Apoptosis

Apoptosis is the process of programmed cell death. It is used both to eliminate unneeded cells and to get rid of irreversibly damaged cells.

In the case of cancer, apoptosis prevents uncontrolled cell division and thus the growth of a tumour.

Thus, oncothermia promotes apoptosis.

Tag Archive for: Apoptosis

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.

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Oncothermia receives the patent as a “tumor vaccine”

Oncothermia como patente cáncer

Oncothermia receives the patent as a “tumor vaccine”

This treatment alerts our immune system by checking the cancer cells.

The Oncothermia EHY-2000 plus device received the patent, US 20150217099 A1 in August 2015, describing this treatment as “a tumor vaccine”. It refers to “a vaccine” because it stimulates the immune system and radiofrequency promotes apoptosis or cell death of tumor cells.

Oncothermia is effective for the primary tumor and its metastases. Therefore, it has a local and systemic effect.

Procedure of action of the “vaccine”

The applied technique is called Modulated Electro-Hyperthermia (mEHT). The cancer cells in our body when treated with mEHT produce “heat shock proteins” when they are heated. This treatment alerts our immune system by checking the cancer cells. In this way, these cells are recognized by our immune system and eliminate them.

We all have approximately 1000 cancer cells that circulate in our body every day. Those with a weak immune system can develop a tumor.

In conclusion

For patients diagnosed with cancer, Oncothermia is an excellent option for immunotherapy to complement conventional treatments: surgery, chemotherapy or radiotherapy, in an integrative oncology framework.

You can obtain more information about the operation of Oncothermia for treatments in cancer patients through this link.

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.