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Drug Discovery Today Jun 2024Cervical cancer (CC) is one of the leading causes of death among women worldwide. The current treatments for this cancer consist of invasive methods such as... (Review)
Review
Cervical cancer (CC) is one of the leading causes of death among women worldwide. The current treatments for this cancer consist of invasive methods such as chemotherapeutic drugs, radiation, immunotherapy and surgery, which could lead to severe side effects and hinder the patient's life quality. Although metal-based therapies, including cisplatin and ruthenium-based compounds, offer promising alternatives, they lack specificity and harm healthy cells. Combining metal nanoparticles with standard approaches has demonstrated remarkable efficacy and safety in the fight against CC. Overall, this review is intended to show the latest advancements and insights into metal-based strategies, creating a promising path for more effective and safer treatments in the battle against CC.
PubMed: 38944184
DOI: 10.1016/j.drudis.2024.104073 -
Cell Reports. Medicine Jun 2024Solid tumor pathology, characterized by abnormalities in the tumor microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased... (Review)
Review
Solid tumor pathology, characterized by abnormalities in the tumor microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased tumor stiffness and accumulation of intratumoral forces, can determine the success of cancer treatments, defining the tumor's "mechanopathology" profile. These abnormalities cause extensive vascular compression, leading to hypoperfusion and hypoxia. Hypoperfusion hinders drug delivery, while hypoxia creates an unfavorable TME, promoting tumor progression through immunosuppression, heightened metastatic potential, drug resistance, and chaotic angiogenesis. Strategies targeting TME mechanopathology, such as vascular and stroma normalization, hold promise in enhancing cancer therapies with some already advancing to the clinic. Normalization can be achieved using anti-angiogenic agents, mechanotherapeutics, immune checkpoint inhibitors, engineered bacterial therapeutics, metronomic nanomedicine, and ultrasound sonopermeation. Here, we review the methods developed to rectify tumor mechanopathology, which have even led to cures in preclinical models, and discuss their bench-to-bedside translation, including the derivation of biomarkers from tumor mechanopathology for personalized therapy.
PubMed: 38944037
DOI: 10.1016/j.xcrm.2024.101626 -
Biomedicine & Pharmacotherapy =... Jun 2024The integration of biochips with AI opened up new possibilities and is expected to revolutionize smart healthcare tools within the next five years. The combination of... (Review)
Review
The integration of biochips with AI opened up new possibilities and is expected to revolutionize smart healthcare tools within the next five years. The combination of miniaturized, multi-functional, rapid, high-throughput sample processing and sensing capabilities of biochips, with the computational data processing and predictive power of AI, allows medical professionals to collect and analyze vast amounts of data quickly and efficiently, leading to more accurate and timely diagnoses and prognostic evaluations. Biochips, as smart healthcare devices, offer continuous monitoring of patient symptoms. Integrated virtual assistants have the potential to send predictive feedback to users and healthcare practitioners, paving the way for personalized and predictive medicine. This review explores the current state-of-the-art biochip technologies including gene-chips, organ-on-a-chips, and neural implants, and the diagnostic and therapeutic utility of AI-assisted biochips in medical practices such as cancer, diabetes, infectious diseases, and neurological disorders. Choosing the appropriate AI model for a specific biomedical application, and possible solutions to the current challenges are explored. Surveying advances in machine learning models for biochip functionality, this paper offers a review of biochips for the future of biomedicine, an essential guide for keeping up with trends in healthcare, while inspiring cross-disciplinary collaboration among biomedical engineering, medicine, and machine learning fields.
PubMed: 38943990
DOI: 10.1016/j.biopha.2024.116997 -
Drug Resistance Updates : Reviews and... Jun 2024Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key... (Review)
Review
Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain susceptible BC cells in G1 phase. Three CDK4/6i are approved for the first-line treatment of patients with advanced/metastatic hormone receptor-positive (HR)/human epidermal growth factor receptor 2-negative (HER2) BC in combination with endocrine therapy (ET). Though this has improved the clinical outcomes for survival of BC patients, there is no established standard next-line treatment to tackle drug resistance. Recent studies suggest that CDK4/6i can modulate other distinct effects in both BC and breast stromal compartments, which may provide new insights into aspects of their clinical activity. This review describes the biochemistry of the CDK4/6-Rb-E2F pathway in HR BC, then discusses how CDK4/6i can trigger other effects in BC/breast stromal compartments, and finally outlines the mechanisms of CDK4/6i resistance that have emerged in recent preclinical studies and clinical cohorts, emphasizing the impact of these findings on novel therapeutic opportunities in BC.
PubMed: 38943828
DOI: 10.1016/j.drup.2024.101103 -
ESMO Open Jun 2024Locally advanced (unresectable) or metastatic dedifferentiated liposarcoma (DDLPS) is a common presentation of liposarcoma. Despite established diagnostic and treatment... (Review)
Review
Current unmet needs in locally advanced (unresectable) or metastatic dedifferentiated liposarcoma, the relevance of progression-free survival as clinical endpoint, and expectations for future clinical trial design: an international Delphi consensus report.
BACKGROUND
Locally advanced (unresectable) or metastatic dedifferentiated liposarcoma (DDLPS) is a common presentation of liposarcoma. Despite established diagnostic and treatment guidelines for DDLPS, critical clinical gaps remain driven by diagnostic challenges, symptom burden and the lack of targeted, safe and effective treatments. The objective of this study was to gather expert opinions from Europe and the United States on the management, unmet needs and expectations for clinical trial design as well as the value of progression-free survival (PFS) in this disease. Other aims included raising awareness and educate key stakeholders across healthcare systems.
MATERIALS AND METHODS
An international panel of 12 sarcoma key opinion leaders (KOLs) was recruited. The study consisted of two rounds of surveys with pre-defined statements. Experts scored each statement on a 9-point Likert scale. Consensus agreement was defined as ≥75% of experts scoring a statement with ≥7. Revised statements were discussed in a consensus meeting.
RESULTS
Consensus was reached on 43 of 55 pre-defined statements across disease burden, treatment paradigm, unmet needs, value of PFS and its association with overall survival (OS), and cross-over trial design. Twelve statements were deprioritised or merged with other statements. There were no statements where experts disagreed.
CONCLUSION
This study constitutes the first international Delphi panel on DDLPS. It aimed to explore KOL perception of the disease burden and unmet need in DDLPS, the value of PFS, and its potential translation to OS benefit, as well as the relevance of a cross-over trial design for DDLPS therapies. Results indicate an alignment across Europe and the United States regarding DDLPS management, unmet needs, and expectations for clinical trials. Raising awareness of critical clinical gaps in relation to DDLPS can contribute to improving patient outcomes and supporting the development of innovative treatments.
PubMed: 38943735
DOI: 10.1016/j.esmoop.2024.103487 -
Nursing Open Jul 2024This study aimed to explore the chain mediating effect of spiritual well-being and anticipatory grief between benefit finding and meaning in life of patients with...
The chain mediating effect of spiritual well-being and anticipatory grief between benefit finding and meaning in life of patients with advanced lung cancer: Empirical research quantitative.
AIM
This study aimed to explore the chain mediating effect of spiritual well-being and anticipatory grief between benefit finding and meaning in life of patients with advanced lung cancer.
DESIGN
This was a cross-sectional study.
METHODS
The research included 400 patients with advanced lung cancer who attended REDACTE from December 2022 to August 2023 as the research subjects. Data were collected using a questionnaire including socio-demographic and clinical characteristics, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being scale (FACIT-Sp-12), the Benefit Finding Scale (BFS), the Preparatory Grief in Advanced Cancer Patients Scale (PGAC), and the Meaning of Life Questionnaire (MLQ). The structural equation model (SEM) was used to analyse the relationship between benefit finding, spiritual well-being, anticipatory grief and meaning in life.
RESULTS
There was a significant correlation between benefit finding, spiritual well-being, anticipatory grief, and meaning in life. Benefit finding could have a direct positive impact on meaning in life of patients with advanced lung cancer, but it could also indirectly affect meaning in life of patients with advanced lung cancer through three pathways: the mediating effect of spiritual well-being, the mediating effect of anticipatory grief and the chain mediating effect of spiritual well-being and anticipatory grief. Nursing staff should develop an integrated program of interventions to enhance the meaning in life of patients with advanced lung cancer.
Topics: Humans; Male; Female; Lung Neoplasms; Cross-Sectional Studies; Middle Aged; Grief; Spirituality; Surveys and Questionnaires; Aged; Quality of Life; Empirical Research; Adaptation, Psychological; Adult
PubMed: 38943318
DOI: 10.1002/nop2.2179 -
Nigerian Journal of Clinical Practice Jun 2024Some parameters of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict tumor chemosensitivity and survival in...
The Prognostic Significance of Tumor SUVmax Value in Pre- and Post-Chemoradiotherapy 18F-FDG PET/CT Imaging in Patients with Localized and Advanced Head and Neck Squamous Cell Carcinoma.
BACKGROUND
Some parameters of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict tumor chemosensitivity and survival in patients with head and neck squamous cell carcinoma (HNSCC).
AIM
The aim of the study was to investigate the prognostic value of pre- and post-treatment maximum standardized uptake values (SUVmax) in 18F-FDG PET/CT imaging for predicting mortality in patients with HNSCC, as well as its prognostic value in terms of disease progression, overall survival (OS), and progression-free survival (PFS).
METHODS
This retrospective study included 37 patients with a histopathological diagnosis of HNSCCs between 2015 and 2018. In patients with HNSCC, the first 18F-FDG PET/CT imaging was performed for pre-treatment staging, and the second imaging was performed to evaluate post-treatment response. In these imaging studies, SUVmax values of the primary tumor before and after treatment were determined. After the second imaging, patients were re-evaluated and followed up. ROC analysis was used to determine the predictive value of 18F-FDG PET/CT SUVmax parameters in terms of death and progression, and Cox regression analysis was used to investigate the prognostic value in terms of OS and PFS.
RESULTS
Cut-off value 15 for SUVmax1 (pre-treatment) had a significant predictive value for mortality (P = 0.02). Cut-off value 3.1 for SUVmax2 (post-treatment) had a significant predictive value for progression (P = 0.024). In univariate analysis, both SUVmax1 and SUVmax2 values were significant prognostic factors for OS (P = 0.047, P = 0.004). However, for PFS, only the SUVmax2 value was a significant prognostic factor (P = 0.001).
CONCLUSION
SUVmax1 value of the primary tumor at diagnosis in HNSCC patients has a predictive value for mortality and a prognostic value for OS. However, the SUVmax2 value in the primary tumor after treatment is a predictive factor for progression and a prognostic factor for both OS and PFS.
Topics: Humans; Fluorodeoxyglucose F18; Male; Positron Emission Tomography Computed Tomography; Female; Middle Aged; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Prognosis; Head and Neck Neoplasms; Aged; Chemoradiotherapy; Adult; Radiopharmaceuticals; Predictive Value of Tests; Disease Progression
PubMed: 38943299
DOI: 10.4103/njcp.njcp_856_23 -
Journal of Nanobiotechnology Jun 2024Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and... (Review)
Review
Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy.
Topics: Nanoparticles; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Animals; Lipids; T-Lymphocytes; Neoplasms; Liposomes
PubMed: 38943167
DOI: 10.1186/s12951-024-02630-1 -
BMC Cancer Jun 2024In terms of survival rate, recurrent oral squamous cell carcinoma (OSCC) after primary surgery is considered as a poor prognostic indicator.
BACKGROUND
In terms of survival rate, recurrent oral squamous cell carcinoma (OSCC) after primary surgery is considered as a poor prognostic indicator.
OBJECTIVE
This study aims to determine the incidence of OSCC recurrence among patients treated at Khartoum Teaching Dental Hospital (KTDH) and possible risk factors associated with it.
METHODS
Records of 303 patients with a history of radical surgery were retrieved from the hospital's archives, and the histopathological records were retrieved from the archival specimens of Professor Ahmed Suleiman Oral Pathology Laboratory, Faculty of Dentistry, and University of Khartoum.
RESULTS
Advanced stages of OSCC (III, IV) were associated with higher recurrence rates, and the poorly differentiated OSCC was the commonest recurrent type.
CONCLUSION
The condition of the surgical margin is a significant predictor of OSCC recurrence and tumor stage. The tumor site, the type of surgical resection, and the tumor differentiation were also identified as significant factors influencing the recurrence of OSCC.
Topics: Humans; Mouth Neoplasms; Male; Female; Neoplasm Recurrence, Local; Retrospective Studies; Middle Aged; Carcinoma, Squamous Cell; Cross-Sectional Studies; Aged; Adult; Risk Factors; Neoplasm Staging; Aged, 80 and over; Prognosis; Hospitals, Teaching
PubMed: 38943108
DOI: 10.1186/s12885-024-12562-6 -
International Journal of Emergency... Jun 2024Cardiopulmonary resuscitation is a crucial skill for emergency medical services. As high-risk-low-frequency events pose an immense mental load to providers, concepts of...
BACKGROUND
Cardiopulmonary resuscitation is a crucial skill for emergency medical services. As high-risk-low-frequency events pose an immense mental load to providers, concepts of crew resource management, non-technical skills and the science of human errors are intended to prepare healthcare providers for high-pressure situations. However, medical errors occur, and organizations and institutions face the challenge of providing a blame-free error culture to achieve continuous improvement by avoiding similar errors in the future. In this case, we report a critical medical error during an anaphylaxis-associated cardiac arrest, its handling and the unexpected yet favourable outcome for the patient.
CASE PRESENTATION
During an out-of-hospital cardiac arrest due to chemotherapy-induced anaphylaxis, a patient received a 10-fold dose of epinephrine due to shortcomings in communication and standardization via a central venous port catheter. The patient converted from a non-shockable rhythm into a pulseless ventricular tachycardia and subsequently into ventricular fibrillation. The patient was cardioverted and defibrillated and had a return of spontaneous circulation with profound hypotension only 6 min after the administration of 10 mg epinephrine. The patient survived without any residues or neurological impairment.
CONCLUSIONS
This case demonstrates the potential deleterious effects of shortcomings in communication and deviation from standard protocols, especially in emergencies. Here, precise instructions, closed-loop communication and unambiguous labelling of syringes would probably have avoided the epinephrine overdose central to this case. Interestingly, this serious error may have saved the patient's life, as it led to the development of a shockable rhythm. Furthermore, as the patient was still in profound hypotension after administering 10 mg of epinephrine, this high dose might have counteracted the severe vasoplegic state in anaphylaxis-associated cardiac arrest. Lastly, as the patient was receiving care for advanced malignancy, the likelihood of termination of resuscitation in the initial non-shockable cardiac arrest was significant and possibly averted by the medication error.
PubMed: 38943049
DOI: 10.1186/s12245-024-00663-9