Hormone-dependent Cancer Research Articles

Steroid sulfatase and sulfotransferases in the estrogen and androgen action of gynecological cancers: current status and perspectives.

Sulfatase (STS) and sulfotransferases (SULT) have important role in the biosynthesis and action of steroid hormones. STS catalyzes the hydrolysis of estrone-sulfate (E1-S) and dehydroepiandrosterone-sulfate (DHEA-S), while sulfotransferases catalyze the reverse reaction and require 3-phosphoadenosine-5-phosphosulfate as a sulfate donor. These enzymes control the concentration of active estrogens and androgens in peripheral tissues. Aberant expression of STS and SULT genes has been found in both, benign hormone-dependent diseases and hormone-dependent cancers. The aim of this review is to present the current knowledge on the role of STS and SULT in gynecological cancers, endometrial (EC) and ovarian cancer (OC). EC is the most common and OC the most lethal gynecological cancer. These cancers primarily affect postmenopausal women and therefore rely on the local production of steroid hormones from inactive precursors, either DHEA-S or E1-S. Following cellular uptake by organic anion transporting polypeptides (OATP) or organic anion transporters (OAT), STS and SULT regulate the formation of active estrogens and androgens, thus disturbed balance between STS and SULT can contribute to the onset and progression of cancer. The importance of these enzymes in peripheral estrogen biosynthesis has long been recognized, and this review provides new data on the important role of STS and SULT in the formation and action of androgens, their regulation and inhibition, and their potential as prognostic biomarkers.

Risk of type 2 diabetes, MASLD and cardiovascular disease in people living with polycystic ovary syndrome.

Abstract Background Polycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype. Methods Using UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes. Results We included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction >5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = <.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=<.01). Conclusion Cardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.

PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [89Zr]Zr-TR1402.

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid. This study explores [89Zr]Zr-TR1402 as a thyroid-stimulating hormone receptor (TSHR)-targeted PET radiopharmaceutical for DTC. [89Zr]Zr-TR1402 was synthesized with a molar activity of 25.9 MBq/nmol by conjugating recombinant human TSH (rhTSH) analogue TR1402 to chelator p-SCN-Bn-deferoxamine (DFO) in a molar ratio of 3:1 (DFO/TR1402) and radiolabeling with 89Zr (t1/2 = 78.4 h, β+ = 22.7%). As TSHR is absent in commonly available DTC-derived cell lines, TSHR was reintroduced via stable transduction by delivering a lentivirus containing the full-length coding region of the human TSHR gene. Receptor-mediated uptake of [89Zr]Zr-TR1402 was evaluated in vitro in stably transduced TSHR+ and wild-type TSHR- DTC cell lines. In vivo PET imaging was performed on Days 1-3 postinjection in male and female athymic nude mice bearing TSHR+ and TSHR- xenografts, along with ex vivo biodistribution on Day 3 postinjection. In vitro uptake of 1 nM [89Zr]Zr-TR1402 was significantly higher in TSHR+ THJ529T (P < 0.0001) and FTC133 (P < 0.01) cells than in TSHR- THJ529T and FTC133 cells. This uptake was shown to be specific in both TSHR+ THJ529T (P < 0.0001) and TSHR+ FTC133 (P < 0.0001) cells by blocking uptake with 250 nm DFO-TR1402. In vivo PET imaging showed accumulation of [89Zr]Zr-TR1402 in TSHR+ tumors, which was the highest on Day 1. In the male FTC133 xenograft model, ex vivo biodistribution confirmed a significant difference (P < 0.001) in uptake between FTC133+ (1.3 ± 0.1%ID/g) and FTC133- (0.8 ± 0.1%ID/g) tumors. A significant difference (P < 0.05) in uptake was also seen in the male THJ529T xenograft model between THJ529T+ (1.8 ± 0.6%ID/g) and THJ529T- (0.8 ± 0.4%ID/g) tumors. The in vitro and in vivo accumulation of [89Zr]Zr-TR1402 in TSHR-expressing DTC cell lines support the continued preclinical optimization of this approach.

P-367 Letrozole or Tamoxifen co-administration during fertility preservation of breast cancer patients: a retrospective cohort study

Abstract Study question How do fertility preservation (FP) outcomes differ between breast cancer patients stimulated with FSH and Tamoxifen versus FSH and Letrozole? Summary answer Letrozole and Tamoxifen co-administration yielded similar number of retrieved and cryopreserved oocytes/embryos, as well as similar oocyte maturation and fertilization and rates. What is known already Oocyte/embryo cryopreservation is recommended before initiation of chemotherapy in cancer patients. The co-administration of Tamoxifen, a selective estrogen receptor modulator, or Letrozole, an aromatase inhibitor, during ovarian stimulation with gonadotropins, are used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the optimal choice between the two is still unclear and with no sound evidence. Study design, size, duration Retrospective cohort study of all FP treatments of newly diagnosed breast cancer patients in two tertiary centers between 2000-2022. Collected data included 354 FP cycles of 290 patients and compared treatment parameters and outcomes of Tamoxifen or Letrozole co-administration. Participants/materials, setting, methods Breast cancer patients who underwent FP before chemotherapy were included. Patients with a history of radiation or gonadotoxic treatment, as well as those undergoing other fertility preservation treatments, such as ovarian tissue cryopreservation were excluded. Main results and the role of chance Overall, 215 Letrozole and 139 Tamoxifen treatment cycles were compared, with no significant demographic differences. Treatments with Letrozole had higher FSH dosages (3970IU vs. 2839IU, p &amp;lt; 0.001) but shorter duration (9.7 vs. 10.5 days, p &amp;lt; 0.001). The Letrozole group achieved lower peak E2 levels and endometrial thickness (1508pmol/L, 8.1mm vs. 8760pmol/L, 9.5mm, p &amp;lt; 0.001). The mean number of retrieved oocytes was comparable between the groups (13.6 with Letrozole vs 14.7 with Tamoxifen, p = 0.06). In 122 Letrozole and 46 Tamoxifen patients that underwent strictly oocytes cryopreservation the mean number of cryopreserved oocytes was comparable (11 vs. 12.1, p = 0.21). Moreover, in embryo cryopreservation cycles of 71 patients treated with Letrozole compared to 76 patients with Tamoxifen, no difference was observed in the number of cryopreserved embryos (6.2 vs. 7.0, p = 0.12). Oocyte maturation rate among strictly oocyte preservation cycles was comparable (86% with Letrozole vs. 83% with Tamoxifen, p = 0.80), as were fertilization rates in embryo cryopreservation cycles (62% vs. 63%, p = 0.8 and 71% vs. 76%, p = 0.3 in IVF and ICSI with Letrozole and Tamoxifen, respectively). Multivariate analysis, controlling for potential confounders showed no significant correlations between Tamoxifen or Letrozole co-administration and the number of retrieved oocytes or oocyte maturation rate. Limitations, reasons for caution The primary limitation of our study is its retrospective design and the variation in treatment duration and gonadotrophin dosages among groups. Wider implications of the findings This study provides reassurance that both Tamoxifen and Letrozole are equally effective options when co-administered in FP treatments of breast cancer patients. Trial registration number not applicable

P-378 Relation between AMH serum levels and recovered mature oocytes in infertile, healthy, and oncological patients

Abstract Study question Does AMH serum levels correlate with the recovered mature oocytes in similar way among infertile, healthy, and oncological patients? Summary answer AMH serum levels correlated well with the number of mature oocytes in infertile, healthy, and oncological patients What is known already AMH is a protein produced by granulosa cells from pre-antral follicles and uses as biomarker of ovarian reserve. The aim of ovarian stimulation in the IVF setting or fertility preservation is obtaining metaphase II oocytes. The value of serum AMH to predict the number of mature oocytes has not been study in a comparative way among infertile patients vs. healthy and oncological population Study design, size, duration Retrospective study of the AMH serum levels and number of recovered mature oocytes in oocyte vitrification cycles from April 2017 to June 2023. We included 78 patients with cancer, 119 healthy patients and 668 infertile patients undergoing oocyte vitrification for fertility preservation or as accumulation of oocytes strategy Participants/materials, setting, methods This single centre study included Infertile patients ≤ 42 with gynaecological pathology (endometriosis, polycystic ovarian syndrome, low ovarian reserve, and/or tubal factor), any type of cancer and healthy women demanding social fertility preservation. We excluded IVF healthy patients (normal patients with exclusively male factor). AMH serum level was measured before ovarian stimulation. We analysed the probability of obtain ≥ 8 mature oocytes considering as normal AMH (1.2 ng/mL). Ethical approval was obtained for this stud Main results and the role of chance IVF patients were older and had higher body mass index than the other two groups. AMH serum level (ng/mL) was similar among groups; in IVF patients (1.88 [1.67-2.09]); oncological patients (2.25 [1.85-2.65]), and healthy women (2.5 [2.2-2.8]). (p= 0.064). Ovarian stimulation was longer and more FSH units were employed in IVF patients. Oestradiol level at the oocyte maturation triggering was lower in oncological patients. The number of MII oocytes was significantly lower in IVF patients (6.1 [5.9-6.4]) compared with oncological and healthy patients (9.2[8.0-10.5]; 9.9 [9.0-10.8], respectively). AMH level correlated well with the number of recovered mature oocytes and similar among groups. The Odds Ratio to recover ≥ 8 mature oocytes considering as normal AMH (1.2 ng/mL) showed a probability 8.3 times higher in healthy patients, but only 0.3 times in IVF patients and 0.5 times in oncological patients. A OR: 9.1 was observed for obtain ≥ 8 mature oocytes between normal vs low AMH. The area under the curve in the ROC curve for AMH was 0.7191 Limitations, reasons for caution This study had limitations in the sample size and differences in ovarian stimulation protocol as oncological patients in hormone-dependent cancer received letrozole while conventional ovarian stimulation with FSH was performed in IVF and healthy patients. IVF patients’ group was heterogeneous in the aetiology of infertility Wider implications of the findings This study remarks the use of AMH in different conditions: infertility, oncological, and healthy status. Although no differences were found in correlation with the number of mature oocytes, the probability to obtain ≥ 8 mature oocytes with normal AMH was higher in healthy women compared with infertile patients Trial registration number 2306-VGO-128-EM

Antibodies and anti-antibodies specific to estradiol and progesterone and tumor proliferation in breast cancer patients

The study was aimed to determine the interrelations between levels of serum antibodies specific to estradiol and progesterone (IgA1-E2 and IgA1-Pg) and corresponding antiidiotypic antibodies (IgG2-E2 and IgG2-Pg) and tumor Ki67 positive cells in breast cancer patients (BCP). Material and Methods. The content of these antibodies in the blood serum of BCP (522 at the I stage and 578 at the II –IV stages) was studied using non-competitive enzyme immunoassay. Ki67 was determined using immunohistochemical method. Statistical analysis of the results was performed using the Statistica 8.0 software. Results. There were no revealed the desired associations in BCP I stage. Tumors with high levels of Ki67 positive cells (&gt;20,0 %) were found more often in BCP II –IV stages with high serum levels of IgA1-E2 together with IgA1-Pg than in BCP with low levels of these antibodies (68.8 vs 58.0 %, р=0.02). In contrast, tumors with Ki67&gt;20,0 % were revealed less often in BCP with high levels of IgG2-E2 together with IgG2-Pg (49.6 vs 65.2 %, р=0.002). Tumors with high levels of Ki67 positive cells were revealed in 42.9 % BCP I stage and in 77.1 % BCP II –IV stages with high serum levels of IgA1-E2 and IgA1-Pg in combination with low serum levels of IgG2-E2 and IgG2-Pg (p&lt;0.001). There were no such differences between BCP I and II -IV stages with low levels of IgA1-E2 and IgA1-Pg in combination with high levels of IgG2-E2 and IgG2-Pg (46.7 vs 48.2 %, accordingly, р=0.985). Conclusion. Antibodies against E2 and Pg synergistically promoted, but corresponding antiidiotypic antibodies synergistically inhibited the tumors proliferation in BCP. Immunoassay of antibodies and anti-antibodies to steroids is recommended for research of human hormone-dependent neoplasms progression.

Is There a Place for De-escalating Therapy in Patients with Metastatic Hormone-sensitive Prostate Cancer?

Although intermittent androgen deprivation therapy was often recommended for metastatic hormone-sensitive cancer therapy in the past, we do not know whether its use can be extrapolated to combination therapy. Trials evaluating intermittent therapy are necessary as this strategy could improve patient quality of life and reduce adverse events and costs.

Odds of developing cancer among male and female volunteer firefighters in Florida: A case-control study design.

Determine whether volunteer firefighters in Florida are at increased odds of developing cancer compared to non-firefighters. A case-control study design was implemented to assess the odds of developing cancer among male and female volunteer firefighters in Florida. Gender-specific age and calendar year-adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were estimated. Male volunteer firefighters were at increased odds for developing prostate (aOR = 1.26; 95%CI;[1.10- 1.44]) and male genital cancers combined (1.22;[1.07-1.39]), while reduced odds for endocrine cancer (0.41;[0.17-1.00]), and all leukemias (0.55;[0.35-0.86]), including lymphocytic (0.48;[0.24-0.97]); and chronic lymphocytic (0.40;[0.17-0.97]) leukemias. Female volunteer firefighters were at increased odds of developing of kidney cancer (2.51;[1.29-4.91]). Male volunteer firefighters are at increased odds for prostate and overall male genital cancers, while female volunteers are increased odds of kidney cancer.

Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study.

Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products. We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity. We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL. In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth. In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.

SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling.

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.

Evaluation of digit ratio (2D:4D) in breast cancer patients

Breast cancer is a hormone-dependent cancer. Hormonal exposure begins in the intrauterine period and continues in later years of life. 2D:4D ratio is accepted as an indicator of this exposure. The aim of this study was to investigate whether there is a difference in 2D:4D ratio between pathological subgroups of breast cancer and healthy control group. In this study, 204 participants, 154 breast cancer patients and 50 healthy control volunteers with similar age distribution, were included. Both hands of all participants were scanned using a digital scanner. The second and fourth finger lengths were measured using a digital measuring ruler with an accuracy of 0.05 mm. The 2D:4D ratio was calculated as the length of the second finger divided by the length of the fourth finger. A total of 204 patients (55 triple negative, 52 luminal B, 33 luminal A, 14 HER2-overexpessing and 50 healthy control volunteers) were subjected to finger scanning. There was no statistically significant difference in mean age between the groups. The right hand 2D:4D ratio was significantly lower in the Luminal A group compared to the other groups (p < 0.048). Although prenatal hormonal exposure is accepted as a risk factor for breast cancer, no study has evaluated patients in pathological subgroups. The 2D:4D ratio may be associated with breast cancer especially in the luminal A group in which hormone receptors are strongly positive and which has a better prognosis compared to the other groups.

Thyroid cancer trends in China and its comparative analysis with G20 countries: Projections for 2020-2040.

Thyroid cancer, a leading type of endocrine cancer, accounts for 3-4% of all cancer diagnoses. This study aims to analyse and compare thyroid cancer patterns in China and the Group twenty (G20) countries, and predict these trend for the upcoming two decades. This observational longitudinal study utilised data from the Global Burden of Disease (GBD) study 2019. We used metrics including incidence, mortality, mortality-incidence ratio (MIR), age-standardised rate (ASR) and average annual percent change (AAPC) to examine thyroid cancer trends. Joinpoint regression analysis was used to identify periods manifesting notable changes. The association between sociodemographic index (SDI) and AAPC were investigated. The autoregressive integrated moving average (ARIMA) model was used to predict thyroid cancer trends from 2020 to 2040. From 1990 to 2019, thyroid cancer incidence cases in China increased by 289.6%, with a higher AAPC of age-standardised incidence rate (ASIR) in men. Contrastingly, the G20 demonstrated a smaller increase, particularly among women over 50. Despite the overall age-standardised mortality rate (ASMR) was higher in the G20, the increase in mortality was less pronounced than in China. Age-standardised incidence rate increased across all age groups and genders, with a notable rise among men aged 15-49. ASMR decreased in specific age groups and genders, especially among women. Conversely, the ASMR significantly increased in group aged over 70. The MIR exhibited a declining trend, but this decrease was less noticeable in men and the group aged over 70. Joinpoint analysis pinpointed significant shifts in overall ASIR and ASMR, with the most pronounced increase in ASIR during 2003-2011 in China and 2003-2010 in the G20. Predictions suggested a continual ASIR uptrend, especially in the 50-69 age group, coupled with a predicted ASMR downturn among the elderly by 2040. Moreover, the proportion of thyroid cancer deaths attributable to high body mass index (BMI) escalated, with significant increase in Saudi Arabia and a rise to 7.4% in China in 2019. Thyroid cancer cases in incidence and mortality are escalating in both China and the G20. The increasing trend may be attributed to factors beyond overdiagnosis, including environmental and genetic factors. These findings emphasise the necessity for augmenting prevention, control, and treatment strategies. They also highlight the significance of international collaboration in addressing the global challenge posed by thyroid cancer.

FOXO3a/PI3K/Akt pathway participates in the ROS- induced apoptosis triggered by α-ZEL and β-ZEL

Zearalenone (ZEN), an estrogenic mycotoxin, is one of the most common food and feed contaminants. Also, its metabolites α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL) are considered to induce oxidative stress, however its effect in prostate cells is not known yet. Our previous observations showed that forehead box transcription factor 3a (FOXO3a) expression is modified in hormone- sensitive cells in the response to mycotoxins, similar to the phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway. Thus, this study evaluated the direct molecular effect of α-ZEL and β-ZEL in a dose of 30 µM in hormone-dependent human prostate cancer (PCa) cells with the focus of the involvement of FOXO3a and PI3K/Akt signaling pathway in that effect. We observed that both active metabolites of ZEN reduced cell viability, induced oxidative stress, cell cycle arrest and apoptosis in PCa cells. Furthermore, we observed that FOXO3a as well as PI3K/Akt signaling pathway participate in ZELs induced toxicity in PCa cells, indicating that this signaling pathway might be a regulator of mycotoxin-induced toxicity generally.

Reviewing the current state of legacy POP-brominated flame retardants in plastic childcare products and toys: a scoping review protocol

BackgroundDue to their adverse environmental and health impacts, brominated flame retardants (BFRs) are listed in Annex A of the Stockholm Convention for global elimination of production and use. Their health impacts include endocrine disruption, cancer, reproductive effects, and neurobehavioral and developmental disorders in children. Emerging literature suggests that legacy POP-BFRs are increasingly found in consumer products, including those used for and by children. The presence of legacy POP-BFRs in children’s products is a big concern. Children are more vulnerable to chemical exposure risks than adults because their bodies are still developing and fragile. The rising problem is contributed to by the global push towards a circular economy that encourages responsible production and consumption by practising the recycling of waste materials. Waste materials such as electronic and electrical equipment plastics often contain POP-BFRs. POP-BFRs in waste materials are transferred into new products through recycling. The recycled products have become a potential source of exposure to legacy POP-BFRs for vulnerable populations, particularly children. Our scoping review aims to map and summarise the emerging literature. This information is needed to inform evidence-based policies to protect children from toxic exposures.MethodsOur scoping review will follow a methodological framework proposed by Arksey and O’Malley. Peer-reviewed and grey literature on the topic will be retrieved from electronic databases and other relevant sites. Two reviewers will screen titles and abstracts, followed by a full-text review of studies for eligibility based on the established inclusion and exclusion criteria. Data will be extracted, and findings will be mapped in a table according to study settings, types of children’s products tested, and concentration of legacy POP-BFRs in contaminated products. A map chart will be created to display how contaminated products are spread globally.DiscussionBecause of their unique vulnerabilities, children continue to suffer disproportionate exposures to toxic chemicals compared to adults. Information on potential exposures, particularly for children, is crucial to make evidence-based policies. We intend to map and summarise the emerging literature on legacy POP-BFRs in children's products. Findings will be disseminated to relevant stakeholders through publishing in a peer-reviewed scientific journal and policy briefs.Systematic review registrationThe protocol is registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/7KDE5).

Anatomical and demographic prognosticators of pancreatic cancer.

e16310 Background: Pancreatic cancer is known to have one of the poorest median of survival (mOS) of all cancers. It is now the third leading cause of cancer-related mortality after lung &amp; colorectal cancer. With the current trends, understanding &amp; knowing prognosticators can aid in determining outcomes of pancreatic cancer. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted pancreatic cancer cases based on primary site encoding for head, body &amp; tail of pancreas, Islets of Langerhans (IoL), other specified parts &amp; overlapping lesion of pancreas, pancreas, NOS (no other specific). The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 221,304 cases were extracted between 2000-2020. The median age of diagnosis was 71 years. 50.54% were males, &amp; 49.45% were females. The incidence rates are shown below. Whites (69.99%) were commonly affected, followed by Blacks (11.05%), Hispanics (10.79%), Asians &amp; Pacific islanders (7.41%), Alaskan natives &amp; American-Indians (0.57%). A distribution in anatomy was notable for head of the pancreas (46.00%), followed by tail (13.20%), body (11.34%), pancreatic duct (0.49%), IoL (0.10%). A survival curves were compared on different variables. Gender showed no statistical difference. mOS for patients diagnosed &gt;70 years was 3 months &amp; &lt;70 years was 8 months (p value &lt;0.0001, CI 0.3716 to 0.3784, HR 1.731). mOS for calculated for Whites (5), Blacks (4), Asian &amp; Pacific islanders (6), Alaskan natives &amp; American-Indians (4), &amp; hispanics (5) (p value &lt;0.0001). mOS based on involved parts of pancreas were compared for: head (6), body (6), tail (5), pancreatic duct (8), IoL (59) (p &lt;0.0001). Conclusions: Median age of diagnosis was in 71, with a slight male predilection. Overall incidence rate is trending up. It is significantly higher for males, &amp; is significantly lower for females than that of the general population. Whites are most commonly affected, &amp; Alaskan natives &amp; American natives are rarely affected. Survival is significantly greater if diagnosed &lt;70 years. Most common site involved is the head of pancreas, &amp; the least is IoL. mOS is ~10 times greater for IoL, but it's an endocrine pancreatic cancer which is treated differently. From the exocrine pancreas, survival is the best for pancreatic duct cancer, &amp; the worst for pancreatic duct. If anatomic &amp; demographic prognosticators are combined with molecular, radiologic factors, it can be beneficial in predicting the outcomes of this cancer with poor prognosis. [Table: see text]

Precision medicine for papillary thyroid carcinoma (PTC) variants: A machine learning approach to prognosis and treatment guidance.

e18072 Background: PTC is a common endocrine cancer with a good prognosis, but aggressive subtypes, such as Hürthle cell (HCC) and columnar cell variants (CCV), pose challenges due to their higher recurrence and metastasis rates. To provide personalized care, we applied machine learning to evaluate the treatment effectiveness and develop precise prognostic models for PTC variants. Methods: The Surveillance, Epidemiology, and End Results (SEER) database provided the data used for this study’s analysis (2000–2019). Patients who met any of the following criteria were excluded: diagnosis not confirmed by histology, previous history of cancer or with other concurrent malignancies, and unknown data. To identify prognostic variables, we conducted Cox regression analysis and constructed prognostic models using machine learning (ML) algorithms to predict the 5-year survival. Patient records were randomly divided into training (70 %) and validation (30 %) sets. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic curve was used to validate the accuracy and reliability of the ML models. Results: The study population comprised 3690 patients. Among them 3180 patients with CCV and 510 patients with HCC, respectively. Most patients (62.8%) were 45 years or older, with a median age of 52 years. A total of 56.9% of patients had a tumor size greater than 2 cm, with a median tumor size of 3.1 cm. The largest racial group was white, comprising 83.8% of the cases, and 11.8% of the cases were Asian. Most cases were regional (53.4%, n=1969), followed by localized (38.3%, n= 1413). Multivariate Cox regression analysis revealed that N1 negatively affected the survival of HCC patients. CCV has a favorable prognosis after surgery, radiotherapy, or total thyroidectomy. Poor prognosis in CCV is associated with black race, large tumor size, and T4 stage. Improved survival in the localized/regional stage and decreased survival with male sex, older age, distant metastasis, and advanced AJCC stage in both PTC subtypes. ML models revealed that the random forest classifier (RFC) and K-Nearest Neighbors (KNN) accurately predicted outcomes, followed by Logistic Regression (LR) models. The highest contributing factors were AJCC staging, tumor size, and T aspect of TNM staging. Conclusions: Our study offers a method for evaluating and treating patients with PTC variants. The machine learning model that we created serves as a useful and personalized resource to aid in clinical decision-making processes.[Table: see text]

Extra-nuclear and cytoplasmic steroid receptor signalling in hormone dependent cancers

Steroid hormone receptors are key mediators in the execution of hormone action through a combination of genomic and non-genomic action. Since their isolation and characterisation in the early 20th Century much of our understanding of the biological actions of steroid hormones are underpinned by their activated receptor activity. Over the past two decades there has been an acceleration of more omics-based research which has resulted in a major uptick in our comprehension of genomic steroid action. However, it is well understood that steroid hormones can induce very rapid signalling events in tandem with their genomic actions wherein they exert their influence through alterations in gene expression. Thus the totality of genomic and non-genomic steroid action occurs in a simultaneous and reciprocal manner and a greater appreciation of whole cell action is required to fully evaluate steroid hormone activity in vivo. In this mini-review we outline the most recent developments in non-genomic steroid action and cytoplasmic steroid hormone receptor biology in endocrine-related cancers with a focus on the 3-keto steroid receptors, in particular the androgen receptor.

Polymorphisms of DNA Repair Genes in Thyroid Cancer.

The incidence of thyroid cancer, one of the most common forms of endocrine cancer, is increasing rapidly worldwide in developed and developing countries. Various risk factors can increase susceptibility to thyroid cancer, but particular emphasis is put on the role of DNA repair genes, which have a significant impact on genome stability. Polymorphisms of these genes can increase the risk of developing thyroid cancer by affecting their function. In this article, we present a concise review on the most common polymorphisms of selected DNA repair genes that may influence the risk of thyroid cancer. We point out significant differences in the frequency of these polymorphisms between various populations and their potential relationship with susceptibility to the disease. A more complete understanding of these differences may lead to the development of effective prevention strategies and targeted therapies for thyroid cancer. Simultaneously, there is a need for further research on the role of polymorphisms of previously uninvestigated DNA repair genes in the context of thyroid cancer, which may contribute to filling the knowledge gaps on this subject.

Evaluation of Blood Culture Results in Patients with Malignancy in Erzurum Province, Turkey.

Bloodstream infections are a serious public health problem that requires follow-up with blood culture; this negatively affects the course of the disease and patient healthcare costs in patients with malignancy. This study aimed to determine the growth frequency of pathogens and their antibiotic resistance profiles in the blood cultures of patients with hematological and oncogenic malignancies. The results of 7451 blood cultures, obtained from 2926 patients between January 2017 and January 2022, were evaluated retrospectively. Of these cultures, 3969 were obtained from patients with malignancy (diagnostic codes C00-D48 in ICD-10) and 3482 from patients without malignancy. The hospital information management system modules were used to acquire patient data and blood culture results. Various microorganisms grew in 10.1% of blood cultures. Of these organisms, 64.1% were isolated from cases of malignancy. Of the pathogens, 49.2% were gram-negative bacteria, 47.7% were gram-positive bacteria, and 3.1% were fungi. The most frequently isolated bacteria were methicillin-resistant coagulase-negative staphylococci (3.2%), Escherichia coli (2.3%), Klebsiella pneumoniae (1.0%), methicillin-sensitive coagulase-negative staphylococci (0.7%), and Staphylococcus aureus (0.6%). Pathogen positivity was highest in the patient cultures with urinary system cancer (23.9%), thyroid and other endocrine gland cancers (20.6%), female and male genital organ cancers (18.2%/16.9%), and digestive organ cancer (14.2%). Gram-negative bacteria to ampicillin, piperacillin, and sulfamethoxazole-trimethoprim and Gram-positive bacteria to penicillin, erythromycin, and sulfamethoxazole-trimethoprim were highly resistant. Combined resistance to imipenem and meropenem was observed in 25 Gram-negative bacteria. Twelve (48%) of the carbapenem-resistant bacteria were isolated from patients with lymphoid, hematopoietic, and related tissue malignant neoplasia. This study reported microorganisms and their antimicrobial resistance in the blood cultures of malignant patients, a special patient group. It pointed out that the antibiotic resistance of Staphylococcus, Klebsiella pneumoniae, and E. coli is high enough to cause problems in the treatment of patients with malignancy.

Washout CYFRA 21-1: A tool to improve diagnostic accuracy of fine needle aspiration in the diagnosis of metastatic lymph nodes in papillary thyroid cancer

Thyroid carcinoma has an increasing incidence of endocrine system cancers. Fine needle aspiration cytology (FNAC) and thyroglobulin (Tg) are the primary diagnostic modalities employed for assessing metastatic lymph nodes (LNs) in thyroid cancer. Due to the limited accuracy, rare patients benefited from these procedures. In this research, we aimed to discover a dependable biomarker that could increase the accuracy of FNAC's ability to diagnose metastatic LNs among patients suffering from papillary thyroid cancer (PTC). From March 2021 to July 2023, 99 LNs from PTC patients who had thyroid ultrasonography suspicions of metastases were examined. All patients underwent FNAC, washout Tg and CYFRA 21-1 measurements. Surgical histology and a subsequent FNAC were utilized to validate the outcomes of LNs. In our study, the optimal cut-off value for CYFRA 21-1 washout fluid was 1.145 ng/mL, with a specificity of 94.00 % (slightly lower than Tg and FNAC at 98 %). However, CYFRA 21-1 demonstrated significantly higher diagnostic sensitivity (85.71 %) and accuracy (86.41 %) compared to Tg (71.43 %, 81.55 %) and FNAC (69.39 %, 80.58 %). Furthermore, FNAC plus washout CYFRA 21-1 performed better in diagnosing the metastatic LNs in PTC than FNAC plus Tg, which may indicate a novel solution for metastatic LNs diagnosis in PTC.