Introduction: Despite the progress in diagnosis and treatment of malignant tumours, the effects of treatment are insufficient. Reduction of the risk of cervical, ovarian, and endometrial cancer is possible by introducing preventative actions.Aim of the study: The aim of the thesis is the analysis of selected risk factors that may affect the increase or decrease in the odds ratio of developing endometrial cancer.Material and methods: The study was conducted among patients of the Gynaecology and Obstetrics Hospital of Poznań University of Medical Sciences in the years 2011-2013.The research included a total of 548 female respondents aged between 40 and 84 years. Women responded to questions assessing elements of lifestyle such as consumption of alcohol, smoking, and eating certain groups of foods.Results: The respondents consuming fruits and vegetables several times a week have a reduced risk of odds ratio and the OR is 0.85; 95% CI: 0.18-4.09, compared to the women who rarely consume vegetables and fruits. Consumption of whole-wheat bread several times a week reduces the risk of developing the cancer, OR = 0.59; 95% CI: 0.14-2.47, compared to women not consuming wholegrain bread at all. Respondents who consumed red meat, such as veal, pork, and lamb in the amount of 101-200 g per day have an increased risk of developing the disease: OR = 2.16; 95% CI: 1.09-4.28, compared to women not consuming red meat at all.Conclusions: A diet rich in fruit and vegetables, onions, garlic, whole grains, and beans should be introduced in order to reduce the risk of endometrial cancer. The consumption of red meat and white pasta should be reduced or even eliminated.Key words: endometrial cancer, risk factors, the odds ratio of developing the disease.

Objectives. The aim of the study was to identify socio-economic factors that may influence the emotional changes which occur among new mothers in the first days postpartum. Materials and method. A group of 541 women completed a questionnaire consisting of 30 multiple-choice questions, Edinburgh Postnatal Depression Scale (EPDS), and Hospital Anxiety and Depression Scale (HADS). Statistical calculations were performed with the use of Statistica v.10 and Cytel Studio v. 9.0.0. Results. The findings revealed the presence of factors which might increase the risk of mood disorders during the postpartum period.Conclusions. Women who demonstrate warning symptoms should be screened for postnatal emotional changes and mood swings during their hospitalization after delivery. EPDS seems to be a suitable tool for early detection of emotional disturbances.

Berubicin (WP744) is a doxorubicin analog that crosses the blood-brain barrier (BBB), shows significant CNS uptake, and induces more DNA damage but lower lethality than doxorubicin at equivalent doses. Berubicin also prolongs the survival time of intracranial orthotopic glioma models in mice compared to temozolomide, currently the standard of care in GBM. A Phase 1 study at MD Anderson in patients with recurrent glioma treated with escalating doses of Berubicin administered qdx3 repeated q21 days showed that it was well tolerated, with myelosuppression (neutropenia and thrombocytopenia) as the dose-limiting toxicity. Of 25 patients evaluable for efficacy, there was 1 complete response (13+ years), 1 partial response, and 10 patients with stable disease for a clinical benefit rate of 48%. To assure a rapid and economically practicable development program, two companies have collaborated to conduct trials in the US and EU, leading to a potentially more rapid approval of Berubicin for treating GBM in patients with limited options. CNS Pharmaceuticals, Inc. has initiated a randomized, controlled clinical trial of Berubicin vs. lomustine in adults with recurrent GBM. WPD Pharmaceuticals has sub-licensed Berubicin to study recurrent GBM in adults in an open-label trial. This is a unique collaboration in which the same overall design, eligibility criteria, procedures, and database for patients receiving Berubicin are used by both companies, ensuring that there will be a more robust and substantial data set for evaluation of activity and safety. The primary endpoint of the CNS study, to be conducted in the US and Europe, is overall survival (OS). The WPD study conducted in the EU has a primary endpoint of overall response rate (ORR). The data from these two trials are expected to provide sufficient information to support a potential registration program in both the US and EU for the treatment of patients with glioblastoma.

Background: MF, the most common variant of cutaneous T-cell lymphoma (CTCL) is a disease in which T-cell lymphocytes become malignant, resulting in highly symptomatic, disfiguring skin lesions even in the earliest stages. Standard therapy for MF includes both local and systemic treatments that have shown efficacy, but some have considerable side effects. The recent understanding of the pathogenesis and signaling pathways promoting MF suggest that a focus on the development of targeted therapies could provide important advances for more effective treatment. The signal transducer and activator of transcription protein3 (STAT3) is an oncogenic transcription factor that drives invasion, angiogenesis, and immune suppression in many tumors. It has been identified as one of the key regulators of MF. STAT3 activation via phosphorylation of tyrosine 705 (p-STAT3) leads to increased proliferation and survival of tumor cells as well as suppression of the immune response. WP1220 is a synthetic analogue of caffeic acid benzyl ester (CABE) that potently inhibits p-STAT3 and effectively inhibits growth of CTCL cell lines in vitro. Methods: This is the first clinical evaluation of WP1220, a p-STAT3 inhibitor in MF. This Phase 1b study was designed to demonstrate the safety and efficacy of topical treatment with a 10% (w/w) WP1220 ointment in adults with Stage I, II or III MF. Topical WP1220 is not absorbed and has no systemic effects. Patients were required to have histopathologic confirmation of the diagnosis of MF and have at least 2 lesions or more up to a maximum total skin area of ≤40cm2.Lesions were selected on the basis of progression despite at least one prior therapy, which could have been either systemic or topical. No concomitant topical therapies on index lesions to which WP1220 was applied was allowed. Patients were trained to apply ointment 2X daily for 3 months on these index lesions, which were evaluated on Days 7, 28, 56 and 84 using the same procedures/assessor throughout the study. The primary endpoint was absolute change from baseline CAILS (Composite Assessment of Index Lesion Severity) scores of the index lesions up to Day 84, with a follow up 1 month later (Day 112). Secondary objectives included monitoring of adverse events (AE) via patient diaries, and photographic documentation validated by independent dermatologic consultation. Biopsies from treated sites were obtained at baseline and at the end of the study to assess histopathology, as well as to perform exploratory evaluations of changes in STAT3 phosphorylation and pathway activation. Results: There were 6 patients screened, and 5 patients enrolled between March and July 2019. Three are evaluable for both safety and efficacy after completing 3 months of treatment, with 2 ongoing and evaluable for safety. The only AE reported potentially related to study drug in one of the five patients was a mild contact dermatitis not requiring treatment. CAILS scores on index lesions were significantly decreased in the first 3 patients, who were stages IA, IB, and IIB, respectively, at entry. A composite score was obtained for all treated lesions for each patient, and percent changes were calculated from baseline to Day 84. There was a median reduction of 70.8% (range 62.1%-76.2%) for the 3 patients. Improvement was noted as early as 7 days after initiation of treatment, and maintenance of improvement was also shown at follow up (1 month after discontinuation, as per protocol). The fourth patient has also shown an initial reduction in the composite CAILS score after 56 days (26.7%), and is continuing on treatment. Independent dermatologic review based on photographic documentation, which will be provided, is in progress, as are evaluations of the biopsy samples for histopathology and status of p-STAT3 in treated lesions. Conclusions: WP1220, an inhibitor of p-STAT3, has shown demonstrable safety and significant efficacy after at least 3 months of topical treatment in 3 patients with progressive MF, with a continuing trend towards improvement in additional patients currently in treatment. This is the first demonstration that inhibition of the STAT3 activation pathway with topical therapy has impacted the course of this disease. The trial is continuing, and updated and more comprehensive data from this study as well as assessment of STAT3 phosphorylation in treated lesions will be reported. Disclosures Klemp: Moleculin Biotech, Inc.: Employment, Equity Ownership. Silberman:Trovagene: Consultancy; Moleculin Biotech: Employment. Priebe:Moleculin Biotech, Inc.: Consultancy, Equity Ownership, Research Funding.

Introduction: An anthracycline combined with cytarabine remains the backbone for induction therapy in the treatment of AML. De novo and acquired multidrug resistance (MDR) limits efficacy of clinically used anthracyclines. L-Annamycin, a novel anthracycline formulated in multilamellar liposomes, has been shown to overcome MDR in preclinical in vitro and in vivo doxorubicin resistant models as well as in clinical studies. Furthermore, preclinical toxicology studies comparing L-Annamycin to doxorubicin determined that the drug displayed dramatically reduced cardiotoxicity. These promising properties justified initiation of Phase I/II clinical trials in both the US and Europe using L-Annamycin for the treatment of R/R AML. Aims: The aim of the Phase I component is to determine the recommended Phase 2 dose (RP2D) of L-Annamycin for the treatment of R/R AML. The expansion Phase IIa studies are designed to assess L-Annamycin efficacy leading to a Phase II registration study for accelerated approval. Methods: The Phase I component is a standard 3+3 design to determine the RP2D. An additional 21 patients expansion phase will be enrolled at the RP2D to confirm efficacy. A DMC will monitor all data and decide if the study should continue and if any changes to the protocol are needed. Cardiotoxicity is being closely studied with stress 2-D echocardiography and biomarkers such as troponin. Results: This study is ongoing in both Europe and the USA. Even at a relatively low starting dose, two patients had sufficient response from a single 3-day course of L-Annamycin to qualify for a potentially curative bone marrow transplant. In total, 11 patients have completed at least one course of L-Annamycin with no signs of cardiotoxicity. Adverse events included one instance of Grade 2 mucositis, which resolved quickly. Summary/Conclusion: Despite progress in the treatment of AML most patients will relapse and die from refractory disease. Properties of L-Annamycin, including the ability to overcome MDR, a critical mechanism of resistance, and the lack of cardiac toxicity, are highly promising and fully justify a Phase II clinical study designed to demonstrate L-Annamycin efficacy in all patients with R/R AML agnostic of mutational status. Disclosures Shepard: Moleculin Biotech Inc: Employment, Equity Ownership. Silberman:Trovagene: Consultancy; Moleculin Biotech: Employment. Priebe:MOLECULIN BIOTECH INC: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.