ClpP Peptidase as a Plausible Target for the Discovery of Novel Antibiotics
Curr Drug Targets. 2023 Dec 27. doi: 10.2174/0113894501274958231220053714. Online ahead of print.ABSTRACTAntimicrobial resistance (AMR) to currently available antibiotics/drugs is a global threat. It is desirable to develop new drugs that work through a novel target(s) to avoid drug resistance. This review discusses the potential of the caseinolytic protease P (ClpP) peptidase complex as a novel target for finding novel antibiotics, emphasising the ClpP's structure and function. ClpP contributes to the survival of bacteria via its ability to destroy misfolded or aggregated proteins. In consequence, its inhibition may lead ...
Source: Current Drug Targets - December 28, 2023 Category: Drugs & Pharmacology Authors: Smriti Bhardwaj Kuldeep K Roy Source Type: research
ClpP Peptidase as a Plausible Target for the Discovery of Novel Antibiotics
Curr Drug Targets. 2023 Dec 27. doi: 10.2174/0113894501274958231220053714. Online ahead of print.ABSTRACTAntimicrobial resistance (AMR) to currently available antibiotics/drugs is a global threat. It is desirable to develop new drugs that work through a novel target(s) to avoid drug resistance. This review discusses the potential of the caseinolytic protease P (ClpP) peptidase complex as a novel target for finding novel antibiotics, emphasising the ClpP's structure and function. ClpP contributes to the survival of bacteria via its ability to destroy misfolded or aggregated proteins. In consequence, its inhibition may lead ...
Source: Current Drug Targets - December 28, 2023 Category: Drugs & Pharmacology Authors: Smriti Bhardwaj Kuldeep K Roy Source Type: research
Diallyl disulfide synergizes with melphalan to increase apoptosis and DNA damage through elevation of reactive oxygen species in multiple myeloma cells
AbstractDiallyl disulfide (DADS), one of the main components of garlic, is well known to have anticancer effects on multiple cancers. However, its efficacy in treating multiple myeloma (MM) is yet to be determined. We explored the effects of DADS on MM cells and investigated the synergistic effects of DADS when combined with five anti-MM drugs, including melphalan, bortezomib, carfilzomib, doxorubicin, and lenalidomide. We analyzed cell viability, cell apoptosis, and DNA damage to determine the efficacy of DADS and the drug combinations. Our findings revealed that DADS induces apoptosis in MM cells through the mitochondria...
Source: Annals of Hematology - December 27, 2023 Category: Hematology Source Type: research
Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells
AbstractPseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30 ...
Source: Human Cell - December 25, 2023 Category: Cytology Source Type: research
Cancers, Vol. 16, Pages 84: Epigenetic Alterations as Vital Aspects of Bortezomib Molecular Action
liński
Bortezomib (BTZ) is widely implemented in the treatment of multiple myeloma (MM). Its main mechanism of action is very well established. BTZ selectively and reversibly inhibits the 26S proteasome. More precisely, it interacts with the chymotryptic site of the 20S proteasome and therefore inhibits the degradation of proteins. This results in the intracellular accumulation of misfolded or otherwise defective proteins leading to growth inhibition and apoptosis. As well as interfering with the ubiquitin–proteasome complex, BTZ elicits various epigenetic alterations which contribute to its cytotoxic ef...
Source: Cancers - December 23, 2023 Category: Cancer & Oncology Authors: Piotr Kulig Karolina Łuczkowska Estera Bakinowska Bart łomiej Baumert Bogus ław Machaliński Tags: Review Source Type: research
Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma
Haematologica. 2023 Dec 21. doi: 10.3324/haematol.2023.283467. Online ahead of print.ABSTRACTREIIBP is a lysine methyltransferase aberrantly expressed through alternative promoter usage of NSD2 locus in t(4;14)-translocated multiple myeloma (MM). Clinically, t(4;14) translocation is an adverse prognostic factor found in approximately 15% of MM patients. The contribution of REIIBP relative to other NSD2 isoforms as a dependency gene in t(4;14)-translocated MM remains to be evaluated. Here, we demonstrated that despite homology with NSD2, REIIBP displayed distinct substrate specificity by preferentially catalyzing H3K4me3 an...
Source: Haematologica - December 21, 2023 Category: Hematology Authors: Phyllis S Y Chong Jing Yuan Chooi Sze Lynn Julia Lim Tae-Hoon Chung Reinhard Brunmeir Aaron Chung Yong Leow Sabrina Hui Min Toh Kalpnaa Balan Muhamad Irfan Bin Azaman Zhengwei Wu Nagavidya Subramaniam Leah A Vardy Wee-Joo Chng Source Type: research
Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma
Haematologica. 2023 Dec 21. doi: 10.3324/haematol.2023.283467. Online ahead of print.ABSTRACTREIIBP is a lysine methyltransferase aberrantly expressed through alternative promoter usage of NSD2 locus in t(4;14)-translocated multiple myeloma (MM). Clinically, t(4;14) translocation is an adverse prognostic factor found in approximately 15% of MM patients. The contribution of REIIBP relative to other NSD2 isoforms as a dependency gene in t(4;14)-translocated MM remains to be evaluated. Here, we demonstrated that despite homology with NSD2, REIIBP displayed distinct substrate specificity by preferentially catalyzing H3K4me3 an...
Source: Haematologica - December 21, 2023 Category: Hematology Authors: Phyllis S Y Chong Jing Yuan Chooi Sze Lynn Julia Lim Tae-Hoon Chung Reinhard Brunmeir Aaron Chung Yong Leow Sabrina Hui Min Toh Kalpnaa Balan Muhamad Irfan Bin Azaman Zhengwei Wu Nagavidya Subramaniam Leah A Vardy Wee-Joo Chng Source Type: research
Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma
Haematologica. 2023 Dec 21. doi: 10.3324/haematol.2023.283467. Online ahead of print.ABSTRACTREIIBP is a lysine methyltransferase aberrantly expressed through alternative promoter usage of NSD2 locus in t(4;14)-translocated multiple myeloma (MM). Clinically, t(4;14) translocation is an adverse prognostic factor found in approximately 15% of MM patients. The contribution of REIIBP relative to other NSD2 isoforms as a dependency gene in t(4;14)-translocated MM remains to be evaluated. Here, we demonstrated that despite homology with NSD2, REIIBP displayed distinct substrate specificity by preferentially catalyzing H3K4me3 an...
Source: Haematologica - December 21, 2023 Category: Hematology Authors: Phyllis S Y Chong Jing Yuan Chooi Sze Lynn Julia Lim Tae-Hoon Chung Reinhard Brunmeir Aaron Chung Yong Leow Sabrina Hui Min Toh Kalpnaa Balan Muhamad Irfan Bin Azaman Zhengwei Wu Nagavidya Subramaniam Leah A Vardy Wee-Joo Chng Source Type: research
Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma
Haematologica. 2023 Dec 21. doi: 10.3324/haematol.2023.283467. Online ahead of print.ABSTRACTREIIBP is a lysine methyltransferase aberrantly expressed through alternative promoter usage of NSD2 locus in t(4;14)-translocated multiple myeloma (MM). Clinically, t(4;14) translocation is an adverse prognostic factor found in approximately 15% of MM patients. The contribution of REIIBP relative to other NSD2 isoforms as a dependency gene in t(4;14)-translocated MM remains to be evaluated. Here, we demonstrated that despite homology with NSD2, REIIBP displayed distinct substrate specificity by preferentially catalyzing H3K4me3 an...
Source: Haematologica - December 21, 2023 Category: Hematology Authors: Phyllis S Y Chong Jing Yuan Chooi Sze Lynn Julia Lim Tae-Hoon Chung Reinhard Brunmeir Aaron Chung Yong Leow Sabrina Hui Min Toh Kalpnaa Balan Muhamad Irfan Bin Azaman Zhengwei Wu Nagavidya Subramaniam Leah A Vardy Wee-Joo Chng Source Type: research
Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma
Haematologica. 2023 Dec 21. doi: 10.3324/haematol.2023.283467. Online ahead of print.ABSTRACTREIIBP is a lysine methyltransferase aberrantly expressed through alternative promoter usage of NSD2 locus in t(4;14)-translocated multiple myeloma (MM). Clinically, t(4;14) translocation is an adverse prognostic factor found in approximately 15% of MM patients. The contribution of REIIBP relative to other NSD2 isoforms as a dependency gene in t(4;14)-translocated MM remains to be evaluated. Here, we demonstrated that despite homology with NSD2, REIIBP displayed distinct substrate specificity by preferentially catalyzing H3K4me3 an...
Source: Haematologica - December 21, 2023 Category: Hematology Authors: Phyllis S Y Chong Jing Yuan Chooi Sze Lynn Julia Lim Tae-Hoon Chung Reinhard Brunmeir Aaron Chung Yong Leow Sabrina Hui Min Toh Kalpnaa Balan Muhamad Irfan Bin Azaman Zhengwei Wu Nagavidya Subramaniam Leah A Vardy Wee-Joo Chng Source Type: research
Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma
Haematologica. 2023 Dec 21. doi: 10.3324/haematol.2023.283467. Online ahead of print.ABSTRACTREIIBP is a lysine methyltransferase aberrantly expressed through alternative promoter usage of NSD2 locus in t(4;14)-translocated multiple myeloma (MM). Clinically, t(4;14) translocation is an adverse prognostic factor found in approximately 15% of MM patients. The contribution of REIIBP relative to other NSD2 isoforms as a dependency gene in t(4;14)-translocated MM remains to be evaluated. Here, we demonstrated that despite homology with NSD2, REIIBP displayed distinct substrate specificity by preferentially catalyzing H3K4me3 an...
Source: Haematologica - December 21, 2023 Category: Hematology Authors: Phyllis S Y Chong Jing Yuan Chooi Sze Lynn Julia Lim Tae-Hoon Chung Reinhard Brunmeir Aaron Chung Yong Leow Sabrina Hui Min Toh Kalpnaa Balan Muhamad Irfan Bin Azaman Zhengwei Wu Nagavidya Subramaniam Leah A Vardy Wee-Joo Chng Source Type: research
Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma
This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and...
Source: Cell Metabolism - December 19, 2023 Category: Cytology Authors: Yinghong Zhu Xingxing Jian Shuping Chen Gang An Duanfeng Jiang Qin Yang Jingyu Zhang Jian Hu Yi Qiu Xiangling Feng Jiaojiao Guo Xun Chen Zhengjiang Li Ruiqi Zhou Cong Hu Nihan He Fangming Shi Siqing Huang Hong Liu Xin Li Lu Xie Yan Zhu Lia Zhao Yichuan Ji Source Type: research
Contribution of post-transplantation therapy to sustained MRD negativity in multiple myeloma: a retrospective analysis
In conclusion, post-transplantation therapy improved PFS and contributed to sustained MRD-negativity in myeloma patients.PMID:38103160 | DOI:10.1007/s12185-023-03682-z (Source: International Journal of Hematology)
Source: International Journal of Hematology - December 16, 2023 Category: Hematology Authors: Kazuhito Suzuki Tadahiro Gunji Masaharu Kawashima Hideki Uryu Riku Nagao Mamiko Momoki Hiroki Yokoyama Hiroto Ishii Susumu Tanoue Takeshi Saito Kaichi Nishiwaki Shingo Yano Source Type: research
Contribution of post-transplantation therapy to sustained MRD negativity in multiple myeloma: a retrospective analysis
In conclusion, post-transplantation therapy improved PFS and contributed to sustained MRD-negativity in myeloma patients.PMID:38103160 | DOI:10.1007/s12185-023-03682-z (Source: International Journal of Hematology)
Source: International Journal of Hematology - December 16, 2023 Category: Hematology Authors: Kazuhito Suzuki Tadahiro Gunji Masaharu Kawashima Hideki Uryu Riku Nagao Mamiko Momoki Hiroki Yokoyama Hiroto Ishii Susumu Tanoue Takeshi Saito Kaichi Nishiwaki Shingo Yano Source Type: research
Contribution of post-transplantation therapy to sustained MRD negativity in multiple myeloma: a retrospective analysis
In conclusion, post-transplantation therapy improved PFS and contributed to sustained MRD-negativity in myeloma patients.PMID:38103160 | DOI:10.1007/s12185-023-03682-z (Source: International Journal of Hematology)
Source: International Journal of Hematology - December 16, 2023 Category: Hematology Authors: Kazuhito Suzuki Tadahiro Gunji Masaharu Kawashima Hideki Uryu Riku Nagao Mamiko Momoki Hiroki Yokoyama Hiroto Ishii Susumu Tanoue Takeshi Saito Kaichi Nishiwaki Shingo Yano Source Type: research
