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The Journal of Pharmacology and... Jun 2024Ovarian cancer is the most lethal gynecological malignancy, with a 5-year survival rate of approximately 50%. The dismal prognosis is due in part to metastatic disease...
Ovarian cancer is the most lethal gynecological malignancy, with a 5-year survival rate of approximately 50%. The dismal prognosis is due in part to metastatic disease and acquired drug resistance to conventional chemotherapies such as taxanes. Colchicine binding site inhibitors (CBSIs) are attractive alternatives to taxanes because they could potentially achieve oral bioavailability and overcome drug resistance associated with the prolonged use of taxanes. VERU-111 is one of the most advanced CBSIs that is orally available, potent, well-tolerated, and has shown good efficacy in several preclinical solid tumor models. Here, we demonstrate for the first time the potency of VERU-111 as well as its efficacy at inhibiting tumor growth and metastasis in an orthotopic ovarian cancer mouse model. VERU-111 has nanomolar potency against ovarian cancer cell lines and strongly inhibits colony formation, proliferation, invasion, and migration. VERU-111 disrupts microtubule formation to induce mitotic catastrophe and, ultimately, apoptosis in a concentration-dependent manner. The efficacy of VERU-111 was comparable with standard chemotherapy paclitaxel, the current first-line treatment for ovarian cancer, with no observed synergy with combination paclitaxel + VERU-111 treatment. , VERU-111 markedly suppressed ovarian tumor growth and completely suppressed distant organ metastasis. Together, these results support VERU-111 for its potential as a novel therapy for ovarian cancer, particularly for late-stage metastatic disease. VERU-111 is an investigational new drug and has comparable efficacy as paclitaxel in suppressing tumor cell proliferation, colony formation, and migration in ovarian cancer models and has potent anti-tumor and anti-metastatic activity in an orthotopic ovarian cancer mouse model. VERU-111 has low systemic toxicity and, unlike paclitaxel, is orally bioavailable and is not a substrate for the major drug efflux transporters, making it a promising and attractive alternative to taxane-based therapy.
PubMed: 38936977
DOI: 10.1124/jpet.124.002298 -
JCO Clinical Cancer Informatics Jun 2024The expanding presence of the electronic health record (EHR) underscores the necessity for improved interoperability. To test the interoperability within the field of...
Minimal Common Oncology Data Elements Genomics Pilot Project: Enhancing Oncology Research Through Electronic Health Record Interoperability at Vanderbilt University Medical Center.
PURPOSE
The expanding presence of the electronic health record (EHR) underscores the necessity for improved interoperability. To test the interoperability within the field of oncology research, our team at Vanderbilt University Medical Center (VUMC) enabled our Epic-based EHR to be compatible with the Minimal Common Oncology Data Elements (mCODE), which is a Fast Healthcare Interoperability Resources (FHIR)-based consensus data standard created to facilitate the transmission of EHRs for patients with cancer.
METHODS
Our approach used an extract, transform, load tool for converting EHR data from the VUMC Epic Clarity database into mCODE-compatible profiles. We established a sandbox environment on Microsoft Azure for data migration, deployed a FHIR server to handle application programming interface (API) requests, and mapped VUMC data to align with mCODE structures. In addition, we constructed a web application to demonstrate the practical use of mCODE profiles in health care.
RESULTS
We developed an end-to-end pipeline that converted EHR data into mCODE-compliant profiles, as well as a web application that visualizes genomic data and provides cancer risk assessments. Despite the complexities of aligning traditional EHR databases with mCODE standards and the limitations of FHIR APIs in supporting advanced statistical methodologies, this project successfully demonstrates the practical integration of mCODE standards into existing health care infrastructures.
CONCLUSION
This study provides a proof of concept for the interoperability of mCODE within a major health care institution's EHR system, highlighting both the potential and the current limitations of FHIR APIs in supporting complex data analysis for oncology research.
Topics: Humans; Electronic Health Records; Pilot Projects; Medical Oncology; Genomics; Academic Medical Centers; Neoplasms; Common Data Elements; Software; Health Information Interoperability
PubMed: 38935887
DOI: 10.1200/CCI.23.00249 -
American Society of Clinical Oncology... Jun 2024The landscape of prostate cancer care has rapidly evolved. We have transitioned from the use of conventional imaging, radical surgeries, and single-agent androgen... (Review)
Review
The landscape of prostate cancer care has rapidly evolved. We have transitioned from the use of conventional imaging, radical surgeries, and single-agent androgen deprivation therapy to an era of advanced imaging, precision diagnostics, genomics, and targeted treatment options. Concurrently, the emergence of large language models (LLMs) has dramatically transformed the paradigm for artificial intelligence (AI). This convergence of advancements in prostate cancer management and AI provides a compelling rationale to comprehensively review the current state of AI applications in prostate cancer care. Here, we review the advancements in AI-driven applications across the continuum of the journey of a patient with prostate cancer from early interception to survivorship care. We subsequently discuss the role of AI in prostate cancer drug discovery, clinical trials, and clinical practice guidelines. In the localized disease setting, deep learning models demonstrated impressive performance in detecting and grading prostate cancer using imaging and pathology data. For biochemically recurrent diseases, machine learning approaches are being tested for improved risk stratification and treatment decisions. In advanced prostate cancer, deep learning can potentially improve prognostication and assist in clinical decision making. Furthermore, LLMs are poised to revolutionize information summarization and extraction, clinical trial design and operations, drug development, evidence synthesis, and clinical practice guidelines. Synergistic integration of multimodal data integration and human-AI integration are emerging as a key strategy to unlock the full potential of AI in prostate cancer care.
Topics: Humans; Male; Prostatic Neoplasms; Artificial Intelligence
PubMed: 38935882
DOI: 10.1200/EDBK_438516 -
American Society of Clinical Oncology... Jun 2024This article endeavors to navigate the clinical journey of bispecific antibodies (BsAbs), from elucidating common toxicities and management strategies to examining novel... (Review)
Review
This article endeavors to navigate the clinical journey of bispecific antibodies (BsAbs), from elucidating common toxicities and management strategies to examining novel agents and broadening access in community health care. These drugs, commonly through T-cell activation, result in shared adverse events such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Variations in target antigens and designs, however, might introduce unique toxicities for different BsAbs, warranting specific management approaches. Recent US Food and Drug Administration approvals of BsAbs targeting CD3 T cells linked to CD20 for non-Hodgkin lymphoma and to B-cell maturation antigen or GPRC5D for multiple myeloma have transformed the treatment landscape for hematologic malignancies. Emerging new agents promise further enhancement and safety, exploring novel antigen targets, innovative structures such as trispecific antibodies, and the engagement of diverse immune cells. Simultaneously, the expansion of BsAbs into community practices is underway, demanding a multifaceted strategy that encompasses educational initiatives, operational adaptations, and collaborative frameworks. This ensures comprehensive treatment access, allowing every patient, irrespective of geographical or socioeconomic status, to benefit from these advancements in cancer therapy.
Topics: Humans; Antibodies, Bispecific; Multiple Myeloma; Lymphoma; Antineoplastic Agents, Immunological
PubMed: 38935881
DOI: 10.1200/EDBK_433516 -
Journal of Cancer Research and... Jun 2024Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related deaths globally, with a five-year survival rate of only 5%.
INTRODUCTION
Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related deaths globally, with a five-year survival rate of only 5%.
OBJECTIVES
Pancreatic ductal adenocarcinoma is often fatal because of the lack of specific early symptoms and effective early screening tools. Therefore, 80%-85% of patients are usually diagnosed in the advanced stages. This study aimed to investigate the analgesic effect of transcutaneous electrical acupoint stimulation in patients with advanced pancreatic cancer.
METHODS
Eighty patients with advanced pancreatic cancer were recruited from the Integrative Medicine Department of our hospital between June 2017 and October 2018 and randomly divided into the experimental group (n = 40) and the control group (n = 40). The experimental group received transcutaneous electrical acupoint stimulation combined with analgesic medication for 3 consecutive days, while the control group received only analgesic medication. The pain scores of the two groups before and after intervention were compared.
RESULTS
The mean pain severity score was significantly lower in the experimental group than in the control group on day 1 (P < 0.001), day 2 (P < 0.001), day 3 (P = 0.005), and day 4 (P = 0.043).
CONCLUSION
Transcutaneous electrical acupoint stimulation therapy effectively alleviates the pain of patients with advanced pancreatic cancer with a high degree of safety and minimal adverse effects, and is worthy of clinical application.
PubMed: 38935575
DOI: 10.4103/jcrt.jcrt_2172_23 -
Hepatology Communications Jul 2024Identifying patients with undiagnosed advanced chronic liver disease (ACLD) is a public health challenge. Patients with advanced fibrosis or compensated cirrhosis have...
BACKGROUND
Identifying patients with undiagnosed advanced chronic liver disease (ACLD) is a public health challenge. Patients with advanced fibrosis or compensated cirrhosis have much better outcomes than those with decompensated disease and may be eligible for interventions to prevent disease progression.
METHODS
A cloud-based software solution ("the Liver Toolkit") was developed to access primary care practice software to identify patients at risk of ACLD. Clinical history and laboratory results were extracted to calculate aspartate aminotransferase-to-platelet ratio index and fibrosis 4 scores. Patients identified were recalled for assessment, including Liver Stiffness Measurement (LSM) via transient elastography. Those with an existing diagnosis of cirrhosis were excluded.
RESULTS
Existing laboratory results of more than 32,000 adults across nine general practices were assessed to identify 703 patients at increased risk of ACLD (2.2% of the cohort). One hundred seventy-nine patients (26%) were successfully recalled, and 23/179 (13%) were identified to have ACLD (LSM ≥10.0 kPa) (10% found at indeterminate risk [LSM 8.0-9.9 kPa] and 77% low risk of fibrosis [LSM <8.0 kPa]). In most cases, the diagnosis of liver disease was new, with the most common etiology being metabolic dysfunction-associated steatotic liver disease (n=20, 83%). Aspartate aminotransferase-to-platelet ratio index ≥1.0 and fibrosis 4 ≥3.25 had a positive predictive value for detecting ACLD of 19% and 24%, respectively. Patients who did not attend recall had markers of more severe disease with a higher median aspartate aminotransferase-to-platelet ratio index score (0.57 vs. 0.46, p=0.041).
CONCLUSIONS
This novel information technology system successfully screened a large primary care cohort using existing laboratory results to identify patients at increased risk ACLD. More than 1 in 5 patients recalled were found to have liver disease requiring specialist follow-up.
Topics: Humans; Female; Male; Middle Aged; Elasticity Imaging Techniques; General Practice; Adult; Liver Cirrhosis; Liver Diseases; Software; Mass Screening; Aged; Aspartate Aminotransferases; Chronic Disease; Platelet Count
PubMed: 38934697
DOI: 10.1097/HC9.0000000000000482 -
Frontiers in Nutrition 2024Life's essential' 8 (LE8) is a newly updated cardiovascular health (CVH) metrics from the American Heart Association, with close relevance to metabolism. Our objective...
BACKGROUND
Life's essential' 8 (LE8) is a newly updated cardiovascular health (CVH) metrics from the American Heart Association, with close relevance to metabolism. Our objective is to explore the association between LE8 scores and incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced liver fibrosis in American adults.
METHODS
This population-based cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018, encompassing adults aged 20 years or older. Validated non-invasive scoring systems were employed to define liver steatosis and advanced liver fibrosis. Multivariable logistic regression and smooth curve fitting techniques were applied to evaluate the associations. All analyses were adjusted for the survey' complex design parameters and accounted for sample weights.
RESULTS
A total of 11,820 participants were included. A higher LE8 score was found to be inversely associated with the incidence of MAFLD and advanced liver fibrosis, with odds ratios (OR) of 0.64 (95% CI: 0.57-0.71) for MAFLD and 0.75 (95% CI: 0.61-0.92) for advanced liver fibrosis per 1 standard deviation (SD) increase in LE8 score. Similar patterns were found in the relationship between health behaviors/factors score and incidence of MAFLD and advanced liver fibrosis. In subgroup analyses, the interaction test showed that age, education level, marital status, CVD, hypertension and diabetes had a significant impact on the association between LE8 score and MAFLD (all for interaction < 0.05). Among male, elderly, wealthy, other race, CVD, diabetes and depression participants, the correlation between LE8 score and advanced liver fibrosis was not statistically significant ( > 0.05). Younger participants exhibited a more pronounced negative association between the CVH metric and both MAFLD and advanced life fibrosis.
CONCLUSION
LE8 and its subscales score were inversely associated with the presence of MAFLD and advanced liver fibrosis in non-linear patterns. Optimal LE8 score may significantly reduce the risk of liver steatosis and fibrosis.
PubMed: 38933880
DOI: 10.3389/fnut.2024.1403720 -
Asia-Pacific Journal of Oncology Nursing Jun 2024
PubMed: 38933687
DOI: 10.1016/j.apjon.2024.100492 -
Radiology Case Reports Aug 2024For maxillary gingival carcinomas, especially those in the molar region, surgical resection is often performed beyond the maxillary tuberosity. Bleeding from the...
For maxillary gingival carcinomas, especially those in the molar region, surgical resection is often performed beyond the maxillary tuberosity. Bleeding from the posterior superior alveolar or maxillary artery into the pterygoid process is difficult to stop during partial maxillary resection. Advances in catheterization and materials have enabled the embolization of various vessels. In this report, we describe two cases of maxillary gingival cancer in which preoperative endovascular arterial embolization prevented bleeding due to unexpected vascular injury, allowing for a safe surgery with minimal blood loss. This technique effectively avoids emergency hemostasis for unexpected bleeding when resecting gingival cancers in the maxillary molar region.
PubMed: 38933655
DOI: 10.1016/j.radcr.2024.05.052 -
Frontiers in Oncology 2024Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human...
INTRODUCTION
Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human monoclonal antibody targeting nectin-4. No validated biomarker predictive of or correlated with response exists for EV. Cutaneous toxicity is among the most common EV-related toxicities and typically emerges in early cycles. This retrospective experience of patients with urothelial cancer treated with EV monotherapy evaluated whether EV-related cutaneous toxicity correlated with improved outcomes including progression-free (PFS) and overall (OS) survival and overall response rate (ORR).
PATIENTS AND METHODS
Patients treated with EV monotherapy at Johns Hopkins were identified, and baseline characteristics, treatment, and toxicity details were extracted through chart review. Univariable Cox hazard ratios (HRs) were calculated for assessing the effect of baseline patient characteristics and cutaneous toxicity in PFS and OS. Based on the univariable analysis and known risk factors, all subsequent analyses were adjusted for: Eastern Cooperative Oncology Group performance status, visceral metastases at baseline, gender as well as EV dose, and weight to account for dosing differences. Multivariable Cox proportional HRs were used for comparing PFS and OS between patients with and without cutaneous toxicity, assessing toxicity and EV dose as a time-dependent variables. Adjusted p-values were calculated to compare ORR and disease control rate (DCR) between groups using the Poisson regression model.
RESULTS
Of the 78 patients analyzed, 42 (53.8%) experienced EV-related cutaneous toxicity that appeared early during treatment (median time to occurrence 0.5 months from EV initiation). Cutaneous toxicity correlated with significantly improved OS [HR, 0.48; 95% confidence interval (CI), 0.25, 0.9; P = 0.0235], ORR (68.3% vs. 20.7%, P = 0.0033) and DCR (82.9% vs. 48.3%, P = 0.0122). Median PFS was numerically longer in the cutaneous toxicity group (6.3 vs. 1.7 months), although no significance was achieved in the multivariable analysis (HR, 0.62; 95% CI: 0.35, 0.108; P = 0.0925).
CONCLUSION
In this retrospective study, EV-related cutaneous toxicity was associated with improved patient outcomes. Confirming this observation and understanding its mechanism could lead to discovery of a new clinical biomarker of EV response that can emerge in the first cycle.
PubMed: 38933451
DOI: 10.3389/fonc.2024.1377842