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Keywords = endometriosis-related cancer

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19 pages, 7854 KiB  
Article
Single-Cell RNA Sequencing of PBMCs Identified Junction Plakoglobin (JUP) as Stratification Biomarker for Endometriosis
by Thomas Andrieu, Angelo Duo, Lea Duempelmann, Magdalena Patzak, Flurina Annacarina Maria Saner, Jitka Skrabalova, Cinzia Donato, Peter Nestorov and Michael D. Mueller
Int. J. Mol. Sci. 2024, 25(23), 13071; https://doi.org/10.3390/ijms252313071 - 5 Dec 2024
Viewed by 1068
Abstract
This study aimed to identify unique characteristics in the peripheral blood mononuclear cells (PBMCs) of endometriosis patients and develop a non-invasive early diagnostic tool. Using single-cell RNA sequencing (scRNA-seq), we constructed the first single-cell atlas of PBMCs from endometriosis patients based on 107,964 [...] Read more.
This study aimed to identify unique characteristics in the peripheral blood mononuclear cells (PBMCs) of endometriosis patients and develop a non-invasive early diagnostic tool. Using single-cell RNA sequencing (scRNA-seq), we constructed the first single-cell atlas of PBMCs from endometriosis patients based on 107,964 cells and 25,847 genes. Within CD16+ monocytes, we discovered JUP as a dysregulated gene. To assess its diagnostic potential, we measured peritoneal fluid (PF) and serum JUP levels in a large cohort of 199 patients including 20 women with ovarian cancer (OC). JUP was barely detectable in PF but was significantly elevated in the serum of patients with endometriosis and OC, with levels 1.33 and 2.34 times higher than controls, respectively. Additionally, JUP was found in conditioned culture media of CD14+/CD16+ monocytes aligning with our scRNA-seq data. Serum JUP levels correlated with endometriosis severity and endometrioma presence but were unaffected by dysmenorrhea, menstrual cycle, or adenomyosis. When combined with CA125 (cancer antigen 125) JUP enhanced the specificity of endometriosis diagnosis from 89.13% (CA125 measured alone) to 100%. While sensitivity remains a challenge at 19%, our results suggest that JUP’s potential to enhance diagnostic accuracy warrants additional investigation. Furthermore, employing serum JUP as a stratification marker unlocked the potential to identify additional endometriosis-related genes, offering novel insights into disease pathogenesis. Full article
(This article belongs to the Special Issue Biomarkers and Early Detection Strategies of Ovarian Tumors)
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19 pages, 2655 KiB  
Article
Extracellular Hsp70 and Circulating Endometriotic Cells as Novel Biomarkers for Endometriosis
by Christiane Guder, Soraya Heinrich, Vanadin Seifert-Klauss, Marion Kiechle, Lisa Bauer, Rupert Öllinger, Andreas Pichlmair, Marie-Nicole Theodoraki, Veena Ramesh, Ali Bashiri Dezfouli, Barbara Wollenberg, Alan Graham Pockley and Gabriele Multhoff
Int. J. Mol. Sci. 2024, 25(21), 11643; https://doi.org/10.3390/ijms252111643 - 30 Oct 2024
Viewed by 1141
Abstract
Stress-inducible heat shock protein 70 (Hsp70), which functions as a molecular chaperone and is frequently overexpressed in different cancer cell types, is present on the cell surface of tumor cells and is actively released into the circulation in free and extracellular lipid vesicle-associated [...] Read more.
Stress-inducible heat shock protein 70 (Hsp70), which functions as a molecular chaperone and is frequently overexpressed in different cancer cell types, is present on the cell surface of tumor cells and is actively released into the circulation in free and extracellular lipid vesicle-associated forms. Since the exact pathomechanism of endometriosis has not yet been elucidated (although it has been associated with the development of endometrial and ovarian cancer), we asked whether extracellular Hsp70 and circulating endometriotic cells (CECs) reflect the presence and development of endometriosis. Therefore, circulating levels of free and lipid microvesicle-associated Hsp70 were measured using the Hsp70-exo ELISA, and the presence of circulating CECs in the peripheral blood of patients with endometriosis was determined using membrane Hsp70 (mHsp70) and EpCAM monoclonal antibody (mAb)-based bead isolation approaches. Isolated CECs were further characterized by immunofluorescence using reagents directed against cytokeratin (epithelial marker), CD45 (leukocyte marker), CD105/CD44 (mesenchymal stemness markers) and by comparative RNA analysis. Similar to the situation in patients with cancer, the levels of circulating Hsp70 were elevated in the blood of patients with histologically proven endometriosis compared to a healthy control cohort, with significantly elevated Hsp70 levels in endometriosis patients with lesions outside the uterine cavity. Moreover, CECs could be isolated using the cmHsp70.1 mAb-based, and to a lesser extent EpCAM mAb-based, bead approach in all patients with endometriosis, with the highest counts obtained using the mHsp70-targeting procedure in patients with extra-uterine involvement. The longevity in cell culture and the expression of the cytokeratins CD105 and CD44, together with differentially expressed genes related to epithelial-to-mesenchymal transition (EMT), revealed similarities between mHsp70-expressing CECs and circulating tumor cells (CTCs) and suggest a mesenchymal stem cell origin. These findings support the involvement of mHsp70-positive stem cell-like cells in the development of endometriotic lesions. In summary, elevated levels of Hsp70 and CECs in the circulation could serve as liquid biopsy markers for endometriosis with extra-uterine involvement and help to elucidate the underlying pathomechanism of the disease. Full article
(This article belongs to the Special Issue Advances in Rare Diseases Biomarkers: 2nd Edition)
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18 pages, 601 KiB  
Article
Association of the Single Nucleotide Polymorphisms rs11556218, rs4778889, rs4072111, and rs1131445 of the Interleukin-16 Gene with Ovarian Cancer
by Rafał Watrowski, Eva Schuster, Toon Van Gorp, Gerda Hofstetter, Michael B. Fischer, Sven Mahner, Stefan Polterauer, Robert Zeillinger and Eva Obermayr
Int. J. Mol. Sci. 2024, 25(19), 10272; https://doi.org/10.3390/ijms251910272 - 24 Sep 2024
Cited by 1 | Viewed by 1026
Abstract
Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 [...] Read more.
Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.5% were diagnosed in late stages (FIGO IIb-IV), and 73.5% had high-grade serous OC (HGSOC). Minor allele frequencies in controls were 9.2% for rs11556218 (G allele), 13.7% for rs4778889 (C allele), 10.4% for rs4072111 (T allele), and 32.3% for rs1131445 (C allele). We found significant associations of rs11556218 (G vs. T allele: OR 2.76, 95% CI 1.84–4.14, p < 0.0001) with elevated OC risk in the whole cohort (p < 0.001) and in both premenopausal (p < 0.001) and postmenopausal (p = 0.001) subgroups. These associations remained significant across heterozygote (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. IL-16 rs4778889 was associated with OC risk predominantly in premenopausal women (p < 0.0001 in almost all models). In the whole cohort, the C allele was associated with OC risk (OR 1.54, CI 95% 1.06–2.23, p = 0.024), and the association of rs4778889 was significant in dominant (p = 0.019), overdominant (p = 0.033), and heterozygote (p = 0.027) models. Furthermore, rs4778889 was linked with HGSOC (p = 0.036) and endometriosis-related OC subtypes (p = 0.002). No significant associations were found for rs4072111 or rs1131445 (p = 0.81 or 0.47, respectively). In conclusion, rs11556218 and rs4778889 SNPs are associated with OC risk, especially in premenopausal women. Full article
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16 pages, 1371 KiB  
Review
The Sweet Relationship between the Endometrium and Protein Glycosylation
by Linyu Zhang, Ying Feng, Yue Zhang, Xinrui Sun, Qianhong Ma and Fang Ma
Biomolecules 2024, 14(7), 770; https://doi.org/10.3390/biom14070770 - 27 Jun 2024
Viewed by 1957
Abstract
The endometrium is an important part of women’s bodies for menstruation and pregnancy. Various proteins are widely expressed on the surface of endometrial cells, and glycosylation is an important post-translational modification of proteins. Glycosylation modification is closely related not only to endometrial receptivity [...] Read more.
The endometrium is an important part of women’s bodies for menstruation and pregnancy. Various proteins are widely expressed on the surface of endometrial cells, and glycosylation is an important post-translational modification of proteins. Glycosylation modification is closely related not only to endometrial receptivity but also to common diseases related to endometrial receptivity. Glycosylation can improve endometrial receptivity, promote embryo localization and trophoblast cell adhesion and invasion, and contribute to successful implantation. Two diseases related to endometrial receptivity include endometriosis and endometrial cancer. As a common benign disease in women, endometriosis is often accompanied by an increased menstrual volume, prolonged menstrual periods, progressive and aggravated dysmenorrhea, and may be accompanied by infertility. Protein glycosylation modification of the endometrial surface indicates the severity of the disease and may be an important pathogenesis of endometriosis. In cancer, glycosylation modifications on the surface of tumor cells can be a marker to distinguish the type and severity of endometrial cancer. This review highlights the role of protein glycosylation in embryo–maternal endometrial dialogue and explores its potential mechanisms in diseases related to endometrial receptivity, which could provide a new clinical approach for their diagnosis and treatment. Full article
(This article belongs to the Collection Feature Papers in Molecular Reproduction)
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16 pages, 2785 KiB  
Article
Association between KRAS and PIK3CA Mutations and Progesterone Resistance in Endometriotic Epithelial Cell Line
by Kosuke Kanno, Kentaro Nakayama, Sultana Razia, Sohel Hasibul Islam, Zahan Umme Farzana, Shahataj Begum Sonia, Hitomi Yamashita, Masako Ishikawa, Tomoka Ishibashi, Kayo Imamura, Tohru Kiyono and Satoru Kyo
Curr. Issues Mol. Biol. 2024, 46(4), 3579-3594; https://doi.org/10.3390/cimb46040224 - 19 Apr 2024
Cited by 1 | Viewed by 1924
Abstract
Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations [...] Read more.
Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain. Full article
(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)
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17 pages, 1380 KiB  
Review
Endometriosis-Related Ovarian Cancer: Where Are We Now? A Narrative Review towards a Pragmatic Approach
by Gabriele Centini, Giorgia Schettini, Emilio Pieri, Matteo Giorgi, Lucia Lazzeri, Francesco Giuseppe Martire, Virginia Mancini, Diego Raimondo, Renato Seracchioli, Nassir Habib, Francesco Fedele and Errico Zupi
J. Clin. Med. 2024, 13(7), 1933; https://doi.org/10.3390/jcm13071933 - 27 Mar 2024
Cited by 13 | Viewed by 3122
Abstract
Background: Endometriosis affects more than 10% of reproductive-aged women, causing pelvic pain and infertility. Despite the benign nature of endometriosis, ovarian endometriomas carry a higher risk of developing endometrioid carcinomas (EnOCs) and clear cell ovarian carcinomas (CCCs). Atypical endometriosis, defined as cytological atypia [...] Read more.
Background: Endometriosis affects more than 10% of reproductive-aged women, causing pelvic pain and infertility. Despite the benign nature of endometriosis, ovarian endometriomas carry a higher risk of developing endometrioid carcinomas (EnOCs) and clear cell ovarian carcinomas (CCCs). Atypical endometriosis, defined as cytological atypia resembling intraepithelial cancer, is considered the precursor of endometriosis-associated ovarian cancer (EAOC). This narrative review aims to provide an overview of EAOC, proposing a practical approach to clinical and therapeutic decision making. Methods: An electronic literature search was conducted from inception up to January 2023, using the MEDLINE database via PubMed to evaluate the existing literature on EAOC, including its pathogenesis, the diagnostic process, and the therapeutic possibilities, with articles not relevant to the topic or lacking scientific merit being excluded. Results: Eighty-one articles were included in the review to present the current state of the art regarding EAOC. A pragmatic clinical flowchart is proposed to guide therapeutic decisions and improve patient outcomes. Conclusions: Endometriosis patients may have an increased risk of developing EAOC (either EnOC or CCC). Despite not being fully accepted, the concept of AE may reshape the endometriosis–ovarian cancer relationship. Further research is needed to understand the unaddressed issues. Full article
(This article belongs to the Special Issue Update on Laparoscopic Management of Gynecologic Malignancies)
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14 pages, 3071 KiB  
Article
Optical Sensor System for 3D Jones Matrix Reconstruction of Optical Anisotropy Maps of Self-Assembled Polycrystalline Soft Matter Films
by Waldemar Wójcik, Zhengbing Hu, Yuriy Ushenko, Andrzej Smolarz, Iryna Soltys, Oleksander Dubolazov, Oleksander Ushenko, Olexandra Litvinenko, Ivan Mikirin, Ivan Gordey, Oleksandr Pavlyukovich, Sergii Pavlov, Natalia Pavlyukovich, Saltanat Amirgaliyeva, Aliya Kalizhanova and Zhalau Aitkulov
Sensors 2024, 24(5), 1589; https://doi.org/10.3390/s24051589 - 29 Feb 2024
Viewed by 1649
Abstract
Our work uses a polarization matrix formalism to analyze and algorithmically represent optical anisotropy by open dehydration of blood plasma films. Analytical relations for Jones matrix reconstruction of optical birefringence maps of protein crystal networks of dehydrated biofluid films are found. A technique [...] Read more.
Our work uses a polarization matrix formalism to analyze and algorithmically represent optical anisotropy by open dehydration of blood plasma films. Analytical relations for Jones matrix reconstruction of optical birefringence maps of protein crystal networks of dehydrated biofluid films are found. A technique for 3D step-by-step measurement of the distributions of the elements of the Jones matrix or Jones matrix images (JMI) of the optically birefringent structure of blood plasma films (BPF) has been created. Correlation between JMI maps and corresponding birefringence images of dehydrated BPF and saliva films (SF) obtained from donors and prostate cancer patients was determined. Within the framework of statistical analysis of layer-by-layer optical birefringence maps, the parameters most sensitive to pathological changes in the structure of dehydrated films were found to be the central statistical moments of the 1st to 4th orders. We physically substantiated and experimentally determined the sensitivity of the method of 3D polarization scanning technique of BPF and SF preparations in the diagnosis of endometriosis of uterine tissue. Full article
(This article belongs to the Special Issue Application and Technology Trends in Optoelectronic Sensors)
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35 pages, 1280 KiB  
Review
Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases—Focus on Epigenetic Mechanisms
by Marta Włodarczyk, Michał Ciebiera, Grażyna Nowicka, Tomasz Łoziński, Mohamed Ali and Ayman Al-Hendy
Nutrients 2024, 16(4), 559; https://doi.org/10.3390/nu16040559 - 17 Feb 2024
Cited by 8 | Viewed by 5123
Abstract
The most common malignant gynecologic diseases are cervical, uterine, ovarian, vaginal, and vulvar cancer. Among them, ovarian cancer causes more deaths than any other cancer of the female reproductive system. A great number of women suffer from endometriosis, uterine fibroids (UFs), adenomyosis, dysmenorrhea, [...] Read more.
The most common malignant gynecologic diseases are cervical, uterine, ovarian, vaginal, and vulvar cancer. Among them, ovarian cancer causes more deaths than any other cancer of the female reproductive system. A great number of women suffer from endometriosis, uterine fibroids (UFs), adenomyosis, dysmenorrhea, and polycystic ovary syndrome (PCOS), which are widespread benign health problems causing troublesome and painful symptoms and significantly impairing the quality of life of affected women, and they are some of the main causes of infertility. In addition to the available surgical and pharmacological options, the effects of supporting standard treatment with naturally occurring compounds, mainly polyphenols, are being studied. Catechins are responsible for the majority of potential health benefits attributed to green tea consumption. Epigallocatechin gallate (EGCG) is considered a non-toxic, natural compound with potential anticancer properties. Antioxidant action is its most common function, but attention is also drawn to its participation in cell division inhibition, apoptosis stimulation and epigenetic regulation. In this narrative review, we describe the role of EGCG consumption in preventing the development of benign reproductive disorders such as UF, endometriosis, and PCOS, as well as malignant gynecologic conditions. We discuss possible epigenetic mechanisms that may be related to the action of EGCG. Full article
(This article belongs to the Special Issue Nutrition and Lifestyle in Gynecological Diseases)
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18 pages, 1716 KiB  
Review
Gynecological Cancers and Microbiota Dynamics: Insights into Pathogenesis and Therapy
by Giovanna Cocomazzi, Lino Del Pup, Viviana Contu, Gabriele Maggio, Lodovico Parmegiani, Walter Ciampaglia, Daniele De Ruvo, Raffaele Faioli, Annamaria Maglione, Giorgio Maria Baldini, Domenico Baldini and Valerio Pazienza
Int. J. Mol. Sci. 2024, 25(4), 2237; https://doi.org/10.3390/ijms25042237 - 13 Feb 2024
Cited by 6 | Viewed by 4195
Abstract
In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied microbiota concern the gastrointestinal tract, recently, the interest has also been extended to other body districts. Female genital [...] Read more.
In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied microbiota concern the gastrointestinal tract, recently, the interest has also been extended to other body districts. Female genital tract dysbiosis and its possible impact on pathologies such as endometriosis, polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), and gynecological cancers have been unveiled. The incursion of pathogenic microbes alters the ecological equilibrium of the vagina, triggering inflammation and compromising immune defense, potentially fostering an environment conducive to cancer development. The most common types of gynecological cancer include cervical, endometrial, and ovarian cancer, which occur in women of any age but especially in postmenopausal women. Several studies highlighted that a low presence of lactobacilli at the vaginal level, and consequently, in related areas (such as the endometrium and ovary), correlates with a higher risk of gynecological pathology and likely contributes to increased incidence and worse prognosis of gynecological cancers. The complex interplay between microbial communities and the development, progression, and treatment of gynecologic malignancies is a burgeoning field not yet fully understood. The intricate crosstalk between the gut microbiota and systemic inflammation introduces a new dimension to our understanding of gynecologic cancers. The objective of this review is to focus attention on the association between vaginal microbiota and gynecological malignancies and provide detailed knowledge for future diagnostic and therapeutic strategies. Full article
(This article belongs to the Special Issue The Role of the Vaginal Microbiome in Women’s Health and Disease)
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21 pages, 3157 KiB  
Article
Identification of miR-30c-5p microRNA in Serum as a Candidate Biomarker to Diagnose Endometriosis
by Lucía Chico-Sordo, Tamara Ruiz-Martínez, Mónica Toribio, Roberto González-Martín, Emanuela Spagnolo, Francisco Domínguez, Alicia Hernández and Juan A. García-Velasco
Int. J. Mol. Sci. 2024, 25(3), 1853; https://doi.org/10.3390/ijms25031853 - 3 Feb 2024
Cited by 3 | Viewed by 2172
Abstract
The diagnosis of endometriosis by laparoscopy is delayed until advanced stages. In recent years, microRNAs have emerged as novel biomarkers for different diseases. These molecules are small non-coding RNA sequences involved in the regulation of gene expression and can be detected in peripheral [...] Read more.
The diagnosis of endometriosis by laparoscopy is delayed until advanced stages. In recent years, microRNAs have emerged as novel biomarkers for different diseases. These molecules are small non-coding RNA sequences involved in the regulation of gene expression and can be detected in peripheral blood. Our aim was to identify candidate serum microRNAs associated with endometriosis and their role as minimally invasive biomarkers. Serum samples were obtained from 159 women, of whom 77 were diagnosed with endometriosis by laparoscopy and 82 were healthy women. First, a preliminary study identified 29 differentially expressed microRNAs between the two study groups. Next, nine of the differentially expressed microRNAs in the preliminary analysis were evaluated in a new cohort of 67 women with endometriosis and 72 healthy women. Upon validation by quantitative real-time PCR technique, the circulating level of miR-30c-5p was significantly higher in the endometriosis group compared with the healthy women group. The area under the curve value of miR-30c-5p was 0.8437, demonstrating its diagnostic potential even when serum samples registered an acceptable limit of hemolysis. Dysregulation of this microRNA was associated with molecular pathways related to cancer and neuronal processes. We concluded that miR-30c-5p is a potential minimally invasive biomarker of endometriosis, with higher expression in the group of women with endometriosis diagnosed by laparoscopy. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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19 pages, 2406 KiB  
Article
Association of Four Interleukin-8 Polymorphisms (−251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes
by Rafał Watrowski, Eva Schuster, Gerda Hofstetter, Michael B. Fischer, Sven Mahner, Toon Van Gorp, Stefan Polterauer, Robert Zeillinger and Eva Obermayr
Biomedicines 2024, 12(2), 321; https://doi.org/10.3390/biomedicines12020321 - 30 Jan 2024
Cited by 4 | Viewed by 2109
Abstract
Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs [...] Read more.
Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ovarian cancer (OC), suggesting an association between two IL-8 SNPs and OC risk. In this study, we investigated four common IL-8 SNPs, rs4073 (−251 A>T), rs2227306 (+781 C>T), rs2227543 (+1633 C>T), and rs1126647 (+2767 A>T), using the restriction fragment length polymorphism (PCR-RFLP) technique. Our study included a cohort of 413 women of Central European descent, consisting of 200 OC patients and 213 healthy controls. The most common (73.5%) histological type was high-grade serous OC (HGSOC), whereas 28/200 (14%) patients had endometriosis-related (clear cell or endometrioid) OC subtypes (EROC). In postmenopausal women, three of the four investigated SNPs, rs4073 (−251 A>T), rs2227306 (+781 C>T), and rs2227543 (+1633 C>T), were associated with OC risk. Furthermore, we are the first to report a significant relationship between the T allele or TT genotype of SNP rs1126647 (+2767 A>T) and the EROC subtype (p = 0.02 in the co-dominant model). The TT homozygotes were found more than twice as often in EROC compared to other OC subtypes (39% vs. 19%, p = 0.015). None of the examined SNPs appeared to influence OC risk in premenopausal women, nor were they associated with the aggressive HGSOC subtype or the stage of disease at the initial diagnosis. Full article
(This article belongs to the Special Issue The Role of Inflammatory Cytokines in Cancer Progression 2.0)
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14 pages, 929 KiB  
Article
Correlation between MRI Features of Adenomyosis and Clinical Presentation
by Youn-Jee Chung, Sung Eun Rha, Mee-Ran Kim and Yu Ri Shin
Diagnostics 2023, 13(17), 2749; https://doi.org/10.3390/diagnostics13172749 - 24 Aug 2023
Cited by 1 | Viewed by 1845
Abstract
This study aimed to explore the correlation between MRI features, clinical risk factors, and symptoms associated with adenomyosis. Overall, 112 patients with pathologically confirmed adenomyosis were included in this retrospective study. MRI findings and clinical presentation, including visual analog scale (VAS) scores, cancer [...] Read more.
This study aimed to explore the correlation between MRI features, clinical risk factors, and symptoms associated with adenomyosis. Overall, 112 patients with pathologically confirmed adenomyosis were included in this retrospective study. MRI findings and clinical presentation, including visual analog scale (VAS) scores, cancer antigen 125 (CA-125) and hemoglobin levels, and parity, were analyzed. Additionally, 131 patients undergoing active surveillance were included to validate the MRI parameters and clinical presentations. Associations between MRI parameters and adenomyosis-related clinical presentations were assessed. Patients with operated adenomyosis were younger and had larger lesions, which were more frequently of the diffuse type and posterior localization, coexisting ovarian endometriosis, deep infiltrating endometriosis, myometrial cysts, and diffusion restriction than the non-operated lesions (p < 0.05). Patients with operated adenomyosis also exhibited higher VAS scores and CA-125 levels, and nulliparity was more common in this group (p < 0.05). In contrast, patients with non-operated adenomyosis showed a higher frequency of entire localization and fibroids (p < 0.05). Among the MRI parameters, size and classification were associated with the VAS and CA-125 levels. Myometrial cysts were associated with CA-125 levels. Classification was also associated with hemoglobin levels, and posterior localization was associated with parity. We identified a significant correlation between MRI features and clinical presentation in patients with adenomyosis. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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22 pages, 2500 KiB  
Review
The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential
by Fengguang Yang, Jinglin Ma, Daxue Zhu, Zhaoheng Wang, Yanhu Li, Xuegang He, Guangzhi Zhang and Xuewen Kang
Biomolecules 2023, 13(7), 1139; https://doi.org/10.3390/biom13071139 - 17 Jul 2023
Cited by 12 | Viewed by 4039
Abstract
S100A6, also known as calcyclin, is a low-molecular-weight Ca2+-binding protein from the S100 family that contains two EF-hands. S100A6 is expressed in a variety of mammalian cells and tissues. It is also expressed in lung, colorectal, pancreatic, and liver cancers, as [...] Read more.
S100A6, also known as calcyclin, is a low-molecular-weight Ca2+-binding protein from the S100 family that contains two EF-hands. S100A6 is expressed in a variety of mammalian cells and tissues. It is also expressed in lung, colorectal, pancreatic, and liver cancers, as well as other cancers such as melanoma. S100A6 has many molecular functions related to cell proliferation, the cell cycle, cell differentiation, and the cytoskeleton. It is not only involved in tumor invasion, proliferation, and migration, but also the pathogenesis of other non-neoplastic diseases. In this review, we focus on the molecular mechanisms and potential therapeutic targets of S100A6 in tumors, nervous system diseases, leukemia, endometriosis, cardiovascular disease, osteoarthritis, and other related diseases. Full article
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24 pages, 1388 KiB  
Review
Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis
by Julieta Griselda Mendoza-Torreblanca, Noemi Cárdenas-Rodríguez, Jazmín Carro-Rodríguez, Itzel Jatziri Contreras-García, David Garciadiego-Cázares, Daniel Ortega-Cuellar, Valentín Martínez-López, Alfonso Alfaro-Rodríguez, Alberto Nayib Evia-Ramírez, Iván Ignacio-Mejía, Marco Antonio Vargas-Hernández and Cindy Bandala
Int. J. Mol. Sci. 2023, 24(12), 10199; https://doi.org/10.3390/ijms241210199 - 15 Jun 2023
Cited by 1 | Viewed by 3071
Abstract
Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and [...] Read more.
Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies. Full article
(This article belongs to the Section Molecular Pharmacology)
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10 pages, 511 KiB  
Review
Insulin-like Growth Factor-1 (IGF-1) Related Drugs in Pain Management
by Seokhyun Jin and Jianguo Cheng
Pharmaceuticals 2023, 16(5), 760; https://doi.org/10.3390/ph16050760 - 18 May 2023
Cited by 1 | Viewed by 3716
Abstract
Objective. The aim of this review is to explore the role of IGF-1 and IGF-1R inhibitors in pain-related conditions and assess the effectiveness of IGF-1-related drugs in pain management. Specifically, this paper investigates the potential involvement of IGF-1 in nociception, nerve regeneration, [...] Read more.
Objective. The aim of this review is to explore the role of IGF-1 and IGF-1R inhibitors in pain-related conditions and assess the effectiveness of IGF-1-related drugs in pain management. Specifically, this paper investigates the potential involvement of IGF-1 in nociception, nerve regeneration, and the development of neuropathic pain. Methods. We conducted a search of the PUBMED/MEDLINE database, Scopus, and the Cochrane Library for all reports published in English on IGF-1 in pain management from origination through November 2022. The resulting 545 articles were screened, and 18 articles were found to be relevant after reading abstracts. After further examination of the full text of these articles, ten were included in the analysis and discussion. The levels of clinical evidence and implications for recommendations of all the included human studies were graded. Results. The search yielded 545 articles, of which 316 articles were deemed irrelevant by reading the titles. There were 18 articles deemed relevant after reading abstracts, of which 8 of the reports were excluded due to lack of IGF-1-related drug treatment after reviewing the full text of the articles. All ten articles were retrieved for analysis and discussion. We found that IGF-1 may have several positive effects on pain management, including promoting the resolution of hyperalgesia, preventing chemotherapy-induced neuropathy, reversing neuronal hyperactivity, and elevating the nociceptive threshold. On the other hand, IGF-1R inhibitors may alleviate pain in mice with injury of the sciatic nerve, bone cancer pain, and endometriosis-induced hyperalgesia. While one study showed marked improvement in thyroid-associated ophthalmopathy in humans treated with IGF-1R inhibitor, two other studies did not find any benefits from IGF-1 treatment. Conclusions. This review highlights the potential of IGF-1 and IGF-1R inhibitors in pain management, but further research is needed to fully understand their efficacy and potential side effects. Full article
(This article belongs to the Special Issue Insulin-Like Growth Factor-1 (IGF-1) Receptor as Drug Targets)
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