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MYC inhibitors in multiple myeloma

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Cancer Drug Resistance 2021年第4期4卷 842-865页

作者： sandra martínez-martín Laura Soucek Preclinical&Translational Research Program Vall d’Hebron Institute of Oncology(VHIO)Vall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Peptomyc S.L. Vall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Department of Biochemistry and Molecular Biology Universitat Autònoma de BarcelonaBellaterra 08193Spain InstitucióCatalana de Recerca i Estudis Avançats(ICREA) Barcelona 08010Spain

The importance of MYC function in cancer was discovered in the late 1970s when the sequence of the avian retrovirus that causes myelocytic leukemia was identified.Since then,over 40 years of unceasing research have highlighted the significance of this protein in malignant transformation,especially in hematologic diseases.Indeed,some of the earliest connections among the higher expression of proto-oncogenes(such as MYC),genetic rearrangements and their relation to cancer development were made in Burkitt lymphoma,chronic myeloid leukemia and mouse plasmacytomas.Multiple myeloma(MM),in particular,is a plasma cell malignancy strictly associated with MYC deregulation,suggesting that therapeutic strategies against it would be beneficial in treating this disease.However,targeting MYC was-and,somehow,still is-challenging due to its unique properties:lack of defined three-dimensional structure,nuclear localization and absence of a targetable enzymatic pocket.Despite these difficulties,however,many studies have shown the potential therapeutic impact of direct or indirect MYC inhibition.Different molecules have been tested,in fact,in the context of MM.In this review,we summarize the current status of the different compounds,including the results of their clinical testing,and propose to continue with the efforts to identify,repurpose,redesign or improve drug candidates to combine them with standard of care therapies to overcome resistance and enable better management of myeloma treatment.

关键词： MYC inhibition multiple myeloma undruggable target targeted therapies transcription factor epigenetics MYC downregulation

Recent Advances in Single-Cell Metabolomics Based on Mass Spectrometry

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CCS Chemistry 2023年第2期5卷 310-324页

作者： Qinlei Liu sandra martínez-Jarquín Renato Zenobi Department of Chemistry and Applied Biosciences ETH ZurichCH-8093 Zurich

Cellular heterogeneity is essential for the physiological functions of organisms,and precise interpretation of the relevant biological mechanisms involved requires accurate measurement of biomolecules,including DnA,RnA,proteins,and metabolites at the single-cell level.Cellular metabolites react most rapidly to environmental and biochemical changes such that their detection is a critical step in determining the physiological state of cells.However,their limited amounts,structural diversity,and significant content variation render single-cell metabolomics analysis technically challenging.Mass spectrometry,with its high sensitivity,good selectivity,and wide dynamic range,has been widely used in the single-cell analysis in recent years.In terms of ionization techniques,there are four main types of single-cell mass spectrometry methods:nano-electrospray ionization mass spectrometry,matrix-assisted laser desorption/ionization mass spectrometry,secondary ion mass spectrometry,and dielectric barrier discharge ionization mass spectrometry.In this mini review,the progress of single-cellmass spectrometrymethodologies and data processing strategies are summarized,and the future trends in single-cell mass spectrometry are outlined.

关键词： single-cell analysis metabolomics mass spectrometry ionization techniques analytical methods

Role of joint aspiration before re-implantation in patients with a cement spacer in place

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World Journal of Orthopedics 2022年第6期13卷 615-621页

作者： sandra Huguet martíBernaus Lucía Gómez Eva Cuchí Alex Soriano Lluís Font-Vizcarra Department of Traumatology and Orthopaedics Hospital Universitari Mútua TerrassaTerrassa 08221Spain Department of Traumatology and Orthopaedics Consorci Sanitari de l’Alt Penedès-GarrafVilafranca del Penedès 08720Spain Department of Traumatology and Orthopaedics Osteoarticular Infections UnitHospital Universitari Mútua TerrassaTerrassa 08221Spain Osteoarticular Infections Unit Hospital Universitari Mútua TerrassaTerrassa 08221Spain Department of Microbiology CATLABViladecavalls 08232Spain Department of Infectious Diseases Osteoarticular Infections UnitHospital ClínicBarcelona 08036Spain

BACKGROUnD The usefulness of a mandatory joint aspiration before re-implantation in patients with a cement spacer already in place is unclear.AIM To evaluate the role of culturing synovial fluid obtained by joint aspiration before re-implantation in patients who underwent a two-stage septic revision.METHODS A retrospective observational study was conducted,including patients that underwent a two-stage septic revision(hip or knee)from 2010 to 2017.After the first stage revision and according to intraoperative culture results,all patients were treated with an antibiotic protocol for 6-8 wk.Following 2 wk without antibiotics,a culture of synovial fluid was obtained.The results of these cultures were recorded and compared with cultures obtained during re-implantation surgery.RESULTS Forty-one patients(20 hip and 21 knee spacers)were included in the final analysis.In 39 cases,the culture of synovial fluid was negative,while in the remaining 2 cases(knee spacers)no analysis was possible due to dry tap.In 5 of the patients,two or more intraoperative cultures taken during the re-implantation surgery were positive.COnCLUSIOn We found no evidence to support mandatory joint aspiration before re-implantation in patients with a cement spacer in place.

关键词： Joint aspiration Synovial fluid Two-stage surgery Revision surgery Periprosthetic joint infection

miR-99a-5p modulates doxorubicin resistance via the COX-2/ABCG2 axis in triple-negative breast cancer: from the discovery to in vivo studies

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Cancer Communications 2022年第12期42卷 1412-1416页

作者： Iris Garrido-Cano Anna Adam-Artigues Ana Lameirinhas Juan F.Blandez Vicente Candela-noguera Federico Rojo sandra Zazo Juan Madoz-Gúrpide Ana Lluch Begoña Bermejo Felix Sancenón Juan Miguel Cejalvo Ramón martínez-Mañez Pilar Eroles Biomedical Research Institute InCLIVA Valencia 46010Spain Bioengineering Biomaterials and Nanomedicine Networking Biomedical Research Centre(CIBER-BBN)Madrid 28029Spain Interuniversity Research Institute for Molecular Recognition and Technological Development(IDM) Polytechnic University of ValenciaUniversity of ValenciaValencia 46010Spain Joint Unit CIPF-UPV of Mechanisms of Diseases and nanomedicine ValenciaPolytechnic University of ValenciaPrince Felipe Research CenterValencia 46012Spain Joint Research Unit in nanomedicine and Sensors Polytechnic University of ValenciaMedical Research Institute Hospital La FeValencia 46026Spain Biomedical Research networking Center in Oncology(CIBEROnC) Madrid 28029Spain Department of Pathology Fundación Jiménez Díaz University Hospital Health Research InstituteMadrid 28040Spain Department of Clinical Oncology University Clinical Hospital of ValenciaValencia 46010Spain Department of Medicine University of ValenciaValencia 46010Spain Department of Physiology University of ValenciaValencia 46010Spain

Dear Editor,Breast cancer(BC)is the most commonly diagnosed cancer and the fifth cause of cancer-related death worldwide[1].Despite the advances in BC targeted therapies,cytotoxic chemotherapy is still widely used[2].However,around 20%-30%of BC patients develop metastasis after treatment as a consequence of drug resistance[3].In this context,microRnAs have emerged as potential therapeutic targets to overcome therapy resistance[4].Therefore,we aimed to elucidate the molecular mechanisms underlying resistance to doxorubicin,one of the most effective chemotherapeutic agents used in BC.Methods are detailed in Supplementary Materials.

关键词： doxorubicin ABCG2 chemotherapy

Sarcoma stratification by combined pH2AX and MAP17(PDZK1IP1)levels for a better outcome on doxorubicin plus olaparib treatment

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Signal Transduction and Targeted Therapy 2020年第1期5卷 697-709页

作者： Marco Perez JoséManuel García-Heredia Blanca Felipe-Abrio sandra Muñoz-Galván Javier martín-Broto Amancio Carnero Instituto de Biomedicina de Sevilla(IBIS) Hospital Universitario Virgen del RocíoUniversidad de SevillaConsejo Superior de Investigaciones CientíficasSevillaSpain Ciber de Cancer IS Carlos IIIMadridSpain Departamento de Bioquímica Vegetal y Biología Molecular Universidad de SevillaSevillaSpain Departamento de Anatomía Patológica Hospital Universitario Virgen del RocíoSevillaSpain

Sarcomas constitute a rare heterogeneous group of tumors,including a wide variety of histological subtypes.Despite advances in our understanding of the pathophysiology of the disease,first-line sarcoma treatment options are still limited and new treatment approaches are needed.Histone H2AX phosphorylation is a sensitive marker for double strand breaks and has recently emerged as biomarker of DnA damage for new drug development.In this study,we explored the role of H2AX phosphorylation at Ser139 alone or in combination with MAP17 protein,an inducer of DnA damage through ROS increase,as prognostic biomarkers in sarcoma tumors.next,we proposed doxorubicin and olaparib combination as potential therapeutic strategies against sarcomas displaying high level of both markers.We evaluate retrospectively the levels of pH2AX(Ser139)and MAP17 in a cohort of 69 patients with different sarcoma types and its relationship with clinical and pathological features.We found that the levels of pH2AX and MAP17 were related to clinical features and poor survival.next,we pursued PARP1 inhibition with olaparib to potentiate the antitumor effect of DnA damaging effect of the DnA damaging agent doxorubicin to achieve an optimal synergy in sarcoma.We demonstrated that the combination of olaparib and doxorubicin was synergistic in vitro,inhibiting cell proliferation and enhancing pH2AX intranuclear accumulation,as a result of DnA damage.The synergism was corroborated in patient-derived xenografts(PDX)where the combination was effective in tumors with high levels of pH2AX and MAP17,suggesting that both biomarkers might potentially identify patients who better benefit from this combined therapy.

关键词： H2AX doxorubicin treatment

Ant Species Richness Variation Mediated by Seasonality in Two Ant-Acacias from Oaxaca, Mexico

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Open Journal of Ecology 2021年第1期11卷 24-31页

作者： sandra Luz Gómez-Acevedo Javier martínez-Toledo Unidad de Morfología y Función Facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de México Mexico City México

Climatic conditions affect the richness of ants resulting in number variation throughout the year. The ants present in the neotropical system Acacia-Pseudomyrmex have been previously studied considering only one sampling season. In contrast, in this study we analyze the richness in two ant-acacia systems during the rainy and dry seasons. The study was carried out on a plot located in the state of Oaxaca, Mexico where 14 ant species, 3 mutualistic and 11 non-mutualistic were found, of which 2 represent new records for the state. Ant species number differed between ant-acacia species and between seasons. The highest richness was recorded in Acacia hindsii in both rainy and dry seasons, corresponding with a low-reward host. During the dry season, A. hindsii represents a highly valuable resource. This study shows that the neotropical system is much more dynamic than it has been previously considered and offers a valuable opportunity for subsequent ecological studies for a better understanding of this complex system.

关键词： Dolichoderinae Formicinae Myrmicinae Pseudomyrmex

Effect of Slice Thickness Reconstruction on Quantitative Vascular Parameters in Perfusion CT

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Open Journal of Radiology 2014年第1期4卷 53-59页

作者： Anxo martínez-de-Alegría Roberto García-Figueiras sandra Baleato-González María José Rodriguez-Alvarez Iago martínez-Souto Carmen Villalba-martín Departments of Radiology Hospital Clínico Universitario Santiago de Compostela Spain General Electric Santiago de Compostela Spain Statistics Hospital Clínico Universitario Santiago de Compostela Spain

Objective: The purpose of this study was to determine how the slice thickness reconstruction influences quantitative perfusion CT parameters. Materials and Methods: Eighteen patients with cancer (15 non-small-cell lung cancer, 2 rectal cancer and 1 renal cancer) were examined prospectively with multidetector row CT. A 90-second perfusion study was performed after intravenous bolus injection of contrast material. Blood flow, blood volume, mean transit time and permeability-surface area product were determined at three different slice thickness reconstruction (1.25, 2.5 and 5 mms) both in tumors and in paraspinal muscle. Mean values, limits of agreement between measurements and within-subject coefficient of correlation were obtained for these thicknesses. Results: Mean ± standard deviation BF, BV, MTT and PS in lesions were 118.7 ± 117.9 mL/min/100g tissue, 8.2 ± 8.2 mL/100g tissue, 7.5 ± 5.4 seconds and 10.3 ± 7.2 mL/min/100g tissue respectively at1.25 mmslice thickness;116.1 ± 115.7 mL/min/100g tissue, 7.8 ± 8.7 mL/100g tissue, 7 ± 4.5 seconds and 10.4 ± 7.5 mL/min/100g tissue at 2.5 mms;and 119.6 ± 115.7 mL/min/100g tissue, 7.8 ± 8.8 mL/100g tissue, 5.4 ± 3.4 seconds and 9.6 ± 7.5 mL/min/100g tissue at 5 mms. Differences between means for different slice thickness where relatively small in all parameters (n MTT where difference was up to 37%. 95% limits of agreement were worse when comparing more different slice thicknesses (e.g. 1.25 vs 5 mms) than when comparing more close slice thicknesses (1.25 vs 2.5 mms or 2.5 vs 5 mms). Conclusions: There is a significant variability in perfusion parameter measurements at different slice thickness reconstruction, particularly in MTT. The more close together the slice thicknesses were, the smaller was the variability.

关键词： Tomography neoplasms Blood Supply Diagnostic Imaging

Expectations and Perspectives of Users with the Screening Program for Cervical Cancer

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Open Journal of nursing 2016年第8期6卷 565-572页

作者： Gutiérrez Enríquez sandra Olimpia Gaytán Hernández Darío martínez martínez Rosa Adriana Gallegos García Verónica Terán Figueroa Yolanda nursing Faculty Autonomic University of San Luis Potosí San Luis Potosí México

Objective: Evaluate user satisfaction before and after taking the Pap. Methodology: Observational and prospective study. It was carried out in two health centers in San Luis Potosicity, Mexico in 93 users which attended for a Pap test from February to June 2015. The satisfaction was assessed using multidimensional scaling SERVQUAL whit 5 dimensions to evaluate the quality of services in an organization: reliability, responsibility, security, empathy and touchable and materials goods (tangible elements). This scaling was obtained internal consistency by Cronbach’s alpha coefficient with a value of 0.74. For data analysis, nonparametric test Wilcoxon for related samples was used. Results: In all cases, perspective was less than expectancy where the means of the scores before attention (expectation) and after care (perspective) there was a statistically significant difference (p = 0.000). Before receiving care users had an expectation of 192.96 points, after care perspective score dropped to 184.49 points indicating that the care provided was not what they expected. The difference in scores was 8.47 points (p = 0.004). Conclusions: Users of the screening program for cervical cancer were unsatisfied because the attention was not what they expected. In most of the indicators studied, a high percentage of dissatisfaction was obtained.

关键词： Cervical Cancer Pap Smears Prevention and Control SERVQUAL

Peripheral Analgesic and Anti-Inflammatory Effects of Smilax canariensis in an Animal Model

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Pharmacology & Pharmacy 2015年第8期6卷 391-400页

作者： sandra Dévora Susana Abdala Domingo martín-Herrera Unidad de Farmacología y Farmacognosia Sección de Farmacia Universidad de La Laguna San Cristóbal de La Laguna Spain

Smilax canariensis Brouss. ex Willd. is an endemic plant of the Canary Islands. Its rhizomes, leaves and stems have been traditionally used in Canary folk medicine to treat a wide variety of conditions including pain. Our objective is to investigate the analgesic and anti-inflammatory activities of different extracts of S. canariensis in Swiss mice, using established biological models for pain and inflammation, such as phenylquinone writhing test, formalin test, tail-flick test and mouse paw edema induced by carrageenan. Oral administration of S. canariensis extracts significantly reduce writhing episodes evoked by phenylquinone injection in a dose-dependent manner;and higher doses result in a reduction of pain similar to or higher than that of the reference drug piroxicam (59.56%;p ndent inhibition of for-malin-induced pain in the second phase but only minimal inhibition of tail-flick behavior, suggesting that S. canariensis is not a centrally acting analgesic. Finally, in the carrageenan-induced hind paw edema model, the extracts show a moderate anti-inflammatory effect, the most active being the ethyl acetate fraction at 200 mg/kg p.o. (33.33%;p nariensis extracts have clear dose-dependent peripheral analgesic effects, which lends support to the traditional use of this medicinal plant to treat pain associated with inflammatory or other processes.

关键词： Smilax canariensis Smilacaceae Medicinal Plant Folk Medicine Analgesic Activity Anti-Inflammatory Activity