Immunobiology of solid cancers: cellular and molecular pathways as potential diagnostic and therapeutic targets

In the last four decades, tumor immunology has shed light on identity and functions of cells and molecules involved in tumor rejection through the involvement of the immune system [1]. Several groups of immune cells have been demonstrated to be able to contrast tumor occurrence and tumor progression by killing immunogenic tumor cells, a phenomenon recognized under the definition of “immunosurveillance” [2]. Unfortunately, cancer may evade immunosurveillance and progress through the modifications of its own antigens, which can reduce tumor immunogenicity and/or increase its immunosuppressive action [3]. After years of investigations, harnessing the immune system to attack cancer has recently led scientists to gather enough clinical data to show what a powerful sword immunotherapy can be

Ultrasound and clinical preoperative characteristics for discrimination between ovarian metastatic colorectal cancer and primary ovarian cancer: A case-control study

The aim of this study was to describe the clinical and sonographic features of ovarian metastases originating from colorectal cancer (mCRC), and to discriminate mCRC from primary ovarian cancer (OC). We conducted a multi-institutional, retrospective study of consecutive patients with ovarian mCRC who had undergone ultrasound examination using the International Ovarian Tumor Analysis (IOTA) terminology, with the addition of evaluating signs of necrosis and abdominal staging. A control group included patients with primary OC. Clinical and ultrasound data, subjective assessment (SA), and an assessment of different neoplasias in the adnexa (ADNEX) model were evaluated. Fisher's exact and Student's t-tests, the area under the receiver-operating characteristic curve (AUC), and classification and regression trees (CART) were used to conduct statistical analyses. In total, 162 patients (81 with OC and 81 with ovarian mCRC) were included. None of the patients with OC had undergone chemotherapy for CRC in the past, compared with 40% of patients with ovarian mCRC (p < 0.001). The ovarian mCRC tumors were significantly larger, a necrosis sign was more frequently present, and tumors had an irregular wall or were fixed less frequently; ascites, omental cake, and carcinomatosis were less common in mCRC than in primary OC. In a subgroup of patients with ovarian mCRC who had not undergone treatment for CRC in anamnesis, tumors were larger, and had fewer papillations and more locules compared with primary OC. The highest AUC for the discrimination of ovarian mCRC from primary OC was for CART (0.768), followed by SA (0.735) and ADNEX calculated with CA-125 (0.680). Ovarian mCRC and primary OC can be distinguished based on patient anamnesis, ultrasound pattern recognition, a proposed decision tree model, and an ADNEX model with CA-125 levels

Efficacy of individualised starting dose (isd) and fixed starting dose (fsd) of niraparib per investigator assessment (ia) in newly diagnosed advanced ovarian cancer (oc) patients

Niraparib is a poly(ADP-ribose) polymerase inhibitor approved for maintenance treatment of patients with newly diagnosed or recurrent OC that responded to platinumbased chemotherapy and treatment in heavily-pretreated recurrent OC. Here we report efficacy in patients receiving the FSD and ISD in the PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016)

Influence of migrant background on patient preference and expectations in breast and gynecological malignancies (NOGGO-expression V study): results of a prospective multicentre study in 606 patients in Germany

Background: An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM). Methods: This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients. Results: A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected. Conclusions: Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status

preoperative c reactive protein and thrombocyte count as potential markers for longterm survival in ovarian cancer

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Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

BRCA1 promoter methylation and clinical outcomes in ovarian cancer: an individual patient data meta-analysis

BACKGROUND BRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal/ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of individual participant data. METHODS 2636 participants' data across 15 studies were analyzed. BRCA1-methylated tumors were defined according to their original study. Associations between BRCA1 methylation and clinico-pathological characteristics were evaluated. The effects of methylation on overall survival (OS) and progression-free survival (PFS) were examined using mixed-effects models. All statistical tests were two-sided. RESULTS 430 (16.3%) tumors were BRCA1-methylated. BRCA1 methylation was associated with younger age and advanced-stage high-grade serous OC. There were no survival differences between BRCA1-methylated and non-BRCA1-methylated OC (median PFS = 20.0 vs 18.5 months, HR = 1.01, 95% CI = 0.87-1.16, P=0.98; median OS = 46.6 vs 48.0 months, HR = 1.02, 95% CI = 0.87-1.18, P=0.96). Where BRCA1/2 mutations were evaluated (n = 1248), BRCA1 methylation displayed no survival advantage over BRCA1/2 intact (BRCA1/2 wild type non-BRCA1-methylated) OC. Studies used different methods to define BRCA1 methylation. Where BRCA1 methylation was determined using methylation-specific PCR and gel electrophoresis (n = 834), it was associated with improved survival (PFS: HR = 0.80, 95% CI = 0.66-0.97, P=0.02; OS: HR = 0.80, 95% CI = 0.63-1.00, P=0.05) on mixed-effects modelling. CONCLUSION BRCA1-methylated OC displays similar clinico-pathological features to BRCA1-mutated OC, but is not associated with survival. Heterogeneity within BRCA1 methylation assays influences associations. Refining these assays may better identify cases with silenced BRCA1 function and improved patient outcomes

WAP four-disulfide core domain protein 2 gene(WFDC2) is a target of estrogen in ovarian cancer cells

BACKGROUND: WAP four-disulfide core domain protein 2 (WFDC2) shows a tumor-restricted upregulated pattern of expression in ovarian cancer. METHODS: We investigated the role of estradiol (E2) on cell growth in estrogen-sensitive or estrogen-insensitive ovarian cancer cell lines. Real-time (RT)-PCR and western blotting were used to examine the expression of WFDC2 at RNA and protein levels. Growth traits of cells transfected with WFDC2-shRNA or blank control were assessed using MMT arrays. Cell apoptosis was analyzed using annexin V-FITC/PI and flow cytometry. Estrogen receptor expression was evaluated using RT-PCR and flow cytometry. Apoptosis-related proteins induced by E2 directly and indirectly were determined using an antibody array comparing cells transfected with WFDC2- shRNA or a blank control. RESULTS: High-dose (625 ng/ml) E2 increased the expression of WFDC2 in HO8910 cells at both the mRNA and protein levels. However, E2 had no effect on WFDC2 expression in estrogen-insensitive SKOV3 cells. Of interest, knockdown of WFDC2 enabled a considerable estrogen response in SKOV3 cells in terms of proliferation, similar to estrogen-responsive HO8910 cells. This transformation of SKOV3 cells into an estrogen-responsive phenotype was accompanied by upregulation of estrogen receptor beta (ERß) and an effect on cell apoptosis under E2 treatment by regulating genes related to cell proliferation and apoptosis. CONCLUSIONS: We postulate that increased WFDC2 expression plays an important role in altering the estrogen pathway in ovarian cancer, and the identification of WFDC2 as a new player in endocrine-related cancer encourages further studies on the significance of this gene in cancer development and therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-015-0210-y) contains supplementary material, which is available to authorized users