scholarly journals Chlorin Endogenous to the North Pacific Brittle Star Ophiura sarsii for Photodynamic Therapy Applications in Breast Cancer and Glioblastoma Models

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 134
Author(s):  
Antonina Klimenko ◽  
Elvira E. Rodina ◽  
Denis Silachev ◽  
Maria Begun ◽  
Valentina A. Babenko ◽  
...  

Photodynamic therapy (PDT) represents a powerful avenue for anticancer treatment. PDT relies on the use of photosensitizers—compounds accumulating in the tumor and converted from benign to cytotoxic upon targeted photoactivation. We here describe (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) as a major metabolite of the North Pacific brittle stars Ophiura sarsii. As a chlorin, ETPA efficiently produces singlet oxygen upon red-light photoactivation and exerts powerful sub-micromolar phototoxicity against a panel of cancer cell lines in vitro. In a mouse model of glioblastoma, intravenous ETPA injection combined with targeted red laser irradiation induced strong necrotic ablation of the brain tumor. Along with the straightforward ETPA purification protocol and abundance of O. sarsii, these studies pave the way for the development of ETPA as a novel natural product-based photodynamic therapeutic.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 118-118 ◽  
Author(s):  
Xiaohuai Wang ◽  
Lucy Qing Li ◽  
Weimin Zhang ◽  
Yifan Luo ◽  
Douglas Graham Mitchell

118 Background: Sonodynamic therapy (SDT), a procedure related with photodynamic therapy, is a promising new modality for treating deep-seated cancer. Two new chlorophyll derived sono-photo-sensitizing agents, along with equipment for systemic SDT, have been developed by EEC Biotech and all approved by regulator for safety on human. Animal studies demonstrate that the sensitizers are specifically absorbed into tumor cells and SDT does inhibit growth of mouse S-180 sarcoma. An in vitro experiment with human breast cancer cell-line showed that SDT was strongly synergetic with chemotherapy. Using sono-photo-dynamic therapy (SPDT) as a supplementary or salvage treatment, we have got some positive results in advanced refractory breast cancers. Methods: Twelve patients were pathologically proven advanced breast carcinoma. Eleven had metastases in viscera including brain, and nine in bones. Ten had chemotherapy before, nine failed at least second lines of conventional chemotherapy. With SPDT, Patients took the sensitizers sublingually on days 1 and 2, red light and multiple ultrasound transducers irradiate tumor area and whole body on days 4 to 6. The treatment was repeated. Nine patients had concurrent chemo with range from moderate to ¼ conventional dosages selected to keep side effects at grade II or better. Results: The twelve patients achieved CR 3(25%), PR 6 (50%), MR 1, SD 2, with an overall response rate of 75%.Median overall survival exceeded 14.5 months. SPDT as sole therapy was effective in three cases. Four treated repeatly with SPDT also achieved positive result after tumor relapsed. One patient with brain metastases showed much reduced. The two SD were TNBC with inflammation-like metastases on the chest surface. The main SPDT side effects were easily reversible mild pain in tumor areas, tiredness and weakness.There was no skin sensitivity.SPDT/dose controlled chemo was well tolerated, even a terminally ill patient was treated safely and effectively. Conclusions: These preliminary data suggest that SPDT has almost no toxicity, and may dramatically enhance chemo efficacy in some refractory advanced breast cancer cases. SPDT has a good trend to be a new systemic, low toxicity tumor therapy and merit for further investigation.


2019 ◽  
Vol 617-618 ◽  
pp. 221-244 ◽  
Author(s):  
MR Baker ◽  
ME Matta ◽  
M Beaulieu ◽  
N Paris ◽  
S Huber ◽  
...  

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