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Frontiers in Molecular Biosciences 2024Cervical cancer (CC) is the fourth most common cancer among women worldwide. As part of the brisk cross-talk between the host and the tumor, prognosis can be affected...
Cervical cancer (CC) is the fourth most common cancer among women worldwide. As part of the brisk cross-talk between the host and the tumor, prognosis can be affected through inflammatory responses or the tumor microenvironment. However, further exploration of the inflammatory response-related genes that have prognostic value, microenvironment infiltration, and chemotherapeutic therapies in CC is needed. The clinical data and mRNA expression profiles of CC patients were downloaded from a public database for this study. In the TCGA cohort, a multigene prognostic signature was constructed by least absolute shrinkage and selection operator (LASSO) and Cox analyses. CC patients from the GEO cohort were used for validation. K‒M analysis was used to compare overall survival (OS) between the high- and low-risk groups. Univariate and multivariate Cox analyses were applied to determine the independent predictors of OS. The immune cell infiltration and immune-related functional score were calculated by single-sample gene set enrichment analysis (GSEA). Immunohistochemistry was utilized to validate the protein expression of prognostic genes in CC tissues. A genetic signature model associated with the inflammatory response was built by LASSO Cox regression analysis. Patients in the high-risk group had a significantly lower OS rate. The predictive ability of the prognostic genes was evaluated by means of receiver operating characteristic (ROC) curve analysis. The risk score was confirmed to be an independent predictor of OS by univariate and multivariate Cox analyses. The immune status differed between the high-risk and low-risk groups, and the cancer-related pathways were enriched in the high-risk group according to functional analysis. The risk score was significantly related to tumor stage and immune infiltration type. The expression levels of five prognostic genes (LCK, GCH1, TNFRSF9, ITGA5, and SLC7A1) were positively related to sensitivity to antitumor drugs. Additionally, the expression of prognostic genes was significantly different between CC tissues and myoma patient cervix (non-tumorous) tissues in the separate sample cohort. A model consisting of 5 inflammation-related genes can be used to predict prognosis and influence immune status in CC patients. Furthermore, the inhibition or enhancement of these genes may become a novel alternative therapy.
PubMed: 38903179
DOI: 10.3389/fmolb.2024.1394902 -
European Journal of Obstetrics,... Jun 2024Uterine fibroids increase the risk of preterm birth. The current study highlights uterine fibroid necrosis as a possible cause of (extreme) preterm birth.
OBJECTIVE
Uterine fibroids increase the risk of preterm birth. The current study highlights uterine fibroid necrosis as a possible cause of (extreme) preterm birth.
STUDY DESIGN
Retrospective cohort study in one Dutch academic hospital. Cases were selected from the 526 participants of the MyoFert study (Netherlands Trial Register, NL7990), which included patients who presented between 2004 and 2018 and were between the age of 18 and 45 years at the time of diagnosis of uterine fibroids. Of these participants, 414 women became pregnant. A retrospective chart review of the first pregnancies was performed. The main outcomes were (imminent) preterm birth and signs of fibroid necrosis on ultrasound. In women with signs of fibroid necrosis, the following data were collected systematically: fibroid characteristics, clinical presentation, pregnancy outcome, and postpartum period.
RESULTS
In total, 66 women had a preterm birth (16 %, 66/414), of which 25 pregnancies ended between 16 and <24 weeks (38 %, 25/66) and 41 pregnancies ended between 24 and <37 weeks of gestation (62 %, 41/66). Of all women with preterm birth and available ultrasound images, 15 % (7/48) had fibroid necrosis at the time of labour. These seven patients, supplemented with three patients with fibroid necrosis during their first pregnancy and at least one episode of imminent preterm birth, are described in more detail. In these ten patients, the fibroids increased substantially in size during the first and second trimester, leading to severe abdominal pain in all patients and hospital admission in seven patients. Ultrasound examination of the fibroids showed heterogenic changes and focal transonic areas in the fibroid, which are characteristics that indicate fibroid necrosis. In four patients, myomectomy was performed and necrosis was confirmed histologically.
CONCLUSION
Fibroid necrosis during pregnancy is likely associated with (imminent) preterm birth. Clinicians are advised to structurally evaluate the myometrium in pregnancy, specifically in women presenting with abdominal pain in the second trimester.
PubMed: 38870742
DOI: 10.1016/j.ejogrb.2024.06.002 -
PloS One 2024Xenoestrogens are synthetic or naturally occurring chemicals capable of altering the endocrine system of humans and animals owing to their molecular similarity to...
BACKGROUND
Xenoestrogens are synthetic or naturally occurring chemicals capable of altering the endocrine system of humans and animals owing to their molecular similarity to endogenous hormones. There is limited data regarding their effects on women´s health. Chronic exposure to xenoestrogens can promote the development of estrogen-related diseases.
OBJECTIVES
To examine xenoestrogen concentration (TEXB-α) differences between women with leiomyomas or endometriosis and control women, and to study the relationship between the clinical and sociodemographic characteristics of these patients and their xenoestrogen levels.
METHODS
Prospective case-control study. We selected 221 women who underwent surgery at Quironsalud Madrid University Hospital between 2017 and 2021. The cases included 117 patients: 74 women who underwent surgery for uterine leiomyomas, 21 with endometriosis, and 22 with both pathologies. The control group comprised 104 healthy women who underwent surgical procedures for other reasons. TEXB-α was determined in the omental fat of all patients. Using a questionnaire and reviewing the patients' medical records, we collected sociodemographic data and other relevant variables.
RESULTS
A significant majority of study participants (68.8%) had detectable levels of xenoestrogens. We found no association between TEXB-α levels in omental fat and the presence of myomas or endometriosis. In the case group, women living or working in Madrid Community exhibited, on average, 3.12 Eeq pM/g higher levels of TEXB-α compared to those working in other areas (p = 0.030). Women who referred to the use of estrogen-containing hormonal contraceptives had, on average, 3.02 Eeq pM/g higher levels of TEXB-α than those who had never used them (p = 0.022).
CONCLUSIONS
This study found no association between omental xenoestrogen levels and leiomyomas or endometriosis. However, their presence in most participants and their association with highly polluted areas emphasizes the importance of limiting environmental exposure to these substances. We also identified an association between hormonal contraceptive use and xenoestrogen concentration.
Topics: Humans; Female; Endometriosis; Leiomyoma; Adult; Case-Control Studies; Middle Aged; Prospective Studies; Uterine Neoplasms; Estrogens
PubMed: 38833439
DOI: 10.1371/journal.pone.0304766 -
Trials May 2024The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low...
The effectiveness of relugolix compared with leuprorelin for preoperative therapy before laparoscopic myomectomy in premenopausal women, diagnosed with uterine fibroids: protocol for a randomized controlled study (MyLacR study).
BACKGROUND
The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low back pain in women with uterine fibroids. Treatment can also help women recover from low hemoglobin levels and possibly shrink the fibroids. However, evidence of preoperative use of relugolix before laparoscopic myomectomy is limited. Nevertheless, the treatment could reduce interoperative blood loss, decrease the risk of developing postoperative anemia, and shorten the operative time. Thus, we aim to test whether 12-week preoperative treatment with relugolix (40 mg orally, once daily) is similar to or not worse than leuprorelin (one injection every 4 weeks) to reduce intraoperative blood loss.
METHODS
Efficacy and safety of preoperative administration of drugs will be studied in a multi-center, randomized, open-label, parallel-group, noninferiority trial enrolling premenopausal women ≥ 20 years of age, diagnosed with uterine fibroids and scheduled for laparoscopic myomectomy. Participants (n = 80) will be recruited in the clinical setting of participating institutions. The minimization method (predefined factors: presence or absence of fibroids ≥ 9 cm and the International Federation of Gynecology and Obstetrics [FIGO] type 1-5 fibroids) with randomization is used in a 1:1 allocation. Relugolix is a 40-mg oral tablet taken once a day before a meal, for 12 weeks, up to the day before surgery. Leuprorelin is a 1.88 mg, or 3.75 mg subcutaneous injection, given in three 4-week intervals during patient visits before the surgery. For the primary outcome measure of intraoperative bleeding, the blood flow is collected from the body cavity, surgical sponges, and collection bag and measured in milliliters. Secondary outcome measures are hemoglobin levels, myoma size, other surgical outcomes, and quality-of-life questionnaire responses (Kupperman Konenki Shogai Index and Uterine Fibroid Symptoms-Quality of Life).
DISCUSSION
Real-world evidence will be collected in a clinical setting to use pre-treatment with an oral gonadotropin-releasing hormone antagonist to reduce intraoperative bleeding in women who undergo laparoscopic myomectomy.
TRIAL REGISTRATION
jRCTs031210564 was registered on 19 January 2022 in the Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ).
Topics: Humans; Female; Leiomyoma; Leuprolide; Uterine Myomectomy; Laparoscopy; Uterine Neoplasms; Premenopause; Treatment Outcome; Multicenter Studies as Topic; Preoperative Care; Equivalence Trials as Topic; Antineoplastic Agents, Hormonal; Adult; Blood Loss, Surgical; Gonadotropin-Releasing Hormone; Time Factors; Randomized Controlled Trials as Topic; Phenylurea Compounds; Pyrimidinones
PubMed: 38790029
DOI: 10.1186/s13063-024-08170-1 -
Cureus May 2024Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that arise in the muscular or submucosal layers of the gastrointestinal tract. Extra-gastrointestinal...
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that arise in the muscular or submucosal layers of the gastrointestinal tract. Extra-gastrointestinal stromal tumors (EGISTs) are rare primary entities that develop outside the digestive tract which are histologically and immunologically similar to GISTs. We present the case of a 52-year-old female diagnosed with a primary EGIST arising in the small bowel mesentery four months after undergoing hormone therapy for multiple uterine myomas. Transvaginal ultrasonography and MRI revealed a pelvic mass suspected to be a GIST. The patient was treated with laparoscopic-assisted partial resection of the small bowel. Histopathological examination of the surgical specimen confirmed the diagnosis of an EGIST. Imatinib treatment was initiated, and no clinical evidence of recurrence or metastasis was detected postoperatively. Because EGISTs are extremely rare, the differences between EGISTs and GISTs, the degree of malignancy, and prognosis have not been fully investigated. Further studies are needed to accumulate additional cases. The present case shows that laparoscopic-assisted excision can be successfully used to manage EGISTs.
PubMed: 38784684
DOI: 10.7759/cureus.60897 -
Biomedicine & Pharmacotherapy =... Jun 2024Rearrangement of the actin cytoskeleton is a prerequisite for carcinoma cells to develop cellular protrusions, which are required for migration, invasion, and...
Rearrangement of the actin cytoskeleton is a prerequisite for carcinoma cells to develop cellular protrusions, which are required for migration, invasion, and metastasis. Fascin is a key protein involved in actin bundling and is expressed in aggressive and invasive carcinomas. Additionally, fascin appears to be involved in tubulin-binding and microtubule rearrangement. Pharmacophoric-based in silico screening was performed to identify compounds with better fascin inhibitory properties than migrastatin, a gold-standard fascin inhibitor. We hypothesized that monastrol displays anti-migratory and anti-invasive properties via fascin blocking in colorectal cancer cell lines. Biophysical (thermofluor and ligand titration followed by fluorescence spectroscopy), biochemical (NMR), and cellular assays (MTT, invasion of human tissue), as well as animal model studies (zebrafish invasion) were performed to characterize the inhibitory effect of monastrol on fascin activity. In silico analysis revealed that monastrol is a potential fascin-binding compound. Biophysical and biochemical assays demonstrated that monastrol binds to fascin and interferes with its actin-bundling activity. Cell culture studies, including a 3D human myoma disc model, showed that monastrol inhibited fascin-driven cytoplasmic protrusions as well as invasion. In silico, confocal microscopy, and immunoprecipitation assays demonstrated that monastrol disrupted fascin-tubulin interactions. These anti-invasive effects were confirmed in vivo. In silico confocal microscopy and immunoprecipitation assays were carried out to test whether monastrol disrupted the fascin-tubulin interaction. This study reports, for the first time, the in vitro and in vivo anti-invasive properties of monastrol in colorectal tumor cells. The number and types of interactions suggest potential binding of monastrol across actin and tubulin sites on fascin, which could be valuable for the development of antitumor therapies.
Topics: Humans; Colorectal Neoplasms; Microfilament Proteins; Carrier Proteins; Neoplasm Invasiveness; Kinesins; Animals; Cell Line, Tumor; Cell Movement; Neoplasm Metastasis; Pyrimidines; Signal Transduction; Thiones; Antineoplastic Agents
PubMed: 38781869
DOI: 10.1016/j.biopha.2024.116785 -
Comprehensive exploration unveiling the sonography and histopathology of uterine leiomyoma in a cow.Veterinary Research Forum : An... 2024Genital tumours are rare among cattle, largely due to their relatively short lifespans. Leio-myoma, a smooth muscle tumour being more prevalent in dogs, appears only at...
Genital tumours are rare among cattle, largely due to their relatively short lifespans. Leio-myoma, a smooth muscle tumour being more prevalent in dogs, appears only at a rate of 1.00 - 2.00% in cattle, affecting reproductive efficiency in cases of complete uterine obstruction. This case report involves an 8-year-old cow with repeated insemination attempts unveiled 5.00 cm intra-luminal uterine mass, obstructing the right uterine horn. Transrectal sonography (TRUS) revealed a highly vascularized mass with normal ovarian function. Confirmation of clinical condition, , uterine leiomyoma, uterine biopsy concluded the presence of neoplastic smooth muscle cells arranged in interlacing bundles showing mild pleomorphism, and special staining using Masson's trichrome revealed an unappreciable amount of connective tissue; subsequently right flank celiotomy was performed to remove the benign tumour. Forty-five days after celiotomy, TRUS examination confirmed an unobstructed uterine horn, and bilateral oviduct patency was adjudged with 2.50% methylene blue. Following treatment for chronic endometritis, artificial insemination led to conception nearly 90 days post-procedure. The TRUS aids preliminary diagnosis, while definitive identification demands necropsy and surgical methods. This case underscores the diagnostic significance of TRUS, histopathology and celiotomy for identifying and managing uterine leiomyoma in cattle.
PubMed: 38770205
DOI: 10.30466/vrf.2024.2018975.4112 -
Revista Brasileira de Ginecologia E... 2024To compare Transforming growth factor beta-1 (TGF-β1) expression in patients with and without adenomyosis.
OBJECTIVE
To compare Transforming growth factor beta-1 (TGF-β1) expression in patients with and without adenomyosis.
METHODS
A prospective design was performed including 49 patients submitted to hysterectomy. Immunohistochemistry was performed on anatomopathological samples staged in paraffin blocks from patients with and without adenomyosis. The sample contained 28 adenomyosis cases and 21 controls. Student's -test and multivariate logistic regression tests were used for statistical analysis. Associations were considered significant at < 0.05.
RESULTS
We found no significant association between adenomyosis and: smoking ( = 0.75), miscarriage ( = 0.29), number of previous pregnancies ( = 0.85), curettage ( = 0.81), pelvic pain ( = 0.72) and myoma ( = 0.15). However, we did find a relationship between adenomyosis and abnormal uterine bleeding (AUB) ( = 0.02) and previous cesarean section ( = 0.02). The mean TGF-β1 intensity (mean ± SD) in the ectopic endometrium of women with adenomyosis showed no significant association (184.17 ± 9.4 vs.184.66 ± 16.08, = 0.86) from the topic endometrium of women without adenomyosis.
CONCLUSION
TGF-β1 expression was not increased in the ectopic endometrium of women with adenomyosis.
Topics: Humans; Female; Adenomyosis; Transforming Growth Factor beta1; Prospective Studies; Adult; Middle Aged; Case-Control Studies
PubMed: 38765506
DOI: 10.61622/rbgo/2024rbgo31 -
Journal of Robotic Surgery May 2024Single-port laparoscopy has gained more attention, but inherent technical challenges hinder its wider use. To overcome the disadvantage of traditional single-port... (Clinical Trial)
Clinical Trial
Single-port laparoscopy has gained more attention, but inherent technical challenges hinder its wider use. To overcome the disadvantage of traditional single-port surgery, robotic laparoendoscopic single-site surgery system was designed and clinically utilized. This multi-center single-arm trial was aimed to present the clinical outcomes of the SHURUI robotic endoscopic single-site surgery system. 63 women with ovary cysts, myoma, cervical epithelial neoplasm, or endometrial carcinoma were recruited at 6 academic medical centers in different districts of China. The trial was registered on September 5, 2023, with the register number: ChiCTR2300075431, retrospectively registered. Patients underwent robotic LESS surgery with the SHURUI endoscopic surgical system from January 17 to May 26, 2023. Demographic information, perioperative parameters, complications, scar healing, and operator satisfaction scores were recorded. Patients were followed up for 30 ± 4 days. Average operative time and estimated blood loss were 157.03 ± 75.24 min and 63.86 ± 98.33 ml, respectively, for all surgeries. Average anal exhaust time and hospitalization stay were 30.99 ± 14.25 h and 3.63 ± 1.59 days, respectively. Patients' postoperative rehabilitation assessment showed satisfactory results on the day of discharge and 30 ± 4 days after surgery. The surgery achieved good cosmetic benefits and was surgeon friendly. There were no conversions to alternative surgical modalities, complications, or readmissions. The SHURUI endoscopic surgical system showed both the technical feasibility and safety of this surgical modality for gynecologic patients. Further randomized studies comparing this modality with traditional LESS surgery are suggested.
Topics: Humans; Female; Robotic Surgical Procedures; Middle Aged; Prospective Studies; Adult; Treatment Outcome; Laparoscopy; Genital Diseases, Female; Aged; Operative Time; Endoscopy
PubMed: 38727869
DOI: 10.1007/s11701-024-01871-4 -
Asian Journal of Surgery May 2024
PubMed: 38724381
DOI: 10.1016/j.asjsur.2024.04.167