Phase II study of induction chemotherapy with TPF followed by radioimmunotherapy with Cetuximab and intensity-modulated radiotherapy (IMRT) in combination with a carbon ion boost for locally advanced tumours of the oro-, hypopharynx and larynx - TPF-C-HIT

<p>Abstract</p> <p>Background</p> <p>Long-term locoregional control in locally advanced squamous cell carcinoma of the head and neck (SCCHN) remains challenging. While recent years have seen various approaches to improve outcome by intensification of treatment schedules through introduction of novel induction and combination chemotherapy regimen and altered fractionation regimen, patient tolerance to higher treatment intensities is limited by accompanying side-effects. Combined radioimmunotherapy with cetuximab as well as modern radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) and carbon ion therapy (C12) are able to limit toxicity while maintaining treatment effects. In order to achieve maximum efficacy with yet acceptable toxicity, this sequential phase II trial combines induction chemotherapy with docetaxel, cisplatin, and 5-FU (TPF) followed by radioimmunotherapy with cetuximab as IMRT plus carbon ion boost. We expect this approach to result in increased cure rates with yet manageable accompanying toxicity.</p> <p>Methods/design</p> <p>The TPF-C-HIT trial is a prospective, mono-centric, open-label, non-randomized phase II trial evaluating efficacy and toxicity of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 50 patients with histologically proven locally advanced SCCHN following TPF induction chemotherapy. Patients receive 24 GyE carbon ions (8 fractions) and 50 Gy IMRT (2.0 Gy/fraction) in combination with weekly cetuximab throughout radiotherapy. Primary endpoint is locoregional control at 12 months, secondary endpoints are disease-free survival, progression-free survival, overall survival, acute and late radiation effects as well as any adverse events of the treatment as well as quality of life (QoL) analyses.</p> <p>Discussion</p> <p>The primary objective of TPF-C-HIT is to evaluate efficacy and toxicity of cetuximab in combination with combined IMRT/carbon ion therapy following TPF induction in locally advanced SCCHN.</p> <p>Trial Registration</p> <p>Clinical Trial Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01245985">NCT01245985</a> (clinicaltrials.gov)</p> <p>EudraCT number: 2009 - 016489- 10</p

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

___Key messages___ The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer

A series of 1,2,3-triazole compounds: Synthesis, characterization, and investigation of the cholinesterase inhibitory properties via in vitro and in silico studies

A series of 1,2,3-triazole compounds derived from a salicylaldehyde moiety were synthesized in high yields using copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. The structures of the newly synthesized 1,2,3-triazole compounds were characterized by FT-IR, NMR, and HRMS analyses. The inhibitory activities of all the target compounds were investigated against electric eel acetylcholinesterase (eeAChE) and equine serum butyrylcholinesterase (eqBChE) enzymes. The activity results were compared with galantamine used as a reference compound. The in vitro biological assays showed that most of the target compounds had quite good inhibition activities for eeAChE, while weaker towards eqBChE. Among them, compound 23f exhibited better activity than both other target compounds and galantamine against both eeAChE (IC50: 0.458 µM) and eqBChE (IC50:1.721 µM). Molecular docking studies of all target compounds were performed on the 3D crystallographic structures of eeAChE, Homo sapiens AChE, and BChE enzymes. The binding energies appear to be consistent with the activity results. Moreover, it was determined that 23f interacted with crucial residues of the catalytic active site (CAS) and peripheral anionic site (PAS) of both AChE and BChE due to its dual binding feature. Finally, in silico ADME and toxicity properties of the compounds were investigated using the Swiss ADME and ProTox-II websites. The compounds have appropriate drug-likeness scores, Additionally, it has been estimated that 23f, the most active compound, and 23c are within the best limits in terms of oral bioavailability and exhibit low levels of toxicity. Consequently, the target compounds, especially 23f, can be considered promising inhibitors for the cholinesterase enzymes. © 2022 Elsevier B.V.Muş Alparslan Üniversitesi: BAP-21-TBMY-4901-01The authors are grateful to Mus Alparslan University for financial support (Grant No. BAP-21-TBMY-4901-01)

The Journey of "Furthur" in the Summer of 1964 and its Significance in the Changing Subcultures of the USA

In the 1960s, a counterculture was being formed in the United States, which was associated with the psychedelic revolution, nonconformism, the generation gap, the anti-war movement, and social experiments. It was during this period that the process of transforming the beat generation of the 1950s into a hippie subculture of the 1960s took place. One of the significant events of this process was the fact that beatnik Neil Cassidy joined the commune «Merry Pranksters» led by writer Ken Kesey. The «Further» trip in the summer of 1964 was a catalyst in this change of subcultures

Investigation of Hydrazide Derivatives İnhibitory Effect on Peroxidase Enzyme Purified from Turnip Roots

Agri Ibrahim Cecen University;IC Foudation2nd International Conference on Advances in Natural and Applied Sciences, ICANAS 2017 -- 18 April 2017 through 21 April 2017 -- -- 127507Peroxidases (EC: 1.11.1.7) are haem proteins and contain iron (III) protoporphyrin IX (ferriprotoporphyrin IX) as the prosthetic group [1]. They are found in all cells and play a critical role in many biological processes, such as the host-defense mechanism [2]. Peroxidases (PODs) are widely used in clinical biochemistry, enzyme immunoassays, synthesis of various aromatic chemicals, treatment of waste water containing phenolic compounds [3, 4]. In this study, peroxidase enzyme was purified with Para amino benzohydrazide (PABH)-L-Tyrosine Sepharose 4B affinity chromatography to investigate the inhibitory effect of hydrazide derivatives on Turnip (Brassica rapa L.). IC50 values and Ki constants were calculated for the molecules of 6-Amino nicotinic hydrazide, 6-Amino-5-bromo nicotinic hydrazide, 2-Amino-5-hydroxy benzohydrazide, 4-Amino-3-hydroxy benzohydrazide on purified enzyme and inhibition type of these molecules were determined. © 2017 Author(s)

Secondary sulfonamides as effective lactoperoxidase inhibitors

PubMed ID: 28538675Secondary sulfonamides (4a-8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives (4a-8h) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives (4a-8h) are effective LPO inhibitors. The Ki values of secondary sulfonamide derivatives (4a-8h) were found in the range of 1.096 ± 10-3 to 1203.83 ?M against LPO. However, the most effective inhibition was found for N-(sulfathiazole)-3,4,5-triacetoxy. © 2017 by the authors

Purification of peroxidase enzyme from radish species in fast and high yield with affinity chromatography technique

PubMed ID: 30939412In this study, an effective single step affinity method is presented for purifying plant peroxidase (POD) enzymes from radish species. This method make possible to purify the enzymes in high yield and purity. Briefly, 10 different 4-amino benzohydrazide derivatives were synthesized and identified as new competitive POD inhibitors. Then, these derivatives were coupled to Sepharose 4B-L-Tyrosine support matrix by diazotization to form the affinity gels. Purification factors were recorded as 54.8% yield - 665-fold, 33.8% yield - 613-fold, 22.7% yield - 595-fold, 34.4% yield - 781-fold, 40.9% yield - 282-fold for turnip (T-POD), black radish (BR-POD), daikon (D-POD), sweet radish (SR-POD) and kohlrabi radish, (KR-POD), respectively. It has also been shown that the affinity gels, which prepared using the 4-amino 3-bromo benzohydrazide and 4-amino 2-nitro benzohydrazide molecules, capable to purify all radish species POD enzymes in high purity and yield. © 2019 Elsevier B.V.215Z386This study was supported by TUBITAK with 215Z386 project number

Avalanche effect for chemically modified dust mitigation from surfaces

Cost effective dust mitigation from surfaces is one of the challenges in various sectors. The reduction of dust adhesion on surfaces plays a vital role for dust mitigation from surfaces under the gravitational influence. Creating an avalanche effect on dusty surfaces improves the dust mitigation rate and provides an effective cleaning process. Hence, solution treatment of dust by low concentration hydrofluoric acid is considered towards reducing dust adhesion on glass surfaces. To increase the rate of dust mitigation, the avalanche influence is created by the higher density and larger size particles (5300 kg/m3 and ~ 50 µm) than the average size dust particles (2800 kg/m3 and 1.2 µm) via locating them in the top region of the dusty glass surfaces. Mitigation velocity of the dust particles is evaluated using a high-speed recording system and the tracker program. Findings revealed that solution treatment (curing) of the dust particles results in the formation of fluorine compounds, such as CaF2 and MgF2, on dust surfaces, which suppress dust adhesion on surfaces. OSHA Globally Harmonized System lists the fluorine compounds formed as environmentally non-harmful. Avalanche's influence results in dust mitigation at a smaller tilt angle of the glass surface (~ 52°) than that of the case with none-avalanche influence (63°). Area cleaned on the glass surface, via dust mitigation, is larger as the avalanche is introduced, which becomes more apparent for the solution treated dust particles. Dust mitigation under avalanche influence improves optical transmittance of the dusty glass samples by a factor of 98%