Benefits of vitamin C in chemotherapy-resistant cancer

Benefits of vitamin C in chemotherapy-resistant cancer

The Department of Translational Oncology of the Fundación Jiménez Díaz in Madrid carried out research on Vitamin C. Its ability to reduce tumor resistance to conventional therapies (chemotherapy) by modulating aberrant metabolism was studied.

The research was managed by the Quirónsalud health group, and its Health Research Institute (IIS-FJD). It was also supported by the Universidad Católica San Antonio de Murcia (UCAM).

The study then detected a surprising and previously unreported role of vitamin C in the regulation of pyruvate dehydrogenase (PDH) activity and its action against the KRAS gene mutation.

Dr Óscar Aguilera, senior research scientist in OncoHealth’s Translational Oncology Department, explained the work:

“We think that metabolic modulation of the tumor can make it much more sensitive to chemotherapy and could significantly increase patients’ life expectancy and improve their quality of life.”

“The almost complete absence of serious side effects of vitamin C in megadoses invites clinical trials with patients in combination with various pharmaceutical molecules of interest.”

Vitamin C and chemotherapy resistance

The authors of the study highlight resistance to conventional chemotherapy and anti-EGFR biologic therapies as the major obstacle facing oncology. The approach of new adjuvant treatments, such as Vitamin C, represents a real progression in cure statistics and in the reduction of cancer mortality.

References

Article published in: https://international.ucam.edu/university-news/significant-advances-effectiveness-vitamin-c-treat-persistent-cancers

More information

You can access the medical study at the following link:

Cenigaonandia-Campillo A, Serna-Blasco R, Gómez-Ocabo L, Solanes-Casado S, Baños-Herraiz N, Puerto-Nevado LD, Cañas JA, Aceñero MJ, García-Foncillas J, Aguilera Ó. Vitamin C activates pyruvate dehydrogenase (PDH) targeting the mitochondrial tricarboxylic acid (TCA) cycle in hypoxic KRAS mutant colon cancer. Theranostics 2021; 11(8):3595-3606. doi:10.7150/thno.51265. Available from https://www.thno.org/v11p3595.htm

For more information, you can visit our website.

Recurrent malignant glioma treated with Oncothermia

Recurrent malignant glioma treated with Oncothermia

Through an observational retrospective clinical study, the Onco-Ematology Department of “Ospedali Riuniti Marche Nord” in Italy evaluates the efficacy and tolerability of Oncothermia (Electro-hyperthermia) for the treatment of recurrent malignant glioma.

Method

This is a retrospective observational clinical study. Patients, diagnosed with malignant glioma, experienced a previous failure with chemotherapy and radiotherapy based on temozolamide. Then, they were told a treatment with Oncothermia (Electro-Hyperthermia).

Oncothermia was performed with short radio waves of 13.56 MHz. The surface temperature of the skin was maintained at 26 ° C. Likewise, the applied power ranged between 40 and 150 watts and the average equivalent temperature calculated in the tumors was above 40 ° C, for more than 90% of the duration of the treatment (20-60 minutes gradually).

Result

Of the 24 patients who were part of the study, 19 (79%) had glioblastoma multiforme (GBM), of which 13 were grade 1-3 and 6 grade 4. The remaining patients (21%) had astrocytoma.

The analysis of tumor response performed two months after the application of Oncotermia (Electro-Hyperthermia), showed the following results:

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  • 2 patients (8%) experienced a complete remission
  • 5 patients (21%) had a partial remission.
  • The average duration of the response was 16 months (range 6-120).

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The median survival of the entire study population was 19.5 months (range 2-156), with 55% survival rate per year and 15% at two years.

In conclusion, the treatment of Oncothermia (Electro-Hyperthermia) seems to have promising efficacy in adults with recurrent malignant glioma.

You can consult the study in the following link.

If you wish, you can find more information about Gliomas treated with Oncotermia on our website.

Oncothermia in the treatment of head and neck cancer

Oncothermia in the treatment of head and neck cancer.

Oncothermia treatment applied in conjunction with radiation or chemotherapy can improve efficacy and increase overall and disease-free survival.

In a recent study published by the Department of Radiation, Oncology at Nanavati Hospital in Mumbai, India, led by Dr. Balabhai, assesses the effects of Oncothermia in conjunction with radiation and chemotherapy.

From a retrospective analysis of patients who received paclitaxel or cisplatin together with radical radiation and weekly sessions of Oncothermia, spectacular survival was obtained in advanced head and neck cancer. Similarly, a randomized trial to assess the role of HT with radiation therapy has shown a statistically significant improvement.

Due to high tobacco use, head and neck cancers constitute a significant burden of all cancers in Indian men.

Method

Patients were randomized to receive radiotherapy (RT) alone (control group), 26 patients, or radiation with Oncothermia (RT + ONC) (trial group), 28 patients.

The mean age of the patients in the control group was 58.42 years (45-76 years) and in the test group it was 57.71 years (31-78 years).

Patients in both groups received radiation up to a total dose of 70 Gy in 7 weeks with conventional fractionation of 5 days a week, without treatment on weekends. On the other hand, patients in the trial group received weekly RF-based ONC in addition to RT. Twenty-one patients in the control group and twenty-two patients in the experimental group received more than 60 Gy.

Result

Initial response was assessed within 7-10 days after completion of treatment, based on clinical evaluation.

A complete response was observed in 11 of 26 (42.4%) patients in the radiation alone group, while 22 of 28 (78.6%) patients had a complete response in the ONC + RT group.

The difference between the mean survival times between the RT + ONC and RT groups was almost 100 days.

In conclusion

Oncothermia is a very powerful hypoxic cell sensitizer. Therefore, Oncothermia together with radiation is an ideal combination to follow. The present randomized study, supported by the Indian Council for Medical Research, has shown a survival benefit from adding Oncothermia to radical radiation therapy.

In conclusion, both the randomized trial and the retrospective data analysis demonstrate a significant improvement in survival due to the addition of Oncothermia.

More information

Study published in the Oncothermia Journal, Volume 10, June 2014. To access the full study, you can consult the following link.

If you wish to expand the information regarding Oncotermia applied to cancers, you can visit the following link.

Oncothermia to Slow Down the Progression and Prevent the Development of Ultimate Pulmonary Fibrosis by COVID-19

Oncothermia to Slow Down the Progression and Prevent the Development of Ultimate Pulmonary Fibrosis by COVID-19

Right now, we are facing a global pandemic caused by the coronavirus SARS-CoV-2 that causes the highly contagious human disease COVID-19. The number of COVID-19 cases is increasing at an alarming rate, more and more people suffer from it, and the death toll is on the rise since December 2019, when COVID-19 has presumably appeared.

We need an urgent solution for the prevention, treatment, and recovery of the involved patients.

Methods

Oncothermia (Modulated electro-hyperthermia, mEHT) is known as an immuno-supportive therapy in oncology. The proposal from a group of scientists from the McGill University, Canada, is to apply this method to prevent the progression of the Pulmonary Fibrosis after its identification, to provide treatment when necessary, and deliver rehabilitation to diminish the fibrotic—often fatal—consequences of the infection.

Hypothesis

The effects of Oncothermia, which are proven for oncological applications, could be utilized for the inactivation of the virus or for treating the fibrotic consequences.

In the other hand, the hypothesized Oncothermia effects, which could have a role in the antiviral treatment, it could be applied for viral-specific immune-activation and for anti-fibrotic treatments.

It´´` is remarcable, that the proposal focuses on the electromagnetic impact, which combines the effects caused by heat and electric field, using their strong synergy. Temperature-dependent and non-temperature dependent factors are combined for optimal treatment. Oncothermia uses the biophysical differences between the malignant and healthy cells to select them and induce apoptotic signals; and immune-mediated abscopal effect.

These method has a long and successful history; it is applied in oncology all over the world.

Radiofrequency current flows into the direction of the lower impedance. (A) The increased metabolic activity of the infected cells allow lower impedance (higher conductance) in their microenvironment than in the healthy cells. (B) The electric field selects the volumes with a high concentration of the infected cells. (C) the lung-lesions are loaded more with the radiofrequency current than the non-infected parts.

The thermal aggregation of the SARS-CoV membrane protein may be one of the reasons for the inactivation of this virus by heat. The Oncothermia is also a partly thermal method, which locally heats the membrane rafts of the targeted cells in-depth.

Antiviral immune-effect of Oncothermia: the Oncothermia selects the infected cells which release a damage-associated molecular pattern through the process of immunogenic cell-death. The DAMP provides viral genetic information to maturate the dendritic cells producing antigen presentation for T-cells, which turn to viral specific CD4+ CD8+ form. Viral-specific T-cells attack the infected cells in all over the body.

More Information

For more information, you can consult the following link.

If you want more information regarding Oncotermia applied to cancers, you can visit the following link.

Combined treatment of Oncothermia for patients with ovarian cancer

Combined treatment of Oncothermia in Multimodal Immunotherapy.

Ovarian cancer is usually a serious disease with a poor prognosis, mainly due to the spread of the disease before diagnosis. Surgery, chemotherapy and antiangiogenesis are essential for first-line treatment. At the time of relapse or metastasis, only palliative treatments can be performed.

However, Active Specific Immunotherapy has proven capable of prolonging overall survival with a good quality of life.

In the following article, different experiences obtained with ovarian cancer patients treated with Multimodal Immunotherapy have been compiled. That is, injections with the Newcastle Disease Virus (NDV), modulated electrohyperthermia (mEHT / Oncothermia), IO-VAC® and immunomodulatory strategies such as: ATRA, low dose cyclophosphamide or checkpoint blockers.

The treatment was performed on an outpatient basis, with very positive results.

If you wish, you can find more information about ovarian cancer treated with Oncotermia on our website you can check this link.

Clinical study: Oncothermia as a palliative treatment for pancreatic cancer

Clinical study: Oncothermia as a palliative treatment for pancreatic cancer

Retrospective observational study of 106 patients with pancreatic cancer (pancreatic adenocarcinoma) led by Giammaria Fiorentini M.D., of the Onco-Hematology Department of the “Ospedali Riuniti Marche Nord” Hospital in Pesaro, Italy, treated with Oncothermia.

Pancreatic adenocarcinoma is one of the cancers with the poorest prognosis, resulting in a <10% survival rate at 5 years. Modulated electro-hyperthermia (mEHT – Oncothermia) combines heat-therapy with an electric field and has been increasingly used in cancer therapy alone or in combination with radiotherapy and chemotherapy.

Methods

Based on retrospective data from 170 patients affected by stage III-IV pancreatic adenocarcinoma, 106 were considered for this study. The sample was divided into two groups: 67 patients that did not receive Oncothermia (non-MEHT) and 39 patients that were treated with Oncothermia (mEHT). 

Oncothermia (mEHT) was performed using a capacitive coupling technique keeping the skin surface at 26°C and 40-42.5°C inside the tumor for > 90% of treatment duration (40-90 minutes). The applied power was 60-150 Watts. Oncothermia was performed in association with chemotherapy in 32 (82%) of patients whereas 7 (18%) received Oncothermia alone. The majority (54%) of no-mEHT group received a second line chemotherapy, whereas 31 (46%) did not receive any further treatment.

Results

106 consecutive patients were enrolled in this study, median age of the sample was 65 (range 31-80) years.

After three months of therapy, tumor response in Oncothermia group was:

  • partial response (PR) in 22 (56%) patients
  • stable disease (SD) in 15 (38%) patients
  • progression disease (PD) in 2 (5%) patients

Tumor response in no-Oncothermia group was:

  • partial response (PR) in 4 (11%) patients
  • stable disease (SD) in 11 (31%) patients
  • progression disease (PD) in 21 (58%) patients.

The median overall survival (OS) of mEHT group was 17.23 (range 2.6-30.4) and 11,33 months (range 0.4-56.25) for non-mEHT group.

In conclusion, Oncothermia may improve tumor response and survival of pancreatic cancer patients.

More information about the study in the following link.

More information about pancreatic cancer treated with Oncothermia on our website (link) or in the following clinical case.

Elevated apoptosis in a radioresistant pancreatic adenocarcinoma cell line

Elevated apoptosis and tumor stem cell destruction in a radioresistant pancreatic adenocarcinoma cell line

A recent study presented by Gertrud Farika, from the 1st Department of  Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. It deals with elevated apoptosis and tumor stem cell destruction in a radioresistant pancreatic adenocarcinoma cell line when radiotherapy is combined with modulated electro-hyperthermia (mEHT- Oncothermia)

Malignant exocrine tumors of the pancreas are among the worst to respond to oncotherapy. Despite sophisticated guidelines and new targeted therapies, the 5-year survival rate of patients with pancreatic adenocarcinomas is under 10%. The most critical factor responsible for this is the high resistance of the tumor cells to the available chemo- or radiotherapies.

Oncothermia (Modulated electro-hyperthermia – mEHT) is a complementary non-invasive cancer treatment using impedance-coupled radiofrequency to generate selective heat of <42°C causing cell stress and destruction in malignant tissue. In this study, we tested the combination of radiotherapy with Oncothermia in a radioresistant pancreatic adenocarcinoma cell line Panc1.

Methods

The study was organizated in 4 groups:

  • control (C)
  • Oncothermia treated for 60 min (mEHT)
  • irradiated with 2 Gy using 137Cs (R)
  • combination treatment: irradiation followed by the same dose of Oncothermia (Oncothermia +R)

Results

Visible morphological changes were observed after 24 hours in the treated groups. An elevated number of apoptotic bodies and cell number loss were appeared. Compared to the control group, the apoptotic ratio was the highest in the Oncothermia +R group and significant elevation was measured also in the Oncothermia group. ALDH+ tumor stem cells decreased significantly after Oncothermia and Oncothermia +R treated groups compared to the control.

As it was expected the irradiated group showed the same amount
of CSC cells as the control group (due to well-known radioresistance of the cell line). The CSCs colony forming capacity was also significantly lower in the Oncothermia and Oncothermia +R group compared to the control group. Furthermore, H2Axγ and calreticulin positive cell fractions, indicating DNA double strand-brakes and ER-stress, respectively, were also significantly increased in the Oncothermia and the Oncothermia +R treated groups.

Apoptosis with Oncothermia

Oncothermia treatment alone can lead to massive apoptosis in Panc1 cells by inducing cell stress and DNA double-strand break. Irradiation alone caused some necrosis but without major effect on CSCs. The combined treatment significantly improved the efficacy of radiotherapy resulting in major apoptosis and reduction of CSCs despite of the inherent radioresistance of Pan1.

This study was funded by a grant of the National Research and Innovation Office.

For more information, you can access the original study in the following link.

Clinical trials: Oncothermia and Cancer

Ensayos clínicos: Oncothermia y Cáncer

Clinical trials: Oncothermia and Cancer.

Oncothermia is an active part of current medical research. There are several Clinical Trials, in patients with cancer, performed in different hospitals around the world.

Clinical trials are a basic tool for the development of drugs and medical devices, in order to improve the current treatment of diseases and develop health tools worldwide.

Clinicaltrials.gov is an internationally recognized web page, where researchers publish the latest clinical trials that are carried out in different hospitals around the world. Oncothermia is present on this website. We will inform you about the latest advances in Oncothermia and Cancer.

Clinical study of Oncothermia applied to a patient with malignant ascites

The clinical study “Oncothermia + intraperitoneal chemotherapy in malignant ascites: Phase II” (Local mEHT * + TCM Versus Intraperitoneal Chemoinfusion in Treatment of Malignant Ascites: Phase II RCT (OTMA-RII) of Prof. Pang, Clifford Hospital, Guangzhou, China) began to include patients in January 2014 and ended in March 2016. The research included two groups of 130 patients. The “experimental group” will be treated with: diet, Chinese herbal medicine and Oncothermia. Instead, the “control group” will be treated with chemotherapy.

We will be attentive to the conclusions of the study!

* Clinical trial “Oncothermia + intraperitoneal chemotherapy in malignant ascites: Phase II“

Effect of Oncothermia at the cellular level. Study in colorectal cancer xenografts

Effect of Oncothermia at the cellular level. Study in colorectal cancer xenografts

Researchers studied the effect of Oncothermia at the cellular level in the process of apoptosis in colorectal cancer cells.

The Department of Radiology of the Medicine and Pharmacy Faculty -University of Toyama, in Toyama, Japan- published in the journal CellStress and Chaperones (Springer) (Cell Stress Chaperones, 2015 Jan; 20 (1): 37-46 ) the results on the effect of Oncothermia in colorectal cancer cells.

Cell apoptosis

First of all, the use of modulated electrohyperthermia (mEHT) or Oncothermia, produces a modification of the electric field and the surrounding temperature of the tumor cell, leading to selective cell death (apoptosis) in malignant tumors without affecting healthy tissue. Certainly, this is possible due to the difference of a tumor cell compared with a healthy cell. Also, the tumor cell is characterized by high glycolysis, increased lactate production (Warburg effect) and reduced electrical impedance.

Oncothermia applied to colorectal cancer

Dr Andocs studied the effect of Oncothermia on HT29 xenografts of colorectal cancer (human colon cancer cells, inoculated in mice). Apoptosis caused by Oncothermia was mediated, predominantly, by the caspase cascade and the activation of the apoptosis inducing factor. The mEHT-related cell stresses studied 0-, 1-, 4-, 8-, 14-, 24-, 48-, 72-, 120-, 168- and 216-h. And post-treatment by focusing on damage-associated molecular pattern (DAMP) signals.

 Apoptosis response was after 4 hours from the treatment with Oncothermia. It was measured using the levels of messenger RNA (mRNA) levels of the “heat shock” proteins Hsp70 and Hsp90.

Results

After that, the treatment resulted in spatiotemporal occurrence of a DAMP protein signal sequence featured by the significant cytoplasmic to cell membrane translocation of calreticulin at 4 h, Hsp70 between 14 and 24 h and Hsp90 between 24- and 216-h post-treatment.

Also, the release of high-mobility group box1 protein (HMGB1) from tumor cell nuclei from 24-h post-treatment and its clearance from tumor cells by 48 h was also detected.

Conclusion

In conclusion, the results suggest that mEHT treatment can induce a DAMP-related signal sequence in colorectal cancer xenografts that may be relevant for promoting immunological cell death response, which need to be further tested in immune-competent animals.

To conclude, the next experimental phase, which is to replicate the study in immunocompetent animals, is necessary.

Further information

If you would like further information on Oncothermia applied to colon cancer, please visit the following link.

Oncothermia and the use of oral transmucosal fentanyl citrate

Oncothermia and the use of oral transmucosal fentanyl citrate

Dr. Lee’s team, Department of Oncology, Institute of Clinical Medicine, Chonbuk University, Jeonju, Republic of Korea, published in the journal Clin Ther. 2016 Dec; 38 (12): 2548-2554, results on the safety of the use of Oncothermia and the drug for pain: transmucosal oral fentanyl citrate.

The purpose of this study was to determine if changes occur in the absorption and disposition of the drug fentanyl when it is administered together with the modulated electrohyperthermia treatment (mEHT, Oncothermia).

A randomized, single-dose, crossover, open-label study was used to investigate the effect of Oncothermia on the pharmacokinetic properties of fentanyl in 12 healthy volunteers.

Method

The 12 healthy volunteers were each administered a single dose of oral transmucosal fentanyl citrate (OTFC) or a single dose of OTFC with Oncothermia. Oncothermia was performed on the abdomen for 1 hour. Blood samples were collected for 24 hours after dosing. The temperature of the abdominal skin surface was assessed before dosing and at 10, 20, and 60 minutes after dosing.

Results

There was an increase in the overall exposure to the drug without implications of any clinical significance. OTFC can be administered without limitations in combination with Oncothermia, and it is not necessary to modify the dosing regimen.

For further information on Oncothermia, please visit the following link.