Publications by authors named "Helen L del Puerto"

Members of the SOX (SRY-related HMG box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development.

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Introduction: Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR.

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Melanoma is an aggressive cancer with fast metastatic spread and reduced survival time. One common event during the neoplastic progression is the epithelial-mesenchymal transition (EMT), which enhances invasiveness, cell migration, and metastasis. In this study, we investigated the effects of metformin at EMT in melanoma cell lines B16-F10 and A-375, in vitro, and the impact of EMT downregulation on melanoma progression in vivo.

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Background: Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27).

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Pure human and canine mammary invasive micropapillary carcinoma is a rare malignant epithelial tumor accounting for 0.9 to 2% of all invasive mammary carcinomas and present a high rate of lymphatic invasion and metastasis, with unfavorable prognosis. Surgery and chemotherapy are standard treatments for almost all mammary cancer in both species, as well as hormonal and target therapies available for human patients.

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Background: Inhibins and their co-receptor betaglycan are members of the transforming growth factor β superfamily, a group of signaling molecules that control the differentiation of human endometrium in the secretory phase of the menstrual cycle.

Objective: Since endometriosis is associated with endometrial dysfunction and infertility, this study aimed at evaluating the expression of α-inhibin and betaglycan mRNA and proteins in endometrial samples of infertile women with and without endometriosis.

Design: This was a cross-sectional study.

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Article Synopsis
  • Clomiphene citrate (CC) and letrozole are ovulatory stimulants associated with high ovulation rates but low pregnancy rates, prompting a study to evaluate their effects on apoptosis in human cumulus cells.
  • The study involved primary cell cultures from IVF patients and utilized various assays to assess cell viability and gene expression; results showed that while these treatments did not significantly affect cell viability, letrozole reduced the percentage of cells in the S phase and CC increased certain gene expressions related to apoptosis.
  • Overall, the findings suggest that CC and letrozole may influence cumulus cells at a cellular level and affect gene expression related to cell death, indicating potential direct effects beyond their traditional roles as ovulatory stimulants.
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Metastatic melanoma is a very aggressive form of cancer in both humans and dogs. Dogs primarily develop oral melanoma of mucosal origin. Although oral melanoma in humans is rare, both diseases are highly aggressive with frequent metastases.

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Background: Human endometrium harbors stem/progenitor cells (SPCs) that may contribute to the establishment of endometriosis when seeded outside the uterus. Oct-4, C-kit and Musashi-1 are some of the many proteins used to characterize SPCs, but their association with endometriosis is uncertain.

Objective And Design: In this study, specimens of normal endometrium (n = 12), eutopic endometrium from women with endometriosis (n = 9), superficial peritoneal endometriosis (SUP, n = 12) and deep endometriosis (DE, n = 13) lesions were evaluated for localization and intensity of immunostaining for Oct-4, C-kit and Musashi-1.

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Objective: Angiotensin-converting-enzyme 2 (ACE2), the cell surface receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is found in a variety of reproductive tissues. The present study evaluated whether uterine fibroids and normal myometrium express ACE2 and, if so, at which tissue compartments.

Methods: We included 13 premenopausal women (age range 33-50 years, median 40 years) with uterine fibroids undergoing elective hysterectomy or myomectomy.

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Article Synopsis
  • The study investigates the expression of pro-caspase-3 and cleaved caspase-3 in luteinized granulosa cells during in vitro fertilization.
  • Pro-caspase-3 was found to be positive in 77% of cells, while cleaved caspase-3 was only present in 4%, indicating pro-caspase-3’s predominant role.
  • The expression of pro-caspase-3 was consistent regardless of patient characteristics or CASP3 mRNA levels, suggesting it's always ready for activation to regulate apoptosis during ovarian stimulation.
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Melanoma is a fast-growing tumour in dogs and represents 7% of the total malignant neoplasms from the skin and is the most common tumour found in the oral cavity. In these tumours, high expression of cyclooxygenase-2 (COX-2) is associated with a poor prognosis. The aim of this study was to verify if the overexpression of COX-2 is related to the modulation of lymphocytes and if it is associated with the angiogenic and proliferative capacity of the melanoma.

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Melanoma progression is associated with the epithelial-mesenchymal transition (EMT) when tumor cells reduce E-cadherin and increase N-cadherin expression resulting in an escape from the microenvironment via loss of cellular adhesion and gain of motility. Transcription factor proteins Snail and ZEB trigger EMT by repression of epithelial markers and activation of mesenchymal properties. This study evaluated E-cadherin, N-cadherin, Snail, ZEB1 and ZEB2 expression by IHC and investigated their relationship with morphological characteristics in cutaneous and oral canine melanoma.

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Background: The epidermal growth factor receptors participate in the physiological processes such as regulation of morphogenesis, proliferation and cell migration, but when overexpressed or overactivated they may play an important role in neoplastic progression. Melanoma is the most aggressive skin neoplasm and is characterized by elevated invasion and low survival rates in both humans and dogs. In human melanomas the overexpression of EGFR, HER3 or HER4 is associated with poor prognosis.

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The quality of oocytes depends on interactions with surrounding granulosa cells. Granulosa cells are essential in normal follicular maturation process since they produce steroidal hormones and growth factors, and they play a crucial role in follicular atresia. The success in reproductive biology and medicine depends on reliable assessment of oocyte and embryo viability which presently mainly bases on oocyte and embryo morphology.

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Accurate noninvasive diagnostic tests for endometriosis are still missing. This study evaluated the predictive value of the neuropeptide urocortin 1 (Ucn1) to detect pelvic endometriosis in symptomatic women. We enrolled prospectively 97 consecutive women submitted to gynecologic laparoscopy for chronic or acute pelvic pain, infertility or adnexal mass.

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Granulosa cells control oocyte maturation through paracrine signalling and changes to the microenvironment around the oocyte. Apoptosis occurs as a physiological mechanism of granulosa cell renewal, but how it relates with the ovarian response to induced ovulation is still unclear. Therefore, this study evaluated apoptosis-related gene expression levels in granulosa cells of patients undergoing controlled ovarian stimulation.

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Study Question: Do angiotensin (Ang)-(1-7) levels in human ovarian follicular fluid (FF) correlate with the number and proportion of mature oocytes obtained for IVF?

Summary Answer: The present study shows for the first time that Ang-(1-7) levels in human FF correlate with the proportion of mature oocytes collected upon ovarian stimulation for IVF.

What Is Known Already: Ang-(1-7) is an active peptide of the renin-angiotensin system that stimulates oocyte maturation in isolated rabbit and rat ovaries. However, its role in human ovulation remains unexplored.

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Embryo implantation involves a complex sequence of events, and a large amount of molecules have been postulated to be involved in the interaction of embryo and endometrium. This study evaluated the endometrial expression of α-inhibin and β-glycan in the mid-secretory phase of women scheduled to in vitro fertilization (IVF) and tested whether these markers are associated with implantation failure. We performed a nested case-control study including 52 women submitted to IVF and embryo transfer, divided into 2 groups: cases with implantation failure (n = 33) and controls with confirmed clinical pregnancy (n = 19).

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Activin A is a growth factor that stimulates decidualization and is abundantly expressed in endometrial proliferative disorders. Nevertheless, whether it directly affects endometrial cell survival is still unknown. This study investigated the effects of activin A on total death and apoptosis rates and on tumor necrosis factor (TNF) release by human endometrial stromal cells (HESC).

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The renin-angiotensin system (RAS) is subject to sex-specific modulation by hormones and gene products. However, sex differences in the balance between the vasoconstrictor/proliferative ACE/ANG II/AT1 axis, and the vasodilator/antiproliferative ACE2/ANG-(1-7)/MAS axis are poorly known. Data in the rat have suggested the male-specific Y-chromosome gene Sry to contribute to balance between these two axes, but why the testis-determining gene has these functions remains unknown.

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Activin A is a growth factor released by mature osteoblasts that has a critical effect on bone formation. We investigated the effect of bone morphogenetic protein (BMP)-4 on activin A gene expression during in vitro osteogenic differentiation of mouse embryonic stem (ES) cells. Embryoid bodies were cultured in retinoic acid (RA) for three days and then without RA for two days.

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Background: Nodal is a growth factor of the transforming growth factor β superfamily that is expressed in high turnover tissues, such as the human endometrium, and in several malignancies. The effects of Nodal are modulated by the coreceptor Cripto and mediated by SMAD proteins. This study evaluated the gene and protein expression of Nodal, Cripto, total and phosphorylated (p) SMAD3, and SMAD4 in the proliferative endometrium of women with and without endometriosis.

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Purpose: This study investigated the usefulness of serum antimüllerian hormone (AMH) measurements at two distinct menstrual cycle phases to predict in vitro fertilization (IVF) outcomes.

Methods: This was a prospective observational study enrolling 135 consecutive patients referred for conventional IVF or ICSI in a university hospital. Blood samples were obtained for serum AMH measurements on days 3 and 18-20, while transvaginal ultrasound was performed for antral follicle count (AFC) at day 3 of the menstrual cycle immediately before treatment.

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