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Brigatinib и Alectinib for ALK Restruction-Positive Under-Spective Meta-Analysis с центральной нервной системой или без нее.

На сегодняшний день ни одно из испытаний не сравнивало эффективность бригатиниба и алектиниба с анапластической лимфатической киназой (АЛК) реструктуризацией положительной (ALK-p), АЛК-инбитор-наив, передовым раком легких немалых клеток (NSCLC) с метастазом центральной нервной системы (CNS). Мы провели непрямое сопоставление между бригатинибом и алектинибом с использованием кризотиниба в качестве общего компаратора, используя байезскую модель с неинформационным предварительным распределением, и провели оценку неоднородности исследований между исследованиями. Основным конечным показателем эффек

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… Huang W.S., Liu S., Zou D., Thomas M., Wang Y., Zhou T., Romero J., Kohlmann A., Li F., Qi J., et al. Discovery of brigatinib (AP26113), a phosphine oxide-containing, potent, orally active inhibitor of anaplastic lymphoma kinase. J. Med. …

Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients.

Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, h

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… Pan T., Qi J., You T., Han S., Yang L., Miao W., Wu D., Ruan C., Zhu L., Han Y. Circulating Heme Oxygenase-1 and Complement Activation in Transplant-Associated Thrombotic Microangiopathy. Biol. Blood Marrow Transplant. J. Am. Soc. …

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy.

Multiple myeloma (MM) is an incurable malignancy of plasma cells with a clinical course characterized by multiple relapses and treatment refractoriness. While recent treatment advancements have extended overall survival (OS), refractory MM has a poor prognosis, with a median OS of between 4 and 6 months. Nuclear export inhibition, specifically inhibition of CRM1/XPO1, is an emerging novel treatment modality that has shown promise in treatment-refractory MM. Initially discovered in yeast in 1983, early clinical applications were met with significant toxicities that limited their utility. The cr

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… Wang J, Barve M, Chiorean E, LoRusso P, Courtney K, Qi D, et al. Interim results from trial of SL-801, a novel XPO-1 inhibitor, in patients with advanced solid tumours. Ann Oncol. 2019;30(Suppl 5):v175. 31. Kalid O, Warshaviak DT, Shechter S, Sherman W, Shacham S. …

COVID-19 Infections and Clinical Outcomes in Patients with Multiple Myeloma in New York City: A Cohort Study from Five Academic Centers.

Patients with multiple myeloma have a compromised immune system, due to both the disease and antimyeloma therapies, and may therefore be particularly susceptible to COVID-19. Here, we report outcomes and risk factors for serious disease in patients with multiple myeloma treated at five large academic centers in New York City in the spring of 2020, during which it was a global epicenter of the SARS-CoV-2 pandemic. Of 100 patients with multiple myeloma (male 58%; median age 68) diagnosed with COVID-19, 75 were admitted; of these, 13 patients (17%) were placed on invasive mechanical ventilation,

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… Pan An, Liu Li, Wang C, Guo H, Hao X, Wang Qi, et al. Association of public health interventions with the epidemiology of the COVID-19 outbreak in Wuhan, China. JAMA 2020;323:1–9. 36. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. …

Towards precision medicine: advances in 5-hydroxymethylcytosine cancer biomarker discovery in liquid biopsy.

Robust and clinically convenient biomarkers for cancer diagnosis, early detection, and prognosis have great potential to improve patient survival and are the key to precision medicine. The advent of next-generation sequencing technologies enables a more sensitive and comprehensive profiling of genetic and epigenetic information in tumor-derived materials. Researchers are now able to monitor the dynamics of tumorigenesis in new dimensions, such as using circulating cell-free DNA (cfDNA) and tumor DNA (ctDNA). Mutation-based assays in liquid biopsy cannot always provide consistent results across

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… Zhang J Han X Gao C Xing Y Qi Z Liu R 5-Hydroxymethylome in circulating cell-free DNA as A potential biomarker for non-small-cell lung cancer Genom Proteom Bioinf 2018 10.1016/j.gpb.2018.06.002 PMC6076378 30010036 86. …

AL Amyloidosis: Unfolding a Complex Disease.

Light chain (AL) amyloidosis is a rare plasma cell dyscrasia. An estimated 12,000 people live with the disease in the United States. AL amyloidosis occurs from the misfolding of proteins that deposit in organs (heart, kidneys, digestive tract, tongue, lungs, and nervous system), leading to progressive organ damage and impairment of quality of life. The treatment of AL amyloidosis has improved greatly over the past several years, with new treatments currently in development. This article will focus on the pathophysiology, diagnosis, and treatment of AL amyloidosis.

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… Palumbo A., Chanan-Khan A., Weisel K., Nooka A., Masszi T., Beksac M.,…Qi M. (2016). Dartaumumab, bortezomib, and dexamethasone for multiple myeloma. New England Journal of Medicine, 357, 754–766. 10.1056/NEJMoa1606038 Picken M. M., & Barton K. (2015). …

New Biomarkers of Ferric Management in Multiple Myeloma and Kidney Disease-Associated Anemia.

Multiple myeloma (MM) is a malignancy of clonal plasma cells accounting for approximately 10% of haematological malignancies. MM mainly affects older patients, more often males and is more frequently seen in African Americans. The most frequent manifestations of MM are anaemia, osteolytic bone lesions, kidney failure and hypercalcemia. The anaemia develops secondary to suppression of erythropoiesis by cytokine networks, similarly to the mechanism of anaemia of chronic disease. The concomitant presence of kidney failure, especially chronic kidney disease (CKD) and MM per se, leading to anaemia

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… Qi Y., Goel R., Kim S., Richards E.M., Carter C.S., Pepine C.J., Raizada M.K., Buford T.W. Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging. J. Am. Med. Dir. Assoc. 2017;18:810. doi: 10.1016/j.jamda.2017.05.018. 61. …

Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma.

The randomized phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with relapsed/refractory multiple myeloma after at least three but not more than six prior regimens, including at least bortezomib and lenalidomide or thalidomide. Patients were randomly assigned (2:1) to receive plitidepsin 5 mg/m2 on D1 and D15 plus DXM 40 mg on D1, D8, D15, and D22 (arm A, n = 171) or DXM 40 mg on D1, D8, D15, and D22 (arm B, n = 84) q4wk. The primary endpoint was progression-free survival (PFS). Median PFS without disease progression (PD) confirmation (IRC asse

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… Li Z Qi CF Shin DM Zingone A Newbery HJ Kovalchuk AL Abbott CM Morse HC 3rd Eef1a2 promotes cell growth, inhibits apoptosis and activates JAK/STAT and AKT signaling in mouse plasmacytomas PLoS One 2010 5 5 e10755 10.1371/journal.pone.0010755 20505761 PMC2873962 21. …

Hypocalcaemia in patients with prostate cancer treated with a bisphosphonate or denosumab: prevention supports treatment completion.

BackgroundMost patients with advanced prostate cancer develop bone metastases, which often result in painful and debilitating skeletal-related events. Inhibitors of bone resorption, such as bisphosphonates and denosumab, can each reduce the incidence of skeletal-related events and delay the progression of bone pain. However, these agents are associated with an increased risk of hypocalcaemia, which, although often mild and transient, can be serious and life-threatening. Here we provide practical advice on managing the risk of hypocalcaemia in patients with advanced prostate cancer who are rece

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… Qi WX, Lin F, He AN, Tang LN, Shen Z, Yao Y. Incidence and risk of denosumab-related hypocalcemia in cancer patients: a systematic review and pooled analysis of randomized controlled studies. Curr Med Res Opin. 2013;29(9):1067–1073. doi: 10.1185/03007995.2013.813840. 14. …

Incidence and risk factors of medical complications and direct medical costs after osteoporotic fracture among patients in China.

UNLABELLED: We analyzed the incidence of medical complications after osteoporotic fractures and estimated its risk factors and cost impacts. Osteoporotic fractures can result in lots of serious medical complications, which is associated with patients' baseline characteristics such as patients' disease history and significantly increased patients' direct medical costs. PURPOSE: The purpose of the study is to investigate the incidence and identify the risk factors of medical complications after osteoporotic fracture, and quantify patients' economic burden. METHODS: Data were obtained from the

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… Liu SY Dong HJ Pan J Qi JM Analysis of complications in hip fracture due to senile osteoporosis J Trauma Surg 2011 13 66 17. …

Identification of small molecules uncoupling the Notch::Jagged interaction through an integrated high-throughput screening.

Notch signaling plays an important role in several cellular functions including growth, differentiation, cell fate determination and stemness. Increased Notch activity has been linked to several types of cancers. Activation of Notch signaling is triggered by the interaction of Notch receptors (Notch1-4) with 5 different ligands (Jagged1-2 and Dll1-3-4) expressed on the neighbouring cells. Currently, indirect approaches to inhibit Notch signalling are based on the inhibition of the key step of Notch activation catalyzed by the γ-Secretase and thereby affect several different γ-Secretase substra

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… PLoS One 9 : e108747 doi: 10.1371/journal.pone.0108747 25314575 10.1371/journal.pone.0108747 PMC4196756 43 Yu HP , Qi ST , Feng WF , Zhang GZ , Zhang HP , et al ( 2015 ) Interference of Notch 2 inhibits the progression of gliomas and induces cell apoptosis by induction of the cell cycle at the G0/G1 …

Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis.

BACKGROUND: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS). Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS. METHODS: We analyzed the expression profiles of 1733 human mature miRNAs using microarray technology in leukocytes obtai

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… H., Valdez G., Moresi V., Qi X., McAnally J., Elliott J. L., et al. (2009). MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science 326, 1549–1554. 10.1126/science.1181046 Yang R., Huang R., Chen D., Song W., Zeng Y., Zhao B., et al. (2011). …

In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs) against multiple myeloma.

Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic strategies are urgently awaited. A rising body of evidence supports the notion that microRNAs (miRNAs), master regulators of eukaryotic gene expression, may exert anti-MM activity. Here, we evaluated the activity of synthetic miR-34a in MM cells. We found that transfection of miR-34a mimics in MM cells induces a significant change of gene expression with relevant effects on multiple signal transduction pathways. We detected early inactivation of pro-survival and proliferative kinases Erk-2 and Akt followed at later

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… Mol Cell 26 : 731 – 743 . 17540598 10.1016/j.molcel.2007.05.017 15 Chim CS , Wong KY , Qi Y , Loong F , Lam WL , et al ( 2010 ) Epigenetic inactivation of the miR-34a in hematological malignancies . …

Epigenetic therapy: use of agents targeting deacetylation and methylation in cancer management.

The emergence of epigenetic mechanisms as key regulators of gene expression has led to dramatic advances in understanding cancer biology. Driven by complex layers that include aberrant DNA methylation and histone modification, epigenetic aberrations have emerged as critical processes that disrupt cellular machinery and homeostasis. Recent discoveries have already translated into successful clinical trials and improved patient care, with several agents approved for hematologic disease and others undergoing study. As the field matures, substantial challenges persist that will require resolution.

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… and beyond Nat Biotechnol 2010 28 12 1259 1266 21139608 10.1038/nbt.1724 85 Yang Z He N Zhou Q Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression Mol Cell Biol 2008 28 3 967 976 18039861 10.1128/MCB.01020-07 PMC2223388 86 Filippakopoulos P Qi …

Revolutionizing in vivo therapy with CRISPR/Cas genome editing: breakthroughs, opportunities and challenges.

Genome editing using the CRISPR/Cas system has revolutionized the field of genetic engineering, offering unprecedented opportunities for therapeutic applications in vivo. Despite the numerous ongoing clinical trials focusing on ex vivo genome editing, recent studies emphasize the therapeutic promise of in vivo gene editing using CRISPR/Cas technology. However, it is worth noting that the complete attainment of the inherent capabilities of in vivo therapy in humans is yet to be accomplished. Before the full realization of in vivo therapeutic potential, it is crucial to achieve enhanced specific

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… The resulting nuclease-null mutants, known as dCas9 and dCas12a, can be fused to different effector domains for efficient transcriptional regulation, including CRISPR-mediated activation (CRISPRa) and inhibition (CRISPRi) ( Bikard et al., 2013 ; Qi et al., 2021 ). …

The roles of lncRNAs and miRNAs in pancreatic cancer: a focus on cancer development and progression and their roles as potential biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) is among the most penetrative malignancies affecting humans, with mounting incidence prevalence worldwide. This cancer is usually not diagnosed in the early stages. There is also no effective therapy against PDAC, and most patients have chemo-resistance. The combination of these factors causes PDAC to have a poor prognosis, and often patients do not live longer than six months. Because of the failure of conventional therapies, the identification of key biomarkers is crucial in the early diagnosis, treatment, and prognosis of pancreatic cancer. 65% of the

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… Carcinogenesis . ( 2018 ) 39 : 1016–25 . doi: 10.1093/carcin/bgy069 29796634 25 Wu C Yang L Qi X Wang T Li M Xu K . Inhibition of long non-coding RNA HOTAIR enhances radiosensitivity via regulating autophagy in pancreatic cancer . … Lab Invest . ( 2018 ) 98 : 814–24 . doi: 10.1038/s41374-018-0048-1 29581580 45 Yang J Qi M Fei X Wang X Wang K . LncRNA H19: A novel oncogene in multiple cancers . Int J Biol Sci . ( 2021 ) 17 : 3188 . doi: 10.7150/ijbs.62573 34421359 PMC8375239 46 Wang J Zhao L Shang K Liu F Che J Li H . …

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023.

With 54 new drugs and seven cellular and gene therapy products, the approvals by the US Food and Drug Administration (FDA) recovered 2023 from the 2022 dent back to the levels of 2020-2021. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition ("first-in-indication"), first drug using a novel molecular mechanism ("first-in-class"), and "next-in-class," i.e., a drug using an already exploited molecular mechanism. We identify four (7%) "first-in-indication," 22 (36%) "first-in-class," and 35 (57%) "next-in-class

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… Moreover, 60% of islet-transplanted diabetic patients maintained insulin independence 5 years post-transplant (Qi et al. 2014 ). For optimal efficacy, donislecel should be used in conjunction with immunosuppressive therapy initiated before the procedure and continued on a long-term basis. …

Liposomes for the Treatment of Brain Cancer-A Review.

Due to their biocompatibility, non-toxicity, and surface-conjugation capabilities, liposomes are effective nanocarriers that can encapsulate chemotherapeutic drugs and facilitate targeted delivery across the blood-brain barrier (BBB). Additionally, strategies have been explored to synthesize liposomes that respond to internal and/or external stimuli to release their payload controllably. Although research into liposomes for brain cancer treatment is still in its infancy, these systems have great potential to fundamentally change the drug delivery landscape. This review paper attempts to consol

Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) shows the opportunity to treat a diverse array of untreated various genetic and complicated disorders. Therapeutic genome editing processes that target disease-causing genes or mutant genes have been greatly accelerated in recent years as a consequence of improvements in sequence-specific nuclease technology. However, the therapeutic promise of genome editing has yet to be explored entirely, many challenges persist that increase the risk of further mutations. Here, we highlighted the main challenges fa

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… Kulikovskaya I, Gupta M, Chen F, Tian L, Gonzalez VE, Xu J, Jung IY, Melenhorst JJ, Plesa G, Shea J, Matlawski T, Cervini A, Gaymon AL, Desjardins S, Lamontagne A, Salas-Mckee J, Fesnak A, Siegel DL, Levine BL, Jadlowsky JK, Young RM, Chew A, Hwang WT, Hexner EO, Carreno BM, Nobles CL, Bushman FD, Parker KR, Qi … Liu H, Wei Z, Dominguez A, Li Y, Wang X, Qi LS. CRISPR-ERA: a comprehensive design tool for CRISPR-mediated gene editing, repression and activation. Bioinformatics. 2015;31(22):3676–8. doi: 10.1093/bioinformatics/btv423. 145. Zhu LJ, Holmes BR, Aronin N, Brodsky MH. …

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.

Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and