177 results found
Ahmed-Salim Y, Galazis N, Bracewell-Milnes T, et al., 2021, The application of metabolomics in ovarian cancer management: a systematic review., Int J Gynecol Cancer, Vol: 31, Pages: 754-774
Metabolomics, the global analysis of metabolites in a biological specimen, could potentially provide a fast method of biomarker identification for ovarian cancer. This systematic review aims to examine findings from studies that apply metabolomics to the diagnosis, prognosis, treatment, and recurrence of ovarian cancer. A systematic search of English language publications was conducted on PubMed, Science Direct, and SciFinder. It was augmented by a snowball strategy, whereby further relevant studies are identified from reference lists of included studies. Studies in humans with ovarian cancer which focus on metabolomics of biofluids and tumor tissue were included. No restriction was placed on the time of publication. A separate review of targeted metabolomic studies was conducted for completion. Qualitative data were summarized in a comprehensive table. The studies were assessed for quality and risk of bias using the ROBINS-I tool. 32 global studies were included in the main systematic review. Most studies applied metabolomics to diagnosing ovarian cancer, within which the most frequently reported metabolite changes were a down-regulation of phospholipids and amino acids: histidine, citrulline, alanine, and methionine. Dysregulated phospholipid metabolism was also reported in the separately reviewed 18 targeted studies. Generally, combinations of more than one significant metabolite as a panel, in different studies, achieved a higher sensitivity and specificity for diagnosis than a single metabolite; for example, combinations of different phospholipids. Widespread metabolite differences were observed in studies examining prognosis, treatment, and recurrence, and limited conclusions could be drawn. Cellular processes of proliferation and invasion may be reflected in metabolic changes present in poor prognosis and recurrence. For example, lower levels of lysine, with increased cell invasion as an underlying mechanism, or glutamine dependency of rapidly proliferating c
Jones BP, Saso S, Yazbek J, et al., 2021, Uterine Transplantation: Scientific Impact Paper No. 65 April 2021., BJOG
Barcroft JF, Galazis N, Jones BP, et al., 2021, Fertility treatment and cancers-the eternal conundrum: a systematic review and meta-analysis., Human Reproduction, Vol: 36, Pages: 1093-1107, ISSN: 0268-1161
STUDY QUESTION: Does fertility treatment (FT) significantly increase the incidence of breast, ovarian, endometrial or cervical cancer? SUMMARY ANSWER: Overall, FT does not significantly increase the incidence of breast, ovarian or endometrial cancer and may even reduce the incidence of cervical cancer. WHAT IS KNOWN ALREADY: Infertility affects more than 14% of couples. Infertility and nulliparity are established risk factors for endometrial, ovarian and breast cancer, yet the association with FT is more contentious. STUDY DESIGN, SIZE, DURATION: A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to December 2019. Peer-reviewed studies stating cancer incidence (breast, ovarian, endometrial or cervical) in FT and no-FT groups were identified. Out of 128 studies identified, 29 retrospective studies fulfilled the criteria and were included (n = 21 070 337). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the final meta-analysis, 29 studies were included: breast (n = 19), ovarian (n = 19), endometrial (n = 15) and cervical (n = 13), 17 studies involved multiple cancer types and so were included in each individual cancer meta-analysis. Primary outcome of interest was cancer incidence (breast, ovarian, endometrial and cervical) in FT and no-FT groups. Secondary outcome was cancer incidence according to specific fertility drug exposure. Odds ratio (OR) and random effects model were used to demonstrate treatment effect and calculate pooled treatment effect, respectively. A meta-regression and eight sub-group analyses were performed to assess the impact of the following variables, maternal age, infertility, study size, outliers and specific FT sub-types, on cancer incidence. MAIN RESULTS AND THE ROLE OF CHANCE: Cervical cancer incidence was significantly lower in the FT group compared with the no-FT group: OR 0.68 (95% CI 0.46-0.99). The incidences
Ahmed-Salim Y, Saso S, Meehan H, et al., 2021, A novel application of calcium electroporation to cutaneous manifestations of gynaecological cancer, European Journal of Gynecological Oncology, ISSN: 0392-2936
Introduction: Calcium electroporation (CaEP) is a new technique whereby intracellular concentrations of calcium are elevated by transient permeabilisation of the cell membrane using high-voltage electrical pulses. Tumour necrosis is induced with little damage to healthy tissue. Within gynaecological cancer, vulval cancer and vulval intraepithelial neoplasia (VIN) pose challenges for treatment, given the high recurrence rate, persistent symptoms and repeated resections required. In certain cases, CaEP may provide a suitable alternative.Methods: We present a case series of six patients with recurrent vulval squamous cell carcinoma(n=2), VIN III (n=2) and metastatic ovarian cancer (n=2), five of whom were treated with CaEP. This is the first known application of CaEP to gynaecological cancers .Results: The median follow-up time was 14 months (range 2-18 months). Within the cohort of patients, CaEP was applied a total of 10 times, achieving a complete response five times and partial response four times. Symptoms improved within six weeks for eight episodes following CaEP application. Beyond six weeks, symptoms eventually recurred in all patients and four patients required more than one CaEP procedure. CaEP was useful for palliation of distressing symptoms in one case of metastatic ovarian cancer. No intra-operative or post-operative complications have been reported to date. Conclusion: CaEP may be a promising short-term treatment in selected patients with recurrent VIN and vulval cancer, where other treatments had failed. If validated, it could provide an acceptable alternative where surgery is unacceptable. Long term follow-up is required to evaluate effects on recurrence.
Sundar S, Manchanda R, Gourley C, et al., 2021, British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for germline and tumor testing for BRCA1/2 variants in ovarian cancer in the United Kingdom, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 31, Pages: 272-278, ISSN: 1048-891X
Jones BP, Rajamanoharan A, Vali S, et al., 2021, Perceptions and Motivations for Uterus Transplant in Transgender Women, JAMA NETWORK OPEN, Vol: 4, ISSN: 2574-3805
Natoli M, Gallon J, Lu H, et al., 2021, Transcriptional analysis of multiple ovarian cancer cohorts reveals prognostic and immunomodulatory consequences of ERV expression, Journal for ImmunoTherapy of Cancer, Vol: 9, ISSN: 2051-1426
Background Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC). Here, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC.Methods ERV expression was assessed using EOC transcriptional data from The Cancer Genome Atlas (TCGA) and from an independent cohort (Hammersmith Hospital, HH), as well as from untreated or DNMTi-treated EOC cell lines. Least absolute shrinkage and selection operator (LASSO) logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro, using EOC cell lines and patient-derived tumor cells.Results ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+T cells (r=0.46, p=0.0001). In the TCGA dataset, a higher ERV score was found in BRCA1/2 mutant tumors, compared to wild type (p=0.015), while a lower ERV score was found in CCNE1 amplified tumors, compared to wild type (p=0.019). In vitro, baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of an ERV expression threshold by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells.Conclusions These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence
Jones BP, Rajamanoharan A, Williams NJ, et al., 2021, Uterine Transplantation Using Living Donation: A Cross-sectional Study Assessing Perceptions, Acceptability, and Suitability, Transplantation Direct
Background. A uterine transplantation is a nonvital, quality-of-life-enhancing solid organ transplant. Given improvements in donor risk profile and the anticipated shortage of suitable deceased donors, nondirected donation could facilitate sustainability as uterine transplantation moves from research into the clinical realm. The aim of this article is to determine perceptions and identify motivations of potential nondirected living uterus donors and assess acceptability and suitability. Methods. A cross-sectional survey using an electronic questionnaire among women who have inquired about donating their uterus for uterine transplantation. Results. The majority of respondents "strongly agreed" or "agreed" that the most prevalent motivations to donate their uterus include helping someone carry and give birth to their own baby (n = 150; 99%), helping others (n = 147; 97%), and because they no longer need their womb (n = 147; 97%). After considering risks of uterus donation, the majority were still keen to donate their uterus (n = 144; 95%), but following a process of exclusion using donor selection criteria, less than a third (n = 42; 29%) were found to be suitable to proceed. Conclusions. This study demonstrates novel insight into the motivations of women who wish to donate their uterus and displays high levels of acceptability after consideration of the risks involved. Despite the physical risk and transient impact upon ability to undertake activities of daily living, women who donate their uterus expect to gain psychological and emotional benefits from enabling another woman to gestate and give birth to their own future children. However, currently used selection criteria reduce the number of potential donors significantly.
Jones BP, Kasaven L, Vali S, et al., 2020, Uterine Transplantation; Review of Livebirths and Reproductive Implications., Transplantation
Uterine transplantation (UTx) is a fertility restoring treatment for women with absolute uterine factor infertility. At a time when there is no question of the procedure's feasibility, and as the number of livebirths begins to increase exponentially, various important reproductive, fetal and maternal medicine implications have emerged. Detailed outcomes from 17 livebirths following UTx are now available, which are reviewed herein, along with contextualized extrapolation from pregnancy outcomes in other solid organ transplants. Differences in recipient demographics and reproductive aspirations between UTx and other transplant recipients make extrapolating management strategies and outcomes in other solid organ transplants inappropriate. Whereas preterm delivery remains prominent, small for gestational age or hypertensive disorders do not appear to be as prevalent following UTx when compared to other solid organ transplants. Given the primary objective of undertaking UTx is to achieve a livebirth, publication of reproductive outcomes is essential at this early stage, to reflect upon and optimize the management of future cases.
Phelps DL, Saso S, Ghaem-Maghami S, 2020, Is ovarian cancer surgery stuck in the dark ages?: a commentary piece reviewing surgical technologies, BRITISH JOURNAL OF CANCER, Vol: 123, Pages: 1471-1473, ISSN: 0007-0920
Phelps DL, Saso S, Ghaem-Maghami S, 2020, Analysis of worldwide surgical outcomes in COVID-19-infected patients: a gynecological oncology perspective, Future Science OA, Vol: 6, Pages: 1-8, ISSN: 2056-5623
Coronavirus Disease 2019 (COVID-19) guidance limits all but the most urgent surgery in the United Kingdom. We review the literature and our experience in gynecology to assess perioperative outcomes. PubMed was searched with (surg*[Title])AND(COVID[Title]), (surg*[Title])AND(2019-nCoV[Title]), and (surg*[Title])AND(SARS-CoV-2[Title]), and 67 COVID-19-positive surgical patients across ten hospitals in four countries are included. Median mortality was 33%. Cardiac and pulmonary co-morbidities associated with higher risk of COVID-19-positive postoperative death. Mortality was high in neurosurgery (80%) and the lowest in gynecological oncology surgery (none). This analysis provides an evidence base on which to consider surgical risk assessment for different specialties. Risk of perioperative death needs to be assessed in the context of patients’ co-morbidities and surgical specialty. An individualized approach toward surgical decision making is imperative.
Tzafetas M, Mitra A, Paraskevaidi M, et al., 2020, The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease (vol 117, pg 7338, 2020), PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 18892-18892, ISSN: 0027-8424
Natoli M, Bonito N, Robinson JD, et al., 2020, Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade, Cancer Immunology Immunotherapy, Vol: 69, Pages: 1391-1401, ISSN: 0340-7004
Immune checkpoint blocking antibodies are currently being tested in ovarian cancer (OC) patients and have shown some responses in early clinical trials. However, it remains unclear how human OC cancer cells regulate lymphocyte activation in response to therapy. In this study, we have established and optimised an in vitro tumour-immune co-culture system (TICS), which is specifically designed to quantify the activation of multiple primary human lymphocyte subsets and human cancer cell killing in response to PD-1/L1 blockade. Human OC cell lines and treatment naïve patient ascites show differential effects on lymphocyte activation and respond differently to PD-1 blocking antibody nivolumab in TICS. Using paired OC cell lines established prior to and after chemotherapy relapse, our data reveal that the resistant cells express low levels of HLA and respond poorly to nivolumab, relative to the treatment naïve cells. In accordance, knockdown of IFNγ receptor expression compromises response to nivolumab in the treatment naïve OC cell line, while enhanced HLA expression induced by a DNA methyltransferase inhibitor promotes lymphocyte activation in TICS. Altogether, our results suggest a 'cross resistance' model, where the acquired chemotherapy resistance in cancer cells may confer resistance to immune checkpoint blockade therapy through down-regulation of antigen presentation machinery. As such, agents that can restore HLA expression may be a suitable combination partner for immunotherapy in chemotherapy-relapsed human ovarian cancer patients.
Natoli M, Bonito N, Robinson JD, et al., 2020, Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade (vol 45, pg 203, 2020), CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol: 69, Pages: 1403-1408, ISSN: 0340-7004
Du Bois A, Sehouli J, Vergote I, et al., 2020, Randomized phase III study to evaluate the impact of secondary cytoreductive surgery in recurrent ovarian cancer: Final analysis of AGO DESKTOP III/ENGOT-ov20., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Jones BP, Vali S, Saso S, et al., 2020, Endometrial autotransplantation in rabbits: Potential for fertility restoration in severe Asherman's syndrome, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 248, Pages: 14-23, ISSN: 0301-2115
Tzafetas M, Mitra A, Paraskevaidi M, et al., 2020, The intelligent-Knife (i-Knife) and its intraoperative diagnostic advantage for the treatment of cervical disease, Proceedings of the National Academy of Sciences of USA, Vol: 117, Pages: 7338-7346, ISSN: 0027-8424
Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.
Tzafetas M, Mitra A, Kalliala I, et al., 2019, THE IKNIFE AND ITS APPLICATION FOR THE TREATMENT OF CERVICAL ABNORMALITIES, Publisher: BMJ PUBLISHING GROUP, Pages: A589-A589, ISSN: 1048-891X
Marcus D, Savage A, Balog J, et al., 2019, ENDOMETRIAL CANCER: CAN THE IKNIFE DIAGNOSE ENDOMETRIAL CANCER?, Publisher: BMJ PUBLISHING GROUP, Pages: A100-A101, ISSN: 1048-891X
L'Heveder A, Jones BP, Saso S, et al., 2019, Conservative management of uterine adenosarcoma: lessons learned from 20 years of follow-up, ARCHIVES OF GYNECOLOGY AND OBSTETRICS, Vol: 300, Pages: 1383-1389, ISSN: 0932-0067
Tzafetas M, Mitra A, Lever S, et al., 2019, ONCOLOGICAL AND REPRODUCTIVE OUTCOMES AFTER FERTILITY-SPARING SURGERY IN WOMEN WITH CERVICAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A76-A77, ISSN: 1048-891X
Crosbie EJ, Ryan NAJ, Arends MJ, et al., 2019, The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome, Genetics in Medicine, Vol: 21, Pages: 2390-2400, ISSN: 1098-3600
PURPOSE: There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients. METHODS: Stakeholders from Europe and North America worked together over a two-day workshop to achieve consensus on best practice. RESULTS: Guidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer. CONCLUSION: This document provides comprehensive clinical guidance that can be referenced by both patients and clinicians so that women with Lynch syndrome can expect and receive appropriate standards of care.
Jones BP, Saso S, Bracewell-Milnes T, et al., 2019, Human uterine transplantation: a review of outcomes from the first 45 cases, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 126, Pages: 1310-1319, ISSN: 1470-0328
Jones B, Saso S, Chan M, et al., 2019, Implementing uterine transplantation into multi-organ retrieval setting: specialist nurse in organ donation and intensive care nurse perspectives, Publisher: WILEY, Pages: 195-195, ISSN: 1470-0328
Jones B, Saso S, Chan M, et al., 2019, Uterine transplantation in the context of a multi-organ retrieval in the UK, Publisher: WILEY, Pages: 192-192, ISSN: 1470-0328
Memtsa M, Jurkovic D, Jauniaux ERM, et al., 2019, Diagnostic Biomarkers for Predicting Adverse Early Pregnancy Outcomes Scientific Impact Paper No. 58, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 126, Pages: E107-E113, ISSN: 1470-0328
Wahba J, Natoli M, Whilding LM, et al., 2018, Chemotherapy-induced apoptosis, autophagy and cell cycle arrest are key drivers of synergy in chemo-immunotherapy of epithelial ovarian cancer, Cancer Immunology, Immunotherapy, Vol: 67, Pages: 1753-1765, ISSN: 1432-0851
Epithelial ovarian cancer (EOC) is the most lethal of all gynecological malignancies in the UK. Recent evidence has shown that there is potential for immunotherapies to be successful in treating this cancer. We have previously shown the effective application of combinations of traditional chemotherapy and CAR (chimeric antigen receptor) T cell immunotherapy in in vitro and in vivo models of EOC. Platinum-based chemotherapy synergizes with ErbB-targeted CAR T cells (named T4), significantly reducing tumor burden in mice. Here, we show that paclitaxel synergizes with T4 as well, and look into the mechanisms behind the effectiveness of chemo-immunotherapy in our system. Impairment of caspase activity using pan-caspase inhibitor Z-VAD reveals this chemotherapy-induced apoptotic pathway as an essential factor in driving synergy. Mannose-6-phosphate receptor-mediated autophagy and the arrest of cell cycle in G2/M are also shown to be induced by chemotherapy and significantly contributing to the synergy. Increased expression of PD-1 on T4 CAR T cells occurred when these were in culture with ovarian tumor cells; on the other hand, EOC cell lines showed increased PD-L1 expression following chemotherapy treatment. These findings provided a rationale to look into testing PD-1 blockade in combination with paclitaxel and T4 immunotherapy. Combination of these three agents in mice resulted in significant reduction of tumor burden, compared to each treatment alone. In conclusion, the mechanism driving synergy in chemo-immunotherapy of EOC is multifactorial. A deeper understanding of such process is needed to better design combination therapies and carefully stratify patients.
Lathouras K, Saso S, Tzafetas M, et al., 2018, Genetic polymorphisms of matrix metalloproteinases 1-3 and their inhibitor are not associated with premature labor, FUTURE SCIENCE OA, Vol: 4, ISSN: 2056-5623
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