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1.
Cureus ; 16(4): e57615, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38707031

RESUMO

Ovarian granulosa cell tumors (GCTs) are rare neoplasms with a unique incidence pattern peaking in postmenopausal women. This case report presents two instances of stage 4 recurrent adult GCTs with a prolonged 20-year follow-up. Patient 1, diagnosed at 54 years, experienced multiple recurrences managed through surgery, hormonal therapy, and chemotherapy, culminating in hepatocellular carcinoma. Patient 2, diagnosed at 67 years, underwent various treatments, including surgery, chemotherapy, and hormonal therapy, demonstrating disease stability. Despite the generally favorable prognosis, these cases highlight the challenges of managing recurrent GCTs, emphasizing the need for tailored therapeutic approaches.

2.
Cureus ; 16(4): e59214, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38807834

RESUMO

A 38-year-old nulliparous woman with severe obesity (BMI 66) and hypertension presented with constipation, fatigue, weakness, and poor appetite that had progressively worsened over the prior two to three weeks. Upon admission, the patient was found to have significant hypercalcemia, leukocytosis, and lactic acidosis. Computed tomography (CT) scan of the chest, abdomen, and pelvis revealed an adnexal mass with extensive lesions throughout her pelvis, abdomen, and chest. An ultrasound-guided omental core biopsy was performed, which was confirmatory for metastatic ovarian small cell carcinoma. Given her poor prognosis and clinical status, chemotherapy was likely to provide minimal benefit and ultimately the patient decided to pursue a comfort-oriented plan of care and passed away on day 9 of admission.

3.
BMC Cancer ; 24(1): 499, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641594

RESUMO

BACKGROUND: Germline mutations in BRCA1 and BRCA2 genes are among the main causes of hereditary ovarian cancer. Identifying these mutations may reduce cancer risk, facilitate early detection, and enable personalized treatment. However, genetic testing is limited in the Brazilian Public Health System, and data regarding germline mutations in many regions are scarce. Therefore, the study aimed to investigate the prevalence of germline mutations in BRCA1 and BRCA2 in women with ovarian cancer treated in the Public Health System in Pernambuco, Brazil. METHODS: A cross-sectional study was conducted in the Hereditary Cancer Program from two reference oncological centers in Pernambuco. Women (n = 45) with high-grade serous ovarian cancer underwent genetic counseling and DNA sequencing for BRCA1 and BRCA2 genes. RESULTS: The prevalence of deleterious mutations in the BRCA1 and BRCA2 genes was 33%. Of the 15 germline mutations found, 13 were in BRCA1 and 2 in BRCA2; two mutations of unknown clinical significance were also found in BRCA2. Mutations c.5266dupC and c.2215 A > T were the most frequent; each was mutation observed in three patients. Additionally, the mutations c.7645dupT and c.921dupT were reported for the first time. CONCLUSION: One in three women showed a pathogenic mutation, demonstrating a significant prevalence of germline mutations in this sample. Additionally, the small sample revealed an interesting number of mutations, indicating the need to explore more regions of the country.


Assuntos
Genes BRCA2 , Neoplasias Ovarianas , Humanos , Feminino , Brasil/epidemiologia , Mutação em Linhagem Germinativa , Estudos Transversais , Saúde Pública , Predisposição Genética para Doença , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteína BRCA2/genética , Proteína BRCA1/genética
4.
Cancer Cell Int ; 24(1): 137, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627767

RESUMO

BACKGROUND: Exosomes derived from tumor cells contribute to the pathogenesis of cancers. Metformin, the most usually used drug for type 2 diabetes, has been frequently investigated for anticancer effects. Here, we examined whether metformin affects exosomes signaling in human ovary cancer cells in vitro. METHODS: Human ovary cancer cells, including A2780 and Skov3 cells, were treated with metformin for either 24-48 h. Cell viability and caspase-3 activity were determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and colorimetric assays respectively. Oil-Red-O staining and in vitro, scratch assays were used to examine cellular toxicity and wound healing rate. After treatment with metformin, exosomes were isolated from cells and quantified by acetylcholinesterase (AChE) assay, Dynamic Light Scattering (DLS), and their markers. Genes related to exosomes signaling were analyzed by real-time PCR or western blotting. RESULTS: Our results showed that metformin decreased the viability of both cells dose/time-dependently (P < 0.05). Metformin increased the activity of caspase-3 (P < 0.05) as well as the number of Oil-Red-O positive cells in both cell lines. In vitro scratch assay showed that the cell migration rate of metformin-treated cells was decreased (P < 0.05), whereas AChE activity of exosomes from metformin-treated cells was increased (P < 0.05). Concurrent with an increase in CD63 protein levels, expression of Alix, CD63, CD81, Lamp-2, and Rab27b up-regulated in treated cells (P < 0.05). CONCLUSION: Results indicated that metformin had a cytotoxic effect on ovary cancer cells and enhanced exosome biogenesis and secretion.

5.
J Gynecol Oncol ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38606823

RESUMO

OBJECTIVE: Signaling lymphocytic activation molecule family members (SLAMFs) play a critical role in immune regulation of malignancies. This study aims to investigate the prognostic value and function of SLAMFs in ovarian cancer (OC). METHODS: The expression analysis of SLAMFs was conducted based on The Cancer Genome Atlas Ovarian Cancer Collection (TCGA-OV) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was further performed on tissue arrays (n=98) to determine the expression of SLAMF7. Kaplan-Meier plotter and multivariate Cox regression model were used to evaluate the correlation of SLAMF7 expression with survival outcomes of patients. The molecular function of SLAMF7 in OC was further investigated using Gene Set Enrichment Analysis (GSEA). RESULTS: SLAMF7 mRNA expression were significantly upregulated in OC tumor tissue compared to normal tissue. IHC revealed that SLAMF7 expression was located in the interstitial parts of tumor tissue, and higher SLAMF7 expression was associated with favorable survival outcomes. GSEA demonstrated that SLAMF7 is involved immune-related pathways. Further analysis showed that SLAMF7 had a strong correlation with the T cell-specific biomarker (CD3) but not with the B cell (CD19, CD22, and CD23) and natural killer cell-specific biomarkers (CD85C, CD336, and CD337). Furthermore, IHC analysis confirmed that SLAMF7 was expressed in tumor-infiltrating T cells, and the IHC score of SLAMF7 was positively correlated with CD3 (r=0.85, p<0.001). CONCLUSION: SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC. Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.

6.
Int J Mol Sci ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38279352

RESUMO

Specifying the role of genetic mutations in cancer development is crucial for effective screening or targeted treatments for people with hereditary cancer predispositions. Our goal here is to find the relationship between a number of cancerogenic mutations and the probability of cancer induction over the lifetime of cancer patients. We believe that the Avrami-Dobrzynski biophysical model can be used to describe this mechanism. Therefore, clinical data from breast and ovarian cancer patients were used to validate this model of cancer induction, which is based on a purely physical concept of the phase-transition process with an analogy to the neoplastic transformation. The obtained values of model parameters established using clinical data confirm the hypothesis that the carcinogenic process strongly follows fractal dynamics. We found that the model's theoretical prediction and population clinical data slightly differed for patients with the age below 30 years old, and that might point to the existence of an ancillary protection mechanism against cancer development. Additionally, we reveal that the existing clinical data predict breast or ovarian cancers onset two years earlier for patients with BRCA1/2 mutations.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Humanos , Feminino , Adulto , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/epidemiologia , Mutação , Predisposição Genética para Doença , Neoplasias da Mama/genética
7.
Diagnostics (Basel) ; 13(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37892079

RESUMO

(1) Background: High-grade serous ovarian carcinoma (HGSOC) is an aggressive subtype of ovarian cancer. Recent advances have introduced prognostic markers and targeted therapies. Programmed cell death ligand 1 (PD-L1) has emerged as a potential biomarker for HGSOC, with implications for prognosis and targeted therapy eligibility; (2) Methods: A literature search was conducted on major databases, and extracted data were categorized and pooled. Subgroup analysis was performed for studies with high heterogeneity. (3) Results: Data from 18 eligible studies were categorized and pooled based on PD-L1 scoring methods, survival analysis types, and endpoints. The result showed an association between high PD-L1 expression and a favorable prognosis in progression-free survival (HR = 0.53, 95% CI = 0.35-0.78, p = 0.0015). Subgroup analyses showed similar associations in subgroups of neoadjuvant chemotherapy patients (HR = 0.6, 95% CI = 0.4-0.88, p = 0.009) and European studies (HR = 0.59, 95% CI = 0.42-0.82, p = 0.0017). In addition, subgroup analyses using data from studies using FDA-approved PD-L1 antibodies suggested a significant association between favorable prognosis and high PD-L1 expression in a subgroup including high and low stage data in overall survival data (HR = 0.46, 95% CI = 0.3-0.73, p = 0.0009). (4) Conclusions: This meta-analysis revealed a potential association between high PD-L1 expression and favorable prognosis. However, caution is warranted due to several limitations. Validation via large-scale studies, with mRNA analysis, whole tissue sections, and assessments using FDA-approved antibodies is needed.

8.
Clin Pract ; 13(5): 1137-1145, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37736938

RESUMO

Mucinous ovarian cancer occurs sporadically, with a frequency of approximately 3-5% among all subtypes of ovarian cancer. Extreme leukocytosis >40,000 and 50,000 has been described in most solid tumors and is associated with a poor prognosis, although there is a lack of literal data of its occurrence after cytoreductive surgery and HIPEC in the treatment of advanced mucinous ovarian cancer. There is higher risk of the occurrence of cholecystitis in oncology patients compared to the general population, although there is no formal evidence for this, and the association with ovarian cancer is accompanied by a relative risk of 1.38. Hypercalcemia-hyperleukocytosis is a syndrome associated with head and neck cancers, although, to our knowledge, it has not been described in mucinous ovarian cancer, especially after cytoreductive surgery and HIPEC.

9.
Discov Oncol ; 14(1): 101, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37318692

RESUMO

Serous ovarian cancer is one of the major causes of cancer related death among women worldwide. The advanced diagnosis worsens the prognosis of patients with serous ovarian cancer. The immune system has an important impact on the progression of ovarian cancer. Herein, we aimed to establish an immune related prognostic signature to assist in the early diagnosis, treatment, and prognostic evaluation of patients with serous ovarian cancer. Multiple public data sets and immune related genes were obtained from various online public databases, and immune related prognostic signatures were developed through differential expression analysis, univariate Cox proportional hazard regression analysis, and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. The nomogram model, Kaplan-Meier survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis showed that this signature had a good prediction potential. In conclusion, an immune related signature with good prediction efficiency was established through systematic bioinformatics analysis, which may play a tumor inhibition role by affecting the abundance of activated dendritic cells.

10.
Adv Biomed Res ; 12: 77, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37200756

RESUMO

Background: Tumor recurrence as one of the main causes of cancer death is a big barrier to cancer complete treatment. Various studies denote the possible role of therapeutics in tumor relapse. Cisplatin as one of the generally used chemotherapy agents is supposed to be the source of therapy resistance through formation of polyploid giant cancer cells (PGCCs). Nevertheless, the mechanisms by which PGCCs promote tumor relapse are not fully understood. Materials and Methods: In this study, we performed experimental and bioinformatic investigations to recognize the mechanisms related to cisplatin resistance. A2780 and SCOV-3 cell lines were treated with cisplatin for 72 hours and were evaluated for their morphology by fluorescent microscopy and DNA content analysis. Furthermore, a microarray dataset of cisplatin-resistant ovarian cancer cells was re-analyzed to determine the significantly altered genes and signaling pathways. Results: Although cisplatin led to death of considerable fraction of cells in both cell lines, a significant number of survived cells became polyploid. On the other hand, our high throughput analysis determined significant change in expression of 1930 genes which mainly related to gene regulatory mechanisms and nuclear processes. Besides, mTOR, hypoxia, Hippo, and 14-3-3 signaling pathways previously shown to have role in PGCCs were determined. Conclusion: Taken together, results of this study demonstrated some key biological mechanisms related to cisplatin-resistant polyploid cancer cells.

11.
J Ovarian Res ; 16(1): 92, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37170143

RESUMO

PURPOSE: The current study aimed to explore the prognosis of ovarian cancer patients in different subgroup using three prognostic research indexes. The current study aimed to build a prognostic model for ovarian cancer patients. METHODS: The study dataset was downloaded from Surveillance Epidemiology and End Results database. Accelerated Failure Time algorithm was used to construct a prognostic model for ovary cancer. RESULTS: The mortality rate in the model group was 51.6% (9,314/18,056), while the mortality rate in the validation group was 52.1% (6,358/12,199). The current study constructed a prognostic model for ovarian cancer patients. The C indexes were 0.741 (95% confidence interval: 0.731-0.751) in model dataset and 0.738 (95% confidence interval: 0.726-0.750) in validation dataset. Brier score was 0.179 for model dataset and validation dataset. The C indexes were 0.741 (95% confidence interval: 0.733-0.749) in bootstrap internal validation dataset. Brier score was 0.178 for bootstrap internal validation dataset. CONCLUSION: The current research indicated that there were significant differences in the survival benefits of treatments among ovarian cancer patients with different stages. The current research developed an individual mortality risk predictive system that could provide valuable predictive information for ovarian cancer patients.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Prognóstico , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/patologia , Algoritmos
12.
Int J Mol Sci ; 24(7)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37047678

RESUMO

Familial cancer syndromes, which are commonly caused by germline mutations in oncogenes and tumor suppressor genes, are generally considered to be the cause of primary multiple malignant neoplasias (PMMNs). Using targeted genomic sequencing, we screened for eight germline mutations: BRCA1 185delAG, BRCA1 T300G, BRCA1 2080delA, BRCA1 4153delA, BRCA1 5382insC, BRCA2 6174delT, CHEK2 1100delC, and BLM C1642T, which provoke the majority of cases of hereditary breast and ovary cancer syndrome (HBOC), in genomic (blood) DNA from 60 women with PMMNs, including breast (BC) and/or ovarian cancer(s) (OC). Pathogenic allelic forms were discovered in nine samples: in seven instances, it was BRCA1 5382insC, and in the following two, BRCA1 4153delA and BRCA1 T300G. The age of onset in these patients (46.8 years) was younger than in the general Russian population (61.0) for BC but was not for OC: 58.3 and 59.4, correspondingly. There were invasive breast carcinomas of no special type and invasive serous ovarian carcinomas in all cases. Two or more tumors of HBOC-spectrum were only in five out of nine families of mutation carriers. Nevertheless, every mutation carrier has relatives who have developed malignant tumors.


Assuntos
Neoplasias da Mama , Neoplasias Primárias Múltiplas , Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias da Mama/patologia , Alelos , Neoplasias Primárias Múltiplas/genética , Proteína BRCA2/genética , Mutação , Predisposição Genética para Doença
13.
J Gastrointest Cancer ; 54(1): 264-267, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34799819

RESUMO

BACKGROUND: Krukenberg tumors are among rare cases of metastatic ovary cancers. They are presented as a solid mass which generally has bilateral and sometimes cystic components and is also known through symptoms related to the mass effect and/or hormonal imbalance. However, they may present findings before the primary tumor or remain asymptomatic for a long time. CASE REPORT: We presented a patient, who was diagnosed with gallbladder cancer nine years ago and whose adjuvant treatment was completed, applied to the outpatient clinic with the complaint of vaginal bleeding. Surgery was recommended to the patient and the patient was diagnosed with metastatic signet ring cell gallbladder cancer. The patient was started on gemcitabine-capecitabine treatment after surgery. CONCLUSION: The case is important both due to the rareness of metastasis of gall bladder cancer on the ovaries and also the detection of metastasis following the nine-year recurrence-free period. This case shows that routine controls including a careful gynecological examination in a patient primarily detected to have gastrointestinal malignity are important for recognizing late metastases.


Assuntos
Neoplasias da Vesícula Biliar , Tumor de Krukenberg , Neoplasias Ovarianas , Feminino , Humanos , Tumor de Krukenberg/diagnóstico , Tumor de Krukenberg/cirurgia , Tumor de Krukenberg/patologia , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Diagnóstico Diferencial
14.
Eur J Cancer Care (Engl) ; 31(6): e13760, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36281480

RESUMO

OBJECTIVE: This study aimed to identify the relationships among sexual function, marital intimacy, type D personality and quality of life (QoL) in patients with ovarian cancer, with spouses. METHODS: A descriptive cross-sectional design was used, and 104 patients were recruited using convenience sampling, from the inpatient and outpatient gynaecological clinics of two tertiary medical centres using structured questionnaires. RESULTS: Of the 104 participants, 31.7% were classified as having a type D personality. The type D group had lower marital intimacy, higher symptoms and lower QoL than the non-type D personality group. The results of a hierarchical regression analysis showed that monthly income, symptoms, marital intimacy and type D personality were independent factors that influenced QoL in patients with ovarian cancer, with spouses. CONCLUSION: Demographic characteristics, symptoms, marital intimacy and type D personality should be considered in patients with ovarian cancer, with spouses when evaluating QoL. Intervention strategies considering these characteristics could improve QoL for patients with ovarian cancer patient, with spouses.


Assuntos
Neoplasias Ovarianas , Cônjuges , Humanos , Feminino , Qualidade de Vida , Estudos Transversais , Personalidade
15.
Int J Mol Med ; 50(5)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36102296

RESUMO

The Aurora kinases, including Aurora A, B and C, play critical roles in cell division. They have been found overexpressed in a number of types of cancer and may thus be potential targets in cancer therapy. Several Aurora kinase inhibitors have been identified and developed. Some of these have been used in clinical trials and have exhibited certain efficacy in cancer treatment. However, none of these has yet been applied clinically due to the poor outcomes. Oxostephanine is an aporphine alkaloid isolated from several plants of the genus Stephania. This compound has been reported to inhibit Aurora kinase activity in kinase assays and in cancer cells. The present study aimed to investigate the real­time effects of oxostephanine extracted from Stephania dielsiana Y.C. Wu leaves on the growth of an ovarian cancer cell line (OVCAR­8, human ovarian carcinoma); these effects were compared to those of the well­known Aurora kinase inhibitor, VX­680. The effects of oxostephanine on stromal cells, as well as endothelial cells were also examined. The results demonstrated that oxostephanine was an Aurora kinase inhibitor through the prevention of histone H3 phosphorylation at serine 10, the mislocalization of Aurora B and the induction of aneuploidy. Moreover, this substance was selectively cytotoxic to human umbilical vein endothelial cells (hUVECs), whereas it was less cytotoxic to human fibroblasts and umbilical cord­derived mesenchymal stem cells. In addition, this compound significantly attenuated the migration and tube formation ability of hUVECs. Taken together, the present study demonstrates that oxostephanine plays dual roles in inhibiting Aurora kinase activity and angiogenesis. Thus, it may have potential for use as a drug in cancer treatment.


Assuntos
Antineoplásicos , Células Endoteliais , Antineoplásicos/farmacologia , Humanos , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases
16.
J Pharm Pract ; : 8971900221129679, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36148892

RESUMO

Objective: To evaluate the effectiveness of hormonal therapy (HT) in patients with recurrent adult ovary granulosa cell tumors. Methods: The clinical and treatments features of the patients who received HT were studied retrospectively. The efficacy and safety of HT were evaluated. The Kaplan-Meier technique was used to conduct survival analysis. Results: The research involved a total of thirteen patients. The median age of the participants was 49 years (range: 34-61). Since diagnosis, the median number of surgeries has been three (range: 2-8). At least one chemotherapy regimen has been administered to 12 (92.3%) patients. Ten of the patients (76.9%) had at least two metastatic areas. Lung metastases were found in two (15.4%) of the patients. Inhibin B levels were elevated in 81.2% of patients before hormone treatment. The patients received different HTs (Leuprolide acetate + anastrozole-three patients, leuprolide acetate + tamoxifen-six patients, only anastrozole-three patients, only tamoxifen-one patients). The median progression-free survival was found 17.7 months (95 % CI: 14.7-20.6). In four (33.4%) patients, an overall response (complete or partial) was identified. A stable response was observed in eight (66.7%) patients. Conclusions: HT is effective in pretreated individuals with recurrent ovarian granulosa cell tumors, according to this research. Despite the limited number of patients and treatment variability, disease control was achieved in all patients. Also, we found that Inhibin B levels were associated with treatment response.

17.
Foods ; 11(16)2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36010518

RESUMO

There is recent interest in a diet that can be recommended for patients suffering from cancer. In this respect, the effects were studied of the extracts of several common fruits, herbs and vegetables on the viability of two human ovary cancer cell lines (SKOV-3 and PEO1) in vitro. Normal human MRC-5 fibroblasts were used as a control cell line. The extracts of garlic, horseradish and curly kale as well as green and black tea were the most effective in lowering the viability of ovarian cancer cells, while not affecting the viability of MRC-5 fibroblasts. Except for garlic and horseradish, the cytotoxic effects of the extracts correlated with their polyphenol content. The examination of changes in the content of ATP and glutathione, in the level of reactive oxygen species, mitochondrial potential and mitochondrial mass did not show a consistent pattern, suggesting that various extracts may act via different mechanisms. Although the extracts' toxicity to cells in vitro is a first and direct suggestion concerning their possible anticancer effects in vivo, these results point to potential vegetable candidates to become diet components recommended for ovary cancer patients.

18.
Epigenomics ; 14(14): 865-886, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35872653

RESUMO

Ovarian cancer is the most lethal gynecological malignancy in women. The phenotype is characterized by delayed diagnosis, recurrence and drug resistance. Inherent immunogenicity potential, oncogenic function and expression of cancer-testis/germline antigen (CTA) in ovarian cancer render them a potential candidate for immunotherapy. Revolutionary clinical findings indicate that tumor antigen-mediated T-cell and dendritic cell-based immunotherapeutic approaches provide an excellent strategy for targeting tumors. Currently, dendritic cell vaccination for the treatment of B-cell lymphoma and CTA-based T-cell receptor transduced T-cell therapy involving MAGE-A4 and NY-ESO-1 are well documented and shown to be effective. This review highlighted the mechanical aspects of epigenetic drugs that can elicit a CTA-based humoral and cellular immune response and implicate T-cell and dendritic cell-based immunotherapeutic approaches.


Despite substantial advancements in prognosis and diagnostic approaches, epithelial ovarian cancer is still the most lethal gynecological malignancy worldwide. In addition to radiotherapy, chemotherapy, hormonal therapy, and surgery, immunotherapy in the clinical setting is promising. Tumor-restricted expression and strong immunogenic potential make cancer-testis/germline antigen (CTA) a potential candidate for efficient T-cell and dendritic cell-mediated cancer immunotherapy. The expression of CTAs is shown to be modulated by a specific epigenetic fine-tuning mechanism. However, the expression and role of CTA in epithelial ovarian cancer immunotherapy are poorly understood. Therefore, in the current work, the authors thoroughly highlight and explore the possible epigenetic mechanisms associated with CTA expression and their implication in T-cell and dendritic cell-based immunotherapy approaches to ovarian cancer. Understanding such a paradigm is essential to adopting a precision medicine approach for better therapeutic options.


Assuntos
Neoplasias Ovarianas , Testículo , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Carcinoma Epitelial do Ovário/genética , Epigênese Genética , Feminino , Humanos , Imunoterapia , Masculino , Proteínas de Membrana/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia
19.
Cancers (Basel) ; 13(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34572914

RESUMO

This study reports the HMGB1 interactomes in prostate and ovary cancer cells lines. Affinity purification coupled to mass spectrometry confirmed that the HMGB1 nuclear interactome is involved in HMGB1 known functions such as maintenance of chromatin stability and regulation of transcription, and also in not as yet reported processes such as mRNA and rRNA processing. We have identified an interaction between HMGB1 and the NuRD complex and validated this by yeast-two-hybrid, confirming that the RBBP7 subunit directly interacts with HMGB1. In addition, we describe for the first time an interaction between two HMGB1 interacting complexes, the septin and THOC complexes, as well as an interaction of these two complexes with Rab11. Analysis of Pan-Cancer Atlas public data indicated that several genes encoding HMGB1-interacting proteins identified in this study are dysregulated in tumours from patients diagnosed with ovary and prostate carcinomas. In PC-3 cells, silencing of HMGB1 leads to downregulation of the expression of key regulators of ribosome biogenesis and RNA processing, namely BOP1, RSS1, UBF1, KRR1 and LYAR. Upregulation of these genes in prostate adenocarcinomas is correlated with worse prognosis, reinforcing their functional significance in cancer progression.

20.
Dokl Biochem Biophys ; 497(1): 144-150, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33895931

RESUMO

Ovarian cancer is the malignant tumour of the female reproductive organ with highest mortality rate among all the types of gynaecological tumours. This study investigated the effect of Dioscorea deltoidea leaf extract (DDLE) on OV-90 and CAOV4 ovarian cancer cells. The results demonstrated that DDLE suppresses OV-90 and CAOV3 cell viability significantly in dose dependent manner. The OV-90 and CAOV3 cell viability were reduced to 24 and 27% respectively with 20 mg/mL DDLE treatment. Five mg/mL DDLE treatment of OV-90 and CAOV4 cells raised percentage of cells in G2-phase to 55.9 and 51.2%, respectively. In 5 mg/mL DDLE -treated OV-90 and CAOV4 cells a prominent suppression in cyclin-D1 and cyclin B1 proteins was observed in 48 h. The DDLE treatment promoted OV-90 and CAOV3 cell apoptosis to 34.65 and 29.89%, respectively. The Fas, FasL, cleaved caspase-3, and Bax levels were up-regulated markedly in the cells after DDLE treatment. Moreover, DDLE treatment suppressed p-mTOR, p-AKT and p-PI3K expression in OV-90 and CAOV3 cells. Thus, DDLE suppressed ovary cancer cell viability and elevated cell apoptosis. Inhibitory effect of DDLE on ovarian cancer cells is associated with targeting PI3K/AKT/mTOR pathway.


Assuntos
Dioscorea/química , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Folhas de Planta/química , Regulação para Cima/efeitos dos fármacos
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