-
Swiss Medical Weekly Jun 2024Anthracycline-based chemotherapy has well-known cardiotoxic effects, butmay also cause skeletal muscle myopathy and negatively affect cardiorespiratory fitness and... (Observational Study)
Observational Study
AIMS
Anthracycline-based chemotherapy has well-known cardiotoxic effects, butmay also cause skeletal muscle myopathy and negatively affect cardiorespiratory fitness and quality of life. The effectiveness of exercise training in improving cardiorespiratory fitness and quality of life during chemotherapy is highly variable. We set out to determine how the effect of exercise training on cardiorespiratory fitness (primary outcome) and quality of life (secondary outcome) in cancer patients is affected by the type of therapy they receive (cardiotoxic therapy with or without anthracyclines; non-cardiotoxic therapy) and the timing of the exercise training (during or after therapy).
METHODS
Consecutive patients with cancer who participated in an exercise-based cardio-oncology rehabilitation programme at a university hospital in Switzerland between January 2014 and February 2022 were eligible. Patients were grouped based on chemotherapy (anthracycline vs non-anthracycline) and timing of exercise training (during vs after chemotherapy). Peak oxygen uptake (VO2) was assessed with cardiopulmonary exercise testing (n = 200), and quality of life with the Functional Assessment of Cancer Therapies questionnaire (n = 77). Robust linear models were performed for change in peak VO2 including type and timing of cardiotoxic therapies, age, training impulse and baseline peak VO2; change in quality of life was analysed with cumulative linked models.
RESULTS
In all patients with valid VO2 (n = 164), median change in peak VO2 from before to after exercise training was 2.3 ml/kg/min (range: -10.1-15.9). The highest median change in peak VO2 was 4.1 ml/kg/min (interquartile range [IQR]: 0.7-7.7) in patients who completed exercise training during non-anthracycline cardiotoxic or non-cardiotoxic therapies, followed by 2.8 ml/kg/min (IQR: 1.2-5.3) and 2.3 ml/kg/min (IQR: 0.1-4.6) in patients who completed exercise training after anthracycline and after non-anthracycline cardiotoxic or non-cardiotoxic therapies, respectively. In patients who completed exercise training during anthracycline therapy, peak VO2 decreased by a median of -2.1 ml/kg/min (IQR: -4.7-2.0). In the robust linear model, there was a significant interaction between type and timing of cancer treatment for anthracycline therapy, with greater increases in peak VO2 when exercise training was performed after anthracycline therapy. For quality of life, higher baseline scores were negatively associated with changes in quality of life.
CONCLUSION
In our cohort, the increase in cardiorespiratory fitness was diminished when exercise training was performed concurrently with anthracyclines. For patients with cardiotoxic treatments other than anthracyclines, cardiorespiratory fitness and quality of life was not associated with timing of exercise training.
Topics: Humans; Male; Female; Cardiorespiratory Fitness; Quality of Life; Middle Aged; Anthracyclines; Longitudinal Studies; Neoplasms; Switzerland; Exercise Therapy; Exercise Test; Cardiac Rehabilitation; Cardiotoxicity; Time Factors; Aged; Oxygen Consumption
PubMed: 38885132
DOI: 10.57187/s.3588 -
Ultrasonography (Seoul, Korea) May 2024Assessing the severity of breast cancer-related lymphedema (BCRL) requires various clinical tools, yet no standardized methodology is available. Ultrasonography shows...
PURPOSE
Assessing the severity of breast cancer-related lymphedema (BCRL) requires various clinical tools, yet no standardized methodology is available. Ultrasonography shows promise for diagnosing lymphedema and evaluating its severity. This study explored the clinical utility of ultrasonography in patients with BCRL.
METHODS
In this retrospective cross-sectional study, patients with unilateral BCRL were examined. The analyzed data included demographics, lymphedema location, International Society of Lymphology (ISL) stage, surgical history, treatment regimens, and arm circumference. Skin, subcutis, and muscle thicknesses were assessed ultrasonographically at predetermined sites, and the percentage of excess thickness was calculated. Multivariate logistic regression analysis was employed to identify associations between ultrasonographic measurements and advanced lymphedema (ISL 2 or 3). The Lymphedema Quality of Life arm questionnaire was used to evaluate patient-reported outcomes regarding lymphedema and their correlations with ultrasonographic findings.
RESULTS
Among 118 patients, 71 were classified as ISL 0-1 and 47 as ISL 2-3. Patients with advanced lymphedema were older, had higher nodal stages, underwent more axillary lymph node dissections, and had higher rates of dominant-arm lymphedema. Multivariate logistic regression revealed significant associations of greater skin thickness (adjusted odds ratio [OR], 4.634; 95% confidence interval [CI], 1.233 to 17.419), subcutis thickness (adjusted OR, 7.741; 95% CI, 1.649 to 36.347), and subcutis echogenicity (adjusted OR, 4.860; 95% CI, 1.517 to 15.566) with advanced lymphedema. Furthermore, greater skin thickness (P=0.016) and subcutis echogenicity (P=0.023) were correlated with appearance-related discomfort.
CONCLUSION
Ultrasonographic measurements were significantly associated with advanced lymphedema in BCRL. Ultrasonography represents a valuable diagnostic and severity assessment tool for lymphedema.
PubMed: 38881309
DOI: 10.14366/usg.24059 -
BMC Cancer Jun 2024Bladder cancer (BC) is among the most prevalent malignant urothelial tumors globally, yet the prognosis for patients with muscle-invasive bladder cancer (MIBC) remains...
BACKGROUND
Bladder cancer (BC) is among the most prevalent malignant urothelial tumors globally, yet the prognosis for patients with muscle-invasive bladder cancer (MIBC) remains dismal, with a very poor 5-year survival rate. Consequently, identifying more effective and less toxic chemotherapeutic alternatives is critical for enhancing clinical outcomes for BC patients. Isorhapontigenin (ISO), a novel stilbene isolated from a Gnetum found in certain provinces of China, has shown potential as an anticancer agent due to its diverse anticancer activities. Despite its promising profile, the specific anticancer effects of ISO on BC and the underlying mechanisms are still largely unexplored.
METHODS
The anchorage-independent growth, migration and invasion of BC cells were assessed by soft agar and transwell invasion assays, respectively. The RNA levels of SOX2, miR-129 and SNHG1 were quantified by qRT-PCR, while the protein expression levels were validated through Western blotting. Furthermore, methylation-specific PCR was employed to assess the methylation status of the miR-129 promoter. Functional assays utilized siRNA knockdown, plasmid-mediated overexpression, and chemical inhibition approaches.
RESULTS
Our study demonstrated that ISO treatment significantly reduced SNHG1 expression in a dose- and time-dependent manner in BC cells, leading to the inhibition of anchorage-independent growth and invasion in human basal MIBC cells. This effect was accompanied by the downregulation of MMP-2 and MMP-9 and the upregulation of the tumor suppressor PTEN. Further mechanistic investigations revealed that SOX2, a key upstream regulator of SNHG1, played a crucial role in mediating the ISO-induced transcriptional suppression of SNHG1. Additionally, we found that ISO treatment led to a decrease in DNMT3b protein levels, which in turn mediated the hypomethylation of the miR-129 promoter and the subsequent suppression of SOX2 mRNA 3'-UTR activity, highlighting a novel pathway through which ISO exerts its anticancer effects.
CONCLUSIONS
Collectively, our study highlights the critical role of SNHG1 downregulation as well as its upstream DNMT3b/miR-129/SOX2 axis in mediating ISO anticancer activity. These findings not only elucidate the mechanism of action of ISO but also suggest novel targets for BC therapy.
Topics: Humans; Urinary Bladder Neoplasms; RNA, Long Noncoding; Cell Line, Tumor; Stilbenes; Down-Regulation; Gene Expression Regulation, Neoplastic; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3B; Neoplasm Invasiveness; Cell Movement; Cell Proliferation; DNA Methylation; MicroRNAs
PubMed: 38879516
DOI: 10.1186/s12885-024-12490-5 -
International Journal of Surgery Case... Jun 2024Disseminated Peritoneal Leiomyomatosis (DPL) is a rare benign proliferation of solid peritoneal lesions along the abdominopelvic cavity comprised of smooth muscle and...
INTRODUCTION AND IMPORTANCE
Disseminated Peritoneal Leiomyomatosis (DPL) is a rare benign proliferation of solid peritoneal lesions along the abdominopelvic cavity comprised of smooth muscle and connective tissue. Though hormonal and iatrogenic causes have been theorized, the exact etiology remains unknown. Most patients with DPL are frequently premenopausal with a history of myomectomy or prior hysterectomy. These patients can present asymptomatically or with abnormal uterine bleeding and abdominal discomfort. DPL is a rare entity with less than 150 cases reported in the literature, showcasing the need of awareness of this poorly understood neoplasm. Imaging, if performed, is helpful as positron emission tomography (PET) can differentiate DPL from malignant peritoneal disease. Treatment involves medical and surgical options based on patient's clinical presentation, with medical treatment with gonadotropin-releasing hormone agonist being first line.
CASE PRESENTATION
We report a case of a previously healthy female presenting for desired laparoscopic tubal ligation with incidental countless peritoneal nodules suspicious for carcinomatosis found during the operative event but proven leiomyomas after histologic examination.
CLINICAL DISCUSSION
Differentiating DPL from mimickers such as leiomyosarcoma, endometriosis, and carcinomatosis remains a challenge as macroscopic appearances are similar ultimately requiring histology evaluation.
CONCLUSION
Awareness of the entity is crucial to avoid misdiagnosis and unnecessary anxiety associated with a presumptive diagnosis of malignancy for a largely benign entity.
PubMed: 38878730
DOI: 10.1016/j.ijscr.2024.109908 -
Medicine Jun 2024Increasing evidence has underscored the role of long noncoding RNAs (lncRNAs) make up the major proportion of the competing endogenous RNAs (ceRNAs) network and can...
Increasing evidence has underscored the role of long noncoding RNAs (lncRNAs) make up the major proportion of the competing endogenous RNAs (ceRNAs) network and can regulate gene expression by competitively binding to miRNAs in the development and progression of tumors. Nevertheless, the role of lncRNA-mediated ceRNAs in gastric cancer (GC) and their regulatory mechanisms have not been elucidated to some extent. This study is aimed at constructing a prognostic risk model for GC based on lncRNAs. A TCGA (The Cancer Genome Atlas) dataset was analyzed using edgeR to identify differentially expressed lncRNAs (DElncRNAs) in GC tissues vs normal tissues. Subsequently, DElncRNAs that could predict GC prognosis were determined using a training set. A prognostic risk model based on the DElncRNAs was then constructed. The performance of the model was tested using a test set. The functions of these lncRNAs in GC were investigated using a lncRNA-miRNA-mRNA network. Analysis of lncRNA expression in 407 TCGA GC cases identified 3 lncRNAs that significantly correlated with prognosis. GC cases with high-risk scores showed markedly poor prognosis relative to those with low-risk scores in both the training and test sets. Univariate and multivariate Cox regression analysis of the relationship between various clinical features and prognosis found that these lncRNAs and stage significantly correlated with GC prognosis. A lncRNA-miRNA-mRNA network based on 3 lncRNAs and functional enrichment analysis of interacting mRNA indicated that these genes are enriched in various intracellular receptor signaling pathways, including regulation of muscle system process, and protein deubiquitylation. The current study provides novel insights into the lncRNA-related ceRNA network in GC and sheds lights on underlying 3 lncRNA biomarkers may be independent prognostic signatures in predicting the survival of GC patients.
Topics: Humans; Stomach Neoplasms; RNA, Long Noncoding; Prognosis; Male; Female; Middle Aged; MicroRNAs; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; RNA, Messenger; Gene Regulatory Networks; Aged; RNA, Competitive Endogenous
PubMed: 38875399
DOI: 10.1097/MD.0000000000038458 -
Frontiers in Immunology 2024A 55-year-old male patient developed a mass in the left inguinal area with left lower limb swelling and first visited a local hospital 3 months earlier because of...
CASE REPORT
A 55-year-old male patient developed a mass in the left inguinal area with left lower limb swelling and first visited a local hospital 3 months earlier because of unrelieved pain. An MRI scan suggested left suprapubic branch and left acetabular bone destruction, abnormal soft tissue signals within the iliopsoas muscle of the anterior edge of the left iliac bone, and enlarged lymph nodes in the left iliac fossa and left inguinal region. The patient subsequently underwent left pelvic lesion open biopsy and inguinal lymph node resection biopsy. According to pathological reports, the left inguinal mass was considered to be a malignant tumor of cutaneous accessory origin (pilomatrix carcinoma) with extensive vitreous changes. The suprapupubis branch mass was considered to be a bone metastatic pilomatrix carcinoma. Immunohistochemistry (IHC) revealed a PDL1 combined positive score (CPS) of 8. DNA next-generation sequencing (NGS) showed L65Rfs*53 mutation. The patient received three cycles of gemcitabine and nedaplatin. However, the lesion progressed.
CONCLUSION
Chemotherapy is not effective for treating pilomatrix carcinoma. PDL1 antibodies and CDK4/6 inhibitors might be treatment options for pilomatrix carcinoma.
Topics: Humans; Male; Middle Aged; Cyclin-Dependent Kinase Inhibitor p16; B7-H1 Antigen; Skin Neoplasms; Pilomatrixoma; Mutation; Hair Diseases
PubMed: 38873609
DOI: 10.3389/fimmu.2024.1337400 -
BJUI Compass Jun 2024Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for...
OBJECTIVES
Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients.
MATERIAL AND METHODS
To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format.
RESULTS
CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low-grade, 32.0% of 178 pTaG2 high-grade, and 43.0% of 93 pTaG3 tumours ( < 0.0001). In 1335 pT2-4 carcinomas, CEA positivity (34.1%) was lower than in pTaG3 tumours. Within pT2-4 carcinomas, CEA staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence free survival, and cancer specific survival ( > 0.25).
CONCLUSION
CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2-4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2-4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti-CEA drugs.
PubMed: 38873357
DOI: 10.1002/bco2.354 -
Cancer Medicine Jun 2024Cross-talk among biological pathways is essential for normal biological function and plays a significant role in cancer progression. Through integrated network analysis,...
INTRODUCTION
Cross-talk among biological pathways is essential for normal biological function and plays a significant role in cancer progression. Through integrated network analysis, this study explores the significance of pathway cross-talk in colorectal cancer (CRC) development at both the pathway and gene levels.
METHODS
In this study, we integrated the gene expression data with domain knowledge to construct state-dependent pathway cross-talk networks. The significance of the genes involved in pathway cross-talk was assessed by analyzing their association with cancer hallmarks, disease-gene relation, genetic alterations, and survival analysis. We also analyzed the gene regulatory network to identify the dysregulated genes and their role in CRC progression.
RESULTS
Cross-talk was observed between immune-related pathways and pathways associated with cell communication and signaling. The PTPRC gene was identified as a mediator, facilitating interactions within the immune system and other signaling pathways. The rewired interactions of ITGA7 were identified as influential in the epithelial-mesenchymal transition in CRC. This study also highlighted the crucial link between cell communication and vascular smooth muscle contraction pathway in CRC progression. The survival analysis of identified gene clusters showed their significant prognostic value in distinguishing high-risk from low-risk CRC groups, and L1000CDS2 revealed seven potential drug molecules in CRC. Nine dysregulated genes (CTNNB1, EP300, JUN, MYC, NFKB1, RELA, SP1, STAT1, and TP53) emerge as transcription factors acting as common regulators across various pathways.
CONCLUSIONS
This study highlights the crucial role of pathway cross-talk in CRC progression and identified the potential prognostic biomarkers and potential drug molecules.
Topics: Humans; Colorectal Neoplasms; Biomarkers, Tumor; Prognosis; Gene Regulatory Networks; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Transcriptome; Signal Transduction; Survival Analysis; Computational Biology
PubMed: 38872418
DOI: 10.1002/cam4.7391 -
Annals of Surgical Treatment and... Jun 2024Traditionally, cancer treatment has focused on the stages of the disease; however, recent studies have highlighted the importance of considering the overall health... (Review)
Review
Traditionally, cancer treatment has focused on the stages of the disease; however, recent studies have highlighted the importance of considering the overall health status of patients in the prognosis of cancer. Loss of skeletal muscle, known as sarcopenia, has been found to significantly affect outcomes in many different types of cancers, including colorectal cancer. In this review, we discuss the guidelines for diagnosing sarcopenia, with a specific focus on CT-based assessments. Many groups worldwide, including those in Europe and Asia, have introduced their own diagnostic guidelines for sarcopenia. Seemingly similar yet subtle discrepancies, particularly in the cutoff values used, limit the use of these guidelines in the general population, warranting a more universal guideline. Although CT-based measurements, such as skeletal muscle index and radiodensity, have shown promise in predicting outcomes, the lack of standardized values in these measurements hinders their universal adoption. To overcome these limitations, innovative approaches are being developed to assess changes in muscle mass trajectories and introduce new indices, such as skeletal and appendicular muscle gauges. Additionally, machine learning models have shown superior performance in predicting sarcopenic status, providing an alternative to CT-based diagnosis, particularly after surgery. CT has tremendous benefits and a significant role in visually as well as quantitatively retrieving information on patient body composition. In order to compensate for the limitation of standard cutoff value, 3-dimensional analysis of the CT, artificial intelligence-based body composition analysis, as well as machine learning algorithms for data interpretation and analysis have been proposed and are being utilized. In conclusion, despite the varying definitions of sarcopenia, CT-based measurements coupled with machine-learning models are promising for evaluating patients with cancer. Standardization efforts can improve diagnostic accuracy, reduce the reliance on CT examinations, and make sarcopenia assessments more accessible in clinical settings.
PubMed: 38868590
DOI: 10.4174/astr.2024.106.6.305 -
BMC Urology Jun 2024To predict outcomes and identify potential therapeutic targets for cancers, it is critical to find novel specific biomarkers. The objective of this study was to search...
BACKGROUND
To predict outcomes and identify potential therapeutic targets for cancers, it is critical to find novel specific biomarkers. The objective of this study was to search for and explore novel bladder cancer-associated protein biomarkers.
METHODS
A library of monoclonal antibodies (mAbs) against the JAM-ICR cell line was first generated, and clones with high affinity were selected. Hybridomas were screened using bladder cancer (BLCA) cell lines and normal cells. The target of the selected mAb was then characterized through immunoaffinity purification, western blotting, and mass spectrometry analysis. Expression of the target antigen was assessed by flow cytometry and IHC methods. Several databases were also used to evaluate the target antigen in BLCA and other types of cancers.
RESULTS
Based on screenings, a 6D6 clone was selected that recognized an isoform of beta-actin (ACTB). Our data showed that ACTB expression on different cell lines was heterogeneous and varied significantly from low to high intensity. 6D6 bound strongly to epithelial cells while showing weak to no reactivity to stromal, endothelial, and smooth muscle cells. There was no association between ACTB intensity and related prognostic factors in BLCA. In silico evaluations revealed a significant correlation between ACTB and overexpressed genes and biomarkers in BLCA. Additionally, the differential expression of ACTB in tumor and healthy tissue as well as its correlation with survival time in a number of cancers were shown.
CONCLUSIONS
The heterogeneous expression of ACTB may suggest the potential value of this marker in the diagnosis or prognosis of cancer.
Topics: Urinary Bladder Neoplasms; Humans; Antibodies, Monoclonal; Actins; Biomarkers, Tumor; Cell Line, Tumor
PubMed: 38867273
DOI: 10.1186/s12894-024-01489-6