14 research outputs found
Viability analysis and apoptosis induction of breast cancer cells in a microfluidic device: effect of cytostatic drugs
Breast cancer is the leading cause of cancer deaths among non-smoking women worldwide. At the moment the treatment regime is such that patients receive different chemotherapeutic and/or hormonal treatments dependent on the hormone receptor status, the menopausal status and age. However, in vitro sensitivity testing of tumor biopsies could rationalize and improve the choice of chemo- and hormone therapy. Lab-on-a-Chip devices, using microfluidic techniques, make detailed cellular analysis possible using fewer cells, enabling working with a patients’ own cells and performing chemo- and hormone sensitivity testing in an ex vivo setting. This article describes the development of two microfluidic devices made in poly(dimethylsiloxane) (PDMS) to validate the cell culture properties and analyze the chemosensitivity of MCF-7 cells (estrogen receptor positive human breast cancer cells) in response to the drug staurosporine (SSP). In both cases, cell viability was assessed using the life-stain Calcein-AM (CAAM) and the death dye propidium iodide (PI). MCF-7 cells could be statically cultured for up to 7 days in the microfluidic chip. A 30 min flow with SSP and a subsequent 24 h static incubation in the incubator induced apoptosis in MCF-7 cells, as shown by a disappearance of the aggregate-like morphology, a decrease in CAAM staining and an increase in PI staining. This work provides valuable leads to develop a microfluidic chip to test the chemosensitivity of tumor cells in response to therapeutics and in this way improve cancer treatment towards personalized medicine
Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers
Identification of nine new susceptibility loci for endometrial cancer
Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study
Lymphedema and Post-Operative Complications after Sentinel Lymph Node Biopsy versus Lymphadenectomy in Endometrial Carcinomas-A Systematic Review and Meta-Analysis
Background: Lymph node dissection (LND) is recommended as staging procedure in presumed low stage endometrial cancer. LND is associated with risk of lower-extremity lymphedema and post-operative complications. The sentinel lymph node (SLN) procedure has been shown to have high diagnostic accuracy, but its effects on complication risk has been little studied. This systematic review compares the risk of lower-extremity lymphedema and post-operative complications in SLN versus LND in patients with endometrial carcinoma. Methods: A systematic search was conducted in PubMed and Cochrane Library. Results: Seven retrospective and prospective studies (total n = 3046 patients) were included. Only three studies reported the odds ratio of lower-extremity lymphedema after SLN compared to LND, which was 0.05 (95% CI 0.01-0.37; p = 0.067), 0.07 (95% CI 0.00-1.21; p = 0.007) and 0.54 (95% CI 0.37-0.80; p = 0.002) in these studies. The pooled odds ratio of any post-operative complications after SLN versus LND was 0.52 (95% CI 0.36-0.73; I-2 = 48%; p < 0.001). For severe post-operative complications the pooled odds ratio was 0.52 (95% CI 0.28-0.96; I-2 = 0%; p = 0.04). Conclusions: There are strong indications that SLN results in a lower incidence of lower-extremity lymphedema and less often severe post-operative complications compared to LND. In spite of the paucity and heterogeneity of studies, direction of results was similar in all studies, supporting the aforementioned conclusion. These results support the increasing uptake of SLN procedures in endometrial cancer
Development of a Framework and the Content for a Psychoeducational Internet-Delivered Intervention for Women after Treatment for Gynecological Cancer
The number of women treated for gynecological cancer is increasing. At the same time, the duration of in-patient hospitalization has decreased, and follow-up with its primary focus on early recognition of recurrence does not meet all patients' needs. One method of follow-up may be digital intervention. This study describes the development of a psychoeducational Internet-delivered intervention targeting women's psychosocial needs during the follow-up period after treatment for gynecological cancer. The project consisted of three phases following the UK Medical Research Council Framework guidelines for the development of complex interventions. Phase one identified the evidence in the field, phase two identified the relevant theoretical framework, and phase three included a two-year work process including focus group interviews and think aloud interviews with users. Through the steps of literature review, theoretical framework, and an iterative development process with users and other stakeholders, a six-week program was developed. The program included psychoeducational information, multimedia, exercises, and weekly telephone follow-up with a dedicated nurse. This Internet-delivered intervention can be a novel method for addressing the gap in the provision of follow-up for women after treatment for gynecological cancer
Incorporating molecular profiling into endometrial cancer management requires prospective studies
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Risk Stratification of Endometrial Cancer Patients: FIGO Stage, Biomarkers and Molecular Classification
Simple Summary: Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. Most patients are sufficiently treated with removal of uterus, tubes and ovaries. It depends on the estimated risk of metastases at diagnosis if more extensive surgery (removal of lymph nodes, peritoneum and/or omentum), to detect small metastases, is indicated. Metastases are associated with a higher risk of recurrence and justify adjuvant treatment (i.e., radiotherapy and/or chemotherapy). Recently it is advised to also subdivide EC into four molecular subgroups. Each subgroup is highly associated to a certain risk of recurrence and helps to decide for adjuvant treatment. What surgery should be performed in each of the subgroups is currently unknown. Moreover, it is uncertain if integration of other factors into the molecular classification could help to improve the risk classification. This review summarizes different aspects of surgery. Moreover, the relation between metastases and other factors including molecular classification are evaluated.Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, microscopic metastases upstages patients, provides important prognostic information and guides adjuvant treatment. The molecular classification subdivides EC into four prognostic subgroups: POLE ultramutated; mismatch repair deficient (MMRd); nonspecific molecular profile (NSMP); and TP53 mutated (p53abn). How surgical staging should be adjusted based on preoperative molecular profiling is currently unknown. Moreover, little is known whether and how other known prognostic biomarkers affect prognosis prediction independent of or in addition to these molecular subgroups. This review summarizes the factors incorporated in surgical staging (i.e., peritoneal washing, lymph node dissection, omentectomy and peritoneal biopsies), and its impact on prognosis and adjuvant treatment decisions in an era of molecular classification of EC. Moreover, the relation between FIGO stage and molecular classification is evaluated including the current gaps in knowledge and future perspectives