Database Query Results : Hyperthermia, ,

HPT, Hyperthermia: Click to Expand ⟱

Features:

Mild Hyperthermia (Approximately 39°C to 41°C
Pathways and Effects:
-Heat Shock Protein (HSP) Induction: Mild heat stress triggers the production of HSPs (e.g., HSP70, HSP90) that help cells cope with stress, which can sometimes provide a transient protective effect. However, these proteins can also act as immunomodulators.
-Modulation of the Immune System: Mild hyperthermia can enhance dendritic cell activation and improve antigen presentation, leading to the stimulation of anti-tumor immune responses.
-Vasodilation: Increased blood flow and improved oxygenation can sensitize tumors to radiation therapy and certain chemotherapeutics.

Moderate Hyperthermia (Approximately 41°C to 43°C)
Pathways and Effects:
-Enhanced Cytotoxicity: At temperatures in this range, tumor cells become more vulnerable to radiation and some chemotherapeutic agents. This is partly due to the inhibition of DNA repair pathways.
-Increased Permeability: Moderate heat can increase the permeability of cellular membranes, aiding in drug delivery and the uptake of chemotherapeutic agents.
-Induction of Apoptosis: Elevated temperatures can trigger apoptotic signaling pathways in cancer cells, sometimes in conjunction with other therapies.

High Hyperthermia / Thermal Ablation (Approximately 43°C to 50°C and above)
Pathways and Effects:
-Direct Cytotoxicity: High temperatures can lead to protein denaturation, membrane disruption, and direct cell death.
-Coagulative Necrosis: Sustained high temperatures cause irreversible cell injury leading to necrosis of tumor tissues.
-Vascular Damage: Hyperthermia in this range can damage tumor vasculature, reducing blood supply and indirectly causing tumor cell death.
-Enhanced Immune Response: Although high temperatures can cause immediate cell death, the release of tumor antigens and damage-associated molecular patterns (DAMPs) can stimulate an anti-tumor immune response

Rank	Pathway / Axis	Cancer / Tumor Context	Normal Tissue Context	TSF	Primary Effect	Notes / Interpretation
1	Proteotoxic stress / protein denaturation	Misfolded protein burden ↑; proteostasis overload ↑	Heat stress response (tolerance higher if well-perfused)	P, R	Core physical stressor	Direct heat disrupts protein folding and complex stability; tumors can be more vulnerable due to baseline stress and poor perfusion.
2	Heat Shock Response (HSF1 → HSPs)	HSP70/HSP90 ↑; stress tolerance ↑ (can be protective)	HSP induction ↑ (protective)	R, G	Adaptive survival program	HSP induction is a major adaptation; can blunt repeated heat exposures and is a key reason scheduling matters.
3	DNA damage repair inhibition / radiosensitization	HR repair ↓; DNA repair capacity ↓ (reported)	↔ (tissue-dependent)	R	Sensitization to radiation	Hyperthermia can impair DNA repair processes (notably homologous recombination), increasing radiation effectiveness when timed appropriately.
4	Tumor perfusion / oxygenation changes	Perfusion ↑ (often) → oxygenation ↑; hypoxia ↓ (context)	Perfusion ↑	P, R	Microenvironment modulation	Improved perfusion can increase oxygenation (helping radiotherapy) and improve delivery of some drugs; effects depend on local vascular state.
5	Cell membrane / cytoskeleton disruption	Membrane permeability ↑; cytoskeletal stress ↑	↔ / injury possible at higher exposures	P, R	Physical cell stress	Heat can increase permeability and alter membrane trafficking; contributes to drug uptake in some settings.
6	Intrinsic apoptosis / necrosis (dose-dependent)	Apoptosis ↑ or necrosis ↑ at higher thermal dose	Collateral injury risk if overdosed	R, G	Direct cytotoxicity (thermal dose dependent)	At moderate hyperthermia, sensitization dominates; at higher thermal dose, direct cell killing becomes more prominent.
7	Immune activation / DAMP release (ICD-like signals)	DAMPs ↑; antigen presentation ↑ (reported)	—	G	Immune support	Heat stress and tumor cell damage can release DAMPs and promote immune visibility; strength varies by regimen and tumor type.
8	Vascular effects (edema, vessel damage) at higher dose	Vascular injury ↑ at higher thermal dose	Normal tissue injury risk ↑	R, G	Toxicity / local control effects	At higher temperatures or prolonged exposure, vascular damage contributes to tumor control but increases normal tissue risk.
9	Chemo-sensitization (drug delivery + stress synergy)	Drug uptake ↑; cytotoxic synergy ↑ (reported)	Systemic toxicity may ↑ depending on regimen	R, G	Combination leverage	Heat can potentiate some agents (e.g., platinum drugs) and improve delivery; regimen-specific.
10	Thermal dose / parameter dependence (time×temp)	Outcome depends on temperature, duration, targeting, and timing vs RT/chemo	Safety depends on precision and monitoring	—	Translation constraint	Hyperthermia is highly dose-dependent; “too little” yields little sensitization, “too much” increases burns/necrosis risk.

Time-Scale Flag (TSF): P / R / G

P: 0–30 min (direct heat stress; perfusion/permeability shifts begin)
R: 30 min–3 hr (HSP induction; DNA repair suppression; apoptosis initiation)
G: >3 hr (phenotype outcomes: immune effects, sensitization results, tissue injury)

Scientific Papers found: Click to Expand⟱

333-

AgNPs,

HPT,

Enhancement effect of cytotoxicity response of silver nanoparticles combined with thermotherapy on C6 rat glioma cells

in-vivo,

GBM,

rat

OS↑,

4358-

AgNPs,

HPT,

Rad,

Silver nanocrystals mediated combination therapy of radiation with magnetic hyperthermia on glioma cells

in-vitro,

GBM,

U251

10 nm silver nanoparticles (AgNPs) on human glioma U251 c

RadioS↑, AgNPs showed both radio and thermo sensitivity on U251 cells from the surviving fraction curve.
eff↑, both X-rays and heat could enhance the content of cells uptake of AgNPs.
TumCD↑, potential application in enhancing effect of RT with MHT combination therapy induced killing of cancer cells.

886-

HPT,

Impact of hyper- and hypothermia on cellular and whole-body physiology

Analysis,

NA,

MMP↓,
OXPHOS↓, impaired oxidative phosphorylation
ATP↓,
ROS↑, increase reactive oxygen species (ROS) production within mitochondria,
Apoptosis↑,
Cyt‑c↑, releasing cytochrome c into the cytoplasm

5049-

HPT,

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

vitro+vivo,

PC,

Panc02

vitro+vivo,

PC,

Bxpc-3

tumCV↓, The thermal effects were confirmed by the following observations: 1) decreased number of vital cells,
proCasp↑, 2) altered expression of pro-caspases, and
ROS↑, 3) production of reactive oxygen species, and
Ki-67↓, 4) altered mRNA expression of Ki-67, TOP2A, and TPX2.
TOP2↓, mRNA expression of the proliferation markers Ki-67, TOP2A, and TPX2 revealed a marked reduction in their expression after PANC-1 cells were treated with MH
TumVol↓, The MH treatment of tumor xenografts significantly (P≤0.05) reduced tumor volumes.

5050-

HPT,

Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review

Review,

Nor,

*ROS↑, Heat stress was suggested to be an environmental factor responsible for stimulating ROS production because of similarities in responses observed following heat stress compared with that occurring following exposure to oxidative stress.
*SOD1↓, Heat stress was also shown to decrease superoxide dismutase 1 (SOD-1) mRNA levels, cytoplasmic SOD protein and enzyme activity, leading to the increase of ROS generation
*GSH↓, Furthermore, several studies demonstrated that heat stress results in a dramatic decrease in glutathione (GSH) levels.
other↑, Nowadays, a variety of diseases and degenerative processes such as cancer, Alzheimer’s and autoimmune diseases are mediated by oxidative stress.
HIF-1↑, heat stress activates hypoxia-inducible factor 1 (HIF-1) through ERK-NADPH oxidase-mediated ROS production, and this enhances tumour oxygenation by up-regulating HIF-1 target gene
ROS↑,

5051-

HPT,

doxoR,

Hyperthermia Enhances Doxorubicin Therapeutic Efficacy against A375 and MNT-1 Melanoma Cells

in-vitro,

Melanoma,

A375

tumCV↓, Combined treatment significantly decreased cell viability, but not in all tested conditions, suggesting that the effect depends on the drug concentration and heat treatment duration.
TumCCA↑, Combined treatment also mediated a G2/M phase arrest in both cell lines, as well as increasing ROS levels.
ROS↑,
eff↑, These findings demonstrate that hyperthermia enhances DOX effect through cell cycle arrest, oxidative stress, and apoptotic cell death.

5052-

HPT,

Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells

in-vitro,

OS,

U2OS

Apoptosis↑, Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells.
ROS↑, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells.
Casp3↑,
mtDam↑, Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax.
Cyt‑c↑,
Bcl-2↓,
Bcl-xL↓,
Bak↑,
BAX↓,
ER Stress↑, Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity.
Ca+2↝,
cal2↑,

5053-

HPT,

Rad,

Chemo,

Association of elevated reactive oxygen species and hyperthermia induced radiosensitivity in cancer stem-like cells

in-vitro,

Var,

CSCs↓, SCs were found to be more susceptible to radiation when combined with HT treatment
TumCP↓, Treated cells showed significantly reduced self-renewal, cell survival and proliferation in vitro, as well as significant reduced tumor formation in vivo.
ROS↑, Further study demonstrated that the radiosensitization effect was associated with increased intracellular reactive oxygen species (ROS) level in CSCs, confirmed by modifying redox status in CSCs bidirectionally.
RadioS↑, new strategy for improving CSCs radiosensitivity

5054-

HPT,

Induction of Oxidative Stress by Hyperthermia and Enhancement of Hyperthermia-Induced Apoptosis by Oxidative Stress Modification

Review,

Var,

eff↓, However, clinical results by HT alone have not always been satisfactory
ROS↑, One of these HT-induced alterations, oxidative stress, has been attributed to the increased production of reactive oxygen spaces (ROS), and is known to play an important role as an intracellular mediator of HT-induced cell death, including apoptosis.
Apoptosis↑,

2252-

MF,

HPT,

Cellular Response to ELF-MF and Heat: Evidence for a Common Involvement of Heat Shock Proteins?

Review,

NA,

HSPs∅, In some studies, no HSP-related effects were detected after ELF-MF exposure ranging from a few μT to mT and from minutes to 24 h, using different cell types such as astroglial cells (30), HL-60, H9c2, and Girardi heart cells (31, 32), and human kerat
*HSPs↑, exposure has also caused changes in HSP levels in a number of primary or non-transformed (“primary like”) cell lines.
eff↝, The hypothesis that non-stressed cells or organisms are quite responsive to HSP induction after ELF-MF exposure is strengthened by some in vivo studies in invertebrates
*eff↑, ELF-MF Exposure Potentiates the Effects of Heat on HSP Induction
eff↑, Interestingly, when HeLa and HL-60 cancer cells were subjected to comparable magnetic flux densities (10–140 µT), exposure durations (20–30 min) and concurrently heat stressed at 43°C, a stronger HSP70 expression was attained in coexposed cells
eff↓, An interesting finding is that MF exposure provides protection against heat-induced effects such as apoptosis, cell cycle disturbances, or proliferation inhibition in both cell models and in organisms

2256-

MF,

HPT,

Effects of exposure to repetitive pulsed magnetic stimulation on cell proliferation and expression of heat shock protein 70 in normal and malignant cells

in-vitro,

BC,

MCF-7

34mT, 50Hz 2-s bursts and 1-s rests.

in-vitro,

Cerv,

HeLa

in-vitro,

Nor,

HBL-100

HSP70/HSPA5↑, HSP70 expression was increased by RPMS exposure under thermal stress at 40 degrees C and 42 degrees C in HBL-100 and HeLa.
HSP70/HSPA5∅, HSP70 was not affected by RPMS at 37°C (Fig. 5A).

2257-

MF,

HPT,

HSP70 Inhibition Synergistically Enhances the Effects of Magnetic Fluid Hyperthermia in Ovarian Cancer

in-vitro,

Ovarian,

eff↑, HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer.
eff↑, A significantly reduction in tumor growth rate was observed with combination therapy

1674-

PBG,

SDT,

HPT,

Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells

in-vitro,

PC,

PANC1

in-vitro,

Nor,

H6c7

tumCV↓, cell viability of a human cancer cell line PANC-1 decreased to a level 80% less than the control
ROS↑, triple treatment showed a significant accumulation of the intracellular ROS (up to a 2.1-fold increase)
eff↑, combination of TC-HT and US also promotes the anticancer effect of the heat-sensitive chemotherapy drug cisplatin on PANC-1 cells
Dose∅, moderate propolis concentration 0.3%, 10-cycles TC-HT and 2.25 MHz US with intensity 0.3 W/cm2 and duration 30 minutes were chosen to avoid the thermotoxicity on PANC-1 cells
selectivity↑, Moreover, normal cells such as the human skin cells Detroit 551 (Figure 1D) and human pancreatic duct cells H6c7 (Figure 1E) were not significantly affected by the triple treatment as well as all the other treatments.
MMP↓, ratio of the cells exhibiting MMP loss was significantly promoted to 23.3% after the double treatment of propolis + TC-HT, and it was further elevated significantly to 34.7% by employing the triple treatment.
mtDam↑, hence caused more mitochondrial dysfunction
cl‑PARP↑, PARP cleavage was further promoted significantly to a 6.2-fold increase by US in the triple treatment
p‑ERK↓, the p-ERK level was suppressed by propolis + TC-HT treatment (0.30-fold decrease), and was further down-regulated when US was introduced in the triple treatment (0.15-fold decrease)
p‑JNK↑, p-JNK and p-p38 levels both exhibited a reverse performance, which were promoted the most in the triple treatment (8.7-fold and 9.2-fold increase, respectively)
p‑p38↑,
eff↓, inhibitory effect of the triple treatment was restored by NAC
ChemoSen↑, cisplatin + TC-HT treatment significantly elevated PARP cleavage to a 3.20-fold increase. This elevation was further increased with the help of US (5.82-fold increase).

94-

QC,

HPT,

Effects of quercetin on the heat-induced cytotoxicity of prostate cancer cells

in-vitro,

Pca,

LNCaP

 12.5, 25, 50, 100 umol/L

in-vitro,

Pca,

PC3

in-vitro,

Pca,

JCA-1

HSP70/HSPA5↓, Quercetin inhibited an increase of hsp70 expression after heat treatment and increased the number of subG1 cells with lower levels of hsp70 in JCA-1 and LNcap cells.
TumCCA↑,
TumCG↓, Quercetin inhibited the growth of JCA-1 and LNcap cells at concentrations over 12.5 mmol/L.
eff↑, the presence of quercetin during heating enhances the growth-inhibitory effect of heat by inducing apoptosis in the JCA-1 and LNcap cells.

97-

QC,

HPT,

Effects of the flavonoid drug Quercetin on the response of human prostate tumours to hyperthermia in vitro and in vivo

in-vitro,

Pca,

PC3

 0-400 uM; 150mg/kg/day

HSP72↑, Quercetin in prostate cancer treatment is that it antagonizes HSP72 production and, thus, sensi- tizes cells to hyperthermia-induce d apoptosis
TumCG↓, Quercetin dose-dependently suppressed PC-3 tumour growth in vitro and in vivo.
eff↑, suggest the use of Quercetin as a hyperthermia sensitizer in the treatment of prostate carcinoma
ChemoSen↑, Quercetin can act as a sensitizer to hyperthermia (® gures 1± 5), chemotherapeutic agents and ionizing radiation4,20
RadioS↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

OS↑, 1, TumVol↓, 1,
Total Targets: 45

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

GSH↓, 1, ROS↑, 1, SOD1↓, 1,

Protein Folding & ER Stress ⓘ

HSPs↑, 1,

Drug Metabolism & Resistance ⓘ

eff↑, 1,
Total Targets: 5

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:%  Cells:%  prod#:98  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Hyperthermia, ,

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Protein Folding & ER Stress ⓘ

Drug Metabolism & Resistance ⓘ

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