Attitudes and awareness related to cervical cancer vaccine.

Cervical cancer causes major morbidity and mortality around the world. This makes prophylactic vaccines a significant tool for preventing the disease. As these vaccines become more widely available, they have the potential to drastically lower the cancer's prevalence and burden in the future.

Results of the re-introduction of the Griffon Vulture () in Vrachanski Balkan Nature Park, Bulgaria - completion of the establishing phase 2010-2020.

The current study analyses and presents the results of the ten-year establishment phase of the Griffon Vulture () local re-introduction in Vrachanski Balkan Nature Park, north-western Bulgaria. Between 2010 and 2020, 61 rehabilitated and captive-bred Griffon Vultures from Spain, France and several European zoos were released from an acclimatisation aviary. The first successful breeding in the wild was reported in 2015.

First results from the releases of Cinereous Vultures () aiming at re-introducing the species in Bulgaria - the start of the establishment phase 2018-2022.

The current work presents the preliminary results of the Cinereous Vulture () releases in the Balkan Mountains in 2018-2022, aiming at the species re-introduction in Bulgaria, where it was listed as locally extinct since 1985. The first imports and releases of Cinereous Vultures in Bulgaria started in 2018. Until mid-2022, 72 individuals were released in the Eastern Balkan Mountains (Kotlenska Planina SPA and Sinite Kamani Nature Park) and Vrachanski Balkan Nature Park.

BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas.

Bromodomain and extraterminal proteins (BET) play key roles in regulation of gene expression, and may play a role in cancer-cell proliferation, survival, and oncogenic progression. CC-90010-ST-001 (NCT03220347) is an open-label phase I study of trotabresib, an oral BET inhibitor, in heavily pretreated patients with advanced solid tumors and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Primary endpoints were the safety, tolerability, maximum tolerated dose, and RP2D of trotabresib.

Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, "window-of-opportunity" study.

Background: The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection.

Methods: Patients received trotabresib 30 mg/day on days 1-4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery.

Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma.

Background: Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas.

Methods: In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM.

Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies.

Background: CC-90011 is an oral, potent, selective, reversible inhibitor of lysine-specific demethylase 1 (LSD1) that was well tolerated, with encouraging activity in patients who had advanced solid tumors or relapsed/refractory marginal zone lymphoma. The authors present long-term safety and efficacy and novel pharmacodynamic and pharmacokinetic data from the first-in-human study of CC-90011.

Methods: CC-90011-ST-001 (ClincalTrials.

Bromodomain and extra-terminal inhibitors-A consensus prioritisation after the Paediatric Strategy Forum for medicinal product development of epigenetic modifiers in children-ACCELERATE.

Based on biology and pre-clinical data, bromodomain and extra-terminal (BET) inhibitors have at least three potential roles in paediatric malignancies: NUT (nuclear protein in testis) carcinomas, MYC/MYCN-driven cancers and fusion-driven malignancies. However, there are now at least 10 BET inhibitors in development, with a limited relevant paediatric population in which to evaluate these medicinal products. Therefore, a meeting was convened with the specific aim to develop a consensus among relevant biopharmaceutical companies, academic researchers, as well as patient and family advocates, about the development of BET inhibitors, including prioritisation and their specific roles in children.

Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma.

Purpose: Lysine-specific demethylase 1 (LSD1) is implicated in multiple tumor types, and its expression in cancer stem cells is associated with chemoresistance. CC-90011 is a potent, selective, and reversible oral LSD1 inhibitor. We examined CC-90011 in advanced solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).

Paediatric Strategy Forum for medicinal product development of epigenetic modifiers for children: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

The fifth multistakeholder Paediatric Strategy Forum focussed on epigenetic modifier therapies for children and adolescents with cancer. As most mutations in paediatric malignancies influence chromatin-associated proteins or transcription and paediatric cancers are driven by developmental gene expression programs, targeting epigenetic mechanisms is predicted to be a very important therapeutic approach in paediatric cancer. The Research to Accelerate Cures and Equity (RACE) for Children Act FDARA amendments to section 505B of the FD&C Act was implemented in August 2020, and as there are many epigenetic targets on the FDA Paediatric Molecular Targets List, clinical evaluation of epigenetic modifiers in paediatric cancers should be considered early in drug development.

Avadomide plus obinutuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (CC-122-NHL-001): a multicentre, dose escalation and expansion phase 1 study.

Background: Avadomide (CC-122) is a novel oral cereblon-modulating agent with promising activity in non-Hodgkin lymphoma. We aimed to examine the safety and preliminary activity of avadomide plus obinutuzumab in patients with relapsed or refractory non-Hodgkin lymphoma.

Methods: CC-122-NHL-001 was a phase 1b dose escalation and expansion study at eight sites in France, Italy, and the Netherlands.

Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma.

Background: Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor.

Patients And Methods: CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL).

The novel, orally bioavailable HSP90 inhibitor NVP-HSP990 induces cell cycle arrest and apoptosis in multiple myeloma cells and acts synergistically with melphalan by increased cleavage of caspases.

Heat shock protein 90 (HSP90) binds and stabilizes numerous proteins and kinases essential for myeloma cell survival and proliferation. We and others have recently demonstrated that inhibition of HSP90 by small molecular mass inhibitors induces cell death in multiple myeloma (MM). However, some of the HSP90 inhibitors involved in early clinical trials have shown limited antitumor activity and unfavorable toxicity profiles.

Deficient recognition of emotional prosody in primary focal dystonia.

Background: Primary dystonia is a movement disorder attributed mainly to basal ganglia dysfunction. Besides motor control, striatopallidal structures are known to implement also non-motor functions including processing of cognitive and emotional information. Previous research has already demonstrated deficient recognition of emotional faces in patients with primary focal dystonia.

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.

Background: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs).

Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day.

Changes of emotional prosody in Parkinson's disease.

Even though the mesocortical dopamine system is known to play an important role in affect control and reward related behaviour, only little is known about the impact of Parkinson's disease on emotional communication. The ability to perceive and express emotions via speech plays an essential role in every day social life. Here, studies investigating perception and production of emotional prosody in Parkinson's disease will be reviewed and own results will be presented.

Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide.

A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor activity compared with HU monotherapy in the treatment of recurrent GBM. The target population consisted of patients with confirmed recurrent GBM and an Eastern Cooperative Oncology Group performance status of 0-2 who had completed previous treatment comprising surgical resection, irradiation therapy, and first-line chemotherapy (preferably temozolomide (TMZ) containing regimen) and who have progressed despite treatment.

Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors.

PURPOSE To study the pharmacokinetics (PK) of imatinib (IM) in patients with advanced GI stromal tumors (GISTs) treated in a randomized phase II study and to explore the potential relationship between IM plasma levels and long-term clinical outcomes. PATIENTS AND METHODS Patients were randomly assigned to receive IM at 400 mg versus 600 mg daily. IM plasma levels were analyzed in a subset of patients (n = 73) for whom PK data on day 1 and at steady-state (SS, day 29) were available.

Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases.

Purpose: To evaluate the activity of imatinib in treating advanced, life-threatening malignancies expressing one or more imatinib-sensitive tyrosine kinases.

Experimental Design: This was a phase II, open-label, single arm study. Patients > or = 15 years old with malignancies showing histologic or molecular evidence of expression/activation of imatinib-sensitive tyrosine kinases were enrolled.

Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT.

Purpose: The outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term with imatinib mesylate is unknown. A previous report of a randomized phase II trial of imatinib mesylate in patients with incurable GIST detailed high response rates at both the 400 and the 600 mg/d dose levels. We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status.

Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders.

Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL-negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL-negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.

Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225.

Purpose: The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib.

Patients And Methods: We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease.