Ozone Therapy for Breast Cancer: An Integrative Literature Review.

Breast cancer is the most prevalent form of cancer in women. Despite significant advances in conventional treatment, additional safer complementary treatment options are needed. Recently, ozone therapy has been considered as a type of medical adjunctive treatment that could inhibit cancer cell survival and reduce chemoresistance. However, only a few studies have been conducted on its use in breast cancer, and the optimal dosage and time of administration are unknown. Currently, preclinical studies suggest that ozone alone or in combination with chemotherapy is an effective method for inhibiting breast cancer cell growth. However, rather than investigating the effects of ozone as an antitumor therapy, current clinical trials have generally assessed its effect as an adjunctive therapy for reducing chemotherapy-induced side effects, increasing oxygen tension, normalizing blood flow, restoring blood lymphocytes more rapidly, and reducing fatigue symptoms. In this article, the use of ozone as a medical adjunctive treatment for breast cancer and its role in integrative therapy are summarized and discussed.

Role of Estrogen Receptor-Positive/Negative Ratios in Regulating Breast Cancer.

The alpha estrogen receptor (ERα) contributes to breast cancer progression and recent guidelines define ER positivity as ≥1% stained cells, and a few tumor tissues show no ERα expression at all or are at 100%. Although ER and aromatase inhibitors are widely used to treat hormone receptor-positive (HR+) breast cancer, their effect on tumor activity at different ERα levels remains unclear. Therefore, we investigated the role of ERα+/ERα- ratios in determining the ERα level. We used ERα stably transfected and wild-type MDA-MB-231 cells (MDA-MB-231Trans-ER and MDA-MB-231WT, respectively) as represented ER+ and ER- cells, respectively, and MCF-7 cells were the positive control. MDA-MB-231Trans-ER and MDA-MB-231WT cells were mixed and cocultured at a ratio of 0%, 20%, 40%, 70%, and 100%. Migration and invasion functions at different cell ratios were evaluated in vitro using the Transwell and scratch test. In a xenograft mouse model, the polarization of the tumor-associated (M2) macrophage and the expression of breast cancer gene 1 (BRCA1), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF)-α were measured. The results showed that the cell invasion and migration were significantly higher at 40% and 70% than they were at other ratios. Additionally, in vivo, the 70% ERα+/ERα-ratio was a critical indicator of cell activity and cytokine expression. The highest M2 level and expression of VEGR, TNF-α, BRCA1, and HER2 were shown at a ratio of 70%. Moreover, the effects of ERα were not linear in breast cancer, indicating that the ERα status requires continuous monitoring during long-term endocrine treatment. These results indicate that during HR+ breast cancer treatment, the ERα+/ERα- ratio may be a useful predictor and should be evaluated further.

Effects of a Chlorogenic Acid-Containing Herbal Medicine (LASNB) on Colon Cancer.

BACKGROUND: Plant polyphenols, which contain phenolic acids such as chlorogenic acid (CGA), can be used for the treatment of gastrointestinal cancer and have gained increasing attention in recent years. In this study, we explored a novel CGA-containing herbal medicine named LASNB, which was extracted from Lonicera japonica Thunb., Agrimonia eupatoria L., and Scutellaria barbata D.Don. METHODS: CGA in LASNB was analyzed using high-performance liquid chromatography (HPLC). The biological functions and molecular mechanisms of LASNB were investigated in colon cancer cell lines (HCT116, HCT15, and CT26), a normal colon cell line (NCM460), and a CT26 xenograft model. To assess safety, hematological toxicity and pathology of the liver, kidney, and lung were evaluated. RESULTS: LASNB suppressed HCT116, HCT15, and CT26 colon cancer progression by inhibiting proliferation capacity, promoting cell apoptosis, and suppressing cell migration both in vitro and in vivo. Investigation into the underlying molecular mechanism indicated that LASNB suppressed the activation of receptor tyrosine kinase- (RTK-) MEK-ERK and NF-κB pathways. With regard to safety, slight interstitial vascular congestion in the lung was observed, but no severe pathological or hematological toxicity was detected. CONCLUSIONS: We found that LASNB suppressed the progression of colon cancer via the RTK-MEK-ERK and NF-κB pathways, with no severe toxicity observed. Therefore, LASNB has the potential to be used as a supplementary herbal medicine for the treatment of colon cancer.

Study on the Anticancer Effect of an Astragaloside- and Chlorogenic Acid-Containing Herbal Medicine (RLT-03) in Breast Cancer.

BACKGROUND: Although surgery, chemotherapy, radiotherapy, and endocrine therapy are widely used in clinical practice for breast cancer treatment, herbal medicines (HMs) are considered as an alternative to palliative treatments because of their coordinated intervention effects and relatively low side effects. Astragaloside (AS) and chlorogenic acid (CGA) are major active ingredients of Radix Astragali and Lonicera japonica, which have shown antitumorigenic properties in certain cancers, but the role of HMs containing both AS and CGA remains unclear in breast cancer. In this study, we explored an AS- and CGA-containing HM (RLT-03) extracted from Radix Astragali, Lonicerae Japonicae Flos, Trichosanthin, and Rhizoma imperatae. METHODS: RLT-03 was extracted using water and n-butanol, and the AS and CGA ingredients in RLT-03 were identified by high-performance liquid chromatography (HPLC) and evaporative light-scattering detector (ELSD). 4T1, EMT6, BT-549, and MDA-MB-231 breast cancer cell lines were used, and an EMT6 xenograft model was established. Cell proliferation, migration, and apoptosis were measured in vitro, and tumor volume and weight were observed in vivo. The expression of VEGF, EGF, IL-10, TGF-ß, and CD34 and cell apoptosis in tumors were examined. RESULTS: RLT-03 inhibited cell viability and induced apoptosis in a dose- and time-dependent manner. In vivo, tumor volume and weight were reduced, and the expression of VEGF, EGF, IL-10, TGF-ß, and CD34 was suppressed in the tumor microenvironment, while cell apoptosis was induced. CONCLUSION: RLT-03 exhibited therapeutic effects against breast cancer by regulating the expression of ligands of receptor tyrosine kinases (RTKs) and inflammatory factors. Thus, RLT-03 represents a potential supplementary HM that can be used in breast cancer therapy.

Severe Bilateral Breast Mucinous Carcinoma with Bilateral Lungs and Cutaneous Metastasis: A Case Report and Literature Review.

The case of a female who had severe, rare, terminal breast mucinous carcinoma (BMC) and failed to receive surgery and chemotherapy was reported. The patient was diagnosed with pure BMC (ER++, PR++, CerbB-2-, and Ki-67 10%) accompanied with bilateral lungs, bilateral chest walls with skin ulcer (D = 14 cm), lymph nodes of bilateral armpits, and right supraclavicular metastases. ECOG (Eastern Cooperative Oncology Group) and NRS (Numeric Rating Scale) pain scores were 4 and 6, respectively. Because the patient refused traditional chemotherapy and radiotherapy on religious grounds, an herbal medicine containing Panax ginseng, Agrimonia pilosa, and white flower Patrinia herb was administered; extensive nursing for tumor debridement was also provided. Quality of Life (QOL) improved and pain reduced. Tumor-bearing survival time was prolonged. The present case dictates that herbal extract medicines and supportive treatment can be helpful for uncommon severe BMC as an appropriate alternative treatment.

Use of a novel herbal medicine in a 75-year-old woman with multi-metastatic pancreatic cancer: A case report and review of the literature.

Pancreatic cancer is one of the most aggressive types of malignant tumors and is associated with an extremely poor prognosis. Despite numerous research efforts over the last few years, little progress has been made in the understanding and treatment of the disease. Gemcitabine-based regimens are considered as the first-line treatment for pancreatic cancer, but the effects of chemotherapy on the disease are limited. Natural products extracted from herbs represent a valuable resource for novel bioactive anticancer agents and could benefit multi-metastasis pancreatic adenocarcinoma patients with an Eastern Cooperative Oncology Group status of 3. Biological intra-control cancer treatment (BICT) is a novel systemic therapy involving palliative care and herbal extract combinations [including ginseng (Panax ginseng C.A. Mey.), Herba Agrimonia (Agrimonia pilosa Ledeb.), White Flower Patrinia Herb (Thlaspi arvense Linn.) and arginine], which has been approved by the State Food and Drug Association. The treatment is intended to regulate and inhibit blood vessel generation and tumor growth by inhibiting epidermal growth factor receptor and vascular endothelial growth factor receptor expression, and to manage symptoms to improve the quality of the treatment. The present study discusses the case of a 75-year-old female diagnosed with pancreatic cancer with multiple metastases in the liver and lymph nodes. The patient was administered BICT and achieved survival for 11 months without side-effects of a severity greater than grade 1 according to the Common Terminology Criteria for Adverse Events. The study also describes a possible approach to providing palliative care and treating late-stage, metastatic pancreatic adenocarcinomas in elderly patients.