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BMC Cancer Jul 2024Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying...
INTRODUCTION
Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa.
METHODS
A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients.
DISCUSSION
If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community.
TRIAL REGISTRATION
The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.
Topics: Humans; Male; Extracellular Vesicles; Cross-Over Studies; Prostatic Neoplasms; Exercise; Muscle, Skeletal; Exercise Therapy; Cytokines; Aged; Middle Aged; Myokines
PubMed: 38951803
DOI: 10.1186/s12885-024-12530-0 -
JPMA. the Journal of the Pakistan... Jun 2024Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of...
Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of urothelial carcinoma in various age groups, its gender distribution, and grades. A total of 131 cases of urothelial carcinoma, received at Department of Pathology, Peshawar Medical College, Peshawar, between January 2017 to December 2022, were included in the study; of them 107 (81.6%) were males while 24 (18.3%) were females with a mean age of 62±13 years. The most common histological subtype was papillary urothelial carcinoma in 117(89.3%) cases, followed by Squamous and Glandular in 5(3.8%) cases. Majority of the urothelial carcinoma with high grade showed a statistically significant relation with muscle invasion 38 (50.66%). Males were four times more likely to have urothelial carcinoma while older age groups were more likely to have high grade urothelial carcinoma.
Topics: Humans; Pakistan; Male; Female; Middle Aged; Aged; Tertiary Care Centers; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Adult; Neoplasm Grading; Aged, 80 and over; Neoplasm Invasiveness; Carcinoma, Papillary; Sex Distribution; Age Distribution; Carcinoma, Squamous Cell
PubMed: 38948990
DOI: 10.47391/JPMA.9546 -
Oncology Research 2024Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.... (Review)
Review
Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate. Diagnostic challenges arise from the diverse pathological presentation, variable symptomatology, and lack of different imaging features. However, IMT is identified by the fusion of the anaplastic lymphoma kinase (ALK) gene, which is present in approximately 70% of cases, with various fusion partners, including ran-binding protein 2 (RANBP2), which allows confirmation of the diagnosis. While surgery is the preferred approach for localized tumors, the optimal long-term treatment for advanced or metastatic disease is difficult to define. Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT. Crizotinib, an ALK tyrosine kinase inhibitor (TKI), was officially approved by the US Food and Drug Administration (FDA) in 2020 to treat IMT with ALK rearrangement. However, most patients face resistance and disease progression, requiring consideration of sequential treatments. Combining radiotherapy with targeted therapy appears to be beneficial in this indication. Early promising results have also been achieved with immunotherapy, indicating potential for combined therapy approaches. However, defined recommendations are still lacking. This review analyzes the available research on IMT, including genetic disorders and their impact on the course of the disease, data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication, as well as summarizing general knowledge about prognostic and predictive factors, also in terms of resistance to systemic therapy.
Topics: Humans; Neoplasms, Muscle Tissue; Anaplastic Lymphoma Kinase; Molecular Targeted Therapy; Protein Kinase Inhibitors
PubMed: 38948020
DOI: 10.32604/or.2024.050350 -
Cureus May 2024Gastrointestinal stromal tumors (GIST) are tumors of mesenchymal origin, accounting for less than 1% of the primary neoplasms of the digestive tract, which can affect...
Gastrointestinal stromal tumors (GIST) are tumors of mesenchymal origin, accounting for less than 1% of the primary neoplasms of the digestive tract, which can affect any segment of the gastrointestinal tract. However, they can also occur in other locations outside the gastrointestinal tract. In such situations, these are known as extragastrointestinal stromal tumors (eGIST). We present a 58-year-old male, who attended the emergency department due to asthenia, anorexia, heartburn, abdominal pain, and distension, who was ultimately diagnosed with an eGIST in the peritoneum. The immunohistochemistry pattern of the tumor sample obtained favored this diagnosis, especially demonstrated by the positivity for discovered on GIST protein 1 (DOG1) and negativity of smooth muscle markers. Due to the rarity of extragastrointestinal tumors and the even greater rarity of those originating in the peritoneum, the authors consider this a pertinent clinical case to be published due to its originality.
PubMed: 38947574
DOI: 10.7759/cureus.61411 -
Yakugaku Zasshi : Journal of the... 2024Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, affects the survival of cancer patients. Anamorelin was the first drug...
Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, affects the survival of cancer patients. Anamorelin was the first drug approved in Japan for the treatment of cachexia. However, cases in which anamorelin is discontinued within 3 weeks are often observed in clinical practice. This study aimed to explore the factors associated with continued anamorelin dosing. We retrospectively reviewed records of patients with lung, gastric, pancreatic, and colorectal cancer who started anamorelin at Fukuoka University Hospital from April 2021 to November 2022. Patients were divided into two groups based on the duration of anamorelin administration: 15 patients were classified into the <3 weeks group and 22 were classified into the ≥3 weeks group. The primary objective was to explore the potential factors associated with the continuation of anamorelin, and the secondary objectives were to compare survival and nutritional indices. In the univariate analysis, there were significant differences between the two groups in terms of cancer type (p=0.007) and serum albumin level (p=0.026). In the multivariate analysis, gastric cancer and albumin 2.7 g/dL or less were associated with the continuation of anamorelin. Survival was significantly shorter in the <3 weeks group (p=0.019). This study suggests that the continuation of anamorelin may be influenced by specific tumor types and serum albumin levels. Furthermore, the duration of anamorelin administration may affect patient survival.
Topics: Humans; Cachexia; Retrospective Studies; Male; Female; Aged; Neoplasms; Middle Aged; Oligopeptides; Time Factors; Aged, 80 and over; Serum Albumin; Hydrazines; Drug Administration Schedule
PubMed: 38945851
DOI: 10.1248/yakushi.24-00002 -
Cancer Genomics & Proteomics 2024Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We,...
BACKGROUND/AIM
Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery.
MATERIALS AND METHODS
The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm) or large (700 mm) tumours were imaged, breathing air then 100% O, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays.
RESULTS
Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour.
CONCLUSION
OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.
Topics: Urinary Bladder Neoplasms; Animals; Humans; Mice; Magnetic Resonance Imaging; Female; Oxygen; Pilot Projects; Mice, Nude; Genomics; Hypoxia; Tumor Hypoxia; Cell Line, Tumor; Heterografts; Xenograft Model Antitumor Assays
PubMed: 38944425
DOI: 10.21873/cgp.20455 -
Trials Jun 2024Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to...
Evaluating the effectiveness of early urethral catheter removal combined with intermittent catheterization for promoting early recovery of bladder function after laparoscopic radical hysterectomy: a study protocol for a randomized controlled trial.
BACKGROUND
Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction.
METHODS
Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study's primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle.
DISCUSSION
The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery.
TRIAL REGISTRATION
ChiCTR2200064041, registered on 24th September, 2022.
Topics: Humans; Hysterectomy; Female; Urinary Bladder; Laparoscopy; Recovery of Function; Uterine Cervical Neoplasms; Randomized Controlled Trials as Topic; Urinary Catheters; Intermittent Urethral Catheterization; Time Factors; Device Removal; Treatment Outcome; Quality of Life; Urodynamics; Middle Aged; Urinary Retention; Adult; Urinary Catheterization; Catheters, Indwelling
PubMed: 38943177
DOI: 10.1186/s13063-024-08266-8 -
Experimental and Therapeutic Medicine Aug 2024Mixed epithelial and stromal tumors (MESTs) of the kidney are rare renal neoplasms, primarily affecting middle-aged women. These tumors are characterized by a mix of...
Mixed epithelial and stromal tumors (MESTs) of the kidney are rare renal neoplasms, primarily affecting middle-aged women. These tumors are characterized by a mix of epithelial and stromal components. While generally benign, MESTs require accurate diagnosis and appropriate management due to the potential for malignant transformation. The present study reports the case of a 75-year-old male patient who underwent a partial nephrectomy following the incidental discovery of a kidney tumor. Histopathological examination revealed a partially cystic tumor with solid areas, measuring 26 mm in diameter. The tumor had cysts lined with cuboidal cells and an ovarian-like stroma. The solid component consisted of elongated cells with eosinophilic cytoplasm and oval nuclei, showing angiocentric growth around small blood vessels without nuclear atypia or mitoses. Since the morphology of the solid component could not reveal the differentiation of those cells, immunohistochemical staining was performed and a myopericytoma/myofibroma component was established, mostly based on the positivity of smooth muscle actin, muscle-specific actin, h-caldesmon, estrogen receptor, progesterone receptor, solute carrier family 2 facilitated glucose transporter member 1 and collagen IV, along with a lack of staining for desmin, CD34, CD31 and CD99. Thus, to the best of our knowledge, for the first time in the literature, MEST with myopericytoma/myofibroma stromal component in a male patient was reported.
PubMed: 38939172
DOI: 10.3892/etm.2024.12610 -
Scientific Reports Jun 2024We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal...
We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92-0.94) and the Lung Cancer Symptom Scale-Mesothelioma (0.79-0.87) at each co-administration of the scales. The CSS also had good sensitivity to worsening disease and global quality-of-life ratings. The MDASI-MPM CSS can be used as an outcome in MPM clinical trials, including in responder analyses and at the individual patient level. It is brief enough to administer frequently, including electronically, to better capture symptom trajectories during and after a trial and in clinical practice. As a single score, the CSS addresses multiplicity issues that can arise when several symptoms increase due to worsening disease. Our process can be adapted to produce a CSS for other advanced-cancer trials.
Topics: Humans; Mesothelioma, Malignant; Male; Female; Pleural Neoplasms; Aged; Middle Aged; Quality of Life; Lung Neoplasms; Mesothelioma; Patient Reported Outcome Measures; Fatigue; Symptom Assessment; Longitudinal Studies; Severity of Illness Index; Symptom Burden
PubMed: 38937473
DOI: 10.1038/s41598-024-62307-5 -
Abdominal Radiology (New York) Jun 2024The purpose of this study was to investigate the impact of different low-energy virtual monochromatic images (VMIs) in dual-energy CT on the performance of radiomics...
OBJECTIVE
The purpose of this study was to investigate the impact of different low-energy virtual monochromatic images (VMIs) in dual-energy CT on the performance of radiomics models for predicting muscle invasive status in bladder cancer (BCa).
MATERIALS AND METHODS
A total of 127 patients with pathologically proven muscle-invasive BCa (n = 49) and non-muscle-invasive BCa (n = 78) were randomly allocated into the training and test cohorts at a ratio of 7:3. Feature extraction was performed on the venous phase images reconstructed at 40, 50, 60 and 70-keV (single-energy analysis) or in combination (multi-energy analysis). Recursive feature elimination (RFE) and the least absolute shrinkage and selection operator (LASSO) were employed to select the most relevant features associated with BCa. Models were built using a support vector machine (SVM) classifier. Diagnostic performance was assessed through receiver operating characteristic curves, evaluating sensitivity, specificity, accuracy, precision, and the area-under-the curve (AUC) values.
RESULTS
In the test cohort, the multi-energy model achieved the best diagnostic performance with AUC, sensitivity, specificity, accuracy, and precision of 0.917, 0.800, 0.833, 0.821, and 0.750, respectively. Conversely, the single-energy model exhibited lower AUC and sensitivity in predicting the muscle invasion status.
CONCLUSIONS
By combining information from VMIs of various energies, the multi-energy model displays superior performance in preoperatively predicting the muscle invasion status of bladder cancer.
PubMed: 38937340
DOI: 10.1007/s00261-024-04459-6