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Related Concept Videos

Local Anesthetics: Adverse Effects01:12

Local Anesthetics: Adverse Effects

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While local anesthetics are generally safe and well-tolerated, they can occasionally cause adverse effects that vary in severity. Local anesthetics can induce toxicity at two distinct levels. They can either produce local effects through direct contact with the neural elements or be absorbed into the bloodstream from the injection site, leading to systemic effects.
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
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Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

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Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
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Cytotoxic T Cells-mediated Immune Response01:27

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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Local Anesthetics: Common Agents and Their Applications01:23

Local Anesthetics: Common Agents and Their Applications

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Local anesthetics (LAs) are commonly used for various applications in medical and dental procedures. Some of the common agents used are cocaine, lidocaine, and bupivacaine.
Cocaine is an ester of benzoic acid and methylecgogine. It is used to anesthetize and vasoconstrict locally. Currently, it is used primarily for topical applications. It is beneficial for surgeries on the upper respiratory tract, providing anesthesia and shrinking the mucosa. Cocaine in the form of cocaine hydrochloride is...
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Local anesthetics elicit immune-dependent anticancer effects.

Lucillia Bezu1,2,3, Alejandra Wu Chuang4,2, Allan Sauvat4,2

  • 1Equipe labellisée par la Ligue contre le cancer, Université de Paris Cité, Sorbonne Université, INSERM UMR1138, Centre de Recherche des Cordeliers, Paris, France lucilliabe@gmail.com kroemer@orange.fr.

Journal for Immunotherapy of Cancer
|April 28, 2022
PubMed
Summary
This summary is machine-generated.

Local anesthetics trigger cancer cell stress responses, including autophagy and endoplasmic reticulum stress, leading to decreased tumor growth and improved survival in mice. These effects are immune-dependent and can be enhanced by immunotherapy.

Keywords:
Adjuvants, ImmunologicCytotoxicity, ImmunologicDrug Evaluation, PreclinicalDrug Therapy, CombinationImmunotherapy

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Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Retrospective studies suggest local anesthetics may reduce cancer relapse and improve survival.
  • The precise anticancer mechanisms of common local anesthetics remain largely unexplored.

Purpose of the Study:

  • To investigate the anticancer effects of six clinically used local anesthetics.
  • To elucidate the cellular and molecular mechanisms underlying their antitumor activity.

Main Methods:

  • In vitro analysis of cancer cell stress responses (oxidative phosphorylation, autophagy, ER stress).
  • In vivo studies in immunocompetent and immunodeficient mice models.
  • Assessment of immunogenic cell death markers and combination therapy with immunotherapy.

Main Results:

  • Local anesthetics induced cancer cell stress, including ER stress and autophagy, dependent on PERK signaling.
  • In vivo, local anesthetics reduced tumor growth and improved survival in immunocompetent mice.
  • Antitumor effects were immune-dependent and enhanced by PD-1 blockade or CALR protein therapy.

Conclusions:

  • Local anesthetics induce immunogenic stress responses in cancer cells, contributing to antitumor effects.
  • These findings highlight the potential of local anesthetics as an adjuvant cancer therapy.