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Cancer Innovation Aug 2024Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor...
BACKGROUND
Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required.
METHODS
The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms.
RESULTS
NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC.
CONCLUSIONS
NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.
PubMed: 38948253
DOI: 10.1002/cai2.122 -
Cancer Innovation Aug 2024The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as...
BACKGROUND
The current standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer is pertuzumab plus trastuzumab and docetaxel as first-line therapy. However, with the development of newer treatment regimens, there is a lack of evidence regarding which is the optimal treatment strategy. The aim of this network meta-analysis was to evaluate the efficacy and safety of first-line regimens for advanced HER2-positive breast cancer by indirect comparisons.
METHODS
A systematic review and Bayesian network meta-analysis were conducted. The PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles published through to December 2023. The hazard ratio (HR) and 95% credible interval (CrI) were used to compare progression-free survival (PFS) between treatments, and the odds ratio and 95% CrI were used to compare the objective response rate (ORR) and safety.
RESULTS
Twenty randomized clinical trials that included 15 regimens and 7094 patients were analyzed. Compared with the traditional trastuzumab and docetaxel regimen, PFS was longer on the pyrotinib and trastuzumab plus docetaxel regimen (HR: 0.41, 95% CrI: 0.22-0.75) and the pertuzumab and trastuzumab plus docetaxel regimen (HR: 0.65, 95% CrI: 0.43-0.98). Consistent with the results for PFS, the ORR was better on the pyrotinib and trastuzumab plus docetaxel regimen and the pertuzumab and trastuzumab plus docetaxel regimen than on the traditional trastuzumab and docetaxel regimen. The surface under the cumulative ranking curve indicated that the pyrotinib and trastuzumab plus docetaxel regimen was most likely to rank first in achieving the best PFS and ORR. Comparable results were found for grade ≥3 AE rates of ≥10%.
CONCLUSIONS
Our results suggest that the pyrotinib and trastuzumab plus docetaxel regimen is most likely to be the optimal first-line therapy for patients with HER2-positive breast cancer.
PubMed: 38948247
DOI: 10.1002/cai2.126 -
Oncology Research 2024Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated...
BACKGROUND
Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated with tumorigenesis. is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer. However, the mechanism underlying its function in cancer progression remains poorly understood.
METHODS
Here, the regulatory role of in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts.
RESULTS
We found that high levels of expression were associated with shorter overall survival rate of patients, whereas knockdown of inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of induced autophagy and apoptosis. Moreover, we showed that interacted with and stabilized the transcriptional co-repressor Switch-independent 3a (SIN3A), which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner. Silencing of SIN3A also reduced proliferation of lung cancer cells, which was correlated with the induction of autophagy. These observations raise the possibility that functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma.
CONCLUSIONS
Our findings thus identify SIN3A as a -associated protein and should help to understand the mechanism underlying -mediated oncogenesis.
Topics: Humans; RNA, Long Noncoding; Autophagy; Lung Neoplasms; Apoptosis; Animals; Mice; Sin3 Histone Deacetylase and Corepressor Complex; Cell Proliferation; Cell Line, Tumor; Repressor Proteins; Gene Expression Regulation, Neoplastic; Protein Stability; Gene Silencing; Oncogenes; Adenocarcinoma of Lung; Xenograft Model Antitumor Assays
PubMed: 38948024
DOI: 10.32604/or.2023.030771 -
World Journal of Transplantation Jun 2024Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients (KTRs) and has been established as the treatment of choice...
BACKGROUND
Kidney transplantation leads to continuous improvement in the survival rates of kidney transplant recipients (KTRs) and has been established as the treatment of choice for patients with end-stage kidney disease. Health-related quality of life (HRQoL) has become an important outcome measure. It is highly important to develop reliable methods to evaluate HRQoL with disease-specific questionnaires.
AIM
To translate the disease-specific instrument Kidney Transplant Questionnaire 25 (KTQ-25) to the Greek language and perform a cross-cultural adaptation.
METHODS
The translation and adaptation of the original English version of the KTQ-25 to the Greek language were performed based on the International Quality of Life Assessment.
RESULTS
Eighty-four KTRs (59 males; mean age 53.5 ± 10.7 years; mean estimated glomerular filtration rate 47.7 ± 15.1 mL/min/1.73 m; mean transplant vintage 100.5 ± 83.2 months) completed the Greek version of the KTQ-25 and the 36-item Short-Form Health Survey, and the results were used to evaluate the reliability of the Greek KTQ-25. The Cronbach alpha coefficients for all the KTQ-25 dimensions were satisfactory (physical symptoms = 0.639, fatigue = 0.856, uncertainty/fear = 0.661, appearance = 0.593, emotions = 0.718, total score = 0.708). The statistically significant correlation coefficients among the KTQ-25 dimensions ranged from 0.226 to 0.644. The correlation coefficients of the KTQ-25 dimensions with the SF-36 physical component summary (PCS) ranged from 0.196 to 0.550; the correlation coefficients of the KTQ-25 with the SF-36 mental component summary (MCS) ranged from 0.260 to 0.655; and the correlation coefficients of the KTQ-25 with the total scores with the SF-36 PCS and MCS were 0.455 and 0.613, respectively.
CONCLUSION
According to the findings, the Greek version of the KTQ-25 is valid and reliable for administration among kidney transplant patients in Greece.
PubMed: 38947968
DOI: 10.5500/wjt.v14.i2.90825 -
Frontiers in Oncology 2024Endoscopic obstruction (eOB) is associated with a poor prognosis in colorectal cancer (CRC). Our study aimed to investigate the association between tumor location and...
BACKGROUND
Endoscopic obstruction (eOB) is associated with a poor prognosis in colorectal cancer (CRC). Our study aimed to investigate the association between tumor location and eOB, as well as the prognostic differences among non-endoscopic obstruction (N-eOB), eOB with tumor size ≤ 5 cm, and eOB with tumor size > 5 cm in non-elderly patients.
METHODS
We retrospectively reviewed the clinicopathological variables of 230 patients with CRC who underwent curative surgery. The multivariable logistic regression model was used to identify risk factors for eOB. The association between eOB with tumor size ≤ 5 cm and disease-free survival (DFS) was evaluated using multivariate cox regression analysis.
RESULTS
A total of 87 patients had eOB while 143 had N-eOB. In multivariate analysis, preoperative carcinoembryonic antigen ( = 0.014), tumor size ( = 0.010), tumor location (left-side colon; = 0.033; rectum; < 0.001), and pT stage (T3, = 0.009; T4, < 0.001) were significant factors of eOB. The DFS rate for eOB with tumor size ≤ 5 cm was significantly lower ( < 0.001) in survival analysis. The eOB with tumor size ≤ 5 cm ( = 0.012) was an unfavorable independent factor for DFS.
CONCLUSIONS
The patients with eOB were significantly associated with right-side colon cancer as opposed to left-side colon cancer and rectal cancer. The eOB with tumor size ≤ 5 cm was an independent poor prognostic factor. Further studies are needed to target these high-risk groups.
PubMed: 38947895
DOI: 10.3389/fonc.2024.1415345 -
Frontiers in Oncology 2024Glioma is the most common type of primary malignant tumor of the central nervous system (CNS), and is characterized by high malignancy, high recurrence rate and poor... (Review)
Review
Glioma is the most common type of primary malignant tumor of the central nervous system (CNS), and is characterized by high malignancy, high recurrence rate and poor survival. Conventional imaging techniques only provide information regarding the anatomical location, morphological characteristics, and enhancement patterns. In contrast, advanced imaging techniques such as dynamic contrast-enhanced (DCE) MRI or DCE CT can reflect tissue microcirculation, including tumor vascular hyperplasia and vessel permeability. Although several studies have used DCE imaging to evaluate gliomas, the results of data analysis using conventional tracer kinetic models (TKMs) such as Tofts or extended-Tofts model (ETM) have been ambiguous. More advanced models such as Brix's conventional two-compartment model (Brix), tissue homogeneity model (TH) and distributed parameter (DP) model have been developed, but their application in clinical trials has been limited. This review attempts to appraise issues on glioma studies using conventional TKMs, such as Tofts or ETM model, highlight advancement of DCE imaging techniques and provides insights on the clinical value of glioma management using more advanced TKMs.
PubMed: 38947892
DOI: 10.3389/fonc.2024.1380793 -
Frontiers in Oncology 2024While the incidence of small-cell lung cancer is low, it has a poor prognosis. Patients with extensive small-cell lung cancer account for about 70% of all cases of...
While the incidence of small-cell lung cancer is low, it has a poor prognosis. Patients with extensive small-cell lung cancer account for about 70% of all cases of small-cell lung cancer, with a median overall survival duration of 8-13 months and a 5-year overall survival rate of only 1%-5%. Herein, we report small-cell lung cancer diagnosed by bronchoscopic biopsy in an adult male patient in 2011. The patient had a clinical stage of cT2N2M1 and stage IV disease (i.e., extensive small-cell lung cancer). Still, he survived for 13 years through a combination of chemotherapy, radiotherapy, and cytokine-induced killer (CIK) immunocell thera. Comprehensive tumor markers, lymphocyte subsets, and lung CT images were obtained through long-term follow-up. After 12 cycles of chemotherapy (CE/IP regimen) and 5940cgy/33f radiotherapy, we found that the patient was in an immunosuppressive state, so the patient was given CIK cell therapy combined with chemotherapy. After 2 years of immunocell-combined chemotherapy, there were no significant changes in the primary lesion or other adverse events. In the 13 years since the patient's initial diagnosis, we monitored the changes in the patient's indicators such as CEA, NSE, CD4/CD8 ratio, and CD3+CD4+ lymphocytes, suggesting that these may be the factors worth evaluating regarding the patient's immune status and the effectiveness of combination therapy. In this case, CIK cell immunotherapy combined with chemotherapy was applied to control tumor progression. With a good prognosis, we concluded that CIK cell immunotherapy combined with chemotherapy can prolong patient survival in cases of extensive small-cell lung cancer, and the advantages of combined therapy are reflected in improving the body's immune capacity and enhancing the killing effect of immune cells.
PubMed: 38947891
DOI: 10.3389/fonc.2024.1389725 -
Journal of Clinical Orthopaedics and... Jun 2024Traumatic cervical spine injury is common among spinal cord injury which requires an intensive, multidisciplinary approach which can affect the immediate postoperative...
BACKGROUND
Traumatic cervical spine injury is common among spinal cord injury which requires an intensive, multidisciplinary approach which can affect the immediate postoperative hospital survival rate. By identifying the risk factors leading to early mortality in cervical spine trauma patients, the prognosis of patients with TCSCI can be better predicted.
OBJECTIVE
The study aims to analyze the variables influencing in-hospital mortality in cervical spine trauma patients treated at a Level I trauma Center.
METHODS
Prospective study was conducted on subaxial cervical spine injuries from July 2019 to March 2022. Patients were divided into two groups: Group A, with in-hospital mortality, and Group B, who got discharged from hospital, and mortality predictors were reviewed and analyzed for as potential risk factors for in-hospital mortality.
RESULTS
Out of 105 patients, 83.8 % were male with mean age of 40.43 ± 12.62 years. On univariate analysis, AIS (p-value: <0.01), ICU stay (p-value: <0.01), level of injury (p-value: <0.01), and MRI parameters like the extent of Parenchymal damage (p-value: <0.01), MSCC (p-value: <0.01), and MCC (p-value: <0.01) were potential risk factors for in-hospital mortality. On multivariate regression analysis AIS at presentation (p-value: 0.02) was the only significant independent parameter for in-hospital mortality.
CONCLUSIONS
AIS grading at presentation, duration of ICU stay, level of injury, rate of tracheostomy, and MRI parameters like the extent of parenchymal damage, MCC, and MSCC influence and predicts in-hospital mortality, whereas AIS is the only independent risk factor.
PubMed: 38947859
DOI: 10.1016/j.jcot.2024.102440 -
Kidney Medicine Jul 2024The option for A2/A2B deceased donor kidney transplantation was integrated into the kidney allocation system in 2014 to improve access for B blood group waitlist...
RATIONALE & OBJECTIVE
The option for A2/A2B deceased donor kidney transplantation was integrated into the kidney allocation system in 2014 to improve access for B blood group waitlist candidates. Despite excellent reported outcomes, center uptake has remained low across the United States. Here, we examined the effect of implementing an A2/A2B protocol using a cutoff titer of ≤1:8 for IgG and ≤1:16 for IgM on blood group B kidney transplant recipients at a single center.
STUDY DESIGN
Retrospective observational study.
SETTING & PARTICIPANTS
Blood group B recipients of deceased donor kidney transplants at a single center from January 1, 2019, to December 2022.
EXPOSURE
Recipients of deceased donor kidney transplants were analyzed based on donor blood type with comparisons of A2/A2B versus blood group compatible.
OUTCOMES
One-year patient survival, death-censored allograft function, primary nonfunction, delayed graft function, allograft function as measured using serum creatinine levels and estimated glomerular filtration rate at 1 year, biopsy-proven rejection, and need for plasmapheresis.
ANALYTICAL APPROACH
Comparison between the A2/A2B and compatible groups were performed using the Fisher test or the χ test for categorical variables and the nonparametric Wilcoxon rank-sum test for continuous variables.
RESULTS
A total of 104 blood type B patients received a deceased donor kidney transplant at our center during the study period, 49 (47.1%) of whom received an A2/A2B transplant. Waiting time was lower in A2/A2B recipients compared with blood group compatible recipients (57.9 months vs 74.7 months, = 0.01). A2/A2B recipients were more likely to receive a donor after cardiac death (24.5% vs 1.8%, < 0.05) and experience delayed graft function (65.3% vs 41.8%). There were no observed differences in the average serum creatinine level or estimated glomerular filtration rate at 1 month, 3 months, and 1 year post kidney transplantation, acute rejection, or primary nonfunction.
LIMITATIONS
Single-center study. Small cohort size limiting outcome analysis.
CONCLUSIONS
Implementation of an A2/A2B protocol increased transplant volumes of blood group B waitlisted patients by 83.6% and decreased the waiting time for transplantation by 22.5% with similar transplant outcomes.
PubMed: 38947773
DOI: 10.1016/j.xkme.2024.100843 -
Endoscopic Ultrasound 2024To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (I) seeds with absolute ethanol for relieving pain in...
Clinical efficacy of EUS-guided celiac plexus neurolysis EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.
BACKGROUND AND OBJECTIVE
To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer.
METHODS
We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups.
RESULTS
EUS-CPN and I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure.
CONCLUSIONS
Both EUS-CPN and EUS-I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.
PubMed: 38947749
DOI: 10.1097/eus.0000000000000048