-
Turkish Journal of Medical Sciences 2024The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer.
BACKGROUND/AIM
The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer.
MATERIALS AND METHODS
A questionnaire was utilized for the study, which included the age of diagnosis, the number of children at the time of diagnosis, the age of the children, and the breastfeeding period of each child.
RESULTS
The study included 828 patients. The median age at diagnosis was 47 years for parous women and 42 years for nonparous women (p < 0.001). The tumor size of the patients diagnosed within the breastfeeding period was significantly larger compared to the other patients. Estrogen and progesterone receptor positivity were lower in patients diagnosed during breastfeeding. Additionally, the mean number of positive lymph nodes, dissected lymph nodes, and positive lymph node/dissected lymph node ratio in parous and breastfed patients with a nonmetastatic disease were statistically significantly higher in multivariable analysis than those patients who were nulliparous and have not breastfed.
CONCLUSION
Breast cancer is seen at a later age in patients who are parous than those who have never given birth. Patients who are parous and have breastfed tend to present with a higher stage of the disease.
Topics: Humans; Female; Breast Neoplasms; Breast Feeding; Parity; Adult; Middle Aged; Pregnancy; Aged; Surveys and Questionnaires; Receptors, Progesterone
PubMed: 38812646
DOI: 10.55730/1300-0144.5784 -
Current Research in Neurobiology 2024Catamenial epilepsy, defined as a periodicity of seizure exacerbation during the menstrual cycle, affects up to 70 % of epileptic women. Seizures in these patients are...
Catamenial epilepsy, defined as a periodicity of seizure exacerbation during the menstrual cycle, affects up to 70 % of epileptic women. Seizures in these patients are often non-responsive to medication; however, our understanding of the relation between menstrual cycle and seizure generation (i.e. ictogenesis) remains limited. We employed here field potential recordings in the 4-aminopyridine model of epileptiform synchronization in female mice (P60-P130) and found that: (i) the estrous phase favors ictal activity in the entorhinal cortex; (ii) these ictal discharges display an onset pattern characterised by the presence of chirps that are thought to mirror synchronous interneuron firing; and (iii) blocking estrogen receptor β-mediated signaling reduces ictal discharge duration. Our findings indicate that the duration of 4AP-induced ictal discharges, , increases during the estrous phase, which corresponds to the human peri-ovulatory period. We propose that these effects are caused by the presumptive enhancement of interneuron excitability due to increased estrogen receptor β-mediated signaling.
PubMed: 38812499
DOI: 10.1016/j.crneur.2024.100131 -
Asian Pacific Journal of Cancer... May 2024Triple-negative breast cancer presents a significant challenge in oncology due to its complex treatment and aggressive nature. This subtype lacks common cancer cell...
OBJECTIVE
Triple-negative breast cancer presents a significant challenge in oncology due to its complex treatment and aggressive nature. This subtype lacks common cancer cell receptors like estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. This study aimed to identify, through bioinformatic analysis, the key genes associated with triple-negative breast cancer. In addition, CBD analogs with potential inhibitory effects on these genes were evaluated through docking and molecular dynamics.
METHODS
Gene expression profiles from the GSE178748 dataset were analyzed, focusing on MDA-MB-231 breast cancer cell lines. Differentially expressed genes were determined through protein-protein interaction networks and subsequently validated. Additionally, the inhibitory effects of cannabidiol analogs on these hub genes were assessed using molecular docking and dynamics.
RESULTS
Analysis of the hub highlighted RPL7A, NHP2L1, and PSMD11 as significant players in TNBC regulation. Ligand 44409296 showed the best affinity energy with RPL7A, while 166505341 exhibited the highest affinity with NHP2L1 and PSMD11, surpassing CBD. Analyses of RMSD, RMSF, SASA, and Gyration Radius indicated structural stability and interactions of the proteins with ligands over time. MMGBSA calculations showed favorable binding energies for the ligands with the target proteins.
CONCLUSION
In conclusion, this study identified key genes, namely RPL7A, NHP2L1, and PSMD11, associated with triple-negative breast cancer and demonstrated promising interactions with cannabidiol analogs, particularly 44409296 and 166505341. These findings suggest potential therapeutic targets and highlight the relevance of further clinical investigations. Additionally, the ligands exhibited favorable ADME properties and low toxicity, underscoring their potential in future drug development for TNBC treatment.
Topics: Triple Negative Breast Neoplasms; Humans; Cannabidiol; Female; Molecular Docking Simulation; Computational Biology; Computer Simulation; Gene Expression Regulation, Neoplastic; Protein Interaction Maps; Molecular Dynamics Simulation; Antineoplastic Agents; Cell Line, Tumor
PubMed: 38809637
DOI: 10.31557/APJCP.2024.25.5.1649 -
Advanced Biomedical Research 2024Inositol 1,4,5-trisphosphate receptor (IP3R), a critical calcium ion (Ca2+) regulator, plays a vital role in breast cancer (BC) metabolism. Dysregulated IP3R in BC cells...
BACKGROUND
Inositol 1,4,5-trisphosphate receptor (IP3R), a critical calcium ion (Ca2+) regulator, plays a vital role in breast cancer (BC) metabolism. Dysregulated IP3R in BC cells can drive abnormal growth or cell death. Estradiol increases IP3R type 3 (IP3R3) levels in BC, promoting cell proliferation and metabolic changes, including enhanced pyruvate dehydrogenase (PDH) activity, which, when reduced, leads to cell apoptosis. The study silenced IP3R3 to assess its impact on PDH.
MATERIALS AND METHODS
The study used IP3R3 small interfering RNA (siRNA) to target Michigan Cancer Foundation-7 (MCF-7) and MDA-MB-231 cell lines. Transfection success was confirmed by flow cytometry. Cell viability and gene silencing were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and real-time quantitative polymerase chain reaction (PCR) assays. Protein expression and cellular activity were analyzed through western blotting and PDH activity measurement.
RESULTS
Transfecting MCF-7 and MDA-MB-231 cells with IP3R3 siRNA achieved a 65% transfection rate without significant toxicity. IP3R3 gene silencing effectively reduced IP3R3 messenger RNA (mRNA) and protein levels in both cell lines, leading to decreased PDH enzyme activity, especially in MDA-MB-231 cells.
CONCLUSION
The study highlights a link between high IP3R3 gene silencing and reduced PDH activity, with higher IP3R3 expression in estrogen-independent (MDA-MB-231) compared to estrogen-dependent (MCF-7) cell lines. This suggests a potential impact on BC metabolism and tumor growth via regulation of PDH activity.
PubMed: 38808320
DOI: 10.4103/abr.abr_413_22 -
NPJ Breast Cancer May 2024Breast cancer is the most commonly diagnosed malignancy and benefits from endocrine agents such as tamoxifen. However, the development of drug resistance in cancerous...
Breast cancer is the most commonly diagnosed malignancy and benefits from endocrine agents such as tamoxifen. However, the development of drug resistance in cancerous cells often leads to recurrence, thus limiting the therapeutic benefit. Identification of potential biomarkers that can predict response to tamoxifen and recognize patients who will clinically benefit from this therapy is urgently needed. In this study, we report that high collagen type XI alpha 1 (COL11A1) expression was associated with poor therapeutic response and prognosis in breast cancer patients treated with tamoxifen. To confirm the role of COL11A1 in the development of tamoxifen resistance, we established MCF-7/COL11A1 and T47D/COL11A1 cell lines, which stably expressed COL11A1. Compared with parental MCF-7 and T47D, MCF-7/COL11A1 and T47D/COL11A1 cells were more resistant to 4-OHT-induced growth inhibition. Moreover, the level of COL11A1 expression was upregulated in tamoxifen-resistant MCF-7/TamR and T47D/TamR cell lines, and depletion of COL11A1 markedly sensitized the cells to 4-OHT in vitro and in vivo. Interestingly, the level of estrogen receptor α (ERα) expression was elevated, probably due to the increased COL11A1 in TamR cells. In addition, knockdown of COL11A1 decreased the expression of ERα and its downstream target genes. Overall, our findings suggest that overexpressed COL11A1 contributes to tamoxifen resistance, and targeting COL11A1 holds great promise for reversing endocrine resistance.
PubMed: 38806505
DOI: 10.1038/s41523-024-00645-3 -
Frontiers in Physiology 2024In addition to loss of sensory and motor function below the level of the lesion, traumatic spinal cord injury (SCI) may reduce circulating steroid hormones that are...
In addition to loss of sensory and motor function below the level of the lesion, traumatic spinal cord injury (SCI) may reduce circulating steroid hormones that are necessary for maintaining normal physiological function for extended time periods. For men, who comprise nearly 80% of new SCI cases each year, testosterone is the most abundant circulating sex steroid. SCI often results in significantly reduced testosterone production and may result in chronic low testosterone levels. Testosterone plays a role in respiratory function and the expression of respiratory neuroplasticity. When testosterone levels are low, young adult male rats are unable to express phrenic long-term facilitation (pLTF), an inducible form of respiratory neuroplasticity invoked by acute, intermittent hypoxia (AIH). However, testosterone replacement can restore this respiratory neuroplasticity. Complicating the interpretation of this finding is that testosterone may exert its influence in three possible ways: 1) directly through androgen receptor (AR) activation, 2) through conversion to dihydrotestosterone (DHT) by way of the enzyme 5α-reductase, or 3) through conversion to 17β-estradiol (E2) by way of the enzyme aromatase. DHT signals via AR activation similar to testosterone, but with higher affinity, while E2 activates local estrogen receptors. Evidence to date supports the idea that exogenous testosterone supplementation exerts its influence through estrogen receptor signaling under conditions of low circulating testosterone. Here we explored both recovery of breathing function (measured with whole body barometric plethysmography) and the expression of AIH-induced pLTF in male rats following C2-hemisection SCI. One week post injury, rats were supplemented with either E2 or DHT for 7 days. We hypothesized that E2 would enhance ventilation and reveal pLTF following AIH in SCI rats. To our surprise, though E2 did beneficially impact overall breathing recovery following C2-hemisection, both E2 supplementation and DHT restored the expression of AIH-induced pLTF 2 weeks post-SCI.
PubMed: 38803364
DOI: 10.3389/fphys.2024.1390777 -
Clinical Case Reports Jun 2024Giant pedunculated hepatic hemangiomas, mostly seen in women, are considered a rare type of giant hepatic hemangioma, with challenging diagnosis. Unlike other types of...
KEY CLINICAL MESSAGE
Giant pedunculated hepatic hemangiomas, mostly seen in women, are considered a rare type of giant hepatic hemangioma, with challenging diagnosis. Unlike other types of liver hemangiomas, they can manifest different kinds of symptoms, and are prone to life-threatening manifestations like rupture or torsion.
ABSTRACT
Hemangioma is the most common benign liver primary tumor. Hepatic hemangioma >4 cm (some studies suggest >10 cm) is referred to as a giant hemangioma. Although hepatic hemangioma does not manifest symptoms in most cases, a giant hepatic hemangioma can manifest different kinds of symptoms. Giant pedunculated hepatic hemangiomas are considered a rare type of giant hepatic hemangioma, with challenging diagnosis, as the thin pedicle could be hard to be detected on imaging. A 41-year-old woman was admitted to our hospital, with dull discomfort of the right upper quadrant and epigastric region and early satiety for the past 7 months, with the history of taking oral contraceptive (OCP) for 10 years. Ultrasound and computed tomography revealed a 130 × 124 × 76 mm solid mass, with central cystic lesion, located in the midline of the epigastric region, attaching to the inferior surface of the third segment of the left lobe of the liver. Due to the potential risk for torsion, and rupture of the hemangioma, the management of the patient proceeded to surgical excision. Pathological examination of the specimen confirmed the diagnosis of hepatic hemangioma. Giant pedunculated hepatic hemangioma is a rare benign tumor. It demonstrates higher incidence rate in women, as some hemangiomas have estrogen receptors, and estrogen can lead to endothelial cell proliferation and organization in vascular structure. Most hemangiomas do not express any symptoms; therefore, no treatment is needed except for the patients who manifest symptoms, or in giant pedunculated hemangiomas, as they are prone to rupture or torsion. In this review most cases were female, and most of them presented with abdominal pain, in most cases the tumor located in the left lobe of the liver. Almost all the reviewed cases underwent surgery. Giant hepatic hemangioma is a differential diagnosis of palpable mass, or other symptoms of the right upper quadrant, and epigastric region specially in women taking OCP. Imaging is needed to rule out these tumors, and most often, pedunculated hemangioma is harder to be defined on imaging. It requires surgery because of the risk of acute problems, such as torsion and rupture.
PubMed: 38803323
DOI: 10.1002/ccr3.8995 -
Scientific Reports May 2024Estrogen receptor-negative [ER(-)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years,...
A novel combinatorial approach using sulforaphane- and withaferin A-rich extracts for prevention of estrogen receptor-negative breast cancer through epigenetic and gut microbial mechanisms.
Estrogen receptor-negative [ER(-)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years, dietary prevention of BC with epigenetically active phytochemicals has received increased attention due to its feasibility, effectiveness, and ease of implementation. In this regard, combinatorial phytochemical intervention enables more efficacious BC inhibition by simultaneously targeting multiple tumorigenic pathways. We, therefore, focused on investigation of the effect of sulforaphane (SFN)-rich broccoli sprouts (BSp) and withaferin A (WA)-rich Ashwagandha (Ash) combination on BC prevention in estrogen receptor-negative [ER(-)] mammary cancer using transgenic mice. Our results indicated that combinatorial BSp + Ash treatment significantly reduced tumor incidence and tumor growth (~ 75%) as well as delayed (~ 21%) tumor latency when compared to the control treatment and combinatorial BSp + Ash treatment was statistically more effective in suppressing BC compared to single BSp or Ash intervention. At the molecular level, the BSp and Ash combination upregulated tumor suppressors (p53, p57) along with apoptosis associated proteins (BAX, PUMA) and BAX:BCL-2 ratio. Furthermore, our result indicated an expressional decline of epigenetic machinery HDAC1 and DNMT3A in mammary tumor tissue because of combinatorial treatment. Interestingly, we have reported multiple synergistic interactions between BSp and Ash that have impacted both tumor phenotype and molecular expression due to combinatorial BSp and Ash treatment. Our RNA-seq analysis results also demonstrated a transcriptome-wide expressional reshuffling of genes associated with multiple cell-signaling pathways, transcription factor activity and epigenetic regulations due to combined BSp and Ash administration. In addition, we discovered an alteration of gut microbial composition change because of combinatorial treatment. Overall, combinatorial BSp and Ash supplementation can prevent ER(-) BC through enhanced tumor suppression, apoptosis induction and transcriptome-wide reshuffling of gene expression possibly influencing multiple cell signaling pathways, epigenetic regulation and reshaping gut microbiota.
Topics: Isothiocyanates; Animals; Withanolides; Sulfoxides; Female; Mice; Epigenesis, Genetic; Breast Neoplasms; Gastrointestinal Microbiome; Mice, Transgenic; Plant Extracts; Receptors, Estrogen; Humans; Brassica; Histone Deacetylase 1; Gene Expression Regulation, Neoplastic; Anticarcinogenic Agents
PubMed: 38802425
DOI: 10.1038/s41598-024-62084-1 -
JBRA Assisted Reproduction May 2024Bisphenol F (BPF) is an endocrinedisrupting chemical, but information about its effect on thyroid hormones has not been fully explored. Omega 3 fatty acids (O3FA), on...
OBJECTIVE
Bisphenol F (BPF) is an endocrinedisrupting chemical, but information about its effect on thyroid hormones has not been fully explored. Omega 3 fatty acids (O3FA), on the other hand, are antioxidant and antiapoptotic agents. Therefore, this study explored the role and associated molecular mechanism of O3FA in BPF-induced hypothyroidism-mediated testicular dysfunction in male Wistar rats.
METHODS
Twenty (20) male Wistar rats were randomized into four groups (n=5/group), namely: the control group; the BPF treated group (30 mg/kg of BPF); and the intervention groups (30mg/kg BPF + 100mg/kg O3FA (BPF+O3FA-L) and 30mg/kg BPF + 300mg/kg of O3FA for 28 days).
RESULTS
Low and high doses of O3FA ameliorated BPF-induced hypothyroidism-mediated reduction in sperm quality, testosterone, luteinizing hormone, follicle-stimulating hormone, catalase, superoxide dismutase, total antioxidant capacity, and nuclear factor erythroid 2-related factor 2 and increases in estrogen, malondialdehyde, c-reactive protein, interleukin 1 beta, caspase 3. Furthermore, O3FA prevented BPF-induced Na+/K+-ATPase and Ca2+-ATPase dysfunction, estrogen receptor beta overexpression, and tumor protein P53 (p53)/ b-cell lymphoma 2 (Bcl-2) imbalance.
CONCLUSIONS
This study showed that O3FA ameliorated BPF-induced dysthyroidism-mediated testicular dysfunction by preventing proton pump dysfunction and p53/BCl-2 imbalance.
PubMed: 38801312
DOI: 10.5935/1518-0557.20240033 -
Frontiers in Oncology 2024Breast cancer is the most prevalent malignancy in women, and is characterized by its heterogeneity; exhibiting various subgroups identifiable through molecular... (Review)
Review
Breast cancer is the most prevalent malignancy in women, and is characterized by its heterogeneity; exhibiting various subgroups identifiable through molecular biomarkers that also serve as predictive indicators. More than two thirds of breast tumors are classified as luminal with positive hormone receptors (HR), indicating that cancer cells proliferation is promoted by hormones. Endocrine therapies play a vital role in the effective treatment of breast cancer by manipulating the signaling of estrogen receptors (ER), leading to a reduction in cell proliferation and growth rate. Selective estrogen receptor modulators (SERMs), such as tamoxifen and toremifene, function by blocking estrogen's effects. Aromatase inhibitors (AI), including anastrozole, letrozole and exemestane, suppress estrogen production. On the other hand, selective estrogen receptor degraders (SERDs), like fulvestrant, act by blocking and damaging estrogen receptors. Tamoxifen and AI are widely used both in early- and advanced-stage disease, while fulvestrant is used as a single agent or in combination with other agents like the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors (palbociclib, abemaciclib, ribociclib) or alpelisib for advanced-stage disease. Currently, SERDs are recognized as an effective therapeutic approach for the treatment of ER-positive breast cancer, showing proficiency in reducing and blocking ER signaling. This review aims to outline the ongoing development of novel oral SERDs from a practical therapeutic perspective, enhancing our understanding of the mechanisms of action underlying these compounds.
PubMed: 38800404
DOI: 10.3389/fonc.2024.1385577