scholarly journals Direct Cytotoxic and Indirect, Immune-Mediated Effects of Local Anesthetics Against Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Alejandra Wu Chuang ◽  
Oliver Kepp ◽  
Guido Kroemer ◽  
Lucillia Bezu
Keyword(s):  
Local Anesthetics ◽  
Oncological Surgery ◽  
Residual Cancer ◽  
Term Survival ◽  
Cytotoxic Effects ◽  
Mediated Effects ◽  
Anticancer Effects ◽  
Immune Mediated ◽  
Fundamental Research

Local anesthetics are frequently employed during surgery in order to control peri- and postoperative pain. Retrospective studies have revealed an unexpected correlation between increased long-term survival and the use of local anesthetics during oncological surgery. This effect of local anesthetics might rely on direct cytotoxic effects on malignant cells or on indirect, immune-mediated effects. It is tempting to speculate, yet needs to be formally proven, that the combination of local anesthetics with oncological surgery and conventional anticancer therapy would offer an opportunity to control residual cancer cells. This review summarizes findings from fundamental research together with clinical data on the use of local anesthetics as anticancer standalone drugs or their combination with conventional treatments. We suggest that a better comprehension of the anticancer effects of local anesthetics at the preclinical and clinical levels may broadly improve the surgical treatment of cancer.

What Is the Role of Transplantation for Indolent Lymphoma?

2012 ◽  
pp. 494-500
Author(s):  
Ryan D. Cassaday ◽  
Ajay K. Gopal
Keyword(s):  
Immune System ◽  
Hematopoietic Cell Transplantation ◽  
Indolent Lymphoma ◽  
Long Term Outcomes ◽  
Relative Risks ◽  
Anticancer Effects ◽  
Immune Mediated ◽  
Conditioning Therapy

Overview: Despite advances in chemoimmunotherapy, indolent B-cell non-Hodgkin lymphomas (B-NHLs) are generally not considered curable with this approach. Much attention has been paid to the prospect of hematopoietic cell transplantation (HCT) as a way to improve long-term outcomes for this group of diseases. Autologous (auto) HCT provides intensive conditioning therapy followed by rescue of hematopoiesis, and this has been shown in randomized studies to prolong survival compared with more standard chemotherapy, albeit with increased short-term toxicity and the potential for higher rates of secondary malignancies. Allogeneic (allo) HCT can provide anticancer effects beyond the conditioning therapy through the immune-mediated graft-versus-lymphoma (GVL) effect. It can be administered following myeloablative (MA) conditioning or reduced-intensity (RI) regimens aimed at sufficiently suppressing the patient's immune system to allow engraftment of donor hematopoiesis. However, this same potentially curative alloreactivity of the engrafted immune system can lead to graft-versus-host disease (GVHD), a significant cause of morbidity and mortality following allo HCT. This article will discuss the current role of both auto HCT and allo HCT in the management of indolent lymphoma as well as the relative risks and benefits of each approach such that the reader can place this in context of the multitude of options available for patients with indolent B-NHL.

Protective Nature of Platelet-Rich Plasma Against Chondrocyte Death When Combined With Corticosteroids or Local Anesthetics

2016 ◽  
Vol 45 (1) ◽  
pp. 218-225 ◽  
Author(s):  
Thomas J.S. Durant ◽  
Corey R. Dwyer ◽  
Mary Beth R. McCarthy ◽  
Mark P. Cote ◽  
James P. Bradley ◽  
...  
Keyword(s):  
Local Anesthetics ◽  
Platelet Rich Plasma ◽  
Symptomatic Relief ◽  
Negative Effects ◽  
Chondrocyte Proliferation ◽  
Cytotoxic Effects ◽  
Chondrocyte Viability ◽  
Chondrocyte Death ◽  
Negative Effect

Background: The use of corticosteroids and local anesthetics to treat osteoarthritis has established benefits, including relief of pain and increased range of motion, but may also have the potential to lead to tissue atrophy or degeneration, specifically on chondrocytes. There is growing evidence that platelet-rich plasma (PRP) has anti-inflammatory characteristics that can limit the cytotoxic effects of corticosteroids and local anesthetics. Hypothesis/Purpose: The purpose of this study was to determine the effects of PRP in chondrocyte cultures when combined with corticosteroids or local anesthetics. The hypothesis of this study was that PRP would (1) dampen the negative effects on chondrocyte viability and (2) improve chondrocyte proliferation seen with corticosteroid or local anesthetic treatment alone. Study Design: Controlled laboratory study. Methods: Peripheral blood was obtained from 8 healthy participants, followed by centrifugation to obtain PRP. Human chondrocytes were treated with PRP alone or in combination with corticosteroids or local anesthetics. Saline (concentration of 0.9%) served as the control. Luminescence and radioactive thymidine assays were performed to examine chondrocyte viability and proliferation, respectively. Cell exposures of 0, 5, 10, and 30 minutes were used for viability and 120 hours for proliferation. Results: The presence of PRP significantly limited the negative effect on chondrocyte viability at tested time points for the examined corticosteroids and local anesthetics ( P < .05). PRP in addition to corticosteroids and local anesthetics significantly improved chondrocyte proliferation ( P < .05). Conclusion: The addition of PRP can significantly reduce the cytotoxic effects of corticosteroids and/or local anesthetics applied to chondrocytes. PRP can improve the proliferation of chondrocytes compared with corticosteroids or local anesthetics alone. Clinical Relevance: With the use of corticosteroids and local anesthetics for temporary symptomatic relief and improvement of function to treat the chronic progressive nature of osteoarthritis, long-term negative effects of these agents can be limited with the parallel use of PRP.

scholarly journals A CASE OF BILE DUCT CANCER WITH LONG-TERM SURVIVAL AFTER OPERATION IN SPITE OF RESIDUAL CANCER AT THE RESECTED MARGIN

2000 ◽  
Vol 61 (2) ◽  
pp. 467-471 ◽  
Author(s):  
Shinichirou OHUCHI ◽  
Taiji SETO ◽  
Takao HANAOKA ◽  
Rikkou LEE ◽  
Yuichi TANAKA ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bile Duct Cancer ◽  
Residual Cancer ◽  
Term Survival ◽  
Long Term Survival ◽  
Duct Cancer ◽  
Resected Margin

Chronic allograft dysfunction

2015 ◽  
Author(s):  
Lorna K. Henderson ◽  
Brian J. Nankivell ◽  
Jeremy R. Chapman
Keyword(s):  
Renal Allograft ◽  
Graft Loss ◽  
Graft Dysfunction ◽  
Short Term ◽  
Tubular Atrophy ◽  
Term Survival ◽  
Chronic Allograft Dysfunction ◽  
Allograft Dysfunction ◽  
Immune Mediated

Despite improvements in short-term renal allograft survival, long-term survival has not appreciably changed. Excepting death with a functioning graft, most late graft loss results from chronic allograft dysfunction. Immune and non-immune-mediated injuries contribute to graft dysfunction over time, ultimately leading to a non-specific and irreversible histological end-point of fibrosis, tubular atrophy, and glomerulosclerosis. Screening and early identification of pathology is crucial to allow timely intervention in order to prevent permanent nephron damage and graft loss. This chapter outlines assessment of renal dysfunction following transplantation, defines the causes of chronic allograft failure, and their pathophysiology, and evaluates current therapeutic strategies used to improve or stabilize chronic allograft dysfunction.

Caspases and apoptosis

2002 ◽  
Vol 38 ◽  
pp. 9-19 ◽  
Author(s):  
Guy S Salvesen
Keyword(s):  
Cysteine Proteases ◽  
Signalling Pathways ◽  
Term Survival ◽  
Mature Adult ◽  
Intracellular Signalling Pathways ◽  
Adult Cell ◽  
Caspase Family ◽  
Cell Fragments ◽  
Pro Inflammatory Cytokines

The ability of metazoan cells to undergo programmed cell death is vital to both the precise development and long-term survival of the mature adult. Cell deaths that result from engagement of this programme end in apoptosis, the ordered dismantling of the cell that results in its 'silent' demise, in which packaged cell fragments are removed by phagocytosis. This co-ordinated demise is mediated by members of a family of cysteine proteases known as caspases, whose activation follows characteristic apoptotic stimuli, and whose substrates include many proteins, the limited cleavage of which causes the characteristic morphology of apoptosis. In vertebrates, a subset of caspases has evolved to participate in the activation of pro-inflammatory cytokines, and thus members of the caspase family participate in one of two very distinct intracellular signalling pathways.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells
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