy
Congying Gao, Lei Zhang, Yun Xu, Xiangyu Ma, Peilei Chen, Zhe-Sheng Chen, Liuya Wei
Summary: In this study, the potent histone deacetylase inhibitor I13 was assessed for its effect on chronic myeloid leukemia (CML) cells harboring T315I-mutated and wild-type BCR-ABL. I13 showed strong activity against both types of cells, inducing cell differentiation and suppressing proliferation by causing cell cycle G0/G1-phase accumulation. It was found that I13 blocked the CML signaling pathway by depleting BCR-ABL, resulting in cell differentiation. These findings highlight I13 as a BCR-ABL modulator for overcoming drug resistance caused by T315I-mutated BCR-ABL and have implications for CML therapy development.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Longyang Liu, Chunlin Chen, Ping Liu, Jing Li, Zhanjun Pang, Jiayu Zhu, Zhongqiu Lin, Haixu Zhou, Yingying Xie, Tiancai Lan, Zhe-Sheng Chen, Zhaoyang Zeng, Weiyi Fang
Summary: In this study, the expression and function of MYH10 in serous ovarian cancer (SOC) were investigated. It was found that MYH10 is associated with the invasive capacity and cisplatin resistance of SOC cells. Further experiments revealed that MYH10 interacts with MYH9 to promote tumorigenesis, progression, and cisplatin resistance in SOC. Clinical samples also showed elevated expression of MYH10 in SOC samples, which correlated positively with MYH9 expression. Co-expression of MYH10+/MYH9+ was identified as an independent prognostic factor for SOC patient survival.
Article
Fisheries
Peng Xu, Kuopeng Cui, Liming Chen, Shaoshu Chen, Zheng Wang
Summary: This study evaluated the potential of Bifidobacterium animalis subsp. lactis BLa80 as a probiotic for Japanese seabass aquaculture. The results showed that BLa80 supplementation improved survival, accelerated growth, enhanced antioxidant capacity, reduced apoptosis, and altered the gut microbiota structure of juvenile Japanese seabass.
AQUACULTURE INTERNATIONAL
(2023)
Article
Pharmacology & Pharmacy
Zhijian Wang, Yuhao Xie, Jing-Quan Wang, Yuanhui Cheng, Joshua Fleishman, Zhe-Sheng Chen, Yun Chen
Summary: On January 25, 2022, the FDA approved tebentafusp for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Tebentafusp targets a specific HLA-A*02:01/gp100 complex, activating T cells to induce tumor cell death. Clinical trials have shown positive overall survival and response rates, as well as manageable adverse events. The approval of tebentafusp is groundbreaking due to the limited efficacy of current treatments for mUM.
Article
Pharmacology & Pharmacy
Xing Liu, Gao-Chuan Fang, Hao Lu, Zhen-Duo Shi, Zhe-Sheng Chen, Cong-Hui Han
Summary: On March 23, 2022, the FDA approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) as the first targeted radioligand therapy for PSMA-positive mCRPC patients. This groundbreaking therapy selectively binds to PSMA, leading to DNA damage and cell death in prostate cancer cells. With its promising mechanism of action and high specificity, it represents an exciting advancement in precision medicine for individualized treatments.