scholarly journals Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring

Medicines ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 78
Author(s):  
Praveen K. Roayapalley ◽  
Hiroshi Sakagami ◽  
Keitaro Satoh ◽  
Shigeru Amano ◽  
Kenjiro Bandow ◽  
...  

A series of 3,5-bis(benzylidene)-4-piperidones 2a-u were prepared as candidate cytotoxic agents. In general, the compounds are highly toxic to human gingival carcinoma (Ca9-22), human squamous carcinoma-2 (HSC-2) and human squamous carcinoma-4 (HSC-4) neoplasms, but less so towards non-malignant human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF) and human pulp cells (HPC), thereby demonstrating tumour-selective toxicity. A further study revealed that most of the compounds in series 2 were more toxic to the human Colo-205 adenocarcinoma cell line (Colo-205), human HT29 colorectal adenocarcinoma cells (HT-29) and human CEM lymphoid cells (CEM) neoplasms than towards non-malignant human foreskin Hs27 fibroblast line (Hs27) cells. The potency of the cytotoxins towards the six malignant cell lines increased as the sigma and sigma star values of the aryl substituents rose. Attempts to condense various aryl aldehydes with 2,2,6,6-tetramethyl-4-piperidone led to the isolation of some 1,5-diaryl-1,4-pentadien-3-ones. The highest specificity for oral cancer cells was displayed by 2e and 2r. In the case of 2r, its selective toxicity exceeded that of doxorubicin and melphalan. The enones 2k, m, o have the highest SI values towards colon cancer and leukemic cells. Both 2e,r inhibited mitosis and increased the subG1 population (with a transient increase in G2/M phase cells). Slight activation of caspase-3, based on the cleavage of poly(ADP-ribose)polymerase (PARP) and procaspase 3, was detected.

Blood ◽  
1978 ◽  
Vol 52 (4) ◽  
pp. 712-718 ◽  
Author(s):  
SD Smith ◽  
EM Uyeki ◽  
JT Lowman

Abstract An assay system in vitro for the growth of malignant lymphoblastic colony-forming cells (CFC) was established. Growth of malignant myeloblastic CFC has been previously reported, but this is the first report of growth of malignant lymphoblastic CFC. Established assay systems in vitro have been very helpful in elucidating the control of growth and differentiation of both normal and malignant bone marrow cells. Lymphoblastic CFC were grown from the bone marrow aspirates of 20 children with acute lymphoblastic leukemia. Growth of these colonies was established on an agar assay system and maintained in the relative hypoxia (7% oxygen) of a Stulberg chamber. The criteria for malignancy of these colonies was based upon cellular cytochemical staining characteristics, the presence of specific cell surface markers, and the ability of these lymphoid cells to grow without the addition of a lymphoid mitogen. With this technique, specific nutritional requirements and drug sensitivities can be established in vitro, and these data may permit tailoring of individual antileukemic therapy.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chu-nan Zhang ◽  
Lin-yi Zhou ◽  
Shu-jiao Qian ◽  
Ying-xin Gu ◽  
Jun-yu Shi ◽  
...  

Abstract Objectives This study aims to evaluate the ability of tantalum-coated titanium to improve human gingival fibroblasts’ adhesion, viability, proliferation, migration performance, and the potential molecular mechanisms. Materials and methods Titanium plates were divided into two groups: (1) no coating (Ti, control), (2) Tantalum-coated titanium (Ta-coated Ti). All samples were characterized by scanning electronic microscopy, surface roughness, and hydrophilicity. Fibroblasts’ performance were analyzed by attached cell number at 1 h, 4 h, and 24 h, morphology at 1 h and 4 h, viability at 1 day, 3 days, 5 days, and 7 days, recovery after wounding at 6 h, 12 h, and 24 h. RT-PCR, western blot were applied to detect attachment-related genes’ expression and protein synthesis at 4 h and 24 h. Student’s t test was used for statistical analysis. Results Tantalum-coated titanium demonstrates a layer of homogeneously distributed nano-grains with mean diameter of 25.98 (± 14.75) nm. It was found that after tantalum deposition, human gingival fibroblasts (HGFs) adhesion, viability, proliferation, and migration were promoted in comparison to the control group. An upregulated level of Integrin β1 and FAK signaling was also detected, which might be the underlying mechanism. Conclusion In the present study, adhesion, viability, proliferation, migration of human gingival fibroblasts are promoted on tantalum-coated titanium, upregulated integrin β1 and FAK might contribute to its superior performance, indicating tantalum coating can be applied in transmucosal part of dental implant. Clinical significance Tantalum deposition on titanium surfaces can promote human gingival fibroblast adhesion, accordingly forming a well-organized soft tissue sealing and may contribute to a successful osseointegration.


Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 343-362 ◽  
Author(s):  
CH Pui ◽  
FG Behm ◽  
WM Crist

Abstract Immunologic marker studies of the lymphoid leukemias have greatly improved the precision of diagnosis of these disorders by providing specific information regarding the lineage and stage of maturation of the malignant cells. Such studies have also enhanced our understanding of normal lymphocyte development, permitting reproducible identification of lymphoid cells in discrete developmental stages. By elucidating the functions of lymphoid cell differentiation antigens, it has been possible to gain insight into the signal transduction mechanisms by which these cells interact among themselves and with other cell types. Similar studies have shown that ALL is an immunophenotypically heterogeneous disease with clinically important subtypes representing clonal expansions of lymphoblasts at different stages of maturation. Furthermore, successful correlation of immunophenotype with certain karyotypic and molecular abnormalities, which appear to underlie most or all leukemias, were made possible by the inclusion of immunologic marker assessment. Interestingly, many of these phenotype-related abnormalities have involved either the Ig or TCR genes, thus providing additional clues to the mechanisms of leukemogenesis. Knowledge of the immunologic features of leukemic cells has been essential for the generation of phenotype-specific response data in the context of modern therapy for ALL. With wider use of intensive treatment, the traditional prognostic distinctions among immunophenotypes have begun to disappear; however, certain classes of agents have more favorable toxicity/efficacy ratios against some immunophenotypes than others, justifying continued efforts to target therapy by immunologic species of ALL. Antibody-toxin conjugates, or immunotoxins, have induced complete responses in preliminary trials and may prove clinically useful, perhaps in combination with chemotherapy, if their toxic side effects can be controlled. Finally, immunologic markers may serve as sensitive targets for the detection of minimal residual disease; the clinical usefulness of this approach will depend on prospective comparisons with molecular methods.


Author(s):  
Cláudio Rodrigues Rezende Costa ◽  
Bruna Rabelo Amorim ◽  
Sandra Márcia Mazutti da Silva ◽  
Ana Carolina Acevedo ◽  
Pérola de Oliveira Magalhães ◽  
...  

Blood ◽  
2004 ◽  
Vol 103 (8) ◽  
pp. 3065-3072 ◽  
Author(s):  
Michael R. Verneris ◽  
Mobin Karami ◽  
Jeanette Baker ◽  
Anishka Jayaswal ◽  
Robert S. Negrin

Abstract Activating and expanding T cells using T-cell receptor (TCR) cross-linking antibodies and interleukin 2 (IL-2) results in potent cytotoxic effector cells capable of recognizing a broad range of malignant cell targets, including autologous leukemic cells. The mechanism of target cell recognition has previously been unknown. Recent studies show that ligation of NKG2D on natural killer (NK) cells directly induces cytotoxicity, whereas on T cells it costimulates TCR signaling. Here we demonstrate that NKG2D expression is up-regulated upon activation and expansion of human CD8+ T cells. Antibody blocking, redirected cytolysis, and small interfering RNA (siRNA) studies using purified CD8+ T cells demonstrate that cytotoxicity against malignant target cells occurs through NKG2D-mediated recognition and signaling and not through the TCR. Activated and expanded CD8+ T cells develop cytotoxicity after 10 to 14 days of culture, coincident with the expression of the adapter protein DAP10. T cells activated and expanded in low (30 U/mL) and high (300 U/mL) concentrations of IL-2 both up-regulated NKG2D expression equally, but only cells cultured in high-dose IL-2 expressed DAP10 and were cytotoxic. Collectively these results establish that NKG2D triggering accounts for the majority of major histocompatibility complex (MHC)–unrestricted cytotoxicity of activated and expanded CD8+ T cells, likely through DAP10-mediated signaling. (Blood. 2004;103: 3065-3072)


Inflammation ◽  
2016 ◽  
Vol 40 (1) ◽  
pp. 144-153 ◽  
Author(s):  
S. Buket Bozkurt ◽  
Sema S. Hakki ◽  
Erdogan E. Hakki ◽  
Yusuf Durak ◽  
Alpdogan Kantarci

2000 ◽  
Vol 30 (3) ◽  
pp. 599
Author(s):  
Yong-Bae Lee ◽  
Sung-Hee Pi ◽  
Tak Kim ◽  
Kwang-Soo Lee ◽  
Hyung-Keun You ◽  
...  

2018 ◽  
Vol 17 (4) ◽  
pp. 556-561
Author(s):  
I Bramanti ◽  
ISR Sudarso ◽  
MSH Wahyuningsih ◽  
T Wibawa ◽  
VM Karina ◽  
...  

Introduction: Garlic is a natural herb which can be used to be a good alternative treatment because cheap and safe. Garlic contains allicin which may has act antibacterial and antiinflammatory effect. Moreover, garlic extract has a good biocompatibility and can stimulate cell growth. Does garlic extract biocompatible and can stimulate cell growth that is seen from the proliferation of human gingival fibroblasts and how its work will be studied.Objective: The aim of this study was to analyze the biocompatibility of garlic extract by observing the viability and proliferation of human gingival fibroblasts in vitro.Methods: Biocompatibility test was conducted using serial concentration of garlic extract. Human gingival fibroblasts was seeded into 96 microwell plate with density of 2x103 cells, added with the fourteen serial concentration of garlic extract, and incubated in 37o C and 5% CO2for 24, 48 and 72 hours. MTT assay was used to analyze the viability and proliferation of human gingival fibroblasts. Data were analyzed by the Kruskal Wallis and U Mann-Whitney test.Results: The result showed that in each time of observation, there is no significant difference in viability fibroblast (p>0,05), but there are significant difference between time of observation at 24, 48, and 72 hours (p <0.05).Data showed that all concentration of garlic extract increased the viability and proliferation of human gingival fibroblasts.Conclusions: The ethanolic garlic extract has a good biocompatibility to human gingival fibroblasts culture cell and can stimulate the proliferation of human gingival fibroblast.Bangladesh Journal of Medical Science Vol.17(4) 2018 p.556-561


2020 ◽  
Vol 10 (12) ◽  
pp. 4290 ◽  
Author(s):  
Nasim Chiniforush ◽  
Maryam Pourhajibagher ◽  
Steven Parker ◽  
Stefano Benedicenti ◽  
Abbas Bahador ◽  
...  

The purpose of this study was to evaluate the in vitro effect of the chlorophyllin–phycocyanin mixture (Photoactive+) as a photosensitizer (PS) during antimicrobial photodynamic therapy (aPDT) on the count of Enterococcus faecalis (E. faecalis) using different light sources. The antimicrobial effect of aPDT with chlorophyllin–phycocyanin mixture using different light sources including diode laser (λ = 660 nm), diode laser (λ = 635 nm), LED (λ = 450 ± 30 nm) alone or in combination was assessed using microbial cell viability assay against E. faecalis. In addition, the cell cytotoxicity of Photoactive+ was assessed on human gingival fibroblast (HuGu) cells by MTT assay; E. faecalis growth when treated by both red wavelengths (635 nm, 660 nm) and combination of LED (420–480 nm) and red wavelengths (635 nm, 660 nm), significantly reduced compared to the control group (p < 0.05). There was no significant reduction in the number of viable cells exposed to Photoactive+ compared to the control group (p < 0.05). This study shows that the application of chlorophyllin–phycocyanin mixture and irradiation with emission of red light achieved a better result for bacterial count reduction, compared to a control. This component can be applied safely due to very negligible cytotoxicity.


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