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Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study.

Primary central nervous system lymphoma (PCNSL) is a rare and frequently fatal lymphoma subtype. The programmed death-1 (PD-1) pathway has emerged as a potential therapeutic target, but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be determined. In this phase 2 trial (ChiCTR1900027433) with a safety run-in, we included patients aged 18-70 with newly diagnosed PCNSL. Participants underwent six 21-day cycles of a SMTR regimen, which includes sintilimab (200 mg, Day 0), rituximab (375 mg/m2, Day 0), methotrexate

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… Morales-Martinez, A. et al. Prognostic factors in primary central nervous system lymphoma. Curr. Opin. Oncol. 34 , 676–684 (2022). 10.1097/CCO.0000000000000896 35. Grommes, C. Circulating Tumor DNA in the Blood: A New Frontier in Primary CNS Lymphoma? J. Clin. …

Boosting and broadening recruitment to UK cancer trials: towards a blueprint for action.

Recruitment and retention in cancer trials are long-standing issues, exacerbated by the COVID-19 pandemic. The UK National Institute of Health Research and leading clinicians have emphasised the urgency to achieve and surpass prepandemic levels of participation. Data from a recent UK trial demonstrated the impact of COVID-19 and highlighted factors that limited recruitment. In response to this worldwide problem, studies have identified strategies for remediation at the levels of funding, the research environment, study design and trial team-related aspects, yet evidence of progress is lacking.

Recommendations on the follow-up of patients with Gaucher disease in Spain: Results from a Delphi survey.

Management of Gaucher disease (GD) is challenging due to its wide genotypic and phenotypic variability and changing clinical manifestations due to effective treatment. Sixteen face-to-face meetings with experts were held in order to discuss daily clinical practice and identify controversies regarding the management of GD. With this information, a questionnaire with 93 recommendations for different clinical scenarios was designed, and a Delphi survey among 86 physicians with experience in GD was conducted. Consensus was reached on 73 out of the 93 items. Recommendations on follow-up of adult an

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… Montserrat Morales reports personal fees for consultancy, support for research projects, and transport for conference attendance from the following companies: Genzyme Corporation, Alnylam, and Takeda. …

Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement.

Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two establis

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… Morales G. Gandhi I. Ozbek U. Aguayo-Hiraldo P. Ayuk F. Baez J. Chanswangphuwana C. Choe H. DeFilipp Z. Evaluation of Elafin as a Prognostic Biomarker in Acute Graft-versus-Host Disease Transplant. Cell. Ther. 2021 27 988-e1 10.1016/j.jtct.2021.08.021 34474163 PMC8671218 22. George L. Mahabal G. …

LncRNA LGALS8-AS1 Promotes Breast Cancer Metastasis Through miR-125b-5p/SOX12 Feedback Regulatory Network.

BackgroundMetastasis is a major factor weakening the long-term survival of breast cancer patients. Increasing evidence revealed that long non-coding RNAs (lncRNAs) were involved in the occurrence and development of breast cancer. In this study, we aimed to investigate the role of LGALS8-AS1 in the metastatic progression of breast cancer cells and its potential mechanisms.ResultsThe lncRNA LGALS8-AS1 was highly expressed in breast cancer and associated with poor survival. LGALS8-AS1 functioned as an oncogenic lncRNA that promoted the metastasis of breast cancer both in vitro and in vivo. It upr

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… Cancer Sci ( 2017 ) 108 ( 10 ): 1927–33 . doi: 10.1111/cas.13342 PMC5623749 28776911 14 Hanniford D Ulloa-Morales A Karz A Berzoti-Coelho M Moubarak R Sánchez-Sendra B . Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis . …

The Polyphenols α-Mangostin and Nordihydroguaiaretic Acid Induce Oxidative Stress, Cell Cycle Arrest, and Apoptosis in a Cellular Model of Medulloblastoma.

Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols α-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of α-mangostin or NDGA for 24 h. The cell viability was analyzed using cr

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… Acknowledgments We acknowledge Rocío Morales Bárcenas for her technical assistance in the flow cytometry measurements. …

Predicting Survival for Patients with Malignant Pleural Effusion: Development of the CONCH Prognostic Model.

BackgroundMalignant pleural effusion (MPE) is a frequent complication of advanced malignancies that leads to a poor quality of life and limits treatment options.ObjectiveThe objective of this study was to identify biomarkers of survival in patients with MPE, which will greatly facilitate the clinical management of this complication.MethodsThis retrospective study recruited patients who had been pathologically diagnosed with MPE, regardless of the type of primary cancer, at Beijing Chao-Yang Hospital over 158 months. Demographic, clinical, hematological, and pleural fluid data were collected an

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… Misharin AV , Morales-Nebreda L , Reyfman PA , et al. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span . J Exp Med . 2017 ; 214 ( 8 ): 2387 – 2404 . doi: 10.1084/jem.20162152 28694385 PMC5551573 31. Li X , Zhu M , Penfold ME , et al. …

Внезапная сердечная смерть при системном склерозе: диагностика для оценки риска и управления информацией

Сердечное заболевание является одной из основных причин смертности при системном склерозе (SSc), а внезапная сердечно-сосудистая смертность (SCD), как считается, чаще встречается в SSc, чем в целом по населению. Диффузный миокардиальный фиброз, миокардит и ишемическая болезнь сердца широко распространены в SSc и могут быть разумно гипотезы, что будет способствовать повышению риска СКД. Несмотря на это, СКР по-прежнему остается относительно недооцененной зоной SSc, где мало что известно о специфических для SSc факторах риска и возможностях первичной профилактики. В этом обзоре мы представляем о

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… Rodriguez-Reyna T.S., Morelos-Guzman M., Hernandez-Reyes P., Montero-Duarte K., Martinez-Reyes C., Reyes-Utrera C., Vazquez-La Madrid J., Morales-Blanhir J., Nunez-Alvarez C., Cabiedes-Contreras J. …

When and how do patients with cardiac amyloidosis die?

BackgroundCardiac amyloidosis (CA) is an underappreciated cause of morbidity and mortality. Light-chain (AL) and transthyretin (ATTR) amyloidosis have different disease trajectories. No data are available on subtype-specific modes of death (MOD) in patients with CA.Methods and resultsWe retrospectively investigated 66 with AL and 48 with wild-type ATTR amyloidosis (ATTRwt) from 2000 to 2018. ATTRwt differed from AL by age (74.6 ± 5.4 years vs. 63 ± 10.8 years), posterior wall thickness (16.8 ± 3.3 mm vs. 14.3 ± 2.2 mm), left ventricular mass index (180.7 ± 63.2 g/m2 vs. 133.5 ± 42.2 g/m2), and

Potential impact of the implementation of multiple-criteria decision analysis (MCDA) on the Polish pricing and reimbursement process of orphan drugs.

BackgroundThe objective of this study was to assess the potential impact of the implementation of multiple-criteria decision analysis (MCDA) on the Polish pricing and reimbursement (P&R) process with regard to orphan drugs.MethodsA four step approach was designed. Firstly, a systematic literature review was conducted to select the MCDA criteria. Secondly, a database of orphan drugs was established. Thirdly, health technology appraisals (HTA recommendations) were categorized and an MCDA appraisal was conducted. Finally, a comparison of HTA and MCDA outcomes was carried out. An MCDA outcome was

Drug repurposing in KRAS G12C-mutant NSCLC: a focus on resistance mechanisms and clinical strategies.

KRAS G12C-mutant non-small cell lung cancer (NSCLC) has transitioned from a therapeutically problematic disease to a precision-targetable cancer, anchored by the landmark approvals of sotorasib and adagrasib. Yet despite these advances, responses remain limited in duration and multiple mechanisms of rapid adaptive resistance emerge under inhibitor pressure. These resistance mechanisms define a therapeutic vulnerability map that can be addressed by repurposing approved agents with established safety profiles. This review emphasises the current understanding of KRAS G12C biology, integrates upda

Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

Biopharmaceuticals for Cancer Treatment: An Update.

Cancer is one of the most debilitating diseases, causing profound physical and psychological impacts on patients. The global number of cancer patients has been steadily rising over the last few decades. The development of effective cancer therapies remains the primary focus in life science research, requiring a precise understanding of specific pathways and the regulation of tumor markers. The approved cancer therapies demonstrate effectiveness by acting on specific regulatory enzymes, components required for cell division, hormones, and cell-specific receptors, etc. While small-molecule drugs

Recent Insights in Multi-Target Drugs in Pharmacology and Medicinal Chemistry.

Many of the drugs used in treatment today have been designed based on the "specificity paradigm". Resistance has developed against drugs designed using this approach, leading to a decrease in their effectiveness. In addition, it is well-documented in the literature that diseases with complex etiologies, such as Alzheimer's, Parkinson's, and cancer are influenced by multiple genetic and/or environmental factors. As a result, specificity paradigm is often insufficient for treating these diseases. Therefore, there is a need to develop drugs that interact with multiple targets simultaneously throu

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… M., Morales L. G. F., Cruz A., Molecules 2024, 29, 4780.39407708 e) Sun T., Zhen T., Harakandi C. H., Wang L., Guo H., Chen Y., Sun H., Eur. J. Med. Chem. 2024, 275, 116569. 10. de Castro S., Camarasa M.‐J., Eur. J. Med. Chem. 2018, 150, 206. 11. Wermuth C. …

The investigation of oncolytic viruses in the field of cancer therapy.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in

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… Nat Med . ( 2023 ) 29 : 450–7 . doi: 10.1038/s41591-023-02210-0 36759673 90 Garza-Morales R Yaddanapudi K Perez-Hernandez R Riedinger E McMasters KM Shirwan H . Temozolomide renders murine cancer cells susceptible to oncolytic adenovirus replication and oncolysis . …

Diagnosis and treatment of Paget's disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS).

INTRODUCTION: Paget's disease of bone is a focal skeletal disorder causing bone deformities and impairing bone quality. Despite the prevalence of asymptomatic cases is increasing, the progression of the disease can lead to invalidating complications that compromise the quality of life. Doubts on clinical and therapeutic management aspects exist, although beneficial effects of antiresorptive drugs, particularly bisphosphonates are known. However, limited information is available from randomized controlled trials on the prevention of disease complications so that somewhat contrasting positions a

Качество жизни пациентов, получающих лекарственный каннабис: систематический обзор и метаанализ результатов первичных исследований 2015-2025.

ЦЕЛЬ: Глобальное бремя хронических заболеваний является значительным. Лекарственный каннабис (МК) является законным вариантом лечения пациентов с хроническими заболеваниями в некоторых странах. Качество жизни, связанное со здоровьем, является важным результатом, о котором сообщают пациенты, во всех хронических заболеваниях. Мы поставили перед собой цель определить, каким образом исследования в области медикаментозной терапии оправдывают, измеряют и сообщают о HRQL, а также оценить имеющиеся данные по HRQL после лечения МЦ. МЕТОДЫ: Систематический обзор поиска AMED, Medline, Web of Science, Sco

Microbiome and pancreatic cancer: time to think about chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by late diagnosis, rapid progression, and a high mortality rate. Its complex biology, characterized by a dense, stromal tumor environment with an immunosuppressive milieu, contributes to resistance against standard treatments like chemotherapy and radiation. This comprehensive review explores the dynamic role of the microbiome in modulating chemotherapy efficacy and outcomes in PDAC. It delves into the microbiome's impact on drug metabolism and resistance, and the interaction between microbial elements, drugs,

Anthracycline-induced cardiotoxicity and renin-angiotensin-aldosterone system-from molecular mechanisms to therapeutic applications.

Few millions of new cancer cases are diagnosed worldwide every year. Due to significant progress in understanding cancer biology and developing new therapies, the mortality rates are decreasing with many of patients that can be completely cured. However, vast majority of them require chemotherapy which comes with high medical costs in terms of adverse events, of which cardiotoxicity is one of the most serious and challenging. Anthracyclines (doxorubicin, epirubicin) are a class of cytotoxic agents used in treatment of breast cancer, sarcomas, or hematological malignancies that are associated w

The Global Obesity Epidemic: Epidemiology, Health Burden and Policy Priorities.

The global prevalence of obesity has more than tripled since 1975, now affecting nearly one billion adults and over 170 million children and adolescents. In 2025, The Lancet Diabetes & Endocrinology Commission on Clinical Obesity redefined obesity as a chronic, multisystem disease characterised by excess adiposity leading to organ dysfunction, distinguishing between preclinical obesity (excess adiposity without end-organ injury) and clinical obesity (manifest metabolic or structural complications). This framework moves beyond reliance on BMI, acknowledging that ectopic fat deposition in the li

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… Escudero-Martínez I Morales-Caba L Segura T. Atrial fibrillation and stroke: a review and new insights. Trends Cardiovasc Med 2023 33 23 9 10.1016/j.tcm.2021.12.001 34890796 44. Savji N Meijers WC Bartz TM The association of obesity and cardiometabolic traits with incident HFpEF and HFrEF. …