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1.
Front Cell Dev Biol ; 12: 1459183, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39386020

RESUMO

Copper (Cu) is an essential trace element involved in a variety of biological processes, such as antioxidant defense, mitochondrial respiration, and bio-compound synthesis. In recent years, a novel theory called cuproptosis has emerged to explain how Cu induces programmed cell death. Cu targets lipoylated enzymes in the tricarboxylic acid cycle and subsequently triggers the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase, leading to the loss of Fe-S clusters and induction of heat shock protein 70. Gynecological malignancies including cervical cancer, ovarian cancer and uterine corpus endometrial carcinoma significantly impact women's quality of life and even pose a threat to their lives. Excessive Cu can promote cancer progression by enhancing tumor growth, proliferation, angiogenesis and metastasis through multiple signaling pathways. However, there are few studies investigating gynecological cancers in relation to cuproptosis. Therefore, this review discusses Cu homeostasis and cuproptosis while exploring the potential use of cuproptosis for prognosis prediction as well as its implications in the progression and treatment of gynecological cancers. Additionally, we explore the application of Cu ionophore therapy in treating gynecological malignancies.

2.
Pathol Res Pract ; 263: 155611, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39357191

RESUMO

Cancer continues to threaten human health regardless of novel therapeutic options. Over the last two decades, targeted therapy has emerged as a significant advancement in treating malignancies, surpassing standard chemoradiotherapy and surgical procedures. Gynecological malignancies, including cervical, endometrial, and ovarian carcinoma, have a bad prognosis in advanced or metastatic stages and are difficult to treat. The advancements in understanding the molecular pathways behind cancer development offer valuable insights into promising targeted medicines, and researchers have always searched for a superior and safe technique to target cancer-related oncoproteins because of the limited therapeutic benefit, drug resistance, and off-target effects of current targeted treatments. Recently, proteolysis-targeting chimeras (PROTACs) have been developed to selectively degrade proteins using the natural ubiquitin-proteasome system (UPS). These approaches have garnered significant attention in the field of cancer research. The rapid progress in PROTACs has also eased the targeting of various oncoproteins in gynecological cancer. Therefore, this review aims to elucidate the mechanism and research advancements of PROTACs and provide a comprehensive overview of their use in gynecological tumors.

3.
Brachytherapy ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39256104

RESUMO

PURPOSE: The lack of training is a significant barrier to practicing brachytherapy (BT). Tata Memorial Centre, alongside international BT experts and BrachyAcademy, developed a hybrid gynecological BT training module. This study outlines the preparation, organization, and execution of the 2022-2023 Mumbai training, evaluates its effectiveness, and highlights areas for improvement. MATERIALS AND METHODS: Participants were radiation oncologists (RO) and medical physicists (MP) with experience in gynecological BT aiming to transition to image-guided brachytherapy (IGBT). The training covered cervical, endometrial, vaginal, vulvar, periurethral cancers, and pelvic reirradiation. The hybrid course included online pre and postcourse homework assignments, a live workshop with hands-on training, a 6-month online follow-up, and a 12-month opportunity to share the transition experience. RESULTS: The December 2022 Mumbai live workshop spanned 2.5 days, attracting 39 participants from 8 countries (Asia, Africa, Australia/Oceania). Feedback rated the course 9/10, with 78% fully meeting expectations. Forty-four percent suggested extending hands-on training. At the 6-month follow-up, response rates were low (33% RO, 11% MP). Among responding RO, 70% reported practice changes after attending the course, 40% implemented IGBT concepts in clinical practice, and 50% increased confidence in image-guided procedures. Overall, 45% of respondent sites could strengthen their intracavitary/interstitial program, while others faced limitations due to lack of access to advanced BT applicators. CONCLUSION: The hybrid gynecological BT training concept was successfully executed. Areas for improvement include extending hands-on training and enhancing participant engagement postcourse. Structured steps beyond training may be needed to improve the utilization of advanced brachytherapy for gynecological cancers.

4.
Biochem Pharmacol ; 229: 116498, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39159874

RESUMO

Gynecological cancers, including ovarian, cervical, endometrial, and vulvar cancers, present significant challenges in diagnosis and treatment globally. The tumor microenvironment (TME) plays a pivotal role in cancer progression and therapy response, necessitating a deeper understanding of its composition and dynamics. This review offers a comprehensive overview of the gynecological cancer tumor microenvironment, emphasizing its cellular complexity and therapeutic potential. The diverse cellular components of the TME, including cancer cells, immune cells, stromal cells, and extracellular matrix elements, are explored, elucidating their interplay in shaping tumor behavior and treatment outcomes. Across various stages of cancer progression, the TME exerts profound effects on tumor heterogeneity, immune modulation, angiogenesis, and metabolic reprogramming. The urgency for novel therapeutic strategies is underscored by understanding immune evasion mechanisms within the TME. Emerging approaches such as immunotherapy, stromal-targeting therapies, anti-angiogenic agents, and metabolic inhibitors are discussed, offering promising avenues for improving patient outcomes. Interdisciplinary collaborations and translational research are emphasized, aiming to advance precision oncology and enhance therapeutic efficacy in gynecological cancers.

5.
Radiol Med ; 129(9): 1329-1351, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39198369

RESUMO

Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed.


Assuntos
Neoplasias dos Genitais Femininos , Lesões por Radiação , Humanos , Feminino , Neoplasias dos Genitais Femininos/radioterapia , Lesões por Radiação/prevenção & controle , Lesões por Radiação/etiologia , Itália , Órgãos em Risco/efeitos da radiação , Radioterapia/efeitos adversos , Sociedades Médicas , Radioterapia (Especialidade)
6.
Gynecol Oncol ; 189: 129-136, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116830

RESUMO

OBJECTIVES: To determine if nutritional status effects response to immunotherapy in women with gynecologic malignancies. METHODS: A retrospective chart review was conducted on gynecologic cancer patients who received immunotherapy at a single institution between 2015 and 2022. Immunotherapy included checkpoint inhibitors and tumor vaccines. The prognostic nutritional index (PNI) was calculated from serum albumin levels and total lymphocyte count. PNI values were determined at the beginning of treatment for each patient and assessed for their association with immunotherapy response. Disease control response (DCR) as an outcome of immunotherapy was defined as complete response, partial response, or stable disease. RESULTS: One hundred and ninety-eight patients received immunotherapy (IT) between 2015 and 2022. The gynecological cancers treated were uterine (38%), cervix (32%), ovarian (25%), and vulvar or vaginal (4%) cancers. The mean PNI for responders was higher than the non-responder group (p < 0.05). The AUC value for PNI as a predictor of response was 49. A PNI value of 49 was 43% sensitive and 85% specific for predicting a DCR. In Cox proportional hazards analysis, after adjusting for ECOG score and the number of prior chemotherapy lines, severe malnutrition was associated with progression-free survival (PFS) (HR = 1.85, p = 0.08) and overall survival (OS) (HR = 3.82, p < 0.001). Patients with PNI < 49 were at a higher risk of IT failure (HR = 2.24, p = 0.0001) and subsequent death (HR = 2.84, p = 9 × 10-5). CONCLUSIONS: PNI can be a prognostic marker to predict response rates of patients with gynecologic cancers treated with immunotherapy. Additional studies needed to understand the mechanistic role of malnutrition in immunotherapy response.


Assuntos
Neoplasias dos Genitais Femininos , Inibidores de Checkpoint Imunológico , Imunoterapia , Estado Nutricional , Humanos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias dos Genitais Femininos/terapia , Neoplasias dos Genitais Femininos/imunologia , Idoso , Imunoterapia/métodos , Adulto , Avaliação Nutricional , Resultado do Tratamento , Idoso de 80 Anos ou mais , Vacinas Anticâncer/uso terapêutico , Vacinas Anticâncer/administração & dosagem
7.
Front Psychiatry ; 15: 1383029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104879

RESUMO

Gynecological cancers are prevalent malignancies among females, and surgical intervention is the primary therapeutic approach offering the possibility of a definitive cure. Recent research has highlighted the susceptibility of gynecological cancer patients to experiencing anxiety symptoms during the perioperative and postoperative phases, with this psychological condition being linked to suboptimal recovery following surgery. Nevertheless, certain interventions have shown promise in mitigating perioperative and postoperative anxiety in gynecological cancer patients. In this study, we conducted a comprehensive review to collect the existing evidence on this subject. Through a systematic search across six common databases, we screened and included 28 pertinent studies. The current review emphasizes the elevated occurrence of perioperative and postoperative anxiety among patients with gynecological cancers (i.e., uterine, cervical, ovarian, endometrial, and vulval cancers). Specific nursing interventions (i.e., crisis intervention nursing, multidisciplinary collaborative continuous nursing, psychological nursing, comprehensive psychological nursing, reminiscence therapy involved care, cognitive behavioral stress management, hospital-family integrated continuation nursing, high-quality nursing care, relaxation-focused nursing program, and relaxation/counseling intervention) and psychotropic medications may serve as dependable approaches to mitigate perioperative and postoperative anxiety. This study represents a novel contribution to the literature by providing a characterization of perioperative and postoperative anxiety in the context of gynecological oncology. The findings underscore the significance of addressing perioperative and postoperative anxiety as a critical clinical concern for individuals with gynecological cancers, emphasizing the need for further research to develop effective interventions.

8.
J Gynecol Obstet Hum Reprod ; 53(9): 102832, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39098583

RESUMO

BACKGROUND: Previous studies have highlighted patients with chronic conditions seek for medical knowledge and therapeutics on their own. So far, no data exist on the health literacy of patients with gynecological conditions and especially those suffering from endometriosis, whose symptoms' have a major impact on their daily lives. METHOD: The objective was to evaluate the health literacy of patients consulting in a referral expert center for the management of endometriosis and gynecological cancers. The secondary objective was to compare the health literacy of patients with endometriosis to patients without. We conducted an observational, prospective, monocentric study in the gynecological department of Tenon Hospital (Paris, France) between July 6, 2022 to January 3, 2023. All patients fulfilled the validated French version of HLS-EU-Q16 questionnaire. RESULTS: One hundred and ten patients were included. The two following questions were identified as the most difficult among patients with endometriosis: "Find information about treatments for their disease" and "know when it would be helpful to have another doctor's opinion". Compared to patients consulting for other conditions, it was more difficult for patients with endometriosis to respectively "find information about treatments for diseases" and "use information given by the doctor to take decisions about the illness" (p = 0.003). Compared to patients consulting for cancer, it was more difficult for patient with endometriosis to "find information about treatments for diseases" (p = 0.02). CONCLUSION: Progresses in the capacity of the health care to better inform the patients would be highly beneficial, especially for those suffering from endometriosis.

9.
Ann Hum Genet ; 88(6): 423-435, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38989824

RESUMO

BACKGROUND: Observational studies have shown that cholelithiasis and cholecystectomy are associated with the risk of breast cancer (BC) and gynecological cancers, but whether these relationships are causal has not been established and remains controversial. METHODS: Our study began with a meta-analysis that synthesized data from prior observational studies to examine the association between cholelithiasis, cholecystectomy, and the risk of BC and gynecological cancers. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing genetic variant data to investigate the potential causal relationship between cholelithiasis, cholecystectomy, and the aforementioned cancers. RESULTS: The results of the meta-analysis demonstrated a significant association between cholecystectomy and the risk of BC (risk ratio [RR] = 1.04, 95% confidence interval [CI]: 1.01-1.06, p = 0.002) and endometrial cancer (EC) (RR = 1.26, 95% CI: 1.02-1.56, p = 0.031). Conversely, no significant association was observed between cholelithiasis and the risk of BC, EC, and ovarian cancer. The MR analysis revealed no discernible causal connection between cholelithiasis and overall BC (p = 0.053), as well as BC subtypes (including estrogen receptor-positive/negative). Similarly, there was no causal effect of cholecystectomy on BC risk (p = 0.399) and its subtypes. Furthermore, no causal associations were identified between cholelithiasis, cholecystectomy, and the risk of gynecological cancers (ovarian, endometrial, and cervical cancer [CC]) (all p > 0.05). CONCLUSION: This study does not support a causal link between cholelithiasis and cholecystectomy and an increased risk of female cancers such as breast, endometrial, ovarian, and CC.


Assuntos
Neoplasias da Mama , Colecistectomia , Colelitíase , Análise da Randomização Mendeliana , Humanos , Feminino , Neoplasias da Mama/genética , Colelitíase/genética , Colelitíase/etiologia , Neoplasias dos Genitais Femininos/genética , Fatores de Risco , Predisposição Genética para Doença
10.
Cureus ; 16(6): e62732, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39036239

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse reaction to many first- and second-line chemotherapy medications that can be debilitating, severe, and often dose-limiting. Treatment options for CIPN are limited. We report a case of a 52-year-old female patient with Stage II ovarian cancer who was hospitalised in the chemotherapy ward for a second round of chemotherapy. We describe the effectiveness of closed kinetic chain (CKC) exercises for the management of CIPN symptoms. The patient was advised to take neurophysiotherapy. The patient complained of pain, tingling in both feet, weakness in the lower limbs, and trouble keeping her balance while walking. Thus, three days after the start of the chemotherapy drugs, physical therapy rehabilitation was started. The patient stated total pain reduction and a noticeable improvement in tingling and numbness in both lower extremities following four weeks of physical therapy. Even though CIPN usually disappears gradually over time, it can persist for an extended period. It seems doubtful that this was a spontaneous resolve, given the regularity of her symptoms before starting physiotherapy sessions and their quick recovery with treatment. Further investigation is required to comprehend the role that physiotherapy and non-pharmacologic interventions play in ameliorating CIPN symptoms and to ascertain if improvements in CIPN symptoms are associated with an increase in blood flow directly or indirectly.

11.
Clin Nurs Res ; : 10547738241267089, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39066618

RESUMO

Gynecological cancers constitute an important global health problem with increasing incidence and prevalence. The aim of this study was to explain gynecologic cancer knowledge, attitudes, and cultural beliefs of Afghan refugee women living in Türkiye. This research was carried out as a descriptive phenomenological design for qualitative research. The study was conducted at the Refugee Support Center Association in Eskisehir, Türkiye, and data were collected between January and April 2023, guided by a semi-structured interview guide. Nineteen Afghan refugee women were interviewed. A purposive sampling method was used to recruit participants. Content analysis method was used for data analysis. Four overarching themes that described Afghan women's gynecologic cancer knowledge, attitudes, and cultural beliefs were identified: (a) limited awareness and knowledge of gynecological cancer among women, (b) women's attitudes toward gynecological cancers, (c) women's cultural beliefs regarding gynecological cancer, and (d) healthcare system factors. In line with the main themes, subthemes were created for each main theme. Afghan refugee women, who were in the double risk group as both women and refugees, had insufficient knowledge of gynecological cancers, and their cultural beliefs and attitudes played an essential role in their access to gynecological cancer-related preventive healthcare services. It is recommended that training be planned to increase the awareness and knowledge of Afghan women on gynecological cancers, considering their cultural characteristics.

12.
J Gynecol Obstet Hum Reprod ; 53(9): 102819, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950735

RESUMO

The main objective of this study was to review and perform a meta-analysis of current literature on the use of indocyanine green for sentinel lymph node detection in pelvic gynecologic cancer. We included all studies focusing on indications and procedures associated with the use of ICG in gynecologic surgery and available on the Medline and Pubmed database. For the meta-analysis, random effect models were used for estimation of the 95 % detection rate and 95 % confidence interval, and stratified analyses by cancer type, concentration and localization of injection were performed. A total of 147 articles were included, of which 91 were studied in a meta-analysis. Results concerning detection rate by indocyanine green injection site were found to be 95.1 % and 97.3 % respectively for intracervical injection in 2 or 4 quadrants, and 77.0 % and 94.8 % for hysteroscopic and intradermal injection respectively. Results concerning detection rate by cancer type were 95.8 %, 95.2 %, 94.7 % and 95.7 % respectively for cervical, endometrial, vulvar and endometrial/cervical cancers. Finally, the results concerning detection rate by indocyanine green concentration were 91.2 %, 95.7 %, 96.7 % and 97.7 % for concentrations of <1.25 mg/ml, 1.25 mg/ml, 2.5 mg/ml and 5 mg/ml respectively. In conclusion, indocyanine green is shown to allow highlighting of sentinel lymph nodes with good reliability with an overall indocyanine green detection rate of 95.5 %. Our literature review revealed that indocyanine green feasibility has also been demonstrated in several surgical contexts, notably for reconstructive surgery and detection of endometriosis.

13.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38892394

RESUMO

Cancer diseases constitute a major health problem which leads to the death of millions of people annually. They are unique among other diseases because cancer cells can perfectly adapt to the environment that they create themselves. This environment is usually highly hostile and for normal cells it would be hugely difficult to survive, however neoplastic cells not only can survive but also manage to proliferate. One of the reasons is that they can alter immunological pathways which allow them to be flexible and change their phenotype to the one needed in specific conditions. The aim of this paper is to describe some of these immunological pathways that play significant roles in gynecologic neoplasms as well as review recent research in this field. It is of high importance to possess extensive knowledge about these processes, as greater understanding leads to creating more specialized therapies which may prove highly effective in the future.


Assuntos
Neoplasias da Mama , Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Femininos/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Microambiente Tumoral/imunologia , Animais
15.
Biology (Basel) ; 13(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38927277

RESUMO

Gynecological diseases are triggered by aberrant molecular pathways that alter gene expression, hormonal balance, and cellular signaling pathways, which may lead to long-term physiological consequences. This study was able to identify highly preserved modules and key hub genes that are mainly associated with gynecological diseases, represented by endometriosis (EM), ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC), through the weighted gene co-expression network analysis (WGCNA) of microarray datasets sourced from the Gene Expression Omnibus (GEO) database. Five highly preserved modules were observed across the EM (GSE51981), OC (GSE63885), CC (GSE63514), and EC (GSE17025) datasets. The functional annotation and pathway enrichment analysis revealed that the highly preserved modules were heavily involved in several inflammatory pathways that are associated with transcription dysregulation, such as NF-kB signaling, JAK-STAT signaling, MAPK-ERK signaling, and mTOR signaling pathways. Furthermore, the results also include pathways that are relevant in gynecological disease prognosis through viral infections. Mutations in the ESR1 gene that encodes for ERα, which were shown to also affect signaling pathways involved in inflammation, further indicate its importance in gynecological disease prognosis. Potential drugs were screened through the Drug Repurposing Encyclopedia (DRE) based on the up-and downregulated hub genes, wherein a bacterial ribosomal subunit inhibitor and a benzodiazepine receptor agonist were the top candidates. Other drug candidates include a dihydrofolate reductase inhibitor, glucocorticoid receptor agonists, cholinergic receptor agonists, selective serotonin reuptake inhibitors, sterol demethylase inhibitors, a bacterial antifolate, and serotonin receptor antagonist drugs which have known anti-inflammatory effects, demonstrating that the gene network highlights specific inflammatory pathways as a therapeutic avenue in designing drug candidates for gynecological diseases.

16.
Cancers (Basel) ; 16(12)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38927920

RESUMO

(1) Background: Currently, an increasing number of women postpone pregnancy beyond the age of 35. Gynecological cancers affect a significant proportion of women of reproductive age, necessitating the development of fertility preservation methods to fulfill family planning. Consequently, providing treatment options that preserve fertility in women diagnosed with gynecological cancers has become a crucial component of care for survivors. (2) Methods: We conducted an extensive search of relevant scientific publications in PubMed and Embase databases and performed a narrative review, including high-quality peer-reviewed research on fertility after being treated for gynecologic cancers, reporting pregnancy rates, birth rates, and pregnancy outcomes in cancer survivors as well as therapeutic options which partially preserve fertility and methods for obtaining a pregnancy in survivors. (3) Discussion: The medicine practiced today is focused on both treating the neoplasm and preserving the quality of life of the patients, with fertility preservation being an important element of this quality. This leads to an improved quality of life, allowing these women to become mothers even in the seemingly adverse circumstances posed by such a pathology. However, although there are guidelines on female fertility preservation in the context of neoplasms, an analysis shows that physicians do not routinely consider it and do not discuss these options with their patients. (4) Conclusions: Advancements in medicine have led to a better understanding and management of gynecological neoplasms, resulting in increased survival rates. Once the battle against these neoplasms is won, the issue of preserving the quality of life for these women arises, with fertility preservation being an important aspect for women who have not yet fulfilled their family planning desires at the time of diagnosis. It is important for patients to be informed about the available options for fertility preservation and to be encouraged to make informed decisions in collaboration with their medical team. Standardized recommendations for onco-fertility into guidelines should be taken into consideration in the future.

17.
Cancers (Basel) ; 16(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38927992

RESUMO

Chemotherapy is one of the leading cancer treatments. Unfortunately, its use can contribute to several side effects, including gynotoxic effects in women. Ovarian reserve suppression and estrogen deficiency result in reduced quality of life for cancer patients and are frequently the cause of infertility and early menopause. Classic alkylating cytostatics are among the most toxic chemotherapeutics in this regard. They cause DNA damage in ovarian follicles and the cells they contain, and they can also induce oxidative stress or affect numerous signaling pathways. In vitro tests, animal models, and a few studies among women have investigated the effects of various agents on the protection of the ovarian reserve during classic chemotherapy. In this review article, we focused on the possible beneficial effects of selected hormones (anti-Müllerian hormone, ghrelin, luteinizing hormone, melatonin), agents affecting the activity of apoptotic pathways and modulating gene expression (C1P, S1P, microRNA), and several natural (quercetin, rapamycin, resveratrol) and synthetic compounds (bortezomib, dexrazoxane, goserelin, gonadoliberin analogs, imatinib, metformin, tamoxifen) in preventing gynotoxic effects induced by commonly used cytostatics. The presented line of research appears to provide a promising strategy for protecting and/or improving the ovarian reserve in the studied group of cancer patients. However, well-designed clinical trials are needed to unequivocally assess the effects of these agents on improving hormonal function and fertility in women treated with ovotoxic anticancer drugs.

18.
Cells ; 13(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891037

RESUMO

Plasma gelsolin (pGSN) overexpression in ovarian cancer (OVCA) disarms immune function, contributing to chemoresistance. The aim of this study was to investigate the immunoregulatory effects of pGSN expression on natural killer (NK) cell function in OVCA. OVCA tissues from primary surgeries underwent immunofluorescent staining of pGSN and the activated NK cell marker natural cytotoxicity triggering receptor 1 to analyze the prognostic impact of pGSN expression and activated NK cell infiltration. The immunoregulatory effects of pGSN on NK cells were assessed using apoptosis assay, cytokine secretion, immune checkpoint-receptor expression, and phosphorylation of STAT3. In OVCA tissue analyses, activated NK cell infiltration provided survival advantages to patients. However, high pGSN expression attenuated the survival benefits of activated NK cell infiltration. In the in vitro experiment, pGSN in OVCA cells induced NK cell death through cell-to-cell contact. pGSN increased T-cell immunoglobulin and mucin-domain-containing-3 expression (TIM-3) on activated NK cells. Further, it decreased interferon-γ production in activated TIM-3+ NK cells, attenuating their anti-tumor effects. Thus, increased pGSN expression suppresses the anti-tumor functions of NK cells. The study provides insights into why immunotherapy is rarely effective in patients with OVCA and suggests novel treatment strategies.


Assuntos
Carcinoma Epitelial do Ovário , Resistencia a Medicamentos Antineoplásicos , Gelsolina , Células Matadoras Naturais , Neoplasias Ovarianas , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Feminino , Gelsolina/metabolismo , Gelsolina/sangue , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Apoptose/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Interferon gama/metabolismo
19.
Infect Agent Cancer ; 19(1): 27, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877504

RESUMO

The vagina hosts a community of microorganisms known as the vaginal microbiota. This community is relatively stable and straightforward, with Lactobacillus species being the most dominant members. The vaginal microbiota has various functions that are essential for maintaining human health and balance. For example, it can metabolise dietary nutrients, produce growth factors, communicate with other bacteria, modulate the immune system, and prevent the invasion of harmful pathogens. When the vaginal microbiota is disrupted, it can lead to diseases and infections. The observed disturbance is distinguished by a reduction in the prevalence of Lactobacillus and a concurrent rise in the number of other bacterial species that exhibit a higher tolerance to low oxygen levels. Gynecologic cancers are a group of cancers that affect the female reproductive organs and tissues, such as the ovaries, uterus, cervix, vagina, vulva, and endometrium. These cancers are a major global health problem for women. Understanding the complex interactions between the host and the vaginal microorganisms may provide new insights into the prevention and treatment of gynecologic cancers. This could improve the quality of life and health outcomes for women.

20.
J Ovarian Res ; 17(1): 113, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796525

RESUMO

Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need. Extracellular vesicles (EVs), that include exosomes provide hope in both diagnostic and therapeutic aspects. They are natural lipid nanovesicles secreted by all cell types and carry molecules that reflect the status of the parent cell. This facilitates their potential use as biomarkers for an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, and have features such as high stability and favorable pharmacokinetic properties. This makes them ideal for tumor-targeted delivery of biological moieties. The International Society of Extracellular Vesicles (ISEV) based on the Minimal Information for Studies on Extracellular Vesicles (MISEV) recommends the usage of the term "small extracellular vesicles (sEVs)" that includes exosomes for particles that are 30-200 nm in size. However, majority of the studies reported in the literature and relevant to this review have used the term "exosomes". Therefore, this review will use the term "exosomes" interchangeably with sEVs for consistency with the literature and avoid confusion to the readers. This review, initially summarizes the different isolation and detection techniques developed to study ovarian cancer-derived exosomes and the potential use of these exosomes as biomarkers for the early diagnosis of this devastating disease. It addresses the role of exosome contents in the pathogenesis of ovarian cancer, discusses strategies to limit exosome-mediated ovarian cancer progression, and provides options to use exosomes for tumor-targeted therapy in ovarian cancer. Finally, it states future research directions and recommends essential research needed to successfully transition exosomes from the laboratory to the gynecologic-oncology clinic.


Assuntos
Biomarcadores Tumorais , Exossomos , Neoplasias Ovarianas , Humanos , Exossomos/metabolismo , Feminino , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo
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