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Ovarian cancer is composed of a complex system of cells best described by features such as clonal evolution, spatial and temporal genetic heterogeneity, and development of drug resistance, thus making it the most lethal gynecologic cancer. Seminal work on cancer as an evolutionary process has a long history; however, recent cost-effective large-scale molecular profiling has started to provide novel insights coupled with the development of mathematical algorithms. In the current review, we have systematically searched for articles that focused on the clonal evolution of ovarian cancer to offer the whole landscape of research that has been done and highlight future research avenues given its characteristic features and connections to evolutionary biology. [ABSTRACT FROM AUTHOR]

Background and aims. Despite their usefulness, CT-guided procedures have a low profile in Romania. The current study has the purpose of describing a first experience in performing these procedures. Methods. Tumors and fluid collections that were inaccessible for biopsy or drainage by ultrasound or endoscopic guidance were included. The procedures were performed using a 64-slice GE Optima CT660 CT scanner. The biopsies were carried out using the coaxial technique with an 18 G semiautomatic needle. The drainages were performed using 10 F pig-tail drains that were inserted using the Seldinger technique. Data regarding the size and location of the target lesion, puncture technique, success and complication rates were recorded. Results. Between May 2017 and April 2018, 30 procedures were performed, of which 26 biopsies and 4 drainage insertions. Of the biopsies 3 were mediastinal, 8 pulmonary, 6 retroperitoneal, 4 pelvic, and 5 of the bone. The drainages were performed for pelvic lymphoceles. The average lesion size was 3.2 cm (0.7-9 cm), with a depth from the skin of 9.1 cm (0.6-15.2 cm). The average procedure duration was 58 minutes (31-93 minutes). A conclusive histopathological diagnosis was set after 92.3% of biopsies. Three procedures resulted in complications, two being minor (hemothorax, soft tissue hematoma) and one severe (tension pneumothorax requiring drainage). Conclusions. CT guidance offers safe access to lesions that cannot be biopsied or drained under ultrasound or endoscopic guidance. [ABSTRACT FROM AUTHOR]

The effects of cancer and its treatment on reproduction and fertility are well-documented, yet knowledge of the psychosocial and behavioral implications of these outcomes for young adult survivors of cancer is limited. The present study aimed to investigate the associations among quality of life determinants on a sample of female patients of reproductive age (102 patients and 102 healthy controls), surgically treated (conisation) for pre-invasive and invasive pathology (cervix dysplasia and microinvasive carcinoma). Our goal was to obtain a structural model, based on previously validated measures, though confirmatory factor analysis. We chose three scales that have been validated on other populations and assessed their construct validity in case of the specific population we were interested in. The mean age of the patients included in the study was 31.8 years, while the mean age of the control group was 32.31 years. Of the 102 patients, 7% reported post-surgery complications, 40% used contraceptive methods, 25% wanted to become pregnant and 17 patients managed to get pregnant, 13 of which managed to deliver liveborns. The FSFI model presented in this paper can be used for assessing four domains of women's sexual functioning and women's overall sexual functioning. The quality of life model based on the EORTC OLQ-C30 allows the assessment of functioning at physical, emotional, and social levels, and defining specific symptoms scales for the target population. [ABSTRACT FROM AUTHOR]

Background: A literature review on 1,104 269 cancer patients concluded that the prevalence of multiple primary malignancies (MPM) is between 0.73% and 11.7%. MPMs seem to have higher incidence than that influenced by hazard only. Aim: The purpose of this study was to investigate clinically useful information for effective screening for synchronous and metachronous second primary cancers and to identify a potential surveillance protocol. Methods: Using statistical and epidemiological indicators we evaluated the patients with MPMs (double locations) admitted to the Institute of Oncology "Prof. Dr. Ion Chiricuţă", Cluj-Napoca between 2001 and 2004. Results: Out of the 63 cases, 22 cases (34.9%) were synchronous tumors while 41 cases (65.1%) were metachronous tumors, the occurrence interval ranging from 6.2 to 254 months, with an average of 34.6 months for the entire group. Almost half of the metachronous tumors (20 cases) occurred between 6.2 and 24 months while 14 cases (20%) were detected after a 5-year interval. The most frequent malignant associations were ovary-colon, ovary-breast, breast-breast. Both primary and secondary tumors tended to be in an advanced stage explained by the low compliance of the patients to follow-up. Conclusions: The possibility that MPMs exist must always be considered during pretreatment evaluation. Screening procedures are especially useful for the early detection of associated tumors, whereas careful monitoring of patients treated for primary cancer and a good communication between patients and medical care team would ensure an early detection for secondary tumors, and, subsequently, an appropriate management. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the feasibility and diagnostic validity of the sentinel lymph node technique in detecting inguinal lymph node metastases in patients with invasive squamous cancer of the vulva. Design: Retrospective analysis of the in-house tumor registry. Setting: Dr. Horst Schmidt Klinik, a tertiary gynecologic oncology unit in Wiesbaden, Germany, June 2000-May 2008. Population: All consecutive operated patients with primary envisaged diagnosis were included. Methods: The sentinel node identification technique was performed and patients were informed accordingly. Patients who consented and were found eligible underwent preoperative lymphscintigraphy on the day before surgery. Main Outcome Measures: Sentinel node detection in specimen from sentinel lymph node biopsy and from full lymphadenectomy (LNE); sentinel lymph node biopsy as a sole surgical groin procedure in patients with histological negative sentinel node; benefit with respect to side effects for sentinel lymph node biopsy compared to full LNE; complication rates; and recurrences of vulvar cancer. Results: In all, 46 of 59 patients with vulvar malignancy underwent inguinofemoral LNE, sentinel lymph node biopsy (SLB) of the groin followed by LNE, or SLB alone. Most patients had been diagnosed in the early stages of the disease. Since no false positive or false negative results were recorded, the sensitivity, specificity, positive predictive value and negative predictive value of the sentinel lymph node were 100%. However, in 6%, a sentinel lymph node could not be detected intraoperatively indicating a feasibility of 94%. Conclusion: The implementation of sentinel lymph node technique for groin staging in squamous cell vulvar cancer seems to provide a feasible and safe technique in tertiary gynecologic oncology. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the impact of perioperative characteristics on the risk of recurrence in patients with uterine leiomyosarcomas. Methods: A sub‐analysis of the SARComa of the UTerus (SARCUT) study, which is a multicentric cross‐sectional pan‐European study that included 390 patients diagnosed with leiomyosarcoma, between 2001 and 2007. Perioperative factors related to risk of recurrence and survival were analyzed. Results: The 5‐year and 10‐year disease‐free survivals (DFS) were 46% and 55%, respectively. Overall survival at 5 and 10 years was 34% and 47%, respectively. The most important factors related to global recurrence were the incomplete cytoreduction (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.91–4.31); performing bilateral adnexectomy (HR 2.71; 95% CI 1.23–5.93); tumor persistence after any treatment (HR 2.38; 95% CI 1.39–4.06); and adjuvant chemotherapy administration (HR 2.55; 95% CI 1.82–3.58) or adjuvant radiotherapy (HR 2.26; 95% CI 1.53–3.32). The major factors significantly associated with pelvic relapse were tumor persistence after any treatment (HR 3.63; 95% CI 1.83–7.20) and adjuvant radiotherapy (HR 2.74; 95% CI 1.44–5.20). Incomplete cytoreduction was the most important factor associated with distant relapse (HR 1.91; 95% CI 1.22–2.97). The most important factors related to overall survival were tumor persistence after any treatment (HR 4.59; 95% CI 2.51–8.40), incomplete cytoreduction (HR 3.68; 95% CI 2.44–5.56), tumor margin involvement (HR 2.41; 95% CI 1.64–3.55) and adjuvant chemotherapy (HR 1.91; 95% CI 1.31–2.78). Conclusions: Complete cytoreduction is the main prognosis factor impacting the DFS and overall survival of patients with uterine leiomyosarcoma. Adjuvant chemotherapy administration was associated with decreased rates of DFS and overall survival. The adjuvant radiotherapy was associated with a higher risk of global recurrence. Synopsis: Complete surgical cytoreduction remains the most important factor to improve survival of patients with uterine leiomyosarcoma. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this survey of long-term survivors (LTS) with ovarian cancer was to enhance the knowledge on the patient characteristics and health concerns of this growing patient cohort in order to tailor follow-up care. Follow-up care is usually carried out within the first five years after initial diagnosis, before they are transferred to general physicians and gynecologists. Interestingly, in our cohort of 1044 LTS from 14 countries, most patients with a median survival time of eleven years after initial diagnosis still received regular follow-up care (94.2%). Forty-six percent still reported cancer- and therapy-related symptoms (i.e., gastrointestinal problems, fatigue, lymphedema, and neurological problems). The present analysis confirms the symptom checklist and clinical relevance of the GCIG consensus guideline on long-term survival with gynecological cancer. Follow-up care should be offered beyond the typical five years as specialized survivorship care with a focus on long-term side effects, lifestyle, and prevention. The aim of this survey was to increase the knowledge on the characteristics and health concerns of long-term survivors (LTS; survival > 5 years) after ovarian cancer in order to tailor follow-up care. This international survey was initiated by the NOGGO and was made available to members of ENGOT and GCIG. The survey is anonymous and consists of 68 questions regarding sociodemographic, medical (cancer) history, health concerns including distress, long-term side effects, and lifestyle. For this analysis, 1044 LTS from 14 countries were recruited. In total, 58% were diagnosed with FIGO stage III/IV ovarian cancer and 43.4% developed recurrent disease, while 26.0% were receiving cancer treatment at the time of filling in the survey. LTS who survived 5–10 years self-estimated their health status as being significantly worse than LTS who survived more than 10 years (p = 0.034), whereas distress also remained high 10 years after cancer diagnosis. Almost half of the cohort (46.1%) reported still having symptoms, which were mainly lymphedema (37.7%), fatigue (23.9%), pain (21.6%), polyneuropathy (16.9%), gastrointestinal problems (16.6%), and memory problems (15.5%). Almost all patients (94.2%) regularly received follow-up care. Specialized survivorship care with a focus on long-term side effects, lifestyle, and prevention should be offered beyond the typical five years of follow-up care. [ABSTRACT FROM AUTHOR]

AimsThe present study aims to investigate the pain, anxiety and other factors that are associated with percutaneous computed tomography (CT)- and ultrasound (US)-guided biopsies of tumors.Material and MethodsThe study prospectively included 60 consecutive patients, of which 24 underwent CT-guided biopsies and 36 US-guided biopsies. The location of targeted tumors was within the thorax, abdomen, pelvis, and limbs. A questionnaire containing numerical rate scales (0-10) regarding procedural and post-procedural pain, anxiety, and other associated parameters was filled out by each patient 2-6 hours after the procedure. CT and ultrasound parameters were compared.  The two groups were then pooled together in order to compare pain scores per targeted organ and to analyze the parameters that were associated with pain.ResultsThere was no significant difference between the CT and US group with the exception of the positional discomfort, which was higher in the CT group (p=0.003). The average procedural pain score (2.0) was significantly higher than the post-procedural pain (1.3, p=0.006) and the phlebotomy pain (0.8, p<0.0001). There was no significant difference between the targeted organs with regards to the pain score. The factors that showed a positive correlation with the procedural pain were procedure-related anxiety (p=0.005), positional discomfort (p=0.01), and phlebotomy pain (p=0.0008). The pre interventional use of an analgesic was negatively correlated with the procedural pain (p=0.02).ConclusionsCT- and US- guided percutaneous biopsies are associated with low levels of pain that are generally well tolerated by patients irrespective of the targeted organ. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to analyze the prognostic factors related to the recurrence rate and overall survival of patients with undifferentiated uterine sarcoma. Methods: An international multicenter study involving 43 international centers, the SARCUT study, collected 966 uterine sarcoma cases; among them 39 cases corresponded to undifferentiated uterine sarcoma and where included in the present subanalysis. The risk factors related to the oncological outcomes where analyzed. Results: The median age of the patients was 63 (range 14–85) years. Seventeen (43.5%) patients presented FIGO stage I. The 5-year overall survival (OS) was 15.3% and 12-months disease-free survival (DFS) 41%. FIGO stage I was significantly associated with a better prognosis. In addition, patients who received adjuvant radiotherapy showed significant longer disease-free survival compared to those without adjuvant radiotherapy (20.5 vs. 4.0 months, respectively; p = 0.04) and longer overall survival (34.7 vs. 18.2 months, respectively; p = 0.05). Chemotherapy administration was associated with shorter DFS (HR 4.41, 95% CI 1.35–14.43, p = 0.014). Persistent disease after primary treatment (HR = 6.86, 95% CI 1.51–31.09, p = 0.012) and FIGO stage IV (HR 4.12, 95%CI 1.37–12.44, p = 0.011) showed significant worse prognosis for OS. Conclusion: FIGO stage seems to be the most important prognostic factor in patients with undifferentiated uterine sarcoma. Adjuvant radiotherapy seems to be significantly associated also to a better disease-free and overall survival. On the contrary, the role of chemotherapy administration remains unclear since was associated to a shorted DFS. [ABSTRACT FROM AUTHOR]

To assess the impact of the lymph node dissection (LND) in the disease-free (DFS) and overall survival (OS) of the women treated surgically of uterine leiomyosarcoma (ULMS). A multicentric retrospective study was conducted among European countries collecting patients diagnosed of uterine sarcoma (SARcoma of the UTerus - SARCUT study). A total of 390 ULMS were selected for the present study to compare patients who underwent LND and those who did not. A further matched-pair subanalysis identified 116 women, 58 pairs (58 with LND and 58 without it) comparable in age, tumor size, surgical procedures, extrauterine disease and adjuvant treatment. Demographic data, pathology results and follow-up were abstracted from medical records and analyzed. Disease-free (DFS) and overall survival (OS) were studied using Kaplan-Meier curves and Cox regression analysis. Among the 390 patients, the 5-year DFS was significantly higher in no-LDN group comparing to the LDN group (57.7% vs. 33.0%; HR 1.75, 95% CI 1.19–2.56; p = 0.007), but not the 5-year OS (64.6% vs. 64.3%; HR 1,10 95% CI 0,77–1,79; p = 0.704). In the matched-pair subanalysis, there were no statistical differences between the study groups. The 5- year DFS was 50.5% in the no-LND and 33.0% in the LND group (HR 1.38; 95% CI 0,83–2.31; p = 0,218) and the 5-year OS was 59.7% and 64.3% respectively (HR 0.81; 95% CI 0,45–1,49; p = 0,509). LND performed in women diagnosed of ULMS have no impact neither in the disease-free nor in the overall survival compared to patients without LDN in a complete homogeneous group. • The role of lymphadenectomy in uterine leiomyosarcomas remains controversial, since only retrospective data is available. • Lymph node dissection did not show an improve of disease-free survival between homogeneous groups. • No impact on overall survival was demonstrated among the patients who underwent lymphadenectomy. • Our study is the first one that compared the role of lymphadenectomy in uterine leiomyosarcoma among cmatched groups. [ABSTRACT FROM AUTHOR]

Two diphenyl formamidine ligands, four dirhodium(II,II) complexes, and three axially modified low-valent dirhodium(II,II) metallodendrimers were synthesized and evaluated as anticancer agents against the A2780, A2780cis, and OVCAR-3 human ovarian cancer cell lines. The dirhodium(II,II) complexes show moderate cytotoxic activity in the tested tumor cell lines, with acetate and methyl-substituted formamidinate compounds displaying increased cytotoxicity that is relative to cisplatin in the A2780cis cisplatin resistant cell line. Additionally, methyl- and fluoro-substituted formamidinate complexes showed comparable and increased cytotoxic activity in the OVCAR-3 cell line when compared to cisplatin. The low-valent metallodendrimers show some activity, but a general decrease in cytotoxicity was observed when compared to the precursor complexes in all but one case, which is where the more active acetate-derived metallodendrimer showed a lower IC50 value in the OVCAR-3 cell line in comparison with the dirhodium(II,II) tetraacetate. [ABSTRACT FROM AUTHOR]

Simple Summary: Uterine carcinosarcoma is a rare disease that represents less than 5% of uterine malignancies, although approximately 16% of the uterine cancer-related deaths are caused by this disease. Nowadays, there seems to be a lack of prognostic stratifying studies that could lead to tailor the management of uterine carcinosarcoma. The aim of our study was to assess the impact of possible different prognostic factors on the survival of patients diagnosed with uterine carcinosarcoma. We observed that incomplete cytoreduction, presence of tumor residual after treatment, advanced FIGO stage, extrauterine disease, and tumor size were significant prognostic factors decreasing disease-free survival and overall survival. Background: The aim of this study was to assess the impact of prognostic factors on the survival of patients diagnosed with uterine carcinosarcoma. Methods: A sub-analysis of the SARCUT study, a multicentric retrospective European study, was carried out. We selected 283 cases of diagnosed uterine carcinosarcoma for the present study. Prognosis factors influencing survival were analyzed. Results: Significant prognostic factors for overall survival were: incomplete cytoreduction (HR = 4.02; 95%CI = 2.68–6.18), FIGO stages III and IV (HR = 3.21; 95%CI = 1.83–5.61), tumor persistence after any treatment (HR = 2.90; 95%CI = 1.97–4.27), presence of extrauterine disease (HR = 2.62; 95%CI = 1.75–3.92), a positive resection margin (HR = 1.56; 95%CI = 1.05–2.34), age (HR = 1.02; 95%CI = 1.00–1.05), and tumor size (HR = 1.01; 95%CI = 1.00–1.01). Significant prognostic factors for disease-free survival were: incomplete cytoreduction (HR = 3.00; 95%CI = 1.67–5.37), tumor persistence after any treatment (HR = 2.64; 95%CI = 1.81–3.86), FIGO stages III and IV (HR = 2.33; 95%CI = 1.59–3.41), presence of extrauterine disease (HR = 2.13; 95%CI = 1.44–3.17), administration of adjuvant chemotherapy (HR = 1.84; 95%CI = 1.27–2.67), a positive resection margin (HR = 1.65; 95%CI = 1.11–2.44), presence of LVSI (HR = 1.61; 95%CI = 1.02–2.55), and tumor size (HR = 1.00; 95%CI = 1.00–1.01). Conclusions: Incomplete cytoreduction, presence of tumor residual after treatment, advanced FIGO stage, extrauterine disease, and tumor size are significant prognostic factors decreasing disease-free survival and overall survival of patients with uterine carcinosarcoma. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease, with a morbidity rate of 27.8% and a mortality rate of 15% among women population worldwide. Understanding how this cancer develops and the mechanisms behind tumor progression and chemoresistance is of utmost importance. Exosomes mediate communication in a population of heterogeneous tumoral cells. They have a cargo composed of oncogenes and oncomiRs which change the transcriptomic scenario of their targeted cells and activate numerous tumor‐promoting signaling pathways. Exosomes secreted by breast cancer cells lead to enhanced cell proliferation, replicative immortality, angiogenesis, invasion, migration, and chemoresistance. Studying exosomes from this perspective offers more in depth understanding of breast malignancy and may aid in the future development of early diagnostic, prognostic and therapeutic options. We present the latest findings in this area and offer practical solutions which may further stimulate the much‐needed research of exosome in breast cancer. [ABSTRACT FROM AUTHOR]

Objective: The impact of angiogenesis on long-term survival of high-grade serous ovarian cancer (HGSOC) patients remains unclear. This study investigated whether angiogenic markers correlated with 5-year progression-free survival (PFS) in a large cohort of matched advanced HGSOC tissue samples. Methods: Tumor samples from 124 primary HGSOC patients were retrospectively collected within the Tumor Bank Ovarian Cancer (http://www.toc-network.de). All patients were in advanced stages (FIGO stage III–IV). No patient had received anti-angiogenesis therapy. The cohort contains 62 long-term survivors and 62 controls matched by age and post-surgical tumor residuals. Long-term survivors were defined as patients with no relapse within 5 years after the end of first-line chemotherapy. Controls were patients who suffered from first relapse within 6–36 months after primary treatment. Samples were assessed for immunohistochemical expression of vascular endothelial growth factor (VEGF) A and VEGF receptor 2 (VEGFR2). Expression profiles of VEGFA and VEGFR2 were compared between the two groups. Results: Significant correlation between VEGFA and VEGFR2 expression was observed (p < 0.0001, Spearman coefficient 0.347). A high expression of VEGFR2 (VEGFR2high) was found more frequently in long-term survivors (77.4%, 48/62) than in controls (51.6%, 30/62, p = 0.001), independent of FIGO stage and VEGFA expression in multivariate analysis (p = 0.005). Also, VEGFR2high was found the most frequently in women with PFS ≥ 10 years (p = 0.001) among all 124 patients. However, no significant association was detected between VEGFA expression and 5-year PFS (p = 0.075). Conclusions: VEGFR2 overexpression significantly correlated with long-term PFS in HGSOC patients, independent of age, FIGO stage, tumor residual and VEGFA expression. [ABSTRACT FROM AUTHOR]

Medical registries provide highly reliable data, challenged hierarchically only by randomized controlled trials. Although registries have been used in several fields of medicine for more than a century and a half, their key role is frequently overlooked and poorly recognized. Medical registries have evolved from calculating basic epidemiological data (incidence, prevalence, mortality) to diverse applications in disease prevention, early diagnosis and screening programs, treatment response, health care planning, decision making and disease control programs. Implementing, maintaining and running a medical registry requires substantial effort. Developing the registry represents a complex task and is one of the major barriers in widespread use of registries. Medical registries have potential to evolve to a next generation by taking benefit from recent semantic web technology developments. This paper is aimed at providing a summary of the basic information available on medical registries and to highlight the progress and potential applications in this field. [ABSTRACT FROM AUTHOR]

Aims: Advanced‐stage ovarian high‐grade serous carcinoma (HGSC) is a poor‐prognosis cancer; however, a small and poorly characterised subset of patients shows long‐term survival. We aimed to establish a cohort of HGSC long‐term survivors for histopathological and molecular analysis. Methods and results: Paraffin blocks from 151 patients with primary FIGO III/IV HGSC and progression‐free survival (PFS) >5 years were collected within the Tumorbank Ovarian Cancer (TOC) Network; 77 HGSC with a PFS <3 years were used as a control group. A standardised analysis of histological type and morphological features was performed. Ki67 index, tumour‐infiltrating lymphocytes (TILs) and major histocompatibility complex expression (MHC1/2) were determined by immunohistochemistry. A total of 117 of 151 tumours (77.5%) in the long‐term survivor group fulfilled the World Health Organisation (WHO) criteria of HGSC after review, and of these, 83 patients (70.9%) fulfilled all clinical criteria for inclusion into our cohort. Tumours of long‐term survivors had significantly higher CD3+ and CD8+ TILs and were more frequently positive for MHC2 than controls (P = 0.004, P = 0.025, P = 0.048). However, there were also long‐term survivors (up to 20%) with low TILs or low MHC expression. TILs and MHC had no impact on survival in long‐term survivors. Morphological and Ki67 analysis revealed no differences between long‐term survivors and controls. Conclusions: HGSC from long‐term survivors have higher‐level T cell infiltration and antigen‐presentation capacity; however, this is not a prerequisite for an excellent prognosis. Histopathological criteria are not capable to identify these patients. Further extensive clinical and molecular characterisation of this enigmatic subgroup is ongoing to understand the reasons of long‐term survival in HGSC. [ABSTRACT FROM AUTHOR]

Abstract A series of mono- and multinuclear [2 + 1] Re(I) tricarbonyl complexes were synthesised and evaluated as antiproliferative agents against the epithelial carcinoma (A431), colon carcinoma (DLD-1) and ovarian cancer (A2780) tumour cell lines and a healthy fibroblast (BJ) cell line. The compounds have moderate to good activity against the tumour cell lines, with the trinuclear and tetranuclear complexes showing selective cytotoxicity towards the tumour cell lines. The Re(I) complexes were found to influence programmed cell death mechanisms in vitro. They were able to inhibit the soluble form of the Fas receptor in malignant cells, allowing the Fas domain to receive the apoptotic signal through an extrinsic pathway. The complexes augmented the pro-apoptotic Bax-α concentrations, with the tetranuclear complex more superior at modulating the Bax-α molecular target in all tested cell lines, which influenced its cell growth inhibitory activity. The tetranuclear complex has the best activity against all tumour cell lines. Graphical abstract Image 1 Highlights • Mono- and multinuclear [2 + 1] Re(I) tricarbonyl complexes have been prepared. • The complexes were characterised using several spectroscopic and analytical techniques. • The complexes were evaluated as antiproliferative agents against A431, DLD-1 and A270 tumour cell lines. • The Re(I) complexes all influence programmed cell death mechanisms. [ABSTRACT FROM AUTHOR]

The objective of this pilot study was to test the efficiency of a cognitivebehavioral psychological intervention, aimed at reducing emotional distress and improving quality of life in breast cancer patients undergoing radiotherapy. This was a quasi-experimental pretest/posttest study design, with a similar/equivalent control group (N=16, experimental group = 8, control group = 8). The statistical mixed design ANOVA method was used for univariate analysis of inter- and intra-group variability. Significant differences between the two groups with similar onset scores, were obtained at the end of the intervention at DT [F (1,14) = 13.63; η2 = 0.493 p = 0.002], FACT-B [t (14) = 4.55, p <0.001), CI = [13,542; 37708] ET: distress [t (14) = 5.50, p <0.001), CI = [- 819; 2069], anxiety [t (14) = - 0.15, p <0.001), CI = [- 6.81; -2.69], depression [t (14) = - 3.08, p = 0.008), CI = [- 5.73; -1.02], need help [t (14) = - 3.50, p =0.004), CI = [- 5.45; 1.30]. The interaction between time and intervention was significant for the level of emotional distress, depression, anxiety, event impact and quality of life. In conclusion, psychological group intervention can be a useful approach to increase the quality of life of breast cancer patients undergoing radiotherapy. The limitations of the study are related to the size of the sample, the compressed therapy sessions, and the absence of follow-up. [ABSTRACT FROM AUTHOR]

Endometriosis is an inflammatory pathology associated with a negative effect on life quality. Recently, this pathology was connected to ovarian cancer, in particular with endometrioid ovarian cancer. microRNAs (miRNAs) are a class of RNA transcripts ~19-22 nucleotides in length, the altered miRNA pattern being connected to pathological status. miRNAs are highly stable transcripts, and these can be assessed from formalin-fixed paraffin-embedded (FFPE) samples leading to the identification of miRNAs that could be developed as diagnostic and prognostic biomarkers, in particular those involved in malignant transformation. The aim of our study was to evaluate miRNA expression pattern in FFPE samples from endometriosis and ovarian cancer patients using PCR-array technology and also to compare the differential expression pattern in ovarian cancer versus endometriosis. For the PCR-array study, we have used nine macrodissected FFPE samples from endometriosis tissue, eight samples of ovarian cancers and five normal ovarian tissues. Quantitative real-time PCR (qRT-PCR) was used for data validation in a new patient cohort of 17 normal samples, 33 endometriosis samples and 28 ovarian cancer macrodissected FFPE samples. Considering 1.5-fold expression difference as a cut-off level and a P-value <0.05, we have identified four miRNAs being overexpressed in endometrial tissue, while in ovarian cancer 15 were differentially expressed (nine overexpressed and six downregulated). The expression level was confirmed by qRT-PCR for miR-93, miR-141, miR-155, miR-429, miR-200c, miR-205 and miR-492. Using the interpretative program Ingenuity Pathway Analysis revealed several deregulated pathways due to abnormal miRNA expression in endometriosis and ovarian cancer, which in turn is responsible for pathogenesis; this differential expression of miRNAs can be exploited as a therapeutic target. A higher number of altered miRNAs were detected in endometriosis versus ovarian cancer tissue, most of them being linked with epithelial-to-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Background: Smartphones and mobile devices have become ubiquitous, and with the rapid advance of technology, the number of health applications (apps) that are available for consumers on these devices is constantly growing. In particular, there has been a recent proliferation of anxiety apps. However, there has been no review of the quality or content of these anxiety apps and little is known about their purpose, the features they contain, and their empirical support. The goal of this systematic review was to assess the commercially available anxiety apps.Methods: A list of anxiety apps was collected in January 2017, using the Power Search function of iTunes and Google Play. Of 5,078 identified apps, 52 met our inclusion criteria (i.e., being defined as an anxiety/worry relief app, and offering psychological techniques aimed primarily at reducing anxiety) and were further reviewed.Results: The majority (67.3%) of the currently available anxiety apps were found to lack the involvement of health care professionals in their development, and very few (3.8%) of them have been rigorously tested.Conclusions: At the moment, although anxiety apps have the potential to enhance access to mental health care, there is a marked discrepancy between the wealth of commercially available apps, and the paucity of data regarding their efficacy and effectiveness. Although the great promise of apps is their ability to increasing access to evidence-based mental health, the field is not quite there yet and the full potential of apps for treating anxiety has yet to be exploited. [ABSTRACT FROM AUTHOR]

Background: The gastrointestinal tract is the primary site of toxin interaction, an interface between the organism and its surroundings. In this study, we assessed the alteration of intestinal mRNA profile in the case of co-occurrence of zearalenone (ZEA), a secondary Fusarium metabolite, and Escherichia coli (E. coli), on the intestinal porcine epithelial cells IPEC-1. We chose this model since the pig is a species which is susceptible to pathogen and mycotoxin co-exposure. Results: After treating the cells with the two contaminants, either separately or in combination, the differential gene expression between groups was assessed, using the microarray technology. Data analysis identified 1691 upregulated and 797 downregulated genes as a response to E. coli exposure, while for ZEA treated cells, 303 genes were upregulated and 49 downregulated. The co-contamination led to 991 upregulated and 800 downregulated genes. The altered gene expression pattern was further classified into 8 functional groups. In the case of co-exposure to ZEA and E.coli, a clear increase of proinflammatory mechanisms. Conclusions: These results demonstrate the complex effect of single or multiple contaminants exposure at cellular and molecular level, with significant implications that might lead to the activation of pathological mechanisms. A better understanding of the effects of co-contamination is mandatory in developing novel exposure regulations and prevention measures. [ABSTRACT FROM AUTHOR]

In this work, two new phenothiazinium dyes containing N -piperidinyl-carbinol auxochrome units have been designed, synthesized and investigated in vitro for ovarian cancer cell fluorescence imaging and cytotoxicity. A solvent free mechanochemical procedure is described as a greener alternative to the previously reported synthetic methodology applied in the preparation of methylene blue analogues by the substitution of the phenothiazinium tetraiodide substrate with nucleophilic secondary amines in solution. The optical properties of the new dyes were evaluated by UV–vis absorption/emission spectroscopy which revealed maxima situated in the red region (λ max absorption = 668-664 nm and λ max emission = 715-698 nm) with large molar extinction coefficients (log ε = 4.5–5.1) and bathochromic shifts of 314–383 cm−1 occurring upon switching from less polar to more polar solvents. The theoretical DFT computational study performed in order to clarify the obtained data indicated that the vertical TD-DFT calculations (typically applied for simulating UV–vis spectra) were within ∼150 nm of the experimental data, but a better agreement with experiment was obtained by using the vibronic corrections which revealed a dominant vibronic component not only for the main absorption/emission maxima, but also for the displayed shoulders which are rather the effects of the vibronic coupling between S 0 and S 1 electronic states. The new dyes presented a hydrophilic character (logP n -octanol/water = −1.15 and −1.29 respectively) comparable to the parent methylene blue and no aggregation tendency was observed in aqueous solution at concentration range 75–150 μM used in this study. Cellular imaging experiments displayed the new dyes' ability to selectively stain the cytoplasm of tumoral OVCAR-3 and A2780 fixed cells. The evaluation of their biological activity encompassed cell grow inhibitory potential (dose-response activity and half maximal inhibitory concentration IC 50), as well as their capacity to influence the tumoral OVCAR-3, A2780 and healthy BJ ovarian cells' metabolic activity. Dye 2 exhibited moderate cytotoxicity against human ovarian cancer cell lines, being the most active against the A2780 ovarian adenocarcinoma cells where its cellular uptake was noteworthy and displayed a deeper influence on the chemoresistant, highly malignant OVCAR-3 cells function by modulating FOLR1, ICAM-1 and VCAM-1 proteins with role in the growth and migration of cancer cells. [Display omitted] • New symmetrical Phenothiazinium dyes containing N-piperidinyl-carbinol auxochrome. • Solvent free mechanochemical procedure for the synthesis of MB analogues. • Optical properties enlightened by theoretical TD-DFT calculations with vibronic correction. • In vitro cytoplasmatic accumulation and staining of ovarian tumor cell lines. • Cytotoxicity and multitarget influence on ovarian tumor cell's functions. [ABSTRACT FROM AUTHOR]

Background: Sample processing is a crucial step for all types of genomic studies. A major challenge for researchers is to understand and predict how RNA quality affects the identification of transcriptional differences (by introducing either false-positive or false-negative errors). Nanotechnologies help improve the quality and quantity control for gene expression studies. Patients and methods: The study was performed on 14 tumor and matched normal pairs of tissue from patients with bladder urothelial carcinomas. We assessed the RNA quantity by using the NanoDrop spectrophotometer and the quality by nano-microfluidic capillary electrophoresis technology provided by Agilent 2100 Bioanalyzer. We evaluated the amplification status of three housekeeping genes and one small nuclear RNA gene using the ViiA 7 platform, with specific primers. Results: Every step of the sample handling protocol, which begins with sample harvest and ends with the data analysis, is of utmost importance due to the fact that it is time consuming, labor intensive, and highly expensive. High temperature of the surgical procedure does not affect the small nucleic acid sequences in comparison with the mRNA. Conclusion: Gene expression is clearly affected by the RNA quality, but less affected in the case of small nuclear RNAs. We proved that the high-temperature, highly invasive transurethral resection of bladder tumor procedure damages the tissue and affects the integrity of the RNA from biological specimens. [ABSTRACT FROM AUTHOR]

Background and aim. Ketamine is a drug used for the induction and maintenance of general anesthesia, for the treatment of postoperative and posttraumatic acute pain, and more recently, for the reduction of postoperative opioid requirements. The main mechanism of action of ketamine is the antagonization of N-methyl-D-aspartate (NMDA) receptors that are associated with central sensitization. In the pathogenesis of chronic pain and particularly in neuropathic pain, an important role is played by the activation of NMDA receptors. Although ketamine is indicated and used for the treatment of chronic cancer pain as an adjuvant to opioids, there are few clinical studies that clearly demonstrate the effectiveness of ketamine in this type of pain. The aim of this study is to analyze evidence-based clinical data on the effectiveness and safety of ketamine administration in the treatment of chronic neoplastic pain, and to summarize the evidence-based recommendations for the use of ketamine in the treatment of chronic cancer pain. Method. We reviewed the literature from the electronic databases ofMEDLINE, COCHRANE, PUBMED, MEDSCAPE (1998-2014), as well as chapters of specialized books (palliative care, pain management, anesthesia). Results. A number of studies support the effectiveness of ketamine in the treatment of chronic cancer pain, one study does not evidence clear clinical benefits for the use of ketamine, and some studies included too few patients to be conclusive. Conclusions. Ketamine represents an option for neoplasic pain that no longer responds to conventional opioid treatment, but this drug should be used with caution, and the development of potential side effects should be carefully monitored. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a highly aggressive phenotype that is resistant to standard therapy. Thus, the development of alternative therapeutic strategies for TNBC is essential. The purpose of our in vitro study was to evaluate the impact of p53 gene silencing in conjunction with the administration of a natural compound, epigallocatechingallate (EGCG). RT2Profiler PCR Array technology was used to evaluate the impact of dual treatment on the main genes involved in apoptosis in the Hs578T cell culture model of TNBC. Gene expression analysis revealed 28 genes were significantly altered (16 upregulated and 12 downregulated) in response to combined p53 siRNA and EGCG treatment. Further analysis revealed that p53 siRNA and EGCG dual therapy leads to the activation of pro-apoptotic genes and the inhibition of pro-survival genes, autophagy, and cell network formation. These results indicate that this dual therapy targets both the apoptotic and angiogenic pathways, which may improve treatment effectiveness for tumors resistant to conventional treatment. [ABSTRACT FROM AUTHOR]

A normal evolution of the cell-cycle phases consists of multiple consecutive events, which makes it a highly complex process. Its preservation is regulated by Cyclin-Cdks (cyclin-dependent kinases) interactions and protein degradation, which is often controlled by the ubiquitin-mediated proteolysis. The goal of this review is to emphasize the most important features of the regulation of the cell-cycle involved in cancerogenesis, by presenting the involvement of E3 ubiquitin ligases SCF (Skp1-Cul1-F-box protein) and APC/C (Anaphase-promoting complex/cyclosome) in human malignancies. Also, we discuss the importance of the ubiquitin proteasome pathway blockade in cancer treatment. We know that a better understanding of the regulatory biology of the cell cycle can lead to the development of new target therapies for cancer. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NSG) is an important method for gathering large amounts of sequencing data for different types of applications regarding the diagnosis and response to treatment of different diseases. An important step in the NGS process is the quality control of sequencing libraries, which can influence the yield and efficiency of the sequencing run. This study evaluated two different methods for library quality control, Agilent Bioanalyzer and qPCR, and showed that both methods can be used. However, as is the case with any analytical method, they have their limitations. The Agilent Bioanalyzer quantifies only the high quality libraries, but it underestimates their concentration, while qPCR also quantifies lower quality libraries, but it overestimates their concentration. [ABSTRACT FROM AUTHOR]

NHERF1 (Na+/H+ exchanger regulatory factor) is a scaffolding protein, consists of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region. NHERF1 recruits macromolecular complexes at the apical membrane of epithelial cells in many epithelial tissues. It is involved in trafficking and regulation of transmembrane ion transporters and G protein- coupled receptors. Further, NHERF1 also linked other molecules involved in cell growth and cancer progression, such as PDGFR, PTEN, ß-catenin, EGFR and HER2/neu. In this review, we focus on the role of NHERF1 during cancer development. Evidences of its involvement in cancer development are present in hepatocellular carcinoma, schwannoma, glioblastoma, colorectal cancer and particularly in breast cancer. Recent findings obtained from our laboratory show that cytoplasmic NHERF1 expression in- creases gradually in breast cancer during carcinogenesis, and its overexpression is associated with aggressive clinical parameters, unfavourable prognosis, and increased tumor hypoxia. Interestingly, also nuclear NHERF1 expression seems to play a role both in carcinogenesis and progression of colorectal cancer. These data suggest that NHERF1 could be a new biomarker of advanced malignancies. [ABSTRACT FROM AUTHOR]

NHERF1 (Na^+/H^+ exchanger regulatory factor) is a scaffolding protein, consists of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region. NHERF1 recruits macromolecular complexes at the apical membrane of epithelial cells in many epithelial tissues. It is involved in trafficking and regulation of transmembrane ion transporters and G protein-coupled receptors. Further, NHERF1 also linked other molecules involved in cell growth and cancer progression, such as PDGFR, PTEN, β-catenin, EGFR and HER2/neu. In this review, we focus on the role of NHERF1 during cancer development. Evidences of its involvement in cancer development are present in hepatocellular carcinoma, schwannoma, glioblastoma, colorectal cancer and particularly in breast cancer. Recent findings obtained from our laboratory show that cytoplasmic NHERF1 expression increases gradually in breast cancer during carcinogenesis, and its overexpression is associated with aggressive clinical parameters, unfavourable prognosis, and increased tumor hypoxia. Interestingly, also nuclear NHERF1 expression seems to play a role both in carcinogenesis and progression of colorectal cancer. These data suggest that NHERF1 could be a new biomarker of advanced malignancies. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NSG) is an important method for gathering large amounts of sequencing data for different types of applications regarding the diagnosis and response to treatment of different diseases. An important step in the NGS process is the quality control of sequencing libraries, which can influence the yield and efficiency of the sequencing run. This study evaluated two different methods for library quality control, Agilent Bioanalyzer and qPCR, and showed that both methods can be used. However, as is the case with any analytical method, they have their limitations. The Agilent Bioanalyzer quantifies only the high quality libraries, but it underestimates their concentration, while qPCR also quantifies lower quality libraries, but it overestimates their concentration. [ABSTRACT FROM AUTHOR]

Introduction: Endometrial cancer is the most common gynecologic malignancy in developed countries. The adequate surgical staging proposed by FIGO (International Federation for Gynaecology and Obstetrics) advocates lymphadenectomy; however, it does not establish the indications, the type and the extent of lymphadenectomy, thus generating multiple controversies. Methods: Retrospective, analytical study of patients treated surgically for endometrial adenocarcinoma in the Oncological Institute "Prof. Dr. Ion Chiricuţă" Cluj-Napoca (IOCN) between January 2008 and December 2012 - 709 cases eligible for the study. Results: 206 pelvic and/or paraaortic lymphadenectomies were performed, the average number of excised lymph nodes being 15.6. Overall in 4.4% of patients the lymph nodes were affected by metastases. The presence of each risk factor analysed was statistically significantly associated with lymph node metastasis (p<0.05). Age above 55 years was statistically significantly associated (p<0.05) with the presence of negative prognostic factors in the study. Conclusions: The analysed histopathological and clinical prognostic factors were statistically significantly associated with lymphatic dissemination in endometrial cancer. We recommend treating endometrial cancer in tertiary centres by surgeons or gynaecologists-oncologists with experience in extensive peritoneal and retroperitoneal surgery [ABSTRACT FROM AUTHOR]

To date, there is no multivariate analysis in literature on the relationships between quality of life (QOL), female sexual functioning, symptomatology, distress and irrational beliefs among women with premalignant and malignant pathology of the cervix, namely aggravator dysplasia and microinvasive carcinoma with conservative surgery - cervix conization. This study investigated the relationships among the five variables using structural equation modelling. One hundred and two women with premalignant and malignant pathology of the cervix were included in the study and filled in a set of measures during the first year after surgery. The following instruments were used: Female Sexual Function Index (FSFI), the European Organisation for Research and Treatment of Cancer Quality of Life C30 (EORTC QOL-C30), the Attitudes and Beliefs Scale, Short Version (ABS-SV) and a distress visual analogue scale. Goodness-of-fit indices were obtained for the final structural model by MLR estimation : Χ²/df ratio=1.54, TLI = 0.87, CFI = 0.88, RMSEA = 0.07 (90% CI: 0.065- 0.084) SRMR = 0.08 and bootstrapping: Χ²/df ratio = 1.30, TLI = 0.89, CFI = 0.90, RMSEA = 0.05 (90% CI : 0.043-0.064 ), SRMR = 0.086. No direct effect of sexual functioning and irrational beliefs on quality of life was found, but there is a tendency of dependence between distress and QOL. There is a positive correlation between irrational beliefs and symptomatology (β=0.40), so that symptoms are more serious, in persons who have more irrational beliefs. Also, there is a correlation between distress and symptomatology (β=0.37), and distress and irrational beliefs (ß=0.41). The model explained 98% of the total variance of QOL. In conclusion, the structural model provides a valid assessment model of QOL, a ranking of levels of QOL by regression weights and the interrelationships between the specified constructs. [ABSTRACT FROM AUTHOR]

The primary approach to controlling the spread of the pandemic SARS-CoV-2 is to diagnose and isolate the infected people quickly. Our paper aimed to investigate the efficiency and the reliability of a hierarchical pooling approach for large-scale PCR testing for SARS-CoV-2 diagnosis. To identify the best conditions for the pooling approach for SARS-CoV-2 diagnosis by RT-qPCR, we investigated four manual methods for both RNA extraction and PCR assessment targeting one or more of the RdRp, N, S, and ORF1a genes, by using two PCR devices and an automated flux for SARS-CoV-2 detection. We determined the most efficient and accurate diagnostic assay, taking into account multiple parameters. The optimal pool size calculation included the prevalence of SARS-CoV-2, the assay sensitivity of 95%, an assay specificity of 100%, and a range of pool sizes of 5 to 15 samples. Our investigation revealed that the most efficient and accurate procedure for detecting the SARS-CoV-2 has a detection limit of 2.5 copies/PCR reaction. This pooling approach proved to be efficient and accurate in detecting SARS-CoV-2 for all samples with individual quantification cycle (Cq) values lower than 35, accounting for more than 94% of all positive specimens. Our data could serve as a comprehensive practical guide for SARS-CoV-2 diagnostic centers planning to address such a pooling strategy. [ABSTRACT FROM AUTHOR]

The Hippo signaling pathway, one of the most conserved in humans, controlling dimensions of organs and tumor growth, is frequently deregulated in several human malignancies, including ovarian cancer (OC). The alteration of Hippo signaling has been reported to contribute to ovarian carcinogenesis and progression. However, the prognostic roles of individual Hippo genes in OC patients remain elusive. Herein we investigated the expression level and prognostic value of key Hippo genes in OC using online databases, followed by a qRT-PCR validation step in an additional patient cohort. Using the GEPIA database, we observed an increased level for TP53 and reduced expression level for LATS1, LATS2, MST1, TAZ, and TEF in tumor tissue versus normal adjacent tissue. Moreover, LATS1, LATS2, TP53, TAZ, and TEF expression levels have prognostic significance correlated with progression-free survival. The qRT-PCR validation step was conducted in an OC patient cohort comprising 29 tumor tissues and 20 normal adjacent tissues, endorsing the expression level for LATS1, LATS2, and TP53, as well as for two of the miRNAs targeting the TP53 gene, revealing miR-25-3p upregulation and miR-181c-5p downregulation. These results display that there are critical prognostic value dysregulations of the Hippo genes in OC. Our data demonstrate the major role the conserved Hippo pathway presents in tumor control, underlying potential therapeutic strategies and controlling several steps modulated by miRNAs and their target genes that could limit ovarian cancer progression. [ABSTRACT FROM AUTHOR]

Prostate cancer represents the most encountered urinary malignancy in males over 50 years old, and the second most diagnosed after lung cancer globally. Digital rectal examination and prostatic specific antigen were the long-time standard tools for diagnosis but with a significant risk of overdiagnosis and overtreatment. Magnetic resonance imaging recently entered the diagnosis process, but to this date, there is no specific biomarker that accurately indicates whether to proceed with the prostate biopsy. Research in this area has gone towards this direction, and recently, serum, urine, imagistic, tissue biomarkers, and Risk Calculators promise to help better diagnose and stratify prostate cancer. In order to eliminate the comorbidities that appear along with the diagnosis and treatment of this disease, there is a constant need to implement new diagnostic strategies. Important uro-oncology associations recommend the use of novel biomarkers in the grey area of prostate cancer, to better distinguish the next step in the diagnostic process. Although it is not that simple, they should be integrated according to the clinical policies, and it should be considered that statistical significance does not always equal clinical significance. In this review, we analyzed the contribution of prostate-specific antigen (PSA)-based biomarkers (PHI, PHID, 4Kscore, STHLM3), imagistic techniques (mp-MRI and mp-US), and combined tests in the early diagnosis process of localized prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is one of the most common oncological diseases in women, as its incidence is rapidly growing. In this study, we have investigated the mechanism of epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs), demonstrating presence of an interconnectedness between them. This interconnectedness plays important roles in patient prognostic, as well as in diagnostic and therapeutic targets. It is identified that there is a common signature between CSCs and EMT, and this is represented by ALDH1A1, SFRP1, miR-139, miR-21, and miR-200c. This finding will provide a better understanding of this mechanism, and will facilitate the development of novel treatment options. Breast cancer is one of the most common oncological diseases in women, as its incidence is rapidly growing, rendering it unpredictable and causing more harm than ever before on an annual basis. Alterations of coding and noncoding genes are related to tumorigenesis and breast cancer progression. In this study, several key genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) features were identified. EMT and CSCs are two key mechanisms responsible for self-renewal, differentiation, and self-protection, thus contributing to drug resistance. Therefore, understanding of the relationship between these processes may identify a therapeutic vulnerability that can be further exploited in clinical practice, and evaluate its correlation with overall survival rate. To determine expression levels of altered coding and noncoding genes, The Cancer Omics Atlas (TCOA) are used, and these data are overlapped with a list of CSCs and EMT-specific genes downloaded from NCBI. As a result, it is observed that CSCs are reciprocally related to EMT, thus identifying common signatures that allow for predicting the overall survival for breast cancer genes (BRCA). In fact, common CSCs and EMT signatures, represented by ALDH1A1, SFRP1, miR-139, miR-21, and miR-200c, are deemed useful as prognostic biomarkers for BRCA. Therefore, by mapping changes in gene expression across CSCs and EMT, suggesting a cross-talk between these two processes, we have been able to identify either the most common or specific genes or miRNA markers associated with overall survival rate. Thus, a better understanding of these mechanisms will lead to more effective treatment options. [ABSTRACT FROM AUTHOR]

The synthesis, characterization and cytotoxic activity against different cancer cell lines of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and, secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption spectroscopy and microscopy. In addition, these systems have been tested against four different cancer cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show that the materials are more active when the quantity of folic acid is higher, especially in those cells that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show that a relatively high concentration of folic acid functionalization of the nanostructured silica together with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of membrane FR-α and by the release of intracellular FR-α. This study validates the potential use of a combination of mesoporous silica materials co-functionalized with folate targeting molecules and an organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing folate receptors. [ABSTRACT FROM AUTHOR]

We report here the synthetic procedure applied for the preparation of new AB3-type and trans-A2B2 type meso-halogenophenothiazinyl-phenyl-porphyrin derivatives, their metal core complexation and their peripheral modification using Suzuki–Miyaura cross coupling reactions with various (hetero)aryl (phenothiazinyl, 7-formyl-phenothiazinyl, (9-carbazolyl)-phenyl and 4-formyl-phenyl, phenyl) boronic acid derivatives. The meso-phenothiazinyl-phenyl-porphyrin (MPP) dyes family was thus extended by a series of novel phenothiazine-bridged porphyrin-(hetero)aryl dyads characterized by UV–Vis absorption/emission properties typical to the porphyrin chromophore, slightly modulated by increasing the size of peripheral substituents. Three phenothiazine-bridged porphyrin-heteroaryl dyads with fluorescence emission above 655 nm were selected as fluorophores in red spectral region for applications in cellular staining of human ovarian tumors. In vitro experiments of cell metabolic activity displayed a moderate toxicity on human ovarian tumor cell lines (OVCAR-3, cisplatin-sensitive A2780 and cisplatin-resistant A2780cis respectively). Visualization of the stained living cells was performed both by fluorescence microscopy imaging and by fluorescence lifetime imaging under two photon excitation (TPE-FLIM), confirming their cellular uptake and the capability of staining the cell nucleus. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is sensitive to upfront chemotherapy, which is likely attributable to defects in DNA damage repair (DDR). Unfortunately, patients relapse and the evolution of DDR competency are poorly described. We examined the expression of proposed effectors in homologous recombination (HR: RAD51, ATM, FANCD2), error-prone non-homologous end-joining (NHEJ: 53BP1), and base excision repair pathways (BER: PAR and PARP1) in a cohort of sequential OC samples obtained at diagnosis, after neoadjuvant chemotherapy (NACT), and/or at relapse from a total of 147 patients. Immunohistochemical (IHC) expression was quantified using the H-score (0–300), where H ≤ 10 defined negativity. Before NACT, a significant number of cases lacked the expression of some effectors: 60%, 60%, and 24% were PAR-, FANCD2-, or RAD51-negative, with a reassuringly similar proportion of negative biomarkers after NACT. In multivariate analysis, there was a poorer progression-free survival (PFS) and overall survival (OS) for cases with competent HR at diagnosis (PRE-NACT 53BP1−/RAD51+, hazard ratio (HR) 3.13, p = 0.009 and HR 2.78, p = 0.024) and after NACT (POST-NACT FANCD2+/RAD51+ HR 1.89, p = 0.05 and HR 2.38, p = 0.02; POST-NACT PARP-1+/RAD51+ HR 1.79, p = 0.038 and HR 2.04, p = 0.034), reflecting proficient DNA repair. Overall, HR-competent tumors appeared to have a dismal prognosis in comparison with tumors utilizing NHEJ, as assessed either at baseline or post-NACT. Accurate knowledge of the HR status during treatment is clinically important for the efficient timing of platinum-based and targeted therapies with poly(ADP-ribose) polymerase inhibitors (PARPi). [ABSTRACT FROM AUTHOR]

Background: Granulosa cell tumor (GCT) is a rare type of ovarian tumors which derives from sex-cord stromal cells. Two distinct histological types are described: adult type (95%) and juvenile type (5%). Hyperestrogenism features and symptoms occur in both types of GCT. In comparison with other ovarian tumors, it has a favorable prognosis, a low risk of malignancy, but a high rate of recurrence. Objective: A 60 years old female patient was admitted for a giant abdominal distension, abdominal pain, inappetence, constipation, inability to move and acute respiratory insufficiency. Material and methods: Biologically, the level of CA-125 was elevated, which raises a suspicion of an ovarian tumor. A CT examination could not be performed due to the giant tumor which enabled the patient to lay down on the bed of the CT scanner. As a result, the patient underwent surgery. The surgical attitude was the resection of the tumor, total hysterectomy, bilateral salpingo-oophorectomy and infracolic omentectomy (the appendix was already removed). Suspect adenopathies were not found. After the resection of the tumor, the patient suffered a hypotensive shock which was managed by receiving 10 units of blood and noradrenaline iv. Results: The histopathological exam reveals an adult granulosa cell tumor of the left ovary T1aNxL0V0, 39x38x9cm with a weight of 38 kilograms, intraepithelial endometrial neoplasia and uterine leiomyoma. Chemotherapy was not recommended. The patient recovery went well, being discharged after 10 days and she is under observation for any potential recurrence. Conclusion: Large abdominal tumors are not usually malignant and they do not require chemotherapy or radiotherapy, but they require immediate resection due to the compressive effects, multiple organs dysfunction and severe anemia. GCT is one of this kind of tumors and even if it is rare, it should be included in the differential diagnosis. [ABSTRACT FROM AUTHOR]

The initial management of the hematology patient in a critical state is crucial and poses a great challenge both for the hematologist and the intensive care unit (ICU) physician. After years of clinical practice, there is still a delay in the proper recognition and treatment of critical situations, which leads to late admission to the ICU. There is a much-needed systematic ABC (Airway, Breathing, Circulation) approach for the patients being treated on the wards as well as in the high dependency units because the underlying hematological disorder, as well as disease-related complications, have an increasing frequency. Focusing on score-based decision-making on the wards (Modified Early Warning Score (MEWS), together with Quick Sofa score), active sepsis screening with inflammation markers (C-reactive protein, procalcitonin, and presepsin), and assessment of microcirculation, organ perfusion, and oxygen supply by using paraclinical parameters from the ICU setting (lactate, central venous oxygen saturation (ScVO2), and venous-to-arterial carbon dioxide difference), hematologists can manage the immediate critical patient and improve the overall outcome. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a highly heterogeneous pathology, exhibiting a number of subtypes commonly associated with a poor outcome. Due to their high stability, microRNAs are often regarded as non-invasive cancer biomarkers, having an expression pattern specific for their 'cell of origin'. Method: Triple negative breast cancer (TNBC: ER-, PR-, Her-2-) and double positive breast cancer (DPBC: ER+, PR+, Her-2) miRNA expression patterns were obtained by analysis of the TCGA (The Cancer Genome Atlas) data, followed by PCR-array analysis on plasma samples from 20 TNBC patients, 14 DPBC patients and 11 controls. Results: Three downregulated and nine upregulated miRNAs were obtained from the TNBC analysis. Five overexpressed miRNAs were identified in the DPBC group. Four of the dysregulated miRNAs (miR-10a, miR-125b, miR-210 and miR-489) were common for both groups. The cluster miR-17-92 (miR-17, miR-20a, miR-20b, and miR-93), along with miR-130, miR-22 and miR-29a/c, were found to differentiate between TNBC and DPBC. A panel of five transcripts (miR-10a, miR-125, miR-193b, miR-200b and miR-489) was validated in a new set of plasma samples. The overlapping of TCGA and plasma profiling data revealed miR-200b, miR-200c, miR-210 and miR-29c as common signature. MiR-200b was validated on additional normal and tumor tissue samples. The expression level of this transcript from the TCGA data was correlated with lung and bone metastatic genes. Conclusion: The miR-200b presents a great potential for the future advancements in the diagnostic/prognostic and therapeutic approach of TNBC, along with other coding or non-coding transcripts. However, this needs to be further integrated in a regulatory network that acts in conjunction with other markers that affect the patients' prognosis or response to therapy. [ABSTRACT FROM AUTHOR]