NO Cancer Research Results

NO, Nitric Oxide: Click to Expand ⟱
Source:
Type:
Once the cancer has begun, NO seems to play a protumoral role rather than antitumoral one as the concentration required to cause tumor cell cytotoxicity cannot be achieved by cancer cells.
The mechanistic roles of nitric oxide (NO) during cancer progression have been important considerations since its discovery as an endogenously generated free radical. Nonetheless, the impacts of this signaling molecule can be seemingly contradictory, being both pro-and antitumorigenic, which complicates the development of cancer treatments based on the modulation of NO fluxes in tumors. At a fundamental level, low levels of NO drive oncogenic pathways, immunosuppression, metastasis, and angiogenesis, while higher levels lead to apoptosis and reduced hypoxia and also sensitize tumors to conventional therapies. However, clinical outcome depends on the type and stage of the tumor as well as the tumor microenvironment.
Nitric oxide is generated by three main nitric oxide synthase isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS).

– In many cancers, especially under inflammatory conditions, iNOS expression is upregulated. In contrast, eNOS levels may also be altered in cancers such as breast or prostate cancer.

• Expression Patterns in Tumors:
– Elevated iNOS expression is commonly observed in various tumor types (e.g., colon, breast, lung, and melanoma) and is often associated with an inflammatory microenvironment.

– Changes in eNOS and nNOS expression have also been reported and may contribute to angiogenesis and tumor blood flow regulation.
Asthma, Asthmatic: Click to Expand ⟱
Asthmatic

Asthma

Definition: Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow obstruction, airway hyperresponsiveness, mucus hypersecretion, and recurrent episodes of wheezing, cough, chest tightness, and shortness of breath. Airflow limitation is often reversible, but chronic inflammation can produce airway remodeling and more persistent obstruction.

Main Pathways Involved in Asthma — Ranked by Importance

Rank Pathway / Target Typical Direction in Asthma Importance Role
1 IL-4 / IL-13 → JAK / STAT6 ↑ Very High Central Type-2 asthma pathway. Promotes Th2 responses, IgE production, mucus hypersecretion, airway hyperresponsiveness, and remodeling.
2 IL-5 → Eosinophils ↑ Very High Drives eosinophil maturation, survival, recruitment, and activation. A major pathway in eosinophilic asthma and a clinically validated therapeutic target.
3 IL-33 → ST2 / IL1RL1 → ILC2 ↑ Very High Major upstream epithelial alarmin pathway. Activates ILC2 and promotes IL-5 and IL-13 production, eosinophilia, mucus secretion, and airway hyperresponsiveness.
4 TSLP ↑ Very High Epithelial alarmin that activates dendritic cells, Th2 immunity, mast cells, and ILC2. Particularly important in allergic and severe Type-2 asthma.
5 IgE → FcεRI → Mast-cell activation ↑ Very High Fundamental allergic-asthma pathway. Allergen-mediated IgE cross-linking activates mast cells and causes release of histamine, leukotrienes, prostaglandins, and cytokines.
6 5-LOX / ALOX5 → LTC4 / LTD4 / LTE4 → CysLT1 ↑ Very High Cysteinyl leukotrienes are potent bronchoconstrictors and promote mucus secretion, vascular permeability, and eosinophilic inflammation.
7 Airway smooth muscle / β2-adrenergic receptor → cAMP / PKA Contraction ↑; therapeutic β2 signaling ↑ Very High Airway smooth-muscle contraction directly causes reversible airflow obstruction. β2-receptor activation increases cAMP and PKA, producing bronchodilation.
8 NF-κB ↑ High Major inflammatory transcription pathway controlling cytokines, chemokines, adhesion molecules, inflammatory enzymes, and immune-cell activation.
9 TGF-β1 → SMAD2 / SMAD3 ↑ High Major driver of chronic airway remodeling, extracellular-matrix deposition, subepithelial fibrosis, and airway smooth-muscle growth.
10 ROS / Oxidative Stress ↔ Nrf2 ROS ↑; Nrf2 often insufficient High Oxidative stress damages airway epithelium and amplifies NF-κB, MAPK, cytokine signaling, mucus production, and airway hyperresponsiveness. Nrf2 provides a protective antioxidant response.
11 IL-17 / Th17 → CXCL8 / IL-8 → Neutrophils ↑ High in Severe / Non-Type-2 Asthma Important in neutrophilic, severe, and corticosteroid-resistant asthma. Promotes neutrophil recruitment and persistent airway inflammation.
12 NLRP3 Inflammasome → IL-1β / IL-18 ↑ Moderate-High Promotes innate inflammatory signaling and neutrophilic airway inflammation, particularly in severe and non-Type-2 asthma.
13 PI3K / AKT ↑ Moderate Supports inflammatory-cell survival, airway smooth-muscle proliferation, mucus production, and corticosteroid resistance.
14 MAPK / ERK / p38 / JNK ↑ Moderate Regulates cytokine production, epithelial responses, smooth-muscle activity, inflammatory-cell activation, and airway remodeling.
15 Epithelial Barrier Integrity ↓ Moderate Impaired epithelial integrity allows greater allergen penetration and promotes release of IL-33, TSLP, and IL-25.
16 E-cadherin / ZO-1 ↓ Moderate Reduced adherens-junction and tight-junction proteins contribute to impaired airway-barrier function and increased inflammatory signaling.
17 MUC5AC / Goblet-cell Hyperplasia ↑ Moderate Drives mucus hypersecretion and mucus plugging, particularly under IL-13 signaling.
18 CCL11 / Eotaxin-1 → CCR3 ↑ Moderate Recruits eosinophils into airway tissue and contributes to Type-2 airway inflammation.
19 TNF-α ↑ Moderate Promotes inflammatory-cell recruitment, endothelial activation, airway hyperresponsiveness, and remodeling.
20 NADPH Oxidase / NOX ↑ Moderate Generates reactive oxygen species and contributes to oxidative injury and inflammatory signaling.
21 VEGF ↑ Secondary / Remodeling Promotes increased airway vascularity, vascular permeability, and airway-wall remodeling.
22 MMP-9 ↑ Secondary / Remodeling Extracellular-matrix remodeling enzyme associated with inflammation, epithelial injury, and structural airway changes.
23 Collagen Deposition ↑ Secondary / Remodeling Contributes to subepithelial fibrosis, airway-wall thickening, and progressively less reversible airflow obstruction.

Core Asthma Pathway Summary

Primary Type-2 pathway:
Allergen / epithelial injury → IL-33 + TSLP + IL-25 ↑ → ILC2 + dendritic cells + Th2 ↑ → IL-4 + IL-5 + IL-13 ↑ → IgE ↑ + eosinophils ↑ + mast-cell activation ↑ → bronchoconstriction + mucus ↑ + airway hyperresponsiveness.

Allergic effector pathway:
Allergen → IgE / FcεRI → mast-cell degranulation → histamine + prostaglandins + cysteinyl leukotrienes → acute bronchoconstriction and airway inflammation.

Oxidative / inflammatory pathway:
Allergens / pollutants / inflammatory cells → ROS ↑ → NF-κB + MAPK + PI3K / AKT ↑ → inflammatory cytokines and chemokines ↑ → epithelial damage and airway inflammation.

Severe / neutrophilic asthma pathway:
NLRP3 ↑ + IL-1β ↑ + Th17 / IL-17 ↑ → CXCL8 ↑ → neutrophils ↑ → persistent inflammation and corticosteroid resistance.

Airway-remodeling pathway:
Chronic inflammation → TGF-β1 / SMAD2 / SMAD3 ↑ → collagen deposition ↑ + VEGF ↑ + MMP-9 dysregulation → subepithelial fibrosis + airway-wall thickening + smooth-muscle hypertrophy → persistent airflow limitation.

Most Important Targets for Product / Mechanism Screening

For screening natural products or other interventions for potential relevance to asthma, the highest-priority targets are: IL-4, IL-5, IL-13, IL-33, ST2 / IL1RL1, ILC2, TSLP, IgE, FcεRI, 5-LOX / ALOX5, CysLT1, NF-κB, TGF-β1, ROS, Nrf2, IL-17, CXCL8, and NLRP3.

Inhaler / Drug Class Examples Main Pathway / Target Direction Main Effect
SABA (Short-Acting β2-Agonist) Salbutamol / Albuterol, Terbutaline β2-adrenergic receptor → Gs → Adenylyl Cyclase → cAMP → PKA ↑ Rapid airway smooth-muscle relaxation and bronchodilation; used for acute symptom relief.
LABA (Long-Acting β2-Agonist) Formoterol, Salmeterol β2-adrenergic receptor → cAMP / PKA ↑ Prolonged bronchodilation and reduced bronchoconstriction. In asthma, generally used with an inhaled corticosteroid.
ICS (Inhaled Corticosteroid) Budesonide, Fluticasone, Beclomethasone, Mometasone Glucocorticoid Receptor / NR3C1 ↑ Activates anti-inflammatory glucocorticoid signaling and suppresses chronic airway inflammation.
ICS (Inhaled Corticosteroid) Budesonide, Fluticasone, Beclomethasone, Mometasone NF-κB ↓ Reduces transcription of inflammatory cytokines, chemokines, and other inflammatory mediators.
ICS (Inhaled Corticosteroid) Budesonide, Fluticasone, Beclomethasone, Mometasone AP-1 ↓ Suppresses inflammatory gene transcription.
ICS (Inhaled Corticosteroid) Budesonide, Fluticasone, Beclomethasone, Mometasone IL-4 / IL-5 / IL-13 ↓ Reduces Type-2 inflammation, eosinophilic inflammation, mucus production, and airway hyperresponsiveness.
ICS / LABA Combination Budesonide/Formoterol, Fluticasone/Salmeterol, Fluticasone/Vilanterol Glucocorticoid Receptor ↑ Suppresses airway inflammation.
ICS / LABA Combination Budesonide/Formoterol, Fluticasone/Salmeterol, Fluticasone/Vilanterol β2-adrenergic receptor → cAMP / PKA ↑ Provides prolonged bronchodilation while the corticosteroid controls inflammation.
SAMA (Short-Acting Muscarinic Antagonist) Ipratropium M3 Muscarinic Receptor ↓ Reduces cholinergic airway smooth-muscle contraction and decreases bronchoconstriction.
SAMA (Short-Acting Muscarinic Antagonist) Ipratropium Gq → PLC → IP3 → intracellular Ca2+ ↓ Reduces intracellular calcium signaling required for airway smooth-muscle contraction.
LAMA (Long-Acting Muscarinic Antagonist) Tiotropium, Glycopyrronium, Umeclidinium M3 Muscarinic Receptor ↓ Produces prolonged inhibition of cholinergic bronchoconstriction and can improve airflow control.
ICS / LABA / LAMA Triple Therapy Fluticasone Furoate / Umeclidinium / Vilanterol Glucocorticoid Receptor ↑ Suppresses airway inflammation.
ICS / LABA / LAMA Triple Therapy Fluticasone Furoate / Umeclidinium / Vilanterol β2-adrenergic receptor → cAMP / PKA ↑ Promotes airway smooth-muscle relaxation and bronchodilation.
ICS / LABA / LAMA Triple Therapy Fluticasone Furoate / Umeclidinium / Vilanterol M3 Muscarinic Receptor ↓ Blocks cholinergic bronchoconstriction and provides additional bronchodilation.

Simplified pathway summary:

β2-Agonists:
β2-AR ↑ → Adenylyl Cyclase ↑ → cAMP ↑ → PKA ↑ → airway smooth-muscle contraction ↓ → bronchodilation ↑.

Inhaled Corticosteroids:
Glucocorticoid Receptor ↑ → NF-κB ↓ + AP-1 ↓ → IL-4 / IL-5 / IL-13 ↓ → eosinophilic airway inflammation ↓.

Muscarinic Antagonists:
M3 Receptor ↓ → Gq / PLC / IP3 / Ca2+ signaling ↓ → airway smooth-muscle contraction ↓ → bronchodilation ↑.



Scientific Papers found: Click to Expand⟱
7932- H2,    Hydrogen Gas Inhalation Alleviates Airway Inflammation and Oxidative Stress on Ovalbumin-Induced Asthmatic BALB/c Mouse Model
- in-vivo, Asthma, NA
*antiOx↑, *Inflam↓, *ROS↓, *TAC↑, *IgE↓, *Dose↝, *NLR↓, *IL4↓, *IL5↓, *IL13↓, *GM-CSF↓, *NO↓, *GPx↑, *Eos↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

Eos↓, 1,   IgE↓, 1,   IL13↓, 1,   NLR↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   GPx↑, 1,   ROS↓, 1,   TAC↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

GM-CSF↓, 1,   IL4↓, 1,   IL5↓, 1,   Inflam↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,  
Total Targets: 14

Scientific Paper Hit Count for: NO, Nitric Oxide
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:80  Cells:%  prod#:%  Target#:563  State#:%  Dir#:1
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