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Journal of Translational Medicine Aug 2023Currently, women around the world are still suffering from various female common diseases with the high incidence, such as ovarian cancer, uterine fibroids and... (Review)
Review
Currently, women around the world are still suffering from various female common diseases with the high incidence, such as ovarian cancer, uterine fibroids and preeclampsia (PE), and some diseases are even with the high mortality rate. As a negative feedback regulator in G Protein-Coupled Receptor signaling (GPCR), the Regulator of G-protein Signaling (RGS) protein family participates in regulating kinds of cell biological functions by destabilizing the enzyme-substrate complex through the transformation of hydrolysis of G Guanosine Triphosphate (GTP). Recent work has indicated that, the Regulator of G-protein Signaling 2 (RGS2), a member belonging to the RGS protein family, is closely associated with the occurrence and development of certain female diseases, providing with the evidence that RGS2 functions in sustaining women's health. In this review paper, we summarize the current knowledge of RGS2 in female common diseases, and also tap and discuss its therapeutic potential by targeting multiple mechanisms.
Topics: Pregnancy; Humans; Female; Women's Health; Signal Transduction; Hydrolysis; Knowledge; Leiomyoma; RGS Proteins
PubMed: 37649067
DOI: 10.1186/s12967-023-04462-3 -
Cancer Epidemiology, Biomarkers &... Oct 2023Despite evidence that low muscle increases the risk of chemotoxicity, most chemotherapies are dosed on body surface area without considering body composition. Among 178...
BACKGROUND
Despite evidence that low muscle increases the risk of chemotoxicity, most chemotherapies are dosed on body surface area without considering body composition. Among 178 patients with colon cancer, we assessed muscle and adipose tissue with multiple techniques and examined their associations with relative dose intensity (RDI) and adverse events.
METHODS
We estimated (i) cross-sectional skeletal muscle area (SMA) and total adipose tissue (TAT) area at L3 from computed tomography (CT); (ii) appendicular lean mass (ALM) and total body fat (TBF) mass from dual-energy X-ray absorptiometry (DXA); and (iii) total body skeletal muscle mass using D3-creatine (D3Cr) dilution. We standardized each measurement by its sex-specific standard deviation (SD). The primary outcome was reduced RDI (RDI <85%). The secondary outcome was the number of moderate and severe adverse events during each cycle of chemotherapy. We estimated the associations of muscle and adipose tissue measurements (per SD increase) with reduced RDI using logistic regression and adverse events using generalized estimating equations for repeated measures.
RESULTS
Higher CT SMA and DXA ALM were significantly associated with a lower risk of reduced RDI [odds ratios: 0.56 (0.38-0.81) for CT SMA; 0.56 (0.37-0.84) for DXA ALM]. No measurements of muscle or adipose tissue were associated with adverse events.
CONCLUSIONS
More muscle was associated with improved chemotherapy completion among patients with colon cancer, whereas muscle and adipose tissue were not associated with adverse events.
IMPACT
Considering body composition may help personalize dosing for colon cancer chemotherapy by identifying patients at risk for poor chemotherapy outcomes.
Topics: Male; Female; Humans; Cross-Sectional Studies; Body Composition; Adipose Tissue; Colonic Neoplasms; Muscle, Skeletal
PubMed: 37450841
DOI: 10.1158/1055-9965.EPI-23-0227 -
European Urology Jan 2024Field cancerization is characterized by areas of normal tissue affected by mutated clones. Bladder field cancerization may explain the development and recurrence of...
BACKGROUND
Field cancerization is characterized by areas of normal tissue affected by mutated clones. Bladder field cancerization may explain the development and recurrence of bladder cancer and may be associated with treatment outcomes.
OBJECTIVE
To investigate the predictive and prognostic roles of field cancerization in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with bacillus Calmette-Guérin (BCG).
DESIGN, SETTING, AND PARTICIPANTS
We conducted comprehensive genomic and proteomic analyses for 751 bladder biopsies and 234 urine samples from 136 patients with NMIBC. The samples were collected at multiple time points during the disease course. Field cancerization in normal-appearing bladder biopsies was measured using deep-targeted sequencing and error correction models.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Endpoints included the rates of recurrence and progression. Cox regression and Wilcoxon rank-sum and Fisher's exact tests were used.
RESULTS AND LIMITATIONS
A high level of field cancerization was associated with high tumor mutational burden (p = 0.007), high tumor neoantigen load (p = 0.029), and high tumor-associated CD8 T-cell exhaustion (p = 0.017). In addition, high field cancerization was associated with worse short-term outcomes (p = 0.029). Nonsynonymous mutations in bladder cancer-associated genes such as KDM6A, ARID1A, and TP53 were identified as early disease drivers already found in normal-appearing bladder biopsies. Urinary tumor DNA (utDNA) levels reflected the bladder tumor burden and originated from tumors and field cancerization. High levels of utDNA after BCG were associated with worse clinical outcomes (p = 0.027) and with disease progression (p = 0.003). High field cancerization resulted in high urinary levels of proteins associated with angiogenesis and proliferation. Limitations include variation in the number of biopsies and time points analyzed.
CONCLUSIONS
Field cancerization levels are associated with tumor development, immune responses, and clinical outcomes. utDNA measurements can be used to monitor disease status and treatment response.
PATIENT SUMMARY
Molecular changes in the tissue lining the bladder result in tumor recurrence. Urinary measurements may be used to monitor bladder cancer status and treatment responses.
Topics: Humans; BCG Vaccine; Non-Muscle Invasive Bladder Neoplasms; Proteomics; T-Cell Exhaustion; Disease-Free Survival; Disease Progression; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Adjuvants, Immunologic; Neoplasm Invasiveness; Administration, Intravesical
PubMed: 37718188
DOI: 10.1016/j.eururo.2023.07.014 -
European Urology Jul 2024Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective of the study was to characterize...
BACKGROUND AND OBJECTIVE
Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective of the study was to characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer.
METHODS
A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis. Spatial immune parameters were compared with histopathological parameters and overall survival data.
KEY FINDINGS AND LIMITATIONS
The identification of > 300 different immune cell subpopulations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. Thirty-nine immune parameters showed prognostic significance in univariate analyses, of which 16 were independent from pT, pN, and histological grade in muscle-invasive bladder cancer. Among all these parameters, the strongest association with prolonged overall survival was identified for intraepithelial CD8 cytotoxic T cells (time-dependent area under receiver operating characteristic curve [AUC]: 0.70), while stromal CD8 T cells were less relevant (AUC: 0.65). A favorable prognosis of inflamed cancers with high levels of "exhaustion markers" suggests that TIM3, PD-L1, PD-1, and CTLA-4 on immune cells do not hinder antitumoral immune response in tumors rich of tumor infiltrating immune cells.
CONCLUSIONS AND CLINICAL IMPLICATIONS
The density of intraepithelial CD8 T cells was the strongest prognostic feature in muscle-invasive bladder cancer. Given that tumor cell killing by CD8 cytotoxic T lymphocytes through direct cell-to-cell-contacts represents the "terminal end route" of antitumor immunity, the quantity of "tumor cell adjacent CD8 T cells" may constitute a surrogate for the efficiency of cancer recognition by the immune system that can be measured straightaway in routine pathology as the CD8 labeling index.
PATIENT SUMMARY
Quantification of intraepithelial CD8 T cells, the strongest prognosticfeature identified in muscle-invasive bladder cancer, can easily be assessed by brightfield immunohistochemistry and is therefore "ready to use" for routine pathology.
Topics: Humans; Urinary Bladder Neoplasms; Prognosis; Lymphocytes, Tumor-Infiltrating; CD8-Positive T-Lymphocytes; Immunohistochemistry; Male; Female; Tissue Array Analysis; Urothelium; Carcinoma, Transitional Cell; Aged; Tumor Microenvironment; Biomarkers, Tumor; Middle Aged
PubMed: 38383257
DOI: 10.1016/j.eururo.2024.01.023 -
Therapeutic Innovation & Regulatory... Sep 2023The purpose of this study is to rank the factors that are most and least important to patients with symptomatic uterine fibroids when considering surgical treatment... (Review)
Review
STUDY OBJECTIVE
The purpose of this study is to rank the factors that are most and least important to patients with symptomatic uterine fibroids when considering surgical treatment options.
MATERIALS AND METHODS
Using a best worst scaling (BWS) preference elicitation approach, participants completed an online survey to rank factors associated with fibroid surgical treatments. Survey content was based on a literature review and included the following factors: symptom relief; surgical complications; repeat treatment; recovery time; cosmetic effects; risk of spreading undiagnosed cancer; sexual outcomes; maintenance of child-bearing; continuation of menses; unpredictable menses; and location of procedure. Participants completed 11 BWS tasks. For each task, we presented participants with a subset of 5 factors from the possible 11, and participants chose the most important and least important factor. Participants' responses were analyzed using conditional logistic regression to determine the relative importance of factors. Patient priorities were further explored via age and race.
RESULTS
285 respondents with symptomatic uterine fibroids (69 physician-confirmed and 216 self-reported) who had not undergone prior surgical treatment completed the survey. Respondents were enrolled from two clinical sites (clinical site cohort) and an online consumer panel (panel cohort). Both cohorts identified symptom relief, cancer risk, repeat treatment and complications as the most important factors in selecting surgical treatment options and location of procedure, return to normal activities after surgery, and cosmetic effects like presence of a scar after the surgical treatment as the least important factors. Of note, younger women (≤ 40) placed greater importance on the ability to have children after the procedure.
CONCLUSION
Information regarding the factors most and least important to patients with symptomatic uterine fibroids might inform development and regulatory evaluation of new technologies and procedures. Study results may be useful in efforts to develop a set of outcomes to include in future fibroids clinical studies.
Topics: Humans; Female; Uterine Neoplasms; Patient Preference; Leiomyoma; Surveys and Questionnaires; Self Report
PubMed: 37210440
DOI: 10.1007/s43441-023-00525-1 -
International Journal of Medical... 2024Uterine leiomyomas (ULM) are the most common benign tumors of the female genitalia, while uterine leiomyosarcomas (ULMS) are rare. The sarcoma is diffuse growth, prone... (Review)
Review
Uterine leiomyomas (ULM) are the most common benign tumors of the female genitalia, while uterine leiomyosarcomas (ULMS) are rare. The sarcoma is diffuse growth, prone to hematogenous metastasis, and has a poor prognosis. Due to their similar clinical symptoms and morphological features, it is sometimes difficult to distinguish them, and the final diagnosis depends on histological diagnosis. Misdiagnosis of ULM as ULMS will lead to more invasive and extensive surgery when it is not needed, while misdiagnosis of ULMS as ULM may lead to delayed treatment and poor prognosis. This review searched and studied the published articles on ULM and ULMS, and summarized the potential markers for the differential diagnosis of ULMS. These markers will facilitate differential diagnosis and personalized treatment, providing timely diagnosis and potentially better prognosis for patients.
Topics: Humans; Female; Leiomyoma; Uterine Neoplasms; Diagnosis, Differential; Leiomyosarcoma; Biomarkers, Tumor; Prognosis
PubMed: 38818470
DOI: 10.7150/ijms.93464 -
HGG Advances Oct 2023Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for...
Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for patients with PRMS, and little is known about the molecular drivers of this disease. To better characterize PRMS, we performed a broad array of genomic and immunostaining analyses on 25 patient samples. In terms of gene expression and methylation, PRMS clustered more closely with other complex karyotype sarcomas than with pediatric alveolar and embryonal rhabdomyosarcoma. Immune infiltrate levels in PRMS were among the highest observed in multiple sarcoma types and contrasted with low levels in other rhabdomyosarcoma subtypes. Lower immune infiltrate was associated with complete loss of both and . This comprehensive characterization of the genetic, epigenetic, and immune landscape of PRMS provides a roadmap for improved prognostications and therapeutic exploration.
Topics: Adult; Humans; Child; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Genomics; Protein Processing, Post-Translational; Soft Tissue Neoplasms; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases; Retinoblastoma Binding Proteins
PubMed: 37593416
DOI: 10.1016/j.xhgg.2023.100224 -
Endocrinology and Metabolism (Seoul,... Dec 2023Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The... (Review)
Review
Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing's syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing's syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.
Topics: Humans; Cushing Syndrome; Neoplasms; Adipose Tissue; Obesity; Diabetes Mellitus; Tumor Microenvironment
PubMed: 37989266
DOI: 10.3803/EnM.2023.1814 -
The Lancet. Oncology Nov 2023Retroperitoneal sarcomas are tumours with a poor prognosis. Upfront characterisation of the tumour is difficult, and under-grading is common. Radiomics has the potential...
A CT-based radiomics classification model for the prediction of histological type and tumour grade in retroperitoneal sarcoma (RADSARC-R): a retrospective multicohort analysis.
BACKGROUND
Retroperitoneal sarcomas are tumours with a poor prognosis. Upfront characterisation of the tumour is difficult, and under-grading is common. Radiomics has the potential to non-invasively characterise the so-called radiological phenotype of tumours. We aimed to develop and independently validate a CT-based radiomics classification model for the prediction of histological type and grade in retroperitoneal leiomyosarcoma and liposarcoma.
METHODS
A retrospective discovery cohort was collated at our centre (Royal Marsden Hospital, London, UK) and an independent validation cohort comprising patients recruited in the phase 3 STRASS study of neoadjuvant radiotherapy in retroperitoneal sarcoma. Patients aged older than 18 years with confirmed primary leiomyosarcoma or liposarcoma proceeding to surgical resection with available contrast-enhanced CT scans were included. Using the discovery dataset, a CT-based radiomics workflow was developed, including manual delineation, sub-segmentation, feature extraction, and predictive model building. Separate probabilistic classifiers for the prediction of histological type and low versus intermediate or high grade tumour types were built and tested. Independent validation was then performed. The primary objective of the study was to develop radiomic classification models for the prediction of retroperitoneal leiomyosarcoma and liposarcoma type and histological grade.
FINDINGS
170 patients recruited between Oct 30, 2016, and Dec 23, 2020, were eligible in the discovery cohort and 89 patients recruited between Jan 18, 2012, and April 10, 2017, were eligible in the validation cohort. In the discovery cohort, the median age was 63 years (range 27-89), with 83 (49%) female and 87 (51%) male patients. In the validation cohort, median age was 59 years (range 33-77), with 46 (52%) female and 43 (48%) male patients. The highest performing model for the prediction of histological type had an area under the receiver operator curve (AUROC) of 0·928 on validation, based on a feature set of radiomics and approximate radiomic volume fraction. The highest performing model for the prediction of histological grade had an AUROC of 0·882 on validation, based on a radiomics feature set.
INTERPRETATION
Our validated radiomics model can predict the histological type and grade of retroperitoneal sarcomas with excellent performance. This could have important implications for improving diagnosis and risk stratification in retroperitoneal sarcomas.
FUNDING
Wellcome Trust, European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group, the National Institutes for Health, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.
Topics: Humans; Male; Female; Aged; Adult; Middle Aged; Aged, 80 and over; Leiomyosarcoma; Retrospective Studies; Sarcoma; Liposarcoma; Soft Tissue Neoplasms; Retroperitoneal Neoplasms; Tomography, X-Ray Computed
PubMed: 37922931
DOI: 10.1016/S1470-2045(23)00462-X -
Medicina (Kaunas, Lithuania) Dec 2023Uterine myomas represent one of the most prevalent pathologies affecting the female population. These benign neoplasms originate from the smooth muscular cells of the... (Review)
Review
Uterine myomas represent one of the most prevalent pathologies affecting the female population. These benign neoplasms originate from the smooth muscular cells of the uterus, and they can be either single or multiple. Often associated with debilitating symptoms such as pelvic heaviness, pain, constipation, and urinary dysfunctions, the surgical management of myomectomy exhibits considerable variability. This diversity in approaches is influenced by factors such as the number and size of myomas, the patient's age, and overall clinical conditions. This study aims to elucidate and compare the advantages and disadvantages of different surgical approaches, specifically endoscopic procedures versus open surgery, providing valuable insights for clinical decision making. A comprehensive bibliographic search spanning from 2013 to 2023 was systematically conducted across databases including Medline, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search utilized keywords such as "myomectomy laparoscopic and open", "myomectomy open and minimally invasive", "myomectomy open and laparoscopic", and "myomectomy open vs. laparoscopic." The research methodology, along with predetermined inclusion and exclusion criteria, was established prior to the search, ensuring a systematic and rigorous approach. Subsequently, data analysis was carried out. Following the study selection process, 25 articles met the eligibility criteria for inclusion in this analysis. The average numbers of myomas were 3.7 (ranging from 1 to 13.7) and 5.4 (ranging from 1 to 13.5) for the minimally invasive surgery and open surgery groups, respectively. In terms of myoma size, the total averages across studies were 7 cm (ranging from 4.8 to 14) for the minimally invasive group and 8 cm (ranging from 3.9 to 11.2) for the open surgery group. The average pregnancy and delivery rates were 29.7% (ranging from 1.8 to 100) for the minimally invasive group and 28.5% (ranging from 1.8 to 100) for the open surgery group. Regarding complications, the average rate was 14.2% (ranging from 0 to 50) for the endoscopic group and 22.3% (ranging from 0 to 60.3) for the laparotomic group. In conclusion, a critical factor influencing the choice of surgical approach is primarily the size and quantity of fibroids. The mini-laparotomic approach emerges as a viable alternative to endoscopy, demonstrating favorable surgical outcomes and aesthetic results. Interestingly, the type of surgical procedure appears to have no significant impact on the pregnancy rate.
Topics: Pregnancy; Female; Humans; Systematic Reviews as Topic; Leiomyoma; Uterine Myomectomy; Laparoscopy; Myoma
PubMed: 38256325
DOI: 10.3390/medicina60010064