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Scientific Reports Jun 2024Metabolic reprogramming is widely recognized as a hallmark of malignant tumors, and the targeting of metabolism has emerged as an appealing approach for cancer...
Metabolic reprogramming is widely recognized as a hallmark of malignant tumors, and the targeting of metabolism has emerged as an appealing approach for cancer treatment. Mitochondria, as pivotal organelles, play a crucial role in the metabolic regulation of tumor cells, and their morphological and functional alterations are intricately linked to the biological characteristics of tumors. As a key regulatory subunit of mitochondria, mitochondrial inner membrane protein (IMMT), plays a vital role in degenerative diseases, but its role in tumor is almost unknown. The objective of this research was to investigate the roles that IMMT play in the development and progression of breast cancer (BC), as well as to elucidate the underlying biological mechanisms that drive these effects. In this study, it was confirmed that the expression of IMMT in BC tissues was significantly higher than that in normal tissues. The analysis of The Cancer Genome Atlas (TCGA) database revealed that IMMT can serve as an independent prognostic factor for BC patients. Additionally, verification in clinical specimens of BC demonstrated a positive association between high IMMT expression and larger tumor size (> 2 cm), Ki-67 expression (> 15%), and HER-2 status. Furthermore, in vitro experiments have substantiated that the suppression of IMMT expression resulted in a reduction in cell proliferation and alterations in mitochondrial cristae, concomitant with the liberation of cytochrome c, but it did not elicit mitochondrial apoptosis. Through Gene Set Enrichment Analysis (GSEA) analysis, we have predicted the associated metabolic genes and discovered that IMMT potentially modulates the advancement of BC through its interaction with 16 metabolic-related genes, and the changes in glycolysis related pathways have been validated in BC cell lines after IMMT inhibition. Consequently, this investigation furnishes compelling evidence supporting the classification of IMMT as prognostic marker in BC, and underscoring its prospective utility as a novel target for metabolic therapy.
Topics: Humans; Breast Neoplasms; Female; Cell Proliferation; Mitochondria; Mitochondrial Proteins; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Middle Aged; Prognosis; Membrane Proteins; Biomarkers, Tumor; MCF-7 Cells; Muscle Proteins
PubMed: 38834715
DOI: 10.1038/s41598-024-63427-8 -
International Journal of Epidemiology Apr 2024While previous studies indicate muscle-strengthening exercises may reduce mortality risk, further research is needed to increase certainty of the evidence. We...
BACKGROUND
While previous studies indicate muscle-strengthening exercises may reduce mortality risk, further research is needed to increase certainty of the evidence. We investigated overall and dose-response associations between weight training and the risks of all-cause, cardiovascular disease (CVD) and cancer mortality in a large cohort of older adults with long follow-up time and a large number of deaths. We also investigated the joint associations of weight training and aerobic exercise with mortality risk.
METHODS
Weight training was assessed via self-report in 2004-05 in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study (USA; n = 216 339), with follow-up to 2019. Cox regression estimated the hazard ratios (HR) and 95% confidence intervals (CI) for the associations between weight training and mortality, after adjusting for confounders including aerobic exercise.
RESULTS
Around 25% of participants [mean age = 69.9 years (standard deviation = 5.4), 58% men] reported engaging in weight training over the past year, and there were 79 107 (37%) deaths. Engaging in any weight training (vs none) was associated with lower risks of all-cause (HR = 0.94; 95% CI = 0.93-0.96), CVD (HR = 0.92; 95% CI = 0.90-0.95) and cancer mortality (HR = 0.95; 95% CI = 0.92-0.98). More time spent in weight training was associated with only marginally greater risk reductions. Larger risk reductions were observed among women than men. Performing both aerobic exercise and weight training conferred the greatest mortality risk reduction; weight training was not associated with mortality risk among participants who did no aerobic exercise.
CONCLUSION
Performing any amount of weight training lowered mortality risk.
Topics: Humans; Male; Female; Cardiovascular Diseases; Aged; Neoplasms; Middle Aged; Exercise; Proportional Hazards Models; United States; Resistance Training; Risk Factors; Cause of Death
PubMed: 38831478
DOI: 10.1093/ije/dyae074 -
International Journal of Colorectal... Jun 2024Lymph node metastasis (LNM) in colorectal cancer (CRC) patients is not only associated with the tumor's local pathological characteristics but also with systemic...
OBJECTIVES
Lymph node metastasis (LNM) in colorectal cancer (CRC) patients is not only associated with the tumor's local pathological characteristics but also with systemic factors. This study aims to assess the feasibility of using body composition and pathological features to predict LNM in early stage colorectal cancer (eCRC) patients.
METHODS
A total of 192 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in the study. The cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat at the L3 vertebral body level in CT scans were measured using Image J software. Logistic regression analysis were conducted to identify the risk factors for LNM. The predictive accuracy and discriminative ability of the indicators were evaluated using receiver operating characteristic (ROC) curves. Delong test was applied to compare area under different ROC curves.
RESULTS
LNM was observed in 32 out of 192 (16.7%) patients with eCRC. Multivariate analysis revealed that the ratio of skeletal muscle area to visceral fat area (SMA/VFA) (OR = 0.021, p = 0.007) and pathological indicators of vascular invasion (OR = 4.074, p = 0.020) were independent risk factors for LNM in eCRC patients. The AUROC for SMA/VFA was determined to be 0.740 (p < 0.001), while for vascular invasion, it was 0.641 (p = 0.012). Integrating both factors into a proposed predictive model resulted in an AUROC of 0.789 (p < 0.001), indicating a substantial improvement in predictive performance compared to relying on a single pathological indicator.
CONCLUSION
The combination of the SMA/VFA ratio and vascular invasion provides better prediction of LNM in eCRC.
Topics: Humans; Male; Female; Colorectal Neoplasms; Middle Aged; Lymphatic Metastasis; Body Composition; ROC Curve; Aged; Neoplasm Invasiveness; Neoplasm Staging; Tomography, X-Ray Computed; Risk Factors; Intra-Abdominal Fat; Adult; Retrospective Studies; Multivariate Analysis; Muscle, Skeletal; Blood Vessels
PubMed: 38829434
DOI: 10.1007/s00384-024-04653-4 -
Oncology Research 2024Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related...
BACKGROUND
Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC.
METHODS
Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.
CONCLUSION
There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.
Topics: Humans; Urinary Bladder Neoplasms; Ataxia Telangiectasia Mutated Proteins; Cisplatin; Cytidine Deaminase; Cell Line, Tumor; Male; Minor Histocompatibility Antigens; Middle Aged; Female; Checkpoint Kinase 1; Apoptosis; Aged; Neoplasm Invasiveness; Cell Proliferation; Cell Survival
PubMed: 38827321
DOI: 10.32604/or.2024.048919 -
Cureus May 2024The incidence of facial nerve paralysis is approximately 30 per 100,000 persons annually. Although it is often idiopathic, as in Bell's palsy, it can also result from... (Review)
Review
The incidence of facial nerve paralysis is approximately 30 per 100,000 persons annually. Although it is often idiopathic, as in Bell's palsy, it can also result from infections, trauma, or neoplasms. Facial nerve paralysis may present with partial or total facial paresis, lagophthalmos, denervation of the lacrimal gland, and other ocular abnormalities. While dry eye is a commonly expected outcome of facial nerve injury, some patients may paradoxically experience epiphora and hyperlacrimation. In this review, we examine this phenomenon and its mechanisms in facial nerve injury. Several mechanisms have been proposed for epiphora and hyperlacrimation, including aberrant axonal regeneration, which is known to cause crocodile tears syndrome; ocular irritation due to dry eye, resulting in increased reflex lacrimation due to disruption of the tear film; and impaired drainage of tears caused by paralysis of the orbicularis oculi muscle and malposition of the eyelids. Understanding the pathophysiology of these symptoms is crucial in guiding the management of patients with facial nerve injury. Further experimental and clinical studies focusing on the quantification of tear production and localization of nerve damage will help improve our understanding of the neuroanatomical correlates of this paradoxical manifestation.
PubMed: 38826950
DOI: 10.7759/cureus.59440 -
Journal of Cardiothoracic Surgery May 2024Lung cancer is the second most diagnosed cancer and the leading cause of cancer deaths worldwide. Surgical lung resection is the best treatment modality in the early...
BACKGROUND
Lung cancer is the second most diagnosed cancer and the leading cause of cancer deaths worldwide. Surgical lung resection is the best treatment modality in the early stages of lung cancer as well as in some locally advanced cases. Postoperative air leak is one of the most common complications after pulmonary resection with incidence ranging between 20 and 33%. The majority of air leaks seal, within 5 days after surgery, on their own by conservative management. However, at least 5% of patients still have prolonged air coming out from the residual lung at discharge. This report describes the management of a thin lady with right lung cancer who underwent a right lower lobectomy and then suffered from a delayed air leak 7 weeks after surgery and required extensive thoracic and general surgery collaboration.
CASE PRESENTATION
A 72-year-old heavy smoker female patient diagnosed with stage I lung cancer underwent right robotic-assisted thoracoscopic surgery converted to thoracotomy because of a fused fissure, right lower lobectomy, and mediastinal lymphadenectomy presented with delayed air leak 49 days after surgery. VATS decortication and mechanical pleurodesis were done 2 weeks after unsuccessful conservative treatment. Still, the lung failed to expand four weeks later so the patient was sent to surgery; she is underweight (BMI of 18) with not many options for a big flap to fill the chest cavity empty space. Accordingly; the decision was to use multiple pedicle flaps; omentum, intercostal muscle, and serratus anterior muscle to cover the bronchopleural fistulas and fill the pleural space in addition to mechanical and chemical pleurodesis. Full expansion of the lung was obtained. The patient was discharged on Post-Operative day 5 without remnant pneumothorax.
CONCLUSIONS
Air leaks After lobectomy usually presents directly postoperatively; various management options are available ranging from conservative and minimally invasive to major operative treatment. We presented what we believe was unusual delayed bronchopleural fistula post-lobectomy in a thin lady which demonstrates clearly how a delayed air leak was detected and how collaborative efforts were crucial for delivering high-quality, safe, and patient-centered care till treated and complete recovery.
Topics: Humans; Female; Aged; Pneumonectomy; Lung Neoplasms; Bronchial Fistula; Pleural Diseases; Postoperative Complications; Thoracic Surgery, Video-Assisted
PubMed: 38822353
DOI: 10.1186/s13019-024-02795-8 -
Cancer Medicine Jun 2024En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist... (Meta-Analysis)
Meta-Analysis Review Comparative Study
BACKGROUND
En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist regarding the comparisons between ERBT and conventional transurethral resection of bladder tumor (cTURBT).
METHODS
We conducted a comprehensive search in PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and performed manual searches of reference lists to collect and extract data. Data evaluation was carried out using Review Manager 5.4.0, Rx64 4.1.3, and relevant packages.
RESULTS
There were nine eligible meta-analyses and nine eligible RCTs in our study. NMIBC patients undergoing ERBT were significant associated with a lower rate of bladder perforation and obturator nerve reflex compared to those receiving cTURBT. Our pooled result indicated that ERBT and cTURBT required similar operation time. Regarding postoperative outcomes, ERBT demonstrated superior performance compared to cTURBT in terms of detrusor muscle presence, catheterization time, and residual tumor. ERBT exhibited a higher rate of three-month recurrence-free survival (RFS) compared to those receiving cTURBT (p < 0.05; I = 0%). In bipolar subgroup, ERBT had a significant better 12-month RFS than cTURBT (p < 0.05; I = 0%). Simultaneously, the exclusion of Hybrid Knife data revealed a significant improvement in 12-month RFS associated with ERBT (p < 0.05; I = 50%).
CONCLUSION
Using a combination of umbrella review and meta-analysis, we demonstrated that ERBT had better or comparable perioperative outcome and improved 3 and 12 month RFS than cTURBT. We suggest that ERBT maybe a better surgical method for patients with NMIBC compared with cTURBT.
Topics: Humans; Urinary Bladder Neoplasms; Cystectomy; Treatment Outcome; Urethra; Neoplasm Invasiveness; Non-Muscle Invasive Bladder Neoplasms
PubMed: 38819629
DOI: 10.1002/cam4.7323 -
BMC Neurology May 2024Spinal cord malignant melanotic schwannoma (MMNST) is a rare central nervous system tumor that originates from the spinal cord or spinal myelin sheath cells and can...
Spinal cord malignant melanotic schwannoma (MMNST) is a rare central nervous system tumor that originates from the spinal cord or spinal myelin sheath cells and can produce melanin. This type of tumor is usually highly aggressive and malignant, with a poor prognosis. The clinical manifestations of spinal cord MMNST are mainly pain, paresthesia, muscle weakness, muscle atrophy, etc., and symptoms of spinal cord compression, such as intestinal and bladder dysfunction, paraplegia, etc. Early detection of tumor lesions can facilitate tumor removal, improve patients' quality of life, and prolong patients' survival. In this case report, a 27-year-old young woman was diagnosed with MMNST of the cervical spinal cord due to weakness of her limbs in our hospital, and underwent surgical resection. The patient's limbs returned to normal after surgery. It is worth mentioning that the patient visited our hospital 7 months ago for "right upper limb pain for 3 days" and was diagnosed with a cervical spine space-occupying lesion at the same position this time, but the pathology report was "hemosiderosis". The patient's limbs returned to normal after surgery. It is worth mentioning that the patient visited our hospital 7 months ago for "right upper limb pain for 3 days" and was diagnosed with a cervical spine space-occupying lesion at the same position this time, but the pathology report was "hemosiderosis". This case report aims to raise awareness of the problem of spinal cord MMNST and contribute to greater knowledge of this rare tumor. This case report aims to raise awareness of the problem of spinal cord MMNST and contribute to greater knowledge of this rare tumor.
Topics: Humans; Female; Adult; Spinal Cord Neoplasms; Neurilemmoma; Cervical Cord; Cervical Vertebrae
PubMed: 38816740
DOI: 10.1186/s12883-024-03686-0 -
Turkish Journal of Medical Sciences 2023Cysteine and glycine-rich protein 1 (CSRP1) is involved in the cysteine-rich protein family and is a marker of smooth muscle lineages. In colon cancer, the expression of...
BACKGROUND/AIM
Cysteine and glycine-rich protein 1 (CSRP1) is involved in the cysteine-rich protein family and is a marker of smooth muscle lineages. In colon cancer, the expression of this gene is associated with poor prognosis. In this study, the aim was to reevaluate its prognostic relationship in independent cohorts and explore potential underlying biological processes that are linked to aggressive behavior in tumors with high CSRP1 expression, such as epithelial-to-mesenchymal transition (EMT), stromal fractions in the tumor microenvironment, and consensus molecular subtypes (CMSs).
MATERIALS AND METHODS
RNA sequencing (RNAseq)-, microarray-, and single-cell RNAseq (scRNAseq)-based transcriptomic data were obtained from public databases. The EMT score was calculated based on the expression of E-cadherin and vimentin genes using a previously published method. The stromal score generated by the ESTIMATE method was utilized for the analysis of correlation with the CSRP1 expression. The scRNAseq data were analyzed via the Seurat R package. The immunohistochemistry-based protein level expression of CSRP1 was evaluated using the Human Protein Atlas database.
RESULTS
Lower CSRP1 expression was noted in colon tumors compared to normal colon tissue. Patients with a high CSRP1 expression had shorter recurrence-free, overall, and disease-specific survivals in the GSE39582 and GSE17536 datasets (p < 0.05). The methylation level of the CSRP1 gene was negatively correlated (r = -0.57, p < 0.0001) with CSRP1 expression in The Cancer Genome Atlas colon adenocarcinoma dataset. CSRP1 expression was positively correlated with the expression of mesenchymal markers, EMT score, and stromal score obtained via the ESTIMATE method. CMS4 colon tumors had a significantly higher CSRP1 expression compared to other CMSs. Analysis of the scRNAseq data revealed that CSRP1 was expressed by epithelial cells and cancer-associated fibroblasts in the colorectal tumor microenvironment, which was also confirmed by the protein expression data from the Human Protein Atlas database.
CONCLUSION
CSRP1 expression is associated with CMS4, a more mesenchymal stroma-rich molecular profile, and poor prognosis in colon cancer.
Topics: Humans; Colonic Neoplasms; Prognosis; Epithelial-Mesenchymal Transition; Male; Biomarkers, Tumor; Female; Tumor Microenvironment; Middle Aged; Repressor Proteins; Aged
PubMed: 38813484
DOI: 10.55730/1300-0144.5736 -
World Journal of Gastroenterology May 2024Cirrhosis is frequently associated with sarcopenia, with reported rates of over 80% in patients with decompensated alcohol-related liver disease. Sarcopenia negatively...
Cirrhosis is frequently associated with sarcopenia, with reported rates of over 80% in patients with decompensated alcohol-related liver disease. Sarcopenia negatively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma (HCC). For these reasons, identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population. Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia, but exposure to radiation and high costs limit its application in this setting, especially for repeated assessments. We believe that ultrasound, a cheap and harmless technique also used for HCC screening in cirrhotic patients, could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.
Topics: Sarcopenia; Humans; Ultrasonography; Liver Cirrhosis; Carcinoma, Hepatocellular; Tomography, X-Ray Computed; Prognosis; Liver Neoplasms; Muscle, Skeletal
PubMed: 38813055
DOI: 10.3748/wjg.v30.i17.2287