Metastasis contributes to over 90% of cancer-related deaths and is initiated when cancer cells detach from the primary tumor, invade the basement membrane, and enter the circulation as circulating tumor cells (CTCs). While metastasis is viewed as an inefficient process with most CTCs dying within the bloodstream, it is evident that some CTCs are capable of resisting hemodynamic shear forces to form secondary tumors in distant tissues. We hypothesized that nuclear lamins A and C (A/C) act as key structural components within CTCs necessary to resist destruction from elevated shear forces of the bloodstream. Herein, we show that, compared with nonmalignant epithelial cells, tumor cells are resistant to elevated fluid shear forces in vitro that mimic those within the bloodstream, as evidenced by significant decreases in cellular apoptosis and necrosis. Knockdown of lamin A/C significantly reduced tumor cell resistance to fluid shear stress, with significantly increased cell death compared with parental tumor cell and nontargeting controls. Interestingly, lamin A/C knockdown increased shear stress-induced tumor cell apoptosis, but did not significantly affect cellular necrosis. These data demonstrate that lamin A/C is an important structural component that enables tumor cell resistance to fluid shear stress-mediated death in the bloodstream, and may thus facilitate survival and hematogenous metastasis of CTCs.

Prostate cancer, once it has progressed from its local to metastatic form, is a disease with poor prognosis and limited treatment options. Here we demonstrate an approach using nanoscale liposomes conjugated with E-selectin adhesion protein and Apo2L/TRAIL (TNF-related apoptosis-inducing ligand) apoptosis ligand that attach to the surface of leukocytes and rapidly clear viable cancer cells from circulating blood, both in human blood samples and in the living mouse. For the first time, it is shown that such an approach can be used to prevent the spontaneous formation and growth of metastatic tumors in an orthotopic xenograft model of prostate cancer, by greatly reducing the number of circulating tumor cells. We conclude that the use of circulating leukocytes as a carrier for the anti-cancer protein TRAIL could be an effective tool to directly target circulating tumor cells for the prevention of prostate cancer metastasis, and potentially other cancers that spread through the bloodstream.

Tumor draining lymph nodes are the first site of metastasis in most types of cancer. The extent of metastasis in the lymph nodes is often used in staging cancer progression. We previously showed that nanoscale TRAIL liposomes conjugated to human natural killer cells enhance their endogenous therapeutic potential in killing cancer cells cultured in engineered lymph node microenvironments. In this work, it is shown that liposomes decorated with apoptosis-inducing ligand TRAIL and an antibody against a mouse natural killer cell marker are carried to the tumor draining inguinal lymph nodes and prevent the lymphatic spread of a subcutaneous tumor in mice. It is shown that targeting natural killer cells with TRAIL liposomes enhances their retention time within the tumor draining lymph nodes to induce apoptosis in cancer cells. It is concluded that this approach can be used to kill cancer cells within the tumor draining lymph nodes to prevent the lymphatic spread of cancer.

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 cancer cells. In conclusion, this review highlights potential metabolites and biochemical pathways which may aid the clinical care of ovarian cancer if further validated.

ObjectivesThe aim of this systematic review is to examine the use of telemedicine in the delivery and teaching of gynaecological clinical practice. To our knowledge, no other systematic review has assessed this broad topic.DesignSystematic review of all studies investigating the use of telemedicine in the provision of gynaecological care and education. The search for eligible studies followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and focused on three online databases: PubMed, Science Direct and SciFinder.Eligibility criteriaOnly studies within gynaecology were considered for this review. Studies covering only obstetrics and with minimal information on gynaecology, or clinical medicine in general were excluded. All English language, peer-reviewed human studies were included. Relevant studies published up to the date of final submission of this review were considered with no restrictions to the publication year.Data extractions and synthesisData extracted included author details, year of publication and country of the study, study aim, sample size, methodology, sample characteristics, outcome measures and a summary of findings. Data extraction and qualitative assessment were performed by the first author and crossed checked by the second author. Quality assessment for each study was assessed using the Newcastle-Ottawa scale.ResultsA literature search carried out in August 2020 yielded 313 records published between 1992 and 2018. Following a rigorous selection process, only 39 studies were included for this review published between 2000 and 2018. Of these, 19 assessed gynaecological clinical practice, eight assessed gynaecological education, one both, and 11 investigated the feasibility of telemedicine within gynaecological practice. 19 studies were classified as good, 12 fair and eight poor using the Newcastle-Ottawa scale. Telecolposcopy and abortion care were two areas where telemedicine was found to be effective in potentially speeding up diagnosis as well as providing patients with a wide range of management options. Studies focusing on education demonstrated that telementoring could improve teaching in a range of scenarios such as live surgery and international teleconferencing.ConclusionsThe results of this review are promising and demonstrate that telemedicine has a role to play in improving clinical effectiveness and education within gynaecology. Its applications have been shown to be safe and effective in providing remote care and training. In the future, randomised controlled studies involving larger numbers of patients and operators with measurable outcomes are required in order to be able to draw reliable conclusions.