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BMC Cancer Jun 2024Basement membrane (BM) is an important component of the extracellular matrix, which plays an important role in the growth and metastasis of tumor cells. However, few...
BACKGROUND
Basement membrane (BM) is an important component of the extracellular matrix, which plays an important role in the growth and metastasis of tumor cells. However, few biomarkers based on BM have been developed for prognostic assessment and prediction of immunotherapy in bladder cancer (BLCA).
METHODS
In this study, we used the BLCA public database to explore the relationship between BM-related genes (BMRGs) and prognosis. A novel molecular typing of BLCA was performed using consensus clustering. LASSO regression was used to construct a signature based on BMRGs, and its relationship with prognosis was explored using survival analysis. The pivotal BMRGs were further analyzed to assess its clinical characteristics and immune landscape. Finally, immunohistochemistry was used to detect the expression of the hub gene in BLCA patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy in our hospital.
RESULTS
We comprehensively analyzed the relationship between BMRGs and BLCA, and established a prognostic-related signature which was an independent influence on the prognostic prediction of BLCA. We further screened and validated the pivotal gene-MMP14 in public database. In addition, we found that MMP14 expression in muscle invasive bladder cancer (MIBC) was significantly higher and high MMP14 expression had a poorer response to ICI treatment in our cohort.
CONCLUSIONS
Our findings highlighted the satisfactory value of BMRGs and suggested that MMP14 may be a potential biomarker in predicting prognosis and response to immunotherapy in BLCA.
Topics: Humans; Urinary Bladder Neoplasms; Prognosis; Immunotherapy; Biomarkers, Tumor; Matrix Metalloproteinase 14; Male; Basement Membrane; Female; Aged; Middle Aged; Immune Checkpoint Inhibitors; Gene Expression Regulation, Neoplastic
PubMed: 38898429
DOI: 10.1186/s12885-024-12489-y -
International Journal of Molecular... Jun 2024Breast cancer is influenced by factors such as diet, a sedentary lifestyle, obesity, and postmenopausal status, which are all linked to prolonged hormonal and...
Breast cancer is influenced by factors such as diet, a sedentary lifestyle, obesity, and postmenopausal status, which are all linked to prolonged hormonal and inflammatory exposure. Physical activity offers protection against breast cancer by modulating hormones, immune responses, and oxidative defenses. This study aimed to assess how a prolonged high-fat diet (HFD) affects the effectiveness of physical activity in preventing and managing mammary tumorigenesis. Ovariectomised C57BL/6 mice were provided with an enriched environment to induce spontaneous physical activity while being fed HFD. After 44 days (short-term, ST HFD) or 88 days (long-term, LT HFD), syngenic EO771 cells were implanted into mammary glands, and tumour growth was monitored until sacrifice. Despite similar physical activity and food intake, the LT HFD group exhibited higher visceral adipose tissue mass and reduced skeletal muscle mass. In the tumour microenvironment, the LT HFD group showed decreased NK cells and TCD8+ cells, with a trend toward increased T regulatory cells, leading to a collapse of the T8/Treg ratio. Additionally, the LT HFD group displayed decreased tumour triglyceride content and altered enzyme activities indicative of oxidative stress. Prolonged exposure to HFD was associated with tumour growth despite elevated physical activity, promoting a tolerogenic tumour microenvironment. Future studies should explore inter-organ exchanges between tumour and tissues.
Topics: Animals; Diet, High-Fat; Female; Mice; Mice, Inbred C57BL; Physical Conditioning, Animal; Tumor Microenvironment; Oxidative Stress; Carcinogenesis; Mammary Neoplasms, Experimental; Cell Line, Tumor; Mammary Neoplasms, Animal; Intra-Abdominal Fat; Killer Cells, Natural
PubMed: 38892407
DOI: 10.3390/ijms25116221 -
International Journal of Molecular... May 2024Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year...
Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year survival rate of only 7%. The anatomical location of the pancreas and lack of symptoms in patients with early onset of disease accounts for late diagnosis. Consequently, 85% of patients present with non-resectable, locally advanced, or advanced metastatic disease at diagnosis and rely on alternative therapies such as chemotherapy, immunotherapy, and others. The response to these therapies highly depends on the stage of disease at the start of therapy. It is, therefore, vital to consider the stages of PDAC models in preclinical studies when testing new therapeutics and treatment modalities. We report a standardized induction of cell-based orthotopic pancreatic cancer models in mice and the identification of vital features of their progression by ultrasound imaging and histological analysis of the level of pancreatic stellate cells, mature fibroblasts, and collagen. The results highlight that early-stage primary tumors are secluded in the pancreas and advance towards infiltrating the omentum at week 5-7 post implantation of the BxPC-3 and Panc-1 models investigated. Late stages show extensive growth, the infiltration of the omentum and/or stomach wall, metastases, augmented fibroblasts, and collagen levels. The findings can serve as suggestions for defining of orthotopic pancreatic cancer models for the preclinical testing of drug efficacy in the future.
Topics: Animals; Pancreatic Neoplasms; Mice; Carcinoma, Pancreatic Ductal; Humans; Disease Models, Animal; Cell Line, Tumor
PubMed: 38891809
DOI: 10.3390/ijms25115619 -
The Journal of Pathology. Clinical... Jul 2024Evidence for the tumour-supporting capacities of the tumour stroma has accumulated rapidly in colorectal cancer (CRC). Tumour stroma is composed of heterogeneous cells...
Evidence for the tumour-supporting capacities of the tumour stroma has accumulated rapidly in colorectal cancer (CRC). Tumour stroma is composed of heterogeneous cells and components including cancer-associated fibroblasts (CAFs), small vessels, immune cells, and extracellular matrix proteins. The present study examined the characteristics of CAFs and collagen, major components of cancer stroma, by immunohistochemistry and Sirius red staining. The expression status of five independent CAF-related or stromal markers, decorin (DCN), fibroblast activation protein (FAP), podoplanin (PDPN), alpha-smooth muscle actin (ACTA2), and collagen, and their association with clinicopathological features and clinical outcomes were analysed. Patients with DCN-high tumours had a significantly worse 5-year survival rate (57.3% versus 79.0%; p = 0.044). Furthermore, hierarchical clustering analyses for these five markers identified three groups that showed specific characteristics: a solid group (cancer cell-rich, DCNPDPN); a PDPN-dominant group (DCNPDPN); and a DCN-dominant group (DCNPDPN), with a significant association with patient survival (p = 0.0085). Cox proportional hazards model identified the PDPN-dominant group (hazard ratio = 0.50, 95% CI = 0.26-0.96, p = 0.037) as a potential favourable factor compared with the DCN-dominant group. Of note, DCN-dominant tumours showed the most advanced pT stage and contained the lowest number of CD8+ and FOXP3+ immune cells. This study has revealed that immunohistochemistry and special staining of five stromal factors with hierarchical clustering analyses could be used for the prognostication of patients with CRC. Cancer stroma-targeting therapies may be candidate treatments for patients with CRC.
Topics: Humans; Colorectal Neoplasms; Male; Female; Biomarkers, Tumor; Cancer-Associated Fibroblasts; Aged; Middle Aged; Cluster Analysis; Immunohistochemistry; Tumor Microenvironment; Prognosis; Membrane Glycoproteins; Stromal Cells; Decorin; Adult; Aged, 80 and over; Kaplan-Meier Estimate
PubMed: 38890810
DOI: 10.1002/2056-4538.12386 -
Cardio-oncology (London, England) Jun 2024The effects of exercise in patients with breast cancer (BC), has shown some profit, but consistency and magnitude of benefit remains unclear. We aimed to conduct a... (Review)
Review
BACKGROUND
The effects of exercise in patients with breast cancer (BC), has shown some profit, but consistency and magnitude of benefit remains unclear. We aimed to conduct a meta-analysis to assess the benefits of varying types of exercises in patients with BC.
METHODS
Literature search was conducted across five electronic databases (MEDLINE, Web of Science, Scopus, Google Scholar and Cochrane) from 1st January 2000 through 19th January 2024. Randomized controlled trials (RCTs) assessing the impact of different types of exercise on outcomes related to fitness and quality of life (QOL) in patients with BC were considered for inclusion. Outcomes of interest included cardiorespiratory fitness (CRF), health-related quality of life (HRQOL), muscle strength, fatigue and physical function. Evaluations were reported as mean differences (MDs) with 95% confidence intervals (CIs) and pooled using random effects model. A p value < 0.05 was considered significant.
RESULTS
Thirty-one relevant articles were included in the final analysis. Exercise intervention did not significantly improved the CRF in patients with BC when compared with control according to treadmill ergometer scale (MD: 4.96; 95%Cl [-2.79, 12.70]; P = 0.21), however exercise significantly improved CRF according to cycle ergometer scales (MD 2.07; 95% Cl [1.03, 3.11]; P = 0.0001). Physical function was significantly improved as well in exercise group reported by 6-MWT scale (MD 80.72; 95% Cl [55.67, 105.77]; P < 0.00001). However, exercise did not significantly improve muscle strength assessed using the hand grip dynamometer (MD 0.55; 95% CI [-1.61, 2.71]; P = 0.62), and fatigue assessed using the MFI-20 (MD -0.09; 95% CI [-5.92, 5.74]; P = 0.98) and Revised Piper scales (MD -0.26; 95% CI [-1.06, 0.55] P = 0.53). Interestingly, exercise was found to improve HRQOL when assessed using the FACT-B scale (MD 8.57; 95% CI [4.53, 12.61]; P < 0.0001) but no significant improvements were noted with the EORTIC QLQ-C30 scale (MD 1.98; 95% CI [-1.43, 5.40]; P = 0.25).
CONCLUSION
Overall exercise significantly improves the HRQOL, CRF and physical function in patients with BC. HRQOL was improved with all exercise types but the effects on CRF vary with cycle versus treadmill ergometer. Exercise failed to improve fatigue-related symptoms and muscle strength. Large RCTs are required to evaluate the effects of exercise in patients with BC in more detail.
PubMed: 38890692
DOI: 10.1186/s40959-024-00235-z -
BMC Cancer Jun 2024Sarcopenia is characterized by reduced skeletal muscle volume and is a condition that is prevalent among elderly patients and associated with poor prognosis as a...
BACKGROUND
Sarcopenia is characterized by reduced skeletal muscle volume and is a condition that is prevalent among elderly patients and associated with poor prognosis as a comorbidity in malignancies. Given the aging population over 80 years old in Japan, an understanding of malignancies, including colorectal cancer (CRC), complicated by sarcopenia is increasingly important. Therefore, the focus of this study is on a novel and practical diagnostic approach of assessment of psoas major muscle volume (PV) using 3-dimensional computed tomography (3D-CT) in diagnosis of sarcopenia in patients with CRC.
METHODS
The subjects were 150 patients aged ≥ 80 years with CRC who underwent primary tumor resection at Juntendo University Hospital between 2004 and 2017. 3D-CT measurement of PV and conventional CT measurement of the psoas major muscle cross-sectional area (PA) were used to identify sarcopenia (group S) and non-sarcopenia (group nS) cases. Clinicopathological characteristics, operative results, postoperative complications, and prognosis were compared between these groups.
RESULTS
The S:nS ratios were 15:135 for the PV method and 52:98 for the PA method. There was a strong positive correlation (r = 0.66, p < 0.01) between PVI (psoas major muscle volume index) and PAI (psoas major muscle cross-sectional area index), which were calculated by dividing PV or PA by the square of height. Surgical results and postoperative complications did not differ significantly in the S and nS groups defined using each method. Overall survival was worse in group S compared to group nS identified by PV (p < 0.01), but not significantly different in groups S and nS identified by PA (p = 0.77). A Cox proportional hazards model for OS identified group S by PV as an independent predictor of a poor prognosis (p < 0.05), whereas group S by PA was not a predictor of prognosis (p = 0.60).
CONCLUSIONS
The PV method for identifying sarcopenia in elderly patients with CRC is more practical and sensitive for prediction of a poor prognosis compared to the conventional method.
Topics: Humans; Sarcopenia; Psoas Muscles; Male; Female; Colorectal Neoplasms; Aged, 80 and over; Tomography, X-Ray Computed; Imaging, Three-Dimensional; Prognosis; Organ Size; Japan; Retrospective Studies
PubMed: 38890682
DOI: 10.1186/s12885-024-12524-y -
Communications Biology Jun 2024Muscle invasive bladder cancer (MIBC) is a molecularly diverse disease with varied clinical outcomes. Molecular studies typically employ bulk sequencing analysis, giving...
Muscle invasive bladder cancer (MIBC) is a molecularly diverse disease with varied clinical outcomes. Molecular studies typically employ bulk sequencing analysis, giving a transcriptomic snapshot of a section of the tumour. However, tumour tissues are not homogeneous, but are composed of distinct compartments such as the tumour and stroma. To investigate the molecular profiles of bladder cancer, whilst also maintaining the spatial complexity of the tumours, we employed whole transcriptome Digital Spatial Profiling (DSP). With this method we generated a dataset of transcriptomic profiles of tumour epithelium, stroma, and immune infiltrate. With these data we investigate the spatial relationship of molecular subtype signatures and ligand signalling events. We find that Basal/Squamous and Classical subtypes are mostly restricted to tumour regions, while the stroma-rich subtype signatures are abundant within the stroma itself. Additionally, we identify ligand signalling events occurring between tumour, stroma, and immune infiltrate regions, such as immune infiltrate derived GPNMB, which was highly correlated with VEGFA expression within the tumour. These findings give us new insights into the diversity of MIBC at a molecular level and provide a dataset with detailed spatial information that was not available before in bladder cancer research.
Topics: Urinary Bladder Neoplasms; Humans; Tumor Microenvironment; Neoplasm Invasiveness; Gene Expression Profiling; Transcriptome; Gene Expression Regulation, Neoplastic; Signal Transduction
PubMed: 38890455
DOI: 10.1038/s42003-024-06426-9 -
Journal of Experimental & Clinical... Jun 2024Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene...
BACKGROUND
Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed.
METHODS
An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency.
RESULTS
Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8 T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses.
CONCLUSIONS
The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with "undruggability." Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses.
Topics: Urinary Bladder Neoplasms; Humans; STAT3 Transcription Factor; Animals; Mice; TOR Serine-Threonine Kinases; Administration, Intravesical; Female; Cell Line, Tumor; Xenograft Model Antitumor Assays
PubMed: 38886756
DOI: 10.1186/s13046-024-03088-7 -
BMC Medical Imaging Jun 2024Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose...
BACKGROUND
Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose of this research is to employ radiomics to evaluate the diagnostic value in determining muscle invasiveness of compressed sensing (CS) accelerated 3D T2-weighted-SPACE sequence with high resolution and short acquisition time.
METHODS
This prospective study involved 108 participants who underwent preoperative 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted sequences. The cohort was divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a Rad-score was constructed based on radiomic features selected by intraclass correlation coefficients, pearson correlation coefficient and least absolute shrinkage and selection operator . Multivariate logistic regression was used to develop a nomogram combined radiomics and clinical indices. In the validation cohort, the performances of the models were evaluated by ROC, calibration, and decision curves.
RESULTS
In the validation cohort, the area under ROC curve of 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted models were 0.87(95% confidence interval (CI):0.73-1.00), 0.79(95%CI:0.63-0.96) and 0.77(95%CI:0.60-0.93), respectively. The differences in signal-to-noise ratio and contrast-to-noise ratio between 3D-CS-T2-weighted-SPACE and 3D-T2-weighted-SPACE sequences were not statistically significant(p > 0.05). While the clinical model composed of three clinical indices was 0.74(95%CI:0.55-0.94) and the radiomics-clinical nomogram model was 0.88(95%CI:0.75-1.00). The calibration curves confirmed high goodness of fit, and the decision curve also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model.
CONCLUSION
The radiomics model based on compressed sensing 3D T2WI sequence, which was acquired within a shorter acquisition time, showed superior diagnostic efficacy in muscle invasion of bladder cancer. Additionally, the nomogram model could enhance the diagnostic performance.
Topics: Humans; Urinary Bladder Neoplasms; Male; Female; Middle Aged; Neoplasm Invasiveness; Prospective Studies; Imaging, Three-Dimensional; Aged; Magnetic Resonance Imaging; ROC Curve; Nomograms; Radiomics
PubMed: 38886638
DOI: 10.1186/s12880-024-01318-0 -
Scientific Reports Jun 2024Temporal muscle thickness measured on 3D MRI has recently been linked to prognosis in glioblastoma patients and may serve as an independent prognostic indicator. This...
Temporal muscle thickness measured on 3D MRI has recently been linked to prognosis in glioblastoma patients and may serve as an independent prognostic indicator. This single-center study looked at temporal muscle thickness and prognosis in patients with primary glioblastoma. Overall survival was the major study outcome. For a retrospective analysis from 2010 to 2020, clinical data from 102 patients with glioblastoma at the Department of Oncology Radiotherapy of the First Affiliated Hospital of Dalian Medical University were gathered. Fifty-five cases from 2016 to 2020 contained glioblastoma molecular typing data, of which 45 were IDH wild-type glioblastomas and were analysed separately. TMT was measured on enhanced T1-weighted magnetic resonance images in patients with newly diagnosed glioblastoma.Overall patient survival (OS) was calculated by the Kaplan-Meier method and survival curves were plotted using the log-rank-sum test to determine differences between groups, and multifactorial analyses were performed using a Cox proportional-risk model.The median TMT for 102 patients was 6.775 mm (range: 4.95-10.45 mm). Patients were grouped according to median TMT, and the median overall survival (23.0 months) was significantly longer in the TMT > median group than in the TMT median group (P 0.001; Log-rank test). Analysing 45 patients with IDH wild type alone, the median overall survival (12 months) of patients in the TMT > median group was significantly longer than that of patients in the TMT ≤ median group (8 months) (P < 0.001; Log-rank test).TMT can serve as an independent prognostic factor for glioblastoma.
Topics: Humans; Glioblastoma; Male; Female; Middle Aged; Prognosis; Temporal Muscle; Adult; Aged; Brain Neoplasms; Retrospective Studies; Magnetic Resonance Imaging; Kaplan-Meier Estimate; Isocitrate Dehydrogenase; Young Adult
PubMed: 38886495
DOI: 10.1038/s41598-024-64947-z