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Journal For Immunotherapy of Cancer Nov 2023The presence of T cells and suppressive myeloid cells in epithelial ovarian cancer (EOC) correlate with good and bad clinical outcome, respectively. This suggests that...
BACKGROUND
The presence of T cells and suppressive myeloid cells in epithelial ovarian cancer (EOC) correlate with good and bad clinical outcome, respectively. This suggests that EOC may be sensitive to adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL), provided that immunosuppression by myeloid-derived suppressor cells and M2 macrophages is reduced. Platinum-based chemotherapy can alleviate such immunosuppression, potentially creating a window of opportunity for T cell-based immunotherapy.
METHODS
We initiated a phase I/II trial (NCT04072263) in patients with recurrent platinum-sensitive EOC receiving TIL during platinum-based chemotherapy. TILs were administered 2 weeks after the second, third and fourth chemotherapy course. Patients were treated in two cohorts with or without interferon-α (IFNa), as conditioning and TIL support regimen. The primary endpoint was to evaluate the feasibility and safety according to CTCAE V.4.03 criteria and the clinical response and immune modulatory effects of this treatment were evaluated as secondary endpoints.
RESULTS
Sixteen patients were enrolled. TIL could be successfully expanded for all patients. TIL treatment during chemotherapy without IFNa (n=13) was safe but the combination with IFNa added to the chemotherapy-induced toxicity with 2 out of 3 patients developing thrombocytopenia as dose-limiting toxicity. Fourteen patients completed treatment with a full TIL cycle and were further evaluated for clinical and immunological response. Platinum-based chemotherapy resulted in reduction of circulating myeloid cell numbers and IL-6 plasma levels, confirming its immunosuppression-alleviating effect. Three complete (CR), nine partial responses and two stable diseases were recorded, resulting in an objective response rate of 86% (Response Evaluation Criteria In Solid Tumors V.1.1). Interestingly, progression free survival that exceeded the previous platinum-free interval was detected in two patients, including an exceptionally long and ongoing CR in one patient that coincided with sustained alleviation of immune suppression.
CONCLUSION
TIL therapy can be safely combined with platinum-based chemotherapy but not in combination with IFNa. The chemotherapy-mediated reduction in immunosuppression and the increase in platinum-free interval for two patients warrants further exploration of properly-timed TIL infusions during platinum-based chemotherapy, possibly further benefiting from IL-2 support, as a novel treatment option for EOC patients.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; T-Lymphocytes; Platinum; Lymphocytes, Tumor-Infiltrating; Ovarian Neoplasms
PubMed: 37949617
DOI: 10.1136/jitc-2023-007697 -
Reviews in Endocrine & Metabolic... Apr 2022This comprehensive review aimed to evaluate the relationship between SARS-CoV-2 infection (the cause of coronavirus disease 2019, or COVID-19) and the metabolic and... (Review)
Review
This comprehensive review aimed to evaluate the relationship between SARS-CoV-2 infection (the cause of coronavirus disease 2019, or COVID-19) and the metabolic and endocrine characteristics frequently found in women with polycystic ovary syndrome (PCOS). In the general population, COVID-19 is more severe in subjects with dyslipidemia, obesity, diabetes mellitus, and arterial hypertension. Because these conditions are comorbidities commonly associated with PCOS, it was hypothesized that women with PCOS would be at higher risk for acquiring COVID-19 and developing more severe clinical presentations. This hypothesis was confirmed in several epidemiological studies. The present review shows that women with PCOS are at 28%-50% higher risk of being infected with the SARS-CoV-2 virus at all ages and that, in these women, COVID-19 is associated with increased rates of hospitalization, morbidity, and mortality. We summarize the mechanisms of the higher risk of COVID-19 infection in women with PCOS, particularly in those with carbohydrate and lipid abnormal metabolism, hyperandrogenism, and central obesity.
Topics: COVID-19; Female; Humans; Hyperandrogenism; Insulin Resistance; Polycystic Ovary Syndrome; SARS-CoV-2
PubMed: 35218458
DOI: 10.1007/s11154-022-09715-y -
Cancer Dec 2019Ovarian cancer is one of the most challenging diseases in gynecologic oncology. The presentation of frequent recurrences requires the establishment and further... (Review)
Review
Ovarian cancer is one of the most challenging diseases in gynecologic oncology. The presentation of frequent recurrences requires the establishment and further development of therapy standards for this patient group. Surgery is crucial in the therapy of patients with primary ovarian cancer, and the postoperative residual tumor mass is the most relevant clinical prognostic factor. The surgical management of recurrent disease is still subject to an emotional international discussion. Only a few prospective clinical trials focused on the effects of surgery in relapsed ovarian cancer have been published. The available data show improvements in the prognosis due to complete cytoreduction in the setting of recurrence. However, the selection of eligible patients is the essential issue. Therefore, the establishment of reliable predictive factors for complete tumor resection as well as a definition of the group of patients who might profit from this approach remains a field for research. Further randomized trials designed to develop and incorporate operative standards for recurrent ovarian cancer should follow.
Topics: Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms
PubMed: 31967681
DOI: 10.1002/cncr.32511 -
BMC Complementary Medicine and Therapies Dec 2023Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include hyperandrogenemia and polycystic ovarian changes. Bailing capsule (BL), a proprietary Chinese medicine that contains fermented Cordyceps sinensis powder, has been applied to treat PCOS. However, the specific active ingredients of BL and its mechanisms of action are yet to be elucidated.
METHODS
Initially, the effectiveness of BL on PCOS model mice was evaluated. Subsequently, the active ingredients of BL were searched in the TCMSP and TCM Systems Pharmacology databases, and their targets were predicted using Swiss Target Prediction and SEA databases. Furthermore, the GEO gene database was used to screen for differentially expressed genes (DEGs) related to PCOS. Data from Gene Card, OMIM, DDT, and Drugbank databases were then combined to establish a PCOS disease gene library. Cross targets were imported into the STRING database to construct a protein-protein interaction network. In addition, GO and KEGG pathway enrichment analyses were performed using Metascape and DAVID databases and visualized using Cytoscape software and R 4.2.3. The core targets were docked with SYBYL-X software, and their expressions in PCOS mice were further verified using qPCR.
RESULTS
The core active ingredients of BL were identified to be linoleyl acetate, cholesteryl palmitate, arachidonic acid, among others. Microarray data sets from four groups containing disease and normal samples were obtained from the GEO database. A total of 491 DEGs and 106 drug-disease cross genes were selected. Estrous cycle and ovarian lesions were found to be improved in PCOS model mice following BL treatment. While the levels of testosterone, progesterone, and prolactin decreased, that of estradiol increased. qPCR findings indicated that the expressions of JAK2, PPARG, PI3K, and AKT1 were upregulated, whereas those of ESR1 and IRS1 were downregulated in PCOS model mice. After the administration of BL, the expressions of associated genes were regulated. This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways.
DISCUSSION
This research clarified the multicomponent, multitarget, and multichannel action of BL and provided a theoretical reference for further investigations on its pharmacological basis and molecular mechanisms against PCOS.
Topics: Female; Humans; Animals; Mice; Polycystic Ovary Syndrome; Network Pharmacology; Ovarian Cysts; PPAR gamma; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Ovarian Neoplasms; Computational Biology
PubMed: 38102584
DOI: 10.1186/s12906-023-04280-6 -
Problemy Endokrinologii Feb 2022Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder caused by both genetic and epigenetic factors. Depending on the period of a woman's life, the clinical...
Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder caused by both genetic and epigenetic factors. Depending on the period of a woman's life, the clinical picture, diagnosis, and treatment tactics of the disease are different. PCOS has a complex of reproductive, metabolic and psychological characteristics. The target audience of these clinical recommendations are obstetrician-gynecologists, endocrinologists, general practitioners, general practitioners. In these clinical guidelines, all information is ranked according to the level of persuasiveness of recommendations and the reliability of evidence, depending on the number and quality of studies on this issue.
Topics: Endocrinologists; Female; Humans; Polycystic Ovary Syndrome; Reproducibility of Results
PubMed: 35488762
DOI: 10.14341/probl12874 -
Cancer Medicine Mar 2023We investigated risk factors influencing the outcome of unexpected ovarian carcinomas. (Review)
Review
BACKGROUND
We investigated risk factors influencing the outcome of unexpected ovarian carcinomas.
METHODS
We reviewed the ovarian carcinoma patients treated at atertiary medical institution between 2000 and 2017 and analyze the clinico-pathological characteristics, treatment strategies, recurrence status, and outcome.
RESULTS
A total of 112 women (65 primary laparoscopic surgery [LSC] and 47 laparotomic surgery [LAPA]) were included in the analysis. The LSC group had smaller ovarian tumors (10.5 ± 7.3 cm vs. 16.6 ± 8.7 cm, p = 0.031) and higher incidence of subsequent staging surgery (56.9% vs. 25.5%, p = 0.0001) compared to the LAPA group. There were 98/112 (86.6%) of early stages (I/II) diseases. The difference between the recurrent rate (27.7% vs. 31.9%), disease-free survival (DFS), and overall survival (OS) were not significant among surgical groups. In the multivariate analysis, FIGO stage (stage II hazard ratio [HR] 6.61, p = 0.007; stage III HR 8.40, p = 0.002) was the only prognostic factor for DFS. FIGO stage (stage II HR 20.78, p = 0.0001; stage III HR 7.99, p = 0.017), histological type (mucinous HR 12.49, p = 0.036), and tumor grade (grade 3 HR 35.01, p = 0.003) were independent prognostic factors for OS, while women with latency >28 days from primary to staging surgery had significantly poorer OS (p = 0.008). Women with latency >28 days between primary surgery and adjuvant chemotherapy had similar DFS (p = 0.31) and a trend of poorer OS (p = 0.064).
CONCLUSIONS
The prognosis of unexpected ovarian cancer is independent from the primary surgical procedure and comprehensive staging surgery should be performed at close proximity after the diagnosis of unexpected ovarian malignancy.
Topics: Humans; Female; Prognosis; Neoplasm Staging; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Disease-Free Survival; Retrospective Studies
PubMed: 36366751
DOI: 10.1002/cam4.5415 -
Reproductive Sciences (Thousand Oaks,... Jan 2023Polycystic ovarian syndrome is an utmost communal endocrine, psychological, reproductive, and metabolic disorder that occurs in women of reproductive age with extensive... (Review)
Review
Polycystic ovarian syndrome is an utmost communal endocrine, psychological, reproductive, and metabolic disorder that occurs in women of reproductive age with extensive range of clinical manifestations. This may even lead to long-term multiple morbidities including obesity, diabetes mellitus, insulin resistance, cardiovascular disease, infertility, cerebrovascular diseases, and ovarian and endometrial cancer. Women affliction from PCOS in midst assemblage of manifestations allied with menstrual dysfunction and androgen exorbitance, which considerably affects eminence of life. PCOS is recognized as a multifactorial disorder and systemic syndrome in first-degree family members; therefore, the etiology of PCOS syndrome has not been copiously interpreted. The disorder of PCOS comprehends numerous allied health conditions and has influenced various metabolic processes. Due to multifaceted pathophysiology engaging several pathways and proteins, single genetic diagnostic tests cannot be supportive to determine in straight way. Clarification of cellular and biochemical pathways and various genetic players underlying PCOS could upsurge our consideration of pathophysiology of this syndrome. It is requisite to know pathophysiological relationship between biomarker and their reflection towards PCOS disease. Biomarkers deliver vibrantly and potent ways to apprehend the spectrum of PCOS with applications in screening, diagnosis, characterization, and monitoring. This paper relies on the endeavor to point out many candidates as potential biomarkers based on omics technologies, thus highlighting correlation between PCOS disease with innovative technologies. Therefore, the objective of existing review is to encapsulate more findings towards cutting-edge advances in prospective use of biomarkers for PCOS disease. Discussed biomarkers may be fruitful in guiding therapies, addressing disease risk, and predicting clinical outcomes in future.
Topics: Female; Humans; Polycystic Ovary Syndrome; Multiomics; Infertility; Insulin Resistance; Biomarkers
PubMed: 35084716
DOI: 10.1007/s43032-022-00863-9 -
Journal of the American Heart... Mar 2023Background Cardiometabolic diseases are highly comorbid, but their relationship with female-specific or overwhelmingly female-predominant health conditions (breast...
Background Cardiometabolic diseases are highly comorbid, but their relationship with female-specific or overwhelmingly female-predominant health conditions (breast cancer, endometriosis, pregnancy complications) is understudied. This study aimed to estimate the cross-trait genetic overlap and influence of genetic burden of cardiometabolic traits on health conditions unique to women. Methods and Results Using electronic health record data from 71 008 ancestrally diverse women, we examined relationships between 23 obstetrical/gynecological conditions and 4 cardiometabolic phenotypes (body mass index, coronary artery disease, type 2 diabetes, and hypertension) by performing 4 analyses: (1) cross-trait genetic correlation analyses to compare genetic architecture, (2) polygenic risk score-based association tests to characterize shared genetic effects on disease risk, (3) Mendelian randomization for significant associations to assess cross-trait causal relationships, and (4) chronology analyses to visualize the timeline of events unique to groups of women with high and low genetic burden for cardiometabolic traits and highlight the disease prevalence in risk groups by age. We observed 27 significant associations between cardiometabolic polygenic scores and obstetrical/gynecological conditions (body mass index and endometrial cancer, body mass index and polycystic ovarian syndrome, type 2 diabetes and gestational diabetes, type 2 diabetes and polycystic ovarian syndrome). Mendelian randomization analysis provided additional evidence of independent causal effects. We also identified an inverse association between coronary artery disease and breast cancer. High cardiometabolic polygenic scores were associated with early development of polycystic ovarian syndrome and gestational hypertension. Conclusions We conclude that polygenic susceptibility to cardiometabolic traits is associated with elevated risk of certain female-specific health conditions.
Topics: Humans; Female; Diabetes Mellitus, Type 2; Coronary Artery Disease; Polycystic Ovary Syndrome; Risk Factors; Phenotype
PubMed: 36846987
DOI: 10.1161/JAHA.121.026561 -
Frontiers in Immunology 2023In recent years, there has been a significant increase in the concomitant incidence of Hashimoto's thyroiditis (HT) and polycystic ovary syndrome (PCOS), both in terms... (Review)
Review
In recent years, there has been a significant increase in the concomitant incidence of Hashimoto's thyroiditis (HT) and polycystic ovary syndrome (PCOS), both in terms of incidence, etiology, and clinical consequences. PCOS patients suffering from autoimmune thyroid diseases show insulin resistance, impaired glucose tolerance, weight gain, and metabolic and reproductive complications. Studies have shown that chronic stress and its consequence, i.e. oxidative stress, play an important role in the pathomechanism of both disorders. It has also been shown that long-term exposure to stress triggers biological mechanisms, in particular related to the regulation of the inflammatory cascade, which plays a key role in autoimmune diseases. The paper is a review of the literature on the role of chronic stress, oxidative stress, and immune processes in the pathogenesis of HT and PCOS. In addition, the review is a source of knowledge about the treatment of these diseases, and in particular the use of antioxidants in therapeutic management.
Topics: Female; Humans; Polycystic Ovary Syndrome; Immune System Diseases; Oxidative Stress; Autoimmune Diseases; Hashimoto Disease
PubMed: 37588599
DOI: 10.3389/fimmu.2023.1211231 -
Journal of Ovarian Research Mar 2024Mesonephric-like adenocarcinoma is a new class of rare subtypes of the female reproductive system. Its clinical symptoms are similar to other types of ovarian tumors....
Mesonephric-like adenocarcinoma is a new class of rare subtypes of the female reproductive system. Its clinical symptoms are similar to other types of ovarian tumors. The diagnosis is based on pathological and immunohistochemical methods. The main treatment option is surgery combined with chemotherapy. Few cases have been reported at home and abroad. We reported a case of a 45-year-old woman with a cystic solid mass in the left adnexa. The postoperative pathological diagnosis was mesonephric-like adenocarcinoma of the left ovary and mature cystic teratoma (partial infiltration of the small intestine). This case had no specific clinical symptoms. Immunohistochemical findings showed positive results of GATA3, TTF1, CD10, ER, and PR. Paclitaxel and carboplatin chemotherapy were given after the operation. Currently, no specific criteria are available for diagnosis and treatment of the disease. This article aims to improve the understanding of clinicians in this disease and create a basis for clinical diagnosis and treatment.
Topics: Female; Humans; Middle Aged; Ovarian Neoplasms; Adenocarcinoma; Pelvis; Carboplatin
PubMed: 38444000
DOI: 10.1186/s13048-024-01383-7