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Recent Advances in CAR-Based Solid Tumor Immunotherapy.

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in

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… Kwon M., Iacoboni G., Reguera J.L., Corral L.L., Morales R.H., Ortiz-Maldonado V., Guerreiro M., Caballero A.C., Domínguez M.L.G., Pina J.M.S., et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma. …

The influence of telehealth-based cancer rehabilitation interventions on disability: a systematic review.

PurposeTo characterize delivery features and explore effectiveness of telehealth-based cancer rehabilitation interventions that address disability in adult cancer survivors.MethodsA systematic review of electronic databases (CINAHL Plus, Cochrane Library: Database of Systematic Reviews, Embase, National Health Service's Health Technology Assessment, PubMed, Scopus, Web of Science) was conducted in December 2019 and updated in April 2021.ResultsSearches identified 3,499 unique studies. Sixty-eight studies met inclusion criteria. There were 81 unique interventions across included studies. Interv

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… Galiano-Castillo N, Arroyo-Morales M, Lozano-Lozano M, et al. Effect of an internet-based telehealth system on functional capacity and cognition in breast cancer survivors: a secondary analysis of a randomized controlled trial. …

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications.

Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves good response, life-threatening toxicities have been reported. Mechanistically, can be divided into two categories: (1) toxicities related to T-cell activation and release of high levels of cytokines: or (2) toxicities resulting from interaction between CAR and CAR targeted antigen expressed on non-malignant cells (i.e., on-target, off-tumor effec

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… Kwon M., Iacoboni G., Reguera J.L., Corral L.L., Morales R.H., Ortiz-Maldonado V., Guerreiro M., Caballero A.C., Domínguez M.L.G., Pina J.M.S., et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma. …

Machine Learning Approaches in Diagnosis, Prognosis and Treatment Selection of Cardiac Amyloidosis.

Cardiac amyloidosis is an uncommon restrictive cardiomyopathy featuring an unregulated amyloid protein deposition that impairs organic function. Early cardiac amyloidosis diagnosis is generally delayed by indistinguishable clinical findings of more frequent hypertrophic diseases. Furthermore, amyloidosis is divided into various groups, according to a generally accepted taxonomy, based on the proteins that make up the amyloid deposits; a careful differentiation between the various forms of amyloidosis is necessary to undertake an adequate therapeutic treatment. Thus, cardiac amyloidosis is thou

Mechanisms, Mediators, and Moderators of the Effects of Exercise on Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of neurotoxic antineoplastic agents commonly used to treat cancer. Patients with CIPN experience debilitating signs and symptoms, such as combinations of tingling, numbness, pain, and cramping in the hands and feet that inhibit their daily function. Among the limited prevention and treatment options for CIPN, exercise has emerged as a promising new intervention that has been investigated in approximately two dozen clinical trials to date. As additional studies test and suggest the efficacy of exercise in treating CIPN, it i

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… Chan A., Hertz D.L., Morales M., Adams E.J., Gordon S., Tan C.J., Staff N.P., Kamath J., Oh J., Shinde S., et al. Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview. Support. …

Recombinant Interferon-β in the Treatment of Polycythemia Vera and Related Neoplasms: Rationales and Perspectives.

About 30 years ago, the first clinical trials of the safety and efficacy of recombinant interferon-α2 (rIFN-α2) were performed. Since then, several single-arm studies have shown rIFN-α2 to be a highly potent anticancer agent against several cancer types. Unfortunately, however, a high toxicity profile in early studies with rIFN-α2 -among other reasons likely due to the high dosages being used-disqualified rIFN-α2, which was accordingly replaced with competitive drugs that might at first glance look more attractive to clinicians. Later, pegylated IFN-α2a (Pegasys) and pegylated IFN-α2b (PegIntr

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… Carrasco-Campos M.I., Pérez-Ramírez C., Macías-Cortés E., Puerta-García E., Sánchez-Pozo A., Arnal-García C., Barrero-Hernández F.J., Calleja-Hernández M.Á., Jiménez-Morales A., Cañadas-Garre M. Pharmacogenetic Predictors of Response to Interferon Beta Therapy in Multiple Sclerosis. Mol. …

Calcium Signalling in Breast Cancer Associated Bone Pain.

Calcium (Ca2+) is involved as a signalling mediator in a broad variety of physiological processes. Some of the fastest responses in human body like neuronal action potential firing, to the slowest gene transcriptional regulation processes are controlled by pathways involving calcium signalling. Under pathological conditions these mechanisms are also involved in tumoral cells reprogramming, resulting in the altered expression of genes associated with cell proliferation, metastatisation and homing to the secondary metastatic site. On the other hand, calcium exerts a central function in nocicepti

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… González-Ramírez R., Chen Y., Liedtke W.B., Morales-Lázaro S.L. TRP Channels and Pain. In: Emir T.L.R., editor. Neurobiology of TRP Channels. CRC Press/Taylor & Francis; Boca Raton, FL, USA: 2017. Frontiers in Neuroscience. 14. Hagenston A.M., Simonetti M. …

Nanoparticle-Based RNAi Therapeutics Targeting Cancer Stem Cells: Update and Prospective.

Cancer stem cells (CSCs) are characterized by intrinsic self-renewal and tumorigenic properties, and play important roles in tumor initiation, progression, and resistance to diverse forms of anticancer therapy. Accordingly, targeting signaling pathways that are critical for CSC maintenance and biofunctions, including the Wnt, Notch, Hippo, and Hedgehog signaling cascades, remains a promising therapeutic strategy in multiple cancer types. Furthermore, advances in various cancer omics approaches have largely increased our knowledge of the molecular basis of CSCs, and provided numerous novel targ

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… Morales F. Giordano A. Overview of CDK9 as a target in cancer research Cell Cycle Georget. Tex. 2016 15 519 527 10.1080/15384101.2016.1138186 26766294 PMC5056610 119. Jiao S. Wang H. Shi Z. Dong A. Zhang W. Song X. He F. Wang Y. Zhang Z. Wang W. …

Inequity in Cardio-Oncology: Identifying Disparities in Cardiotoxicity and Links to Cardiac and Cancer Outcomes.

Minority and underresourced communities experience disproportionately high rates of fatal cancer and cardiovascular disease. The intersection of these disparities within the multidisciplinary field of cardio-oncology is in critical need of examination, given the risk of perpetuating health inequities in the growing vulnerable population of patients with cancer and cardiovascular disease. This review identifies 13 cohort studies and 2 meta-analyses investigating disparate outcomes in treatment-associated cardiotoxicity and situates these data within the context of oncologic disparities, preexis

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… Am J Hematol . 2010 ; 85 : 894 – 896 . doi: 10.1002/ajh.21840 20872550 91 Bosch X , Rovira M , Sitges M , Domenech A , Ortiz‐Perez JT , de Caralt TM , Morales‐Ruiz M , Perea RJ , Monzo M , Esteve J . …

Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer.

Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆9-tetrahydrocannabinol (∆9-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-r

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… Muller C., Morales P., Reggio P.H. Cannabinoid Ligands Targeting TRP Channels. Front. Mol. Neurosci. 2018;11:487. doi: 10.3389/fnmol.2018.00487. 74. Im J.H., Kang K.W., Kim S.Y., Kim Y.G., An Y.J., Park S., Jeong B.H., Choi S.Y., Lee J.S., Kang K.W. …

Associations between chronic comorbidity and exacerbation risk in primary care patients with COPD.

BACKGROUND: COPD often coexists with chronic conditions that may influence disease prognosis. We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients. METHOD: Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices. Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes. Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, de

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… Garcia-Olmos L Alberquilla A Ayala V Garcia-Sagredo P Morales L Carmona M Comorbidity in patients with chronic obstructive pulmonary disease in family practice: a cross sectional study BMC Fam Pract 2013 14 11 10.1186/1471-2296-14-11 23324308 PMC3556139 9. …

Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures.

Chemotherapy and targeted therapy have opened new avenues in clinical oncology. However, there is a lack of response in a substantial percentage of cancer patients and diseases frequently relapse in those who even initially respond. Resistance is, at present, the major barrier to conquering cancer, the most lethal age-related pathology. Identification of mechanisms underlying resistance and development of effective strategies to circumvent treatment pitfalls thereby improving clinical outcomes remain overarching tasks for scientists and clinicians. Growing bodies of data indicate that stromal

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… Muranen T, Selfors LM, Worster DT, Iwanicki MP, Song L, Morales FC, Gao S, Mills GB, Brugge JS. Inhibition of PI3K/mTOR leads to adaptive resistance in matrix-attached cancer cells. Cancer Cell. 2012;21(2):227–239. doi: 10.1016/j.ccr.2011.12.024. 120. …

Clostridium butyricum alleviates multiple myeloma by remodeling the bone marrow microenvironment and inhibiting PI3K/AKT pathway through the gut‒bone axis.

Emerging evidence reveals a strong connection between the gut microbiota and cancer. However, the exact role of gut microbiota dysbiosis in multiple myeloma (MM) is poorly understood, and the therapeutic potential of microbiota-targeted interventions represents a promising strategy that demands urgent mechanistic and translational investigation. First, we conducted a comprehensive microbiome-metabolite analysis between MM patients and healthy individuals. The result revealed a marked compositional difference characterized by reduced abundances of butyrate-producing bacteria and diminished buty

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… Rodríguez-García A, Arroyo A, García-Vicente R, Morales ML, Gómez-Gordo R, Justo P, Cuéllar C, Sánchez-Pina J, López N, Alonso R, et al. Short-chain fatty acid production by gut microbiota predicts treatment response in multiple myeloma. …

Механистическая взаимосвязь между множественной миеломой и тяжелой SARS-CoV-2 Инфекция: терапевтическое обещание месенхимальных стволовых ячеек с внешней клеткой.

Пациенты с множественной миеломой (ММ) демонстрируют глубокое иммунное регулирование, предвосхищая их до тяжелых результатов после SARS-CoV-2 инфекция. Текущие данные свидетельствуют о наличии общих иммунопатологических механизмов, связывающих ММ и COVID-19, с уделением особого внимания interleukin-6 (В тыс.IL-6) ось как общий усилитель воспаления, а не как единственный движитель болезни. Для ММ характерна исходная провоспалительная среда, частично обусловленная: IL-6, которая еще больше усиливается в течение SARS-CoV-2 Инфекция, приводящая к эскалации цитокина, дополняет активацию, коагулопат

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… Lopes-Pacheco M., Silva P.L., Cruz F.F., Battaglini D., Robba C., Pelosi P., Morales M.M., Caruso Neves C., Rocco P.R.M. Pathogenesis of Multiple Organ Injury in COVID-19 and Potential Therapeutic Strategies. Front. Physiol. 2021;12:593223. doi: 10.3389/fphys.2021.593223. 83. …

Redesigning CAR therapy to tackle immune effector cell-associated hematotoxicity.

Although recognized, the field has yet to fully explore the mechanisms and solutions to Immune effector Cell-Associated Hematotoxicity (ICAHT) - a major contributor to long term morbidity and mortality following CAR therapy. About 20–40% of the patients develop ICAHT of grade 3 or above, with at least 33% developing late ICAHT across both CD28 and 4-1BB CAR. ICAHT post-CAR therapy influences the effectiveness of the subsequent treatment and incidence of secondary malignancies. Aside from CAR-HEMATOTOX model, N-ICAHT and T-ICAHT grading system is engaged to monitor the neutropenia and thrombocy

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… Morales-Mantilla DE, King KY (2018) The role of interferon-Gamma in hematopoietic stem cell development, homeostasis, and disease. Curr Stem Cell Rep 4:264–271 46. …

Липидированные мезофорные наночастицы, нагруженные тимокиноном, в качестве нового метода лечения аутоиммунного энцефаломиелита у крыс.

AIMS: Пересечение мозгового барьера (BBB) по-прежнему является серьезной проблемой для доставки терапевтических агентов в центральную нервную систему. Цель этого исследования состояла в том, чтобы оценить потенциал новых наноформуляционных силикатных силиканочастиц (MSN), покрытых липидным двуслойным слоем (LB), с тем чтобы повысить уровень доставки и потенциальное ремиелионирующее воздействие тимокинона (TQ). МЕТОДЫ: Составы характеризовались микроскопией передачи электронов и динамическим рассеиванием света для определения потенциала зета и размера частиц. Экспериментальная аутоиммунная энце

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… Ortega E, Blanco S, Ruiz A, Peinado MÁ, Peralta S, Morales ME. Lipid nanoparticles for the transport of drugs like dopamine through the blood-brain Barrier. J Nanopart Res. 2021;23(4):1–11. 10.1007/s11051-021-05218-0. 44. Pollak Y, Ovadia H, Goshen I, Gurevich R, Monsa K, Avitsur R, et al. …

Нацеливаюсь на гормональное лечение мозга в менопаузе.

Эстрогены являются нейрозащитными, и менопауза может способствовать нейродегенерации. Эстриол преимущественно связывает бета-рецептор эстрогена (ERβ) в мозге для обеспечения нейрозащиты. Ранее пероральный эстриол повышал скорость когнитивной обработки и уменьшил атрофию коры головного мозга в месяц лечения twelve в случае женщин с множественным склерозом (МС). В данном случае лечение с помощью волдыря, предназначенного для здоровых менопаузальных женщин, содержащих эстриол и прогестерон (Pearlpak), оценивалось с точки зрения его воздействия на когнитивные симптомы, характерные для домена, в ря

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… Tiwari-Woodruff, S., Morales, L. B., Lee, R. & Voskuhl, R. R. Differential neuroprotective and antiinflammatory effects of estrogen receptor (ER)alpha and ERbeta ligand treatment. Proc. Natl. Acad. Sci. U S A 104 , 14813–14818. 10.1073/pnas.0703783104 (2007). 52. Palaszynski, K. …

Adoptive immune cell therapy for colorectal cancer.

Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide, with limited options for patients at advanced stages. Immunotherapy, particularly immune cell-based therapies, has gained significant attention as an innovative approach for targeting CRC. This review summarizes the progress in various immune cell therapies, including DC vaccine, CAR/TCR-T cells, CAR-NK cells et al, each engineered to recognize and attack cancer cells expressing specific antigens. CAR-T cell therapy, which has been successful in hematologic cancers, faces challenges in CRC due to the

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… Palazón A, Martínez-Forero I, Teijeira A, Morales-Kastresana A, Alfaro C, Sanmamed MF, et al. The HIF-1α hypoxia response in tumor-infiltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy. Cancer Discov. (2012) 2:608–23. doi: 10.1158/2159-8290.CD-11-0314 135. …

HDACs in the Brain: From Chromatin Remodeling to Neurodegenerative Disease.

Histone deacetylases (HDACs) are key epigenetic regulators that influence chromatin remodeling, gene expression, and cellular plasticity in the central nervous system (CNS). This review provides a comprehensive overview of the classification and functional diversity of HDACs, with particular emphasis on their roles in neural progenitor cells, mature neurons, and glial populations. In neural stem and progenitor cells, HDACs modulate neurogenesis, fate specification, and lineage commitment. In differentiated neurons, HDACs govern synaptic plasticity, memory formation, and survival. In glial cell

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… Morales-Prieto N. Foley T. Collins L.M. Sullivan A.M. O’Keeffe G.W. Peripheral administration of the Class-IIa HDAC inhibitor MC1568 partially protects against nigrostriatal neurodegeneration in the striatal 6-OHDA rat model of Parkinson’s disease Brain Behav. …

Quality indicators and patient outcome measures for palliative care in cancer patients: a systematic review.

IntroductionWith the exponential rise in global cancer incidence, the surge in demand for palliative care has outstripped capacity, limiting patients' access to quality and holistic palliative care, especially in low- and middle-income countries. Despite an upturn in research activity, evidence in palliative care remains limited, given its complexity as well as the shortage of standardised quality indicators (QIs) and patient outcome measures (POMs). The objective of this systematic review is to assess the QIs and POMs used to evaluate palliative care service on aggregated and individual level

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… Tabuyo-Martin A, Torres-Morales A, Pitteloud MJ, et al. Palliative medicine referral and end-of-life interventions among racial and ethnic minority patients with advanced or recurrent gynecologic cancer. Cancer Control. 2023;30:107327482311571. doi: 10.1177/10732748231157191. 32. …