Therapeutic results of a novel enzyme-targeting radiosensitization treatment, Kochi oxydol-radiation therapy for unresectable carcinomas II, in patients with stage I primary breast cancer

Aoyama, N.; Ogawa, Yasuhiro; Yasuoka, Miki; Ohgi, K.; Iwasa, Hitomi; Miyatake, Kana; Yoshimatsu, Rika; Yamanishi, Tomoaki; Hamada, Norihiko; Tamura, Tomohide; Kobayashi, Kana; Murata, Yoriko; Miyamura, Mitsuhiko; Yamagami, Takuji

doi:10.3892/ol.2017.6074

Cited by 11 publications

(15 citation statements)

References 28 publications

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“…[126] Futhermore, many researchers worked on many cells, including LY2603618, MK87776, and AZD1775 on human papillomavirus(+) human head-and-neck squamous cell carcinoma (HNSCC) cells; UD-SCC-2, UM-SCC-47, and UPCI-SCC-154, EhB4 on HNSCC cells; Cal27, MSK-921, and Fadu, Human polo-like kinase 1 (PLK1) on human esophageal squamous cell carcinoma cells; KYSE 70, and KYSE 150, ganetespib on human Hepatocellular carcinoma cells; Hep3b, HepG2 and HUH, AZD6738 and ATM inhibitor KU-55933 on different cell lines; CAL27, FaDu, A549, PJ34, PJ41, T24, A2780, RT4, NCI-H1838, NCI-H1373, and DU-4475, MZ-6 and MZ-14 on human hepatocellular liver carcinoma cell line HepG2. [382728293031] Outcomes of this study are in good agreement with their results.…”

Section: Discussionsupporting

confidence: 88%

“…Clinically conventional treatment has been adopted for BC treatment mainly including chemotherapy, surgery, radiotherapy (RT), and some combined treatment strategies. [ 1 2 3 4 5 ] Chemotherapy is used for systemic control, whereas surgery and RT are used to the management of cancer. RT is commonly recommended as primary or adjuvant treatment modality for BC with the benefit rate as high as 80%–90%.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the majority of cancer types contain a high degree of heterogeneity in microenvironment, phenotype, genotype, many hypoxic cells, and huge amount of enzymes should be protected cells to RT and variability in radiation sensitivity. [ 1 2 3 4 ] To address these challenges, tumor-selective radiosensitizers which can increase the selectivity of ionizing radiation (IR) to cancer cell without hampering the activities of healthy cells are extremely desired and have been widely investigated. The use of radiosensitizers combined with low-linear energy transfer radiations can increase normal tissue radioresistance, therapeutic efficacy by allowing to decrease the essential treatment irradiation dose, and resulting in minimizing the risk of recurrence.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the radiosensitizing potency of bromelain for radiation therapy of 4T1 breast cancer cells

et al. 2019

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Breast cancer (BC) remains the leading cause of death in women worldwide, despite the improvements of cancer screening and treatment methods. Recently, development of novel anticancer drugs for the improved prevention and treatment of BC is in the center of research. The anticancer effects of bromelain, as enzyme extract derived from the pineapples, contains chemicals that interfere with the growth of tumor cells. The aim of this study was to evaluate the effect of radiosensitizing of bromelain in 4T1 BC cells. This investigation utilized the 3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyltetrazolium bromide assay to characterize the cytotoxicity of bromelain. Colony formation method was used to establish the truth of the capability of bromelain to make sensitive to radiation therapy. Flowcytometry performed to define the contribution the apoptosis effect to bromelain mediated radiosensitization of 4T1 cells. Bromelain reduced growth and proliferation of 4T1 cell as a concentration-dependence manner significantly. The survival of 4T1 cancer cells was decreased after combined treatment in a number and size-dependent manner with regard to the control group (P < 0.05). Combination of bromelain with radiation does not influence 4T1 cell apoptosis. The results suggested that bromelain can inhibit the growth and proliferation and reduce survival of 4T1 BC cells and might be used as a candidate radiosensitizer in BC patient.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of the radiosensitizing potency of bromelain for radiation therapy of 4T1 breast cancer cells

et al. 2019

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“…The novel KORTUC II radiosensitizer, which contains H 2 O 2 and sodium hyaluronate, was developed to address this shortcoming. The effectiveness of KORTUC II for the treatment of chemotherapy-resistant supraclavicular lymph node metastases, recurrent breast cancer, and stage-IV primary breast cancer has previously been demonstrated. − Because KORTUC II administers radiation therapy after injecting a drug containing H 2 O 2 into the tumor tissue, it is assumed that there is a high concentration of H 2 O 2 in the tumor region. Therefore, our methodology might be used to understand the localization of radicals within the treatment site by administration of DMPO.…”

Section: Resultsmentioning

confidence: 99%

Imaging of Hydroxyl-Radical Generation Using Dynamic Nuclear Polarization-Magnetic Resonance Imaging and a Spin-Trapping Agent

et al. 2020

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Reactive oxygen species (ROS) play an important role in cell metabolism, but they can cause oxidative damage to biomolecules. Among ROS, the hydroxyl radical (·OH) is one of the most reactive molecules in biological systems because of its high reaction rate constant. Therefore, imaging of ·OH could be useful for evaluation of the redox mechanism and diagnosis of oxidative diseases. In vivo dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) is a noninvasive imaging method to obtain spatiotemporal information about free radicals with MRI anatomical resolution. In this study, we investigated the visualization of hydroxyl radicals generated from the Fenton reaction by combining DNP-MRI with a spin-trapping agent (DMPO: 5,5-dimethyl-1-pyrroline N-oxide) for ·OH. Additionally, we demonstrated the radical-scavenging effect using four thiol-related reagents by DNP-MRI. We demonstrated that DNP enhancement could be induced by the DMPO-OH radical using the DNP-MRI/spin-trapping method and visualized ·OH generation for the first time. Maximum DNP enhancement was observed at an electron paramagnetic resonance irradiation frequency of 474.5 MHz. Furthermore, the radical-scavenging effect was simultaneously evaluated by the decrease in the DNP image value of DMPO-OH. An advantage of our methods is that they simultaneously investigate compound activity and the radical-scavenging effect.

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“…This suggests it is a safe sensitizer if proper dosage is used and attention is paid to avoid procedural problems such as incorrect administration into blood vessels (5). The severity of acute-phase adverse events, such as radio-dermatitis, has been reported to be comparable with that following adjuvant radiation for regular breast-conserving therapy (13)(14)(15). Also, no particular delay in acute-phase injuries has been observed.…”

Section: Discussionmentioning

confidence: 99%

New enzyme‑targeting radiosensitizer (KORTUC II) treatment for locally advanced or recurrent breast cancer

et al. 2021

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Kochi oxydol radiation therapy for unresectable carcinomas II (KORTUC II) is currently the most widely used radiosensitizer in Japan. This sensitizer is a solution consisting of 0.83% sodium hyaluronate and 0.5% hydrogen peroxide. The mixture is injected intratumorally just before radiation therapy (RT) several times. KORTUC II has the effect of neutralizing antioxidant enzymes, while increasing the oxygen tension into the tumor tissue, and achieves marked local effects without notable adverse events. The present report describes cases in which KORTUC II was used to treat patients with locally advanced breast cancer (LABC) or recurrent breast cancer (LRBC). The present study included 30 patients with LABC (n=9) or LRBC (n=21) aimed at local control of tumors, who were followed up for ≥3 months after treatment. The irradiation dose and extent fields were determined by the attending physicians considering various patient factors, such as a performance status, prognosis and presence or absence of adjuvant therapy. The median irradiation dose was 60.4 Gy3.5 (43.6-76.1 Gy3.5) based on the calculation of equivalents of 2 Gy fractions, and the median total number of sensitizer injections was 5 ( 2-7 ) times. The median maximum tumor shrinkage was 97.0% and 15 patients (50%) were assessed to have achieved a clinical complete response. The proportion with loco-regional control at 1, 2 and 3 years was 100, 94.7 and 75.4%, respectively, and progression free survival after RT at 1 and 2 years was 59.0 and 24.1%, respectively. KORTUC II exhibited high rates of local tumor control for LABC and LRBC. KORTUC II is expected to be an inexpensive and promising RT method because it is safe and has an excellent radio-sensitizing effect.

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Therapeutic results of a novel enzyme-targeting radiosensitization treatment, Kochi oxydol-radiation therapy for unresectable carcinomas II, in patients with stage I primary breast cancer

Cited by 11 publications

References 28 publications

Evaluation of the radiosensitizing potency of bromelain for radiation therapy of 4T1 breast cancer cells

Evaluation of the radiosensitizing potency of bromelain for radiation therapy of 4T1 breast cancer cells

Imaging of Hydroxyl-Radical Generation Using Dynamic Nuclear Polarization-Magnetic Resonance Imaging and a Spin-Trapping Agent

New enzyme‑targeting radiosensitizer (KORTUC II) treatment for locally advanced or recurrent breast cancer

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