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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]

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]

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]

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]