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Coelenterazine-Dependent Luciferases as a Powerful Analytical Tool for Research and Biomedical Applications.
Krasitskaya, VV, Bashmakova, EE, Frank, LA
International journal of molecular sciences. 2020;(20)
Abstract
: The functioning of bioluminescent systems in most of the known marine organisms is based on the oxidation reaction of the same substrate-coelenterazine (CTZ), catalyzed by luciferase. Despite the diversity in structures and the functioning mechanisms, these enzymes can be united into a common group called CTZ-dependent luciferases. Among these, there are two sharply different types of the system organization-Ca2+-regulated photoproteins and luciferases themselves that function in accordance with the classical enzyme-substrate kinetics. Along with deep and comprehensive fundamental research on these systems, approaches and methods of their practical use as highly sensitive reporters in analytics have been developed. The research aiming at the creation of artificial luciferases and synthetic CTZ analogues with new unique properties has led to the development of new experimental analytical methods based on them. The commercial availability of many ready-to-use assay systems based on CTZ-dependent luciferases is also important when choosing them by first-time-users. The development of analytical methods based on these bioluminescent systems is currently booming. The bioluminescent systems under consideration were successfully applied in various biological research areas, which confirms them to be a powerful analytical tool. In this review, we consider the main directions, results, and achievements in research involving these luciferases.
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2.
Novel tyrosine-kinase inhibitors for the treatment of chronic myeloid leukemia: safety and efficacy.
Massaro, F, Colafigli, G, Molica, M, Breccia, M
Expert review of hematology. 2018;(4):301-306
Abstract
Chronic myeloid leukemia (CML) is characterized by a pathognomonic chromosomal translocation, which leads to the fusion of breakpoint cluster region (BCR) and Abelson leukemia virus 1 (ABL1) genes, generating an oncoprotein with deregulated tyrosine kinase activity. Areas covered: In the last two decades, BCR/ABL1 kinase has become the molecular target for tyrosine kinase inhibitors (TKIs), a class of drugs that impressively improved overall survival. Despite these results, a proportion of patients experiences resistance to TKIs and need to change treatment. Furthermore, TKIs are unable to eradicate leukemic stem cells, allowing the persistence of neoplastic clones. Therefore, there is still clinical need for new agents to overcome common resistance mechanisms to available drugs. This review explores the horizon of drugs actually under investigation for CML patients resistant to conventional treatment. Expert commentary: Radotinib is an ATP-competitive TKI that showed significant activity also in front-line setting and could find employment indications in CML. Asciminib, an allosteric ABL1 inhibitor, could demonstrate a higher capacity in overcoming common TKIs resistant mutations, including T315I, but clinical findings are needed. CML stem cell target will probably require new therapeutic strategies: combinations of several compounds acting with different mechanisms of action are actually under investigation.
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Review of empagliflozin monotherapy for previously untreated patients with type 2 diabetes mellitus: Comparison with sitagliptin.
Cornell, S
Postgraduate medicine. 2015;(3):277-81
Abstract
This Practice Pearl provides a review and brief commentary of the 24-week, double-blind, parallel-group, randomized, Phase III study by Roden et al., which assessed the efficacy and safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin, 10 mg or 25 mg as monotherapy, versus placebo and the dipeptidyl peptidase-4 inhibitor sitagliptin, in previously untreated patients with type 2 diabetes mellitus (T2DM). Compared to placebo, empagliflozin improved glycemic control, with additional benefits on bodyweight and systolic blood pressure, versus placebo and sitagliptin. Treatment was well tolerated. The authors concluded that empagliflozin is a potential new approach to treat patients with T2DM who are inadequately controlled with diet and exercise alone. This paper advances our understanding of empagliflozin, which so far, appears to be a promising therapeutic option for the management of patients with T2DM.
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Successful treatment of severe immune hemolytic anemia after allogeneic stem cell transplantation with bortezomib: report of a case and review of literature.
Hosoba, S, Jaye, DL, Cohen, C, Roback, JD, Waller, EK
Transfusion. 2015;(2):259-64
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Abstract
BACKGROUND Immune hemolytic anemia is a well-known complication after allogeneic hematopoietic stem cell transplantation (HSCT). Posttransplant hemolytic anemia results in increased red blood cell transfusions and medical sequelae including iron overload. CASE REPORT We present a case report of immune hemolytic anemia that occurred after allogeneic HSCT from an ABO major-mismatched, HLA-matched unrelated donor. The patient had high anti-donor A type antibodies that were unresponsive to treatment with steroids and rituximab, resulting in persistent transfusion dependence. A detailed time course of anti-A titers, plasma cell content of the marrow, and B-cell content of the blood is presented. Treatment with bortezomib, a protease inhibitor, eliminated residual host-type plasma cells secreting anti-A and restored normal donor-derived erythropoiesis. CONCLUSION This report, and a review of literature for treatment of immune hemolytic anemia after allogeneic HSCT, supports the utility of bortezomib as plasma cell-targeted therapy in this setting.
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5.
[New drugs; exenatide and sitagliptin].
van Bronswijk, H, Dubois, EA, Pijl, H, Cohen, AF
Nederlands tijdschrift voor geneeskunde. 2008;(15):876-9
Abstract
Incretin hormones, secreted upon food intake, play an important role in the regulation of blood glucose levels. In type 2 diabetes mellitus, the incretin response is decreased. Substitution of incretin is a novel pharmacological target which restores postprandial glucose homeostasis. Exenatide is a mimetic of the incretin glucagon-like peptide-I (GLP-I). Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4 (DPP-4), which breaks down GLP-I. Both drugs increase the GLP-I concentration, thereby improving insulin secretion from pancreatic p cells, restoring glycaemic control, preventing beta cell destruction, delaying gastric emptying, and reducing food intake.
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6.
Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature.
Argyriou, AA, Iconomou, G, Kalofonos, HP
Blood. 2008;(5):1593-9
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Abstract
Bortezomib has demonstrated significant activity in clinical trials, mainly against recurrent or newly diagnosed multiple myeloma (MM). Peripheral neuropathy is a significant toxicity of bortezomib, requiring dose modification and potential changes in the treatment plan when it occurs. The mechanism underlying bortezomib-induced peripheral neuropathy (BIPN) is unknown. Metabolic changes resulting from the accumulation of bortezomib in the dorsal root ganglia cells, mitochondrial-mediated disregulation of Ca(++) homeostasis, and disregulation of neurotrophins may contribute to the pathogenesis of BIPN. It is increasingly recognized that BIPN may be a proteasome inhibitor class effect, producing primarily a small fiber and painful, axonal, sensory distal neuropathy. Incidence of BIPN is mainly related to various risk factors, including cumulative dose and evidence of preexisting neuropathy. Assessment of BIPN is based primarily on neurologic clinical examination and neurophysiologic methods. To date, apart from the use of dose reduction and schedule change algorithm, there is no effective treatment with neuroprotective agents for BIPN. Analgesics, tricyclic antidepressants, anticonvulsants, and vitamin supplements have been used as symptomatic treatment against bortezomib-associated neuropathic pain with some success. This review looks critically at the pathogenesis, incidence, risk factors, diagnosis, characteristics, and management of BIPN, and highlights areas for future research.
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7.
[Molecular targeting therapy for multiple myeloma].
Takatoku, M
Nihon rinsho. Japanese journal of clinical medicine. 2007;(12):2345-50
Abstract
Molecular target therapy is the most progressive and promising anticancer therapy in last decade. Multiple myeloma is also one of the major therapeutic targets for using molecular based technology. The recent availability of clinical data regarding thalidomide-, lenalidomide-, and bortezomib-based regimens has provided new, effective treatment options for patients with both newly diagnosed and relapsed/refractory multiple myeloma. We are expecting that future clinical trials can be designed to achieve a high likelihood of success based on molecular studies, cell-signaling, and correlative science studies. Studies with these agents also provide new insight into the cancer biology underlying multiple myeloma in humans.
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[Progress of the study on effective integredients from Chinese herbal medicine in anti-tumor metastasis].
Wang, X, Ling, CQ
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2004;(2):178-81
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9.
[Development of bladder cancer chemoprevention].
Dai, G, Wang, X
Wei sheng yan jiu = Journal of hygiene research. 2003;(2):159-62
Abstract
Bladder cancer is one of the most common malignant tumor. The morbidity increased every year because of high recurrence. It is widely accepted that prevention may be the effective way to decrease the rate of recurrence and morbidity. Being the biological mechanism of bladder cancer lucubrated, several biomarkers and chemopreventive agents were discovered for the detection and prevention, and even reversion of the precancerous lesion. In this paper, the progress in bladder cancer chemoprevention was reviewed.
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10.
Nontraditional cytotoxic therapies for relapsed/refractory multiple myeloma.
Hussein, MA
The oncologist. 2002;:20-9
Abstract
Multiple myeloma remains an incurable disease, with median survival rates of 4-6 years even with aggressive, high-dose chemotherapy, bone marrow transplantation, and intensive supportive care. Additionally, multiple myeloma is primarily a disease of the elderly, many of whom cannot tolerate aggressive chemotherapy. Thus, newer treatments with good safety profiles are needed to improve the quality of responses and, hopefully, to translate into prolonged progression and overall survival. The pathophysiology of multiple myeloma is complex, involving many pathways and interactions among cytokines, adhesion molecules, angiogenesis, and mechanisms of resistance, which, taken together, provide multiple targets for novel therapeutic modalities. Agents currently under investigation for treating multiple myeloma include thalidomide and its successors, PS-341, and arsenic trioxide. Thalidomide and immunomodulatory drugs both exhibit activity against multiple myeloma by affecting different levels of the immune system. PS-341 is a proteasome inhibitor that halts the cell cycle, resulting in apoptosis; it also inhibits a key transcription factor and may have antiangiogenic activity. Arsenic trioxide activates multicellular mechanisms to induce apoptosis, inhibit angiogenesis, and stimulate immune responses. Preclinical and early clinical data suggest that combination regimens should be pursued, given the different mechanisms of action of these compounds on the immune system and their non-overlapping toxicities at low dosages.