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Urology Practice Jul 2024Intravesical sequential doublet chemotherapy (SDC) is being used increasingly as a rescue treatment for nonmuscle-invasive bladder cancer failing bacillus... (Review)
Review
INTRODUCTION
Intravesical sequential doublet chemotherapy (SDC) is being used increasingly as a rescue treatment for nonmuscle-invasive bladder cancer failing bacillus Calmette-Guérin (BCG), as single-agent chemotherapies are less effective, especially for carcinoma in situ. Considering the current BCG shortage, intravesical SDC also provides an efficacious alternative to BCG. Our aim is to detail the implementation to assist with establishing an efficient and practical intravesical SDC clinic for urologic practice.
METHODS
We searched PubMed for published studies with the Medical Subject Heading of "intravesical chemotherapy" and "non-muscle invasive bladder cancer." The search was limited to English-language journals and full papers only. The initial search resulted in 260 articles, of which 20 relevant studies were selected.
RESULTS
Five important processes were identified in the successful and efficient administration of intravesical SDC: (1) patient preparation, (2) medication procurement, (3) medication administration, (4) medication immediate aftermath, and (5) patient instruction and education. Safety precautions should be taken when handling each chemotherapy drug. A clinical pharmacist may be required for drug preparation. An important step in providing intravesical SDC is to use a closed system for the instillation of the chemo-solution. A special protocol should be adopted for every drug with its proper dwell time. The induction course consists of weekly instillation for 6 weeks. If an initial response is noted, maintenance therapy is recommended, typically monthly for 24 months.
CONCLUSIONS
Successful intravesical SDC clinics necessitate appropriate patient selection, standardized workflow procedures, patient education, and good communication between the urologist, clinical pharmacists, and oncology nurses.
Topics: Humans; Urinary Bladder Neoplasms; Administration, Intravesical; Neoplasm Invasiveness; Antineoplastic Combined Chemotherapy Protocols; Ambulatory Care Facilities
PubMed: 38899680
DOI: 10.1097/UPJ.0000000000000576 -
Frontiers in Oncology 2024To investigate the application value of complete laparoscopy and Da Vinci robot esophagogastric anastomosis double muscle flap plasty in radical resection of proximal...
OBJECTIVE
To investigate the application value of complete laparoscopy and Da Vinci robot esophagogastric anastomosis double muscle flap plasty in radical resection of proximal gastric cancer.
METHOD
A retrospective descriptive study was used. The clinicopathological data of 35 patients undergoing radical operation for proximal gastric cancer admitted to Liaoning Cancer Hospital from January 2020 to December 2023 were collected. Variables evaluated: 1. Transoperative,2. Postoperative, 3. Follow-up. In relation to follow-up, esophageal disease status reflux, anastomosis, nutritional status score, serum hemoglobin, tumor recurrence, and metastasis were investigated. The trans and postoperative variables were obtained from the clinical records and the patients were followed up in outpatient department and by telephone.
RESULT
Among the 35 patients, 17 underwent robotic surgery and 18 underwent laparoscopic surgery. There were 29 males and 6 females. 1) Transoperative: Robotic surgery: The operation time was (305.59 ± 22.07) min, the esophagogastric anastomosis double muscle flap plasty time was (149.76 ± 14.91) min, the average number of lymph nodes cleared was 30, and the average intraoperative blood loss was 30 ml. Laparoscopic surgery: The mean operation time was 305.17 ± 26.92min, the operation time of esophagogastric anastomosis double muscle flap was (194.06 ± 22.52) min, the average number of lymph nodes cleared was 24, and the average intraoperative blood loss was 52.5 ml. 2) Postoperative: Robotic surgery: the average time for patients to have their first postoperative anal emission was 3 days, the average time to first postoperative feeding was 4 days, and the average length of hospitalization after surgery was 8 days. Laparoscopic surgery: the average time for patients to have their first postoperative anal emission was 5 days, the average time to first postoperative feeding was 6 days, the average length of hospitalization after surgery was 10 days. 3) Follow-up: The follow-up time ranged from 1 to 42 months, with a median follow-up time of 24 months.
CONCLUSION
Complete Da Vinci robot and laparoscopic esophagogastric anastomosis double muscle flap plasty for radical resection of proximal gastric cancer can minimize surgical incision, reduce abdominal exposure, accelerate postoperative recovery of patients, and effectively prevent reflux esophagitis and maintain good hemoglobin concentration and nutritional status. The advantages of robotic surgery is less intraoperative bleeding and faster post-surgical recovery, but it is relatively more expensive.
PubMed: 38898957
DOI: 10.3389/fonc.2024.1395549 -
Journal of Cellular and Molecular... Jun 2024Cancer-related fatigue (CRF) significantly impacts the quality of life of cancer patients. This study investigates the therapeutic potential of Shenqi Fuzheng injection...
Cancer-related fatigue (CRF) significantly impacts the quality of life of cancer patients. This study investigates the therapeutic potential of Shenqi Fuzheng injection (SFI) in managing CRF, focusing on its mechanistic action in skeletal muscle. We utilized a CRF mouse model to examine the effects of SFI on physical endurance, monitoring activity levels, swimming times and rest periods. Proteomic analysis of the gastrocnemius muscle was performed using isobaric tags and liquid chromatography-tandem mass spectrometry to map the muscle proteome changes post-SFI treatment. Mitochondrial function in skeletal muscle was assessed via ATP bioluminescence assay. Furthermore, the regulatory role of the hypoxia inducible factor 1 subunit alpha (HIF-1α) signalling pathway in mediating SFI's effects was explored through western blotting. In CRF-induced C2C12 myoblasts, we evaluated cell viability (CCK-8 assay), apoptosis (flow cytometry) and mitophagy (electron microscopy). The study also employed pulldown, luciferase and chromatin immunoprecipitation assays to elucidate the molecular mechanisms underlying SFI's action, particularly focusing on the transcriptional regulation of PINK1 through HIF-1α binding at the PINK1 promoter region. Our findings reveal that SFI enhances physical mobility, reduces fatigue symptoms and exerts protective effects on skeletal muscles by mitigating mitochondrial damage and augmenting antioxidative responses. SFI promotes cell viability and induces mitophagy while decreasing apoptosis, primarily through the modulation of HIF-1α, PINK1 and p62 proteins. These results underscore SFI's efficacy in enhancing mitochondrial autophagy, thereby offering a promising approach for ameliorating CRF. The study not only provides insight into SFI's potential therapeutic mechanisms but also establishes a foundation for further exploration of SFI interventions in CRF management.
Topics: Animals; Mitophagy; Drugs, Chinese Herbal; Muscle, Skeletal; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Ubiquitination; Neoplasms; Fatigue; Male; Apoptosis; Humans; Proteomics; Disease Models, Animal; Cell Line
PubMed: 38898772
DOI: 10.1111/jcmm.18455 -
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