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Cancer Innovation Feb 2024Numerous studies have revealed a tight connection between tumor development and the coagulation system. However, the effects of coagulation on the prognosis and tumor...
BACKGROUND
Numerous studies have revealed a tight connection between tumor development and the coagulation system. However, the effects of coagulation on the prognosis and tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain poorly understood.
METHODS
We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns. Subsequently, we examined variations in the overall survival (OS), genomic profiles, and TME characteristics between these subtypes. To develop a prognostic coagulation-related risk score (CRRS) model, we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses. We also created a nomogram to aid in the clinical application of the risk score, evaluating the relationships between the CRRS and the immune microenvironment, responsiveness to immunotherapy, and targeted treatment. The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed.
RESULTS
There were significant differences in clinical features, prognostic stratification, genomic variation, and TME characteristics between the two coagulation-related subtypes. We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients. Significant variations in survival outcomes were observed between the high- and low-risk groups. The nomogram was proficient in predicting the 1-, 3-, and 5-year OS. Additionally, the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC. Moreover, we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis. PLAUR knockdown notably inhibited ccRCC cell proliferation and migration.
CONCLUSION
Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC.
PubMed: 38948537
DOI: 10.1002/cai2.105 -
Cancer Innovation Feb 2024Bone health management for breast cancer spans the entire cycle of patient care, including the prevention and treatment of bone loss caused by early breast cancer...
Bone health management for breast cancer spans the entire cycle of patient care, including the prevention and treatment of bone loss caused by early breast cancer treatment, the adjuvant application of bone-modifying agents to improve prognosis, and the diagnosis and treatment of advanced bone metastases. Making good bone health management means formulating appropriate treatment strategies and dealing with adverse drug reactions, and will help to improve patients' quality of life and survival rates. The Breast Cancer Expert Committee of the National Cancer Center for Quality Control organized relevant experts to conduct an in-depth discussion on the full-cycle management of breast cancer bone health based on evidence-based medicine, and put forward reasonable suggestions to guide clinicians to better deal with health issues in bone health clinics.
PubMed: 38948531
DOI: 10.1002/cai2.111 -
Frontiers in Endocrinology 2024Cellular senescence is a common biological process with a well-established link to cancer. However, the impact of cellular senescence on tumor progression remains...
BACKGROUND
Cellular senescence is a common biological process with a well-established link to cancer. However, the impact of cellular senescence on tumor progression remains unclear. To investigate this relationship, we utilized transcriptomic data from a senescence gene set to explore the connection between senescence and cancer prognosis.
METHODS
We developed the senescence score by the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. We obtained transcriptomic information of the senescence gene set from The Cancer Genome Atlas (TCGA) program. Additionally, we created a nomogram that integrates these senescence scores with clinical characteristics, providing a more comprehensive tool for prognosis evaluation.
RESULTS
We calculated the senescence score based on the expression level of 42 senescence-related genes. We established the nomogram based on the senescence score and clinical characteristics. The senescence score showed a positive correlation with epithelial-to-mesenchymal transition, cell cycle, and glycolysis, and a negative correlation with autophagy. Furthermore, we carried out Gene Ontology (GO) analysis to explore the signaling pathways and biological process in different senescence score groups.
CONCLUSIONS
The senescence score, a novel tool constructed in this study, shows promise in predicting survival outcomes across various cancer types. These findings not only highlight the complex interplay between senescence and cancer but also indicate that cellular senescence might serve as a biomarker for tumor prognosis.
PubMed: 38948528
DOI: 10.3389/fendo.2024.1378356 -
Frontiers in Endocrinology 2024Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical,...
BACKGROUND
Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy.
METHODS
Thirty-five patients received LuPRRT for G1/G2 midgut NETs between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 h after the second and the fourth LuPRRT, and at 6-month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT.
RESULTS
Focusing on four mRNAs and three miRNAs, we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year ( < 0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first 2 months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level ( < 0.05) for patients with progressive disease.
CONCLUSION
We present a pilot study exploring a miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in a larger series of patients.
PubMed: 38948517
DOI: 10.3389/fendo.2024.1385079 -
Frontiers in Pharmacology 2024Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated...
Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated with a considerably worse prognosis. Approximately one-third of patients are diagnosed with metastatic disease, with liver metastases being the most prevalent. Diagnosis relies on histopathological alterations including squamous vesicles, positive staining for CK8/CK18/CK19, and nuclear displacement of β-catenin. Additionally, liver metastases demonstrate substantial enhancement during the arterial phase of a contrast-enhanced computed tomography (CT) scan. Surgical resection serves as the principal therapeutic approach for addressing primary lesions and liver metastatic PB. In instances where surgical intervention is not viable, patients may derive benefits from systemic therapy and radiotherapy. This particular case report presents the clinical details of a 27-year-old female patient diagnosed with PB, who subsequently developed multiple liver metastases following a pancreaticoduodenectomy. Genomic examinations revealed the presence of ERBB2 amplification, RAD54L deletion, low TMB-L, and MSS in the patient. Despite the patient undergoing chemotherapy and Her-2 targeted therapy in conjunction with immunotherapy, no reduction in lesion size was observed until the administration of surufatinib. Subsequently, a notable outcome ensued, where the metastatic lesions were effectively excised via surgical intervention. Surufatinib has demonstrated a progression-free survival (PFS) of no less than 14 months, and the patient's survival has endured for a duration of 33 months. This indicates the potential efficacy of surufatinib as a viable therapeutic alternative for adult patients afflicted with PB.
PubMed: 38948477
DOI: 10.3389/fphar.2024.1361628 -
Frontiers in Pharmacology 2024Unfortunately, ovarian cancer is still diagnosed most often only in an advanced stage and is also the most lethal gynecological cancer. Another problem is the fact that... (Review)
Review
Unfortunately, ovarian cancer is still diagnosed most often only in an advanced stage and is also the most lethal gynecological cancer. Another problem is the fact that treated patients have a high risk of disease recurrence. Moreover, ovarian cancer is very diverse in terms of molecular, histological features and mutations. Many patients may also develop platinum resistance, resulting in poor response to subsequent lines of treatment. To improve the prognosis of patients with ovarian cancer, it is expected to make better existing and implement new, promising treatment methods. Targeted therapies seem very promising. Currently, bevacizumab - a VEGF inhibitor and therapy with olaparib - a polyADP-ribose polymerase inhibitor are approved. Other methods worth considering in the future include: folate receptor α, immune checkpoints or other immunotherapy methods. To improve the treatment of ovarian cancer, it is also important to ameliorate the determination of molecular features to describe and understand which group of patients will benefit most from a given treatment method. This is important because a larger group of patients treated for ovarian cancer can have a greater chance of surviving longer without recurrence.
PubMed: 38948462
DOI: 10.3389/fphar.2024.1416555 -
World Journal of Hepatology Jun 2024Non-alcoholic fatty liver disease (NAFLD) was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess...
Non-alcoholic fatty liver disease (NAFLD) was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol. Alcoholic liver disease (ALD) has many similarities to NAFLD in both pathogenesis and histology. This entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of obesity. Attempts to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver disease. This new term, however, has the disadvantage of the use of terms that may be perceived as derogatory. The terms fatty and non-alcoholic have negative connotations in many cultures. In addition, non-alcoholic is not usually a term applicable to pediatric cases of hepatic steatosis. Recently, an international collaborative effort, with participants from 56 countries, after a global consultation process, recommended to change the nomenclature to steatotic liver disease -including metabolic dysfunction- associated steatotic liver disease, metabolic-associated steatohepatitis and metabolic dysfunction-associated ALD. The new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis, prognosis and treatment.
PubMed: 38948440
DOI: 10.4254/wjh.v16.i6.863 -
World Journal of Hepatology Jun 2024Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly...
BACKGROUND
Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published.
AIM
To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.
METHODS
DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. experiment in Huh7 cell was carried out.
RESULTS
LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 .
CONCLUSION
LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.
PubMed: 38948436
DOI: 10.4254/wjh.v16.i6.932 -
World Journal of Hepatology Jun 2024This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the...
This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the treatment of portal hypertension complications worldwide. Innovative ideas, subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice. At the moment, the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents. The transition from bare metal stents to extended polytetrafluoroethylene-covered stent grafts made it possible to significantly prevent shunt dysfunction. However, the question of its preferred diameter, which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy, remains relevant. Currently, hepatic encephalopathy is one of the most common complications of TIPS, significantly affecting its effectiveness and prognosis. Careful selection of patients based on cognitive indicators, nutritional status, assessment of liver function, , will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results. Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications. At the same time, there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.
PubMed: 38948432
DOI: 10.4254/wjh.v16.i6.891 -
Acute Medicine & Surgery 2024When treating burn patients, some patients die in the chronic phase, even if they overcome the acute phase of the burn. To elucidate the timing of death and its...
AIM
When treating burn patients, some patients die in the chronic phase, even if they overcome the acute phase of the burn. To elucidate the timing of death and its underlying causes among burn patients.
METHODS
Patients evaluated were admitted to our burn center between January 2015, and December 2019. Patient information, time, and cause of death were retrospectively collected from their medical records.
RESULTS
Among 342 admitted patients, 49 died. The time of death was as follows: within 24 h ( = 9), within 3 days ( = 7), within 1 week ( = 5), within 2 weeks ( = 4), within 3 weeks ( = 3), within 30 days ( = 6), within 60 days ( = 5), and after 60 days ( = 9). The causes of death within 3 days were hypoxic encephalopathy, extensive burns (>80%), severe heat stroke, and acute coronary syndrome. The causes of death after 3 days were sepsis, pneumonia, intestinal ischemia, pancreatitis, and worsening of chronic diseases. The mortality rate was similar for patients ≥65 years of age and those with a burn area of ≥20%, with both groups showing a particularly poor prognosis.
CONCLUSIONS
The timing of death in hospitalized burn patients showed a bimodal distribution as approximately 40% of patients who survived the resuscitation period died after 30 days. Elderly patients were at particularly high risk for mortality. In burn care, treatment planning should consider not only the short-term but also the long-term prognosis.
PubMed: 38948425
DOI: 10.1002/ams2.970