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Szasz A. Bioelectromagnetism for Cancer Treatment-Modulated Electro-Hyperthermia. Curr Oncol 2025; 32:158. [PMID: 40136362 PMCID: PMC11941104 DOI: 10.3390/curroncol32030158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 03/04/2025] [Accepted: 03/09/2025] [Indexed: 03/27/2025] Open
Abstract
Bioelectromagnetism has the potential to revolutionize cancer treatment by providing a noninvasive, targeted, and potentially more effective complement to traditional therapies. Among bioelectromagnetic techniques, modulated electro-hyperthermia (mEHT) stands out due to its unique characteristics, which have been supported by experimental evidence and clinical validation. Unlike conventional hyperthermia methods, mEHT leverages nonthermal bioelectromagnetic processes, offering a distinct and promising approach in oncology. This differentiation underscores the broader potential for bioelectromagnetic applications in cancer treatment, paving the way for innovative therapeutic strategies.
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Affiliation(s)
- Andras Szasz
- Department of Biotechnics, Hungarian University of Agriculture and Life Sciences, 2100 Gödöllő, Hungary
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Wang H, Jiang M, Ma S, Hu Y, Zhang X, Zhu H, Zhang J, Wang Y. Formation mechanism, prevention of malignant ascites effusion and reduction of intestinal mucosal irritation of natural microemulsion from Euphorbia lathyris Pulveratum. Biomed Pharmacother 2024; 178:117253. [PMID: 39111084 DOI: 10.1016/j.biopha.2024.117253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/28/2024] [Accepted: 07/31/2024] [Indexed: 08/25/2024] Open
Abstract
Malignant ascites effusion (MAE) is a common complication of advanced malignant tumors with limited treatments. Euphorbia lathyris (EL) has a long history of application in patients with edema and ascites. Herein, we reported for the first time a mode in which EL and EL Pulveratum (PEL) spontaneously formed natural microemulsions (ELM and PELM) without the addition of any carriers and excipients, and found that the protein and phospholipid contained in them encapsulated fatty oil and diterpenoid esters through non-covalent interactions. The denaturation and degradation of protein in PELM resulted in stronger binding of diterpenoid esters to the hydrophobic region of protein, which facilitated the sustained and slow release of diterpenoid esters and improved their bioavailability in vivo, thereby retaining the efficacy of preventing MAE while alleviating the irritation of intestinal mucosa. The mechanism by which PELM retained efficacy might be related to increased feces moisture and urine volume, and decreased expression of AVPR2, cAMP, PKA and AQP3 in MAE mice. And its mechanism of reducing intestinal mucosal irritation was related to decreased cell apoptosis, amelioration of oxidative stress, elevation of mitochondrial membrane potential, and up-regulation of Occludin and Claudin-1 expression in IEC-6 cells. This nano-adjuvant-free natural microemulsions may be a promising therapeutic strategy in the field of phytochemistry for promoting the application of natural and efficient nano-aggregates spontaneously formed by medicinal plants in MAE, and provide a new perspective for advancing the development of the fusion of Chinese herbal medicine and nanomedicine and its clinical translation.
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Affiliation(s)
- Huinan Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China
| | - Mingrui Jiang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China
| | - Siyuan Ma
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China
| | - Yufeng Hu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China
| | - Xinning Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China
| | - Haiting Zhu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China
| | - Junli Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China
| | - Yingzi Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, PR China.
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Dai S, Zhou S, Ju Y, Yao W, Tang Y, Zheng J, Ma S, Zhang Y, Zhang L. Synergistic effect of Euphorbia kansui stir-fried with vinegar and bile acids on malignant ascites effusion through modulation of gut microbiota. Front Pharmacol 2023; 14:1249910. [PMID: 38026948 PMCID: PMC10665909 DOI: 10.3389/fphar.2023.1249910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 09/18/2023] [Indexed: 12/01/2023] Open
Abstract
Background: Toxic Euphorbia kansui (EK) is employed to treat malignant ascites effusion (MAE). EK stir-fried with vinegar (VEK) has been demonstrated to reduce toxicity due to its preserved water-expelling effect. This was demonstrated to be correlated with gut microbiota. Therein, bile acids (BAs) have a bidirectional relationship with the gut microbiota. Therefore, the aim of this study is to explore whether BA-mediated gut microbiota influences the water-expelling effect of VEK against MAE. Methods: The MAE rat model was established by intraperitoneal injection of Walker-256 tumor cells. A reliable simultaneous method for the determination of 15 bile acids in rat feces using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established and applied to analyze the fecal BAs in rats treated with VEK. The screened BA was then administered to VEK-treated MAE rats. The water-expelling effect was evaluated using histopathological analysis, biochemical examination, inflammatory factors in ascites, urine volume, ascites amount, and intestinal aquaporin expression. The microbial composition was determined using 16S rRNA sequencing, and the contents of bile acids were finally measured. Results: VEK decreased the content of fecal deoxycholic acid (DCA), lithocholic acid (LCA), and taurocholic acid (TCA) while increasing the content of ursodeoxycholic acid (UDCA). VEK alleviated liver, stomach, and intestinal injuries; oxidative damage; and inflammation, which were further ameliorated with UDCA intervention. VEK alleviated MAE by increasing the fecal water content, urine volume, and AQP3 protein expression and decreasing the urine levels of Na+, K+, and Cl-. This was retained with the intervention of UDCA. UDCA and VEK regulated the BA metabolism disorder to a certain extent. Analysis of gut microbiota showed that VEK increased the abundance of Lactobacillus and decreased that of Prevotella_9 in MAE rats. The combined administration of UDCA and VEK showed a better modulation of the microbiota structure than that of VEK alone, and the effect of this administration reached closer to the reference state. Conclusion: The water-expelling effect of VEK did not directly depend on the BA-mediated gut microbiota. However, VEK and BAs had a synergistic effect on malignant ascites effusion through the regulation of the gut microbiota. These results provided a scientific basis for the reasonable usage of VEK and the novel combination treatment strategy of VEK and UDCA.
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Affiliation(s)
- Shengyun Dai
- Institute for Control of Chinese Traditional Medicine and Ethnic Medicine, National Institute for Food and Drug Control, Beijing, China
| | - Shikang Zhou
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yonghui Ju
- School of Medicine and Chemical Materials, Zhenjiang College, Zhenjiang, China
| | - Weifeng Yao
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuping Tang
- College of Pharmacy and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi’an, China
| | - Jian Zheng
- Institute for Control of Chinese Traditional Medicine and Ethnic Medicine, National Institute for Food and Drug Control, Beijing, China
| | - Shuangcheng Ma
- Institute for Control of Chinese Traditional Medicine and Ethnic Medicine, National Institute for Food and Drug Control, Beijing, China
| | - Yi Zhang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
| | - Li Zhang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China
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Lee SY, Lorant G, Grand L, Szasz AM. The Clinical Validation of Modulated Electro-Hyperthermia (mEHT). Cancers (Basel) 2023; 15:4569. [PMID: 37760538 PMCID: PMC10526385 DOI: 10.3390/cancers15184569] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 08/30/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023] Open
Abstract
The mEHT method uses tissues' thermal and bioelectromagnetic heterogeneity for the selective mechanisms. The success of the therapy for advanced, relapsed, and metastatic aggressive tumors can only be demonstrated by measuring survival time and quality of life (QoL). The complication is that mEHT-treated patients cannot be curatively treated any longer with "gold standards", where the permanent progression of the disease, the refractory, relapsing situation, the organ failure, the worsening of blood counts, etc., block them. Collecting a cohort of these patients is frequently impossible. Only an intent-to-treat (ITT) patient group was available. Due to the above limitations, many studies have single-arm data collection. The Phase III trial of advanced cervix tumors subgrouping of HIV-negative and -positive patients showed the stable efficacy of mEHT in all patients' subgroups. The single-arm represents lower-level evidence, which can be improved by comparing the survival data of various studies from different institutes. The Kaplan-Meier probability comparison had no significant differences, so pooled data were compared to other methods. Following this approach, we demonstrate the feasibility and superiority of mEHT in the cases of glioblastoma multiform, pancreas carcinomas, lung tumors, and colorectal tumors.
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Affiliation(s)
- Sun-Young Lee
- Department of Radiation Oncology, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea;
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
| | - Gergo Lorant
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, H-1083 Budapest, Hungary;
| | - Laszlo Grand
- Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, H-1083 Budapest, Hungary;
| | - Attila Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, H-1083 Budapest, Hungary;
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Li Z, Qi J, Guo T, Li J. Research progress of Astragalus membranaceus in treating peritoneal metastatic cancer. JOURNAL OF ETHNOPHARMACOLOGY 2023; 305:116086. [PMID: 36587879 DOI: 10.1016/j.jep.2022.116086] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 12/19/2022] [Accepted: 12/20/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Peritoneal metastasis is a manifestation of advanced cancer often associated with a poor prognosis and poor response to treatment. Astragalus membranaceus (Fisch.) Bunge is a commonly used medicinal material in traditional Chinese medicine with various biological activities. In patients with cancer, Astragalus membranaceus has demonstrated anti-tumor effects, immune regulation, postoperative recurrence and metastasis prevention, and survival prolongation. AIM OF THE STUDY Peritoneal metastasis results from tumor cell and peritoneal microenvironment co-evolution. We aimed to introduce and discuss the specific mechanism of action of Astragalus membranaceus in peritoneal metastasis treatment to provide a new perspective for treatment and further research. MATERIALS AND METHODS We consulted reports on the anti-peritoneal metastases effects of Astragalus membranaceus from PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases, as well as Google Scholar. Meanwhile, we also obtained data from published medical works and doctoral and master's theses. Then, we focused on the research progress of Astragalus membranaceus in peritoneal metastatic cancer treatment. Plant names are provided in accordance with "The Plant List" (www.theplantlist.org). RESULTS To date, more than 200 compounds have been isolated from Astragalus membranaceus. Among them, Astragalus polysaccharides, saponins, and flavonoids are the main bioactive components, and their effects on cancer have been extensively studied. In this review, we systematically summarize the effects of Astragalus membranaceus on the peritoneal metastasis microenvironment and related mechanisms, including maintaining the integrity of peritoneal mesothelial cells, restoring the peritoneal immune microenvironment, and inhibiting the formation of tumor blood vessels, matrix metalloproteinase, and dense tumor spheroids. CONCLUSIONS Our analysis demonstrates that Astragalus membranaceus could be a potential therapeutic for preventing the occurrence of peritoneal metastasis. However, it might be too early to recommend its use owing to the paucity of reliable in vivo experiment, clinical data, and evidence of clinical efficacy. In addition, previous studies of Astragalus membranaceus report inconsistent and contradictory findings. Therefore, detailed in vitro, in vivo, and clinical studies on the mechanism of Astragalus membranaceus in peritoneal metastatic cancer treatment are warranted.
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Affiliation(s)
- Zhiyuan Li
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, 730030, China
| | - Jinfeng Qi
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, 730030, China
| | - Tiankang Guo
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, 730030, China
| | - Junliang Li
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, 730030, China; The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, 730030, China; The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, China.
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Chia BSH, Ho SZ, Tan HQ, Chua MLK, Tuan JKL. A Review of the Current Clinical Evidence for Loco-Regional Moderate Hyperthermia in the Adjunct Management of Cancers. Cancers (Basel) 2023; 15:cancers15020346. [PMID: 36672300 PMCID: PMC9856725 DOI: 10.3390/cancers15020346] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/23/2022] [Accepted: 12/27/2022] [Indexed: 01/06/2023] Open
Abstract
Regional hyperthermia therapy (RHT) is a treatment that applies moderate heat to tumours in an attempt to potentiate the effects of oncological treatments and improve responses. Although it has been used for many years, the mechanisms of action are not fully understood. Heterogenous practices, poor quality assurance, conflicting clinical evidence and lack of familiarity have hindered its use. Despite this, several centres recognise its potential and have adopted it in their standard treatment protocols. In recent times, significant technical improvements have been made and there is an increasing pool of evidence that could revolutionise its use. Our narrative review aims to summarise the recently published prospective trial evidence and present the clinical effects of RHT when added to standard cancer treatments. In total, 31 studies with higher-quality evidence across various subsites are discussed herein. Although not all of these studies are level 1 evidence, benefits of moderate RHT in improving local tumour control, survival outcomes and quality of life scores were observed across the different cancer subsites with minimal increase in toxicities. This paper may serve as a reference when considering this technique for specific indications.
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Affiliation(s)
- Brendan Seng Hup Chia
- Division of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore
- Correspondence:
| | - Shaun Zhirui Ho
- Department of Radiation Oncology, 585 North Bridge Rd, Level 10 Raffles Specialist Centre, Singapore 188770, Singapore
| | - Hong Qi Tan
- Division of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore
| | - Melvin Lee Kiang Chua
- Division of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore
| | - Jeffrey Kit Loong Tuan
- Division of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore
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Youn BY, Kim JH, Jo YK, Yoon S, Im JY, Kim HJ, Lee JD, Ko SG. Current Characteristics of Herbal Medicine Interventions for Cancer on Clinical Databases: A Cross-Sectional Study. Integr Cancer Ther 2023; 22:15347354231218255. [PMID: 38099482 PMCID: PMC10725141 DOI: 10.1177/15347354231218255] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 09/09/2023] [Accepted: 11/13/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND The utilization of herbal medicine has been noteworthy for treating cancer; however, there is not enough information regarding the characteristics of clinical trials of herbal medicine interventions. This study aimed to evaluate the characteristic of registered trials using herbal medicine interventions for cancer. METHODS A cross-sectional study was performed via the website ClinicalTrials.gov, ISRCTN registry, Chinese clinical trial registry, and international clinical trials registry platform to gather associated registered clinical trials using an advanced search with the developed keyword strategy as of March 26, 2023. All obtainable information from the trials was collected without any restrictions to conduct a comprehensive review. RESULTS A total of 169 registered trials were included for evaluation. Of all trials, 102 trials were eligible for this study. Countries from Asia registered the most trials (62.75%), and hospitals sponsored most of the trials (42.16%). Randomized, Phase 2, interventional trials were dominant, and approximately 64.71% of the trials anticipated recruiting less than 100 participants. More than half of the trials were from 2016 to 2023 (53.92%). While 45 trials were completed, only 16 trials had results for further analysis. According to the completed results, the types of herbal medicines from the trials mainly focused on lung, breast, and colorectal cancer. CONCLUSION This study is the first to explore the characteristics of clinical trials of herbal medicine for cancer registered in large clinical databases. The acquired trials had relatively informative data; however, better-designed trials may be needed for health professionals to consider herbal medicine as an option when treating cancer patients.
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Affiliation(s)
- Bo-Young Youn
- Hwasung Medi-Science University, Hwaseong-si, Gyeonggi-do, South Korea
| | - Ji-Hyun Kim
- Kyung Hee University, Seoul, Republic of Korea
| | - Yong-Kyu Jo
- Kyung Hee University, Seoul, Republic of Korea
| | | | - Ji-Yeong Im
- Kyung Hee University, Seoul, Republic of Korea
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Hübner J, Dörfler J, Liebl C, Käsmann L. Answer to Commentary on "Systematic review about complementary medical hyperthermia in oncology" by Liebl et al. Clin Exp Med 2022; 22:673-678. [PMID: 36239870 PMCID: PMC9588464 DOI: 10.1007/s10238-022-00901-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 09/10/2022] [Indexed: 11/27/2022]
Affiliation(s)
- J Hübner
- Klinik für Innere Medizin II; Universitätsklinikum Jena, Jena, Germany.
| | - J Dörfler
- Klinik für Innere Medizin II; Universitätsklinikum Jena, Jena, Germany
| | - C Liebl
- Klinik für Innere Medizin II; Universitätsklinikum Jena, Jena, Germany
| | - L Käsmann
- LMU Klinikum Munich, Munich, Germany
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Liebl CM, Kutschan S, Dörfler J, Käsmann L, Hübner J. Systematic review about complementary medical hyperthermia in oncology. Clin Exp Med 2022; 22:519-565. [PMID: 35767077 PMCID: PMC9244386 DOI: 10.1007/s10238-022-00846-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/25/2022] [Indexed: 11/24/2022]
Abstract
Hyperthermia is a generic term for different techniques using heat in cancer therapies. Temperatures of about 42° Celsius in combination with chemo- or radiotherapy may improve the effectiveness of those treatments. Clinical benefit is shown in "standard hyperthermia" with tumour temperatures assessed during treatment. This systematic review thoroughly assesses the state of evidence concerning the benefits and side effects of electro hyperthermia or whole-body hyperthermia ("alternative hyperthermia") in oncology. From 26 April 2021 to 09 May 2021, a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsycINFO, CINAHL and Medline) to find studies concerning the use, effectiveness and potential harm of alternative medical hyperthermia therapy on cancer patients. From all 47,388 search results, 53 publications concerning 53 studies with 2006 patients were included in this systematic review. The patients were diagnosed with different types of cancer. The hyperthermic methods included whole-body hyperthermia (WBH) with different methods and electro hyperthermia (EH). The majority of the included studies were single-arm studies, counting in total 32 studies. Six studies were randomized controlled trials (RCT). In addition, one systematic review (SR) was found. The most critical endpoints were tumour response, survival data, pain relief, myelosuppression and toxicities. Outcome was heterogeneous, and considering the methodological limitations, clinical evidence for the benefit of alternative hyperthermia in cancer patients is lacking. Neither for whole-body hyperthermia nor for electro hyperthermia there is any evidence with respect to improvement of survival or quality of life in cancer patients.
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Affiliation(s)
- Christina Maria Liebl
- Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Sabine Kutschan
- Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Jennifer Dörfler
- Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Lukas Käsmann
- Klinik und Poliklinik für Strahlentherapie, LMU Klinikum, Munich, Germany
| | - Jutta Hübner
- Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Germany.
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Arrojo E, Fiorentini G, Ghadjar P, Minnaar C, Szasz AM, Szasz A. Commentary on "Systematic review about complementary medical hyperthermia in oncology" by Liebl et al. Clin Exp Med 2022; 22:667-672. [PMID: 36239869 PMCID: PMC9588469 DOI: 10.1007/s10238-022-00902-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 07/30/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Elisabeth Arrojo
- University Hospital Marques de Valdecilla, Santender, Cantabria, Spain
- Medical Institute of Advanced Oncology (INMOA), Madrid, Spain
| | - Giammaria Fiorentini
- Former Director Medical Oncology Unit and Hyperthermia Service, Onco-Hematology Department, Azienda Ospedaliera Marche Nord, Pesaro, Italy
| | - Pirus Ghadjar
- Department of Radiation Oncology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany
| | - Carrie Minnaar
- Department of Radiation Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Wits Donald Gordon Academic Hospital, Johannesburg, South Africa.
| | - A Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Andras Szasz
- Biotechnics Department, Hungarian University of Agriculture and Life Sciences, Godollo, Hungary
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Khinsar KH, Abdul S, Hussain A, Ud Din R, Lei L, Cao J, Abbasi M, Ur Rehman A, Farooqui N, Yi X, Min H, Wang L, Mintao Z. Anti-tumor effect of polysaccharide from Pleurotus ostreatus on H22 mouse Hepatoma ascites in-vivo and hepatocellular carcinoma in-vitro model. AMB Express 2021; 11:160. [PMID: 34855004 PMCID: PMC8640000 DOI: 10.1186/s13568-021-01314-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 11/01/2021] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma is one of the leading causes of cancer-associated death across the globe. Malignant ascites are the major clinical attributes in cancer patients. Despite the advancements in HCC treatments such as chemotherapy, radiotherapy, surgery, and hormonal therapy, researchers are pursuing novel natural edible compounds for the treatment of cancer to eliminate dreadful side effects. Pleurotus ostreatus is one of the most edible cuisines in Asia as well as all over the world. It has been a source of nutritious diet since it was classified as an edible mushroom with no or negligible side effects. The present study focused on the natural anti-cancerous and anti-ascites capabilities of polysaccharides extracted from Pleurotus ostreatus in-vivo as well as in-vitro. Administration of polysaccharide Pleurotus ostreatus showed a significant decrease in tumor cell metastasis while the increase in the survival period among mice models of H22 malignant ascites. Downregulation of regenerative genes Foxp3 and Stat3 and secretion of immunological factors such as IL-2, TNF α, and INF γ were observed after treating with the partially pure extracted polysaccharide. Twining with the hypothesis of tumor suppression in-vivo model polysaccharide showed a decrease in invasion and migration abilities and henceforth responsible for the gene regulation such Cytochrome C which supposedly induced the chain of gene regulation process resulting in apoptosis in HCC cell lines observed in-vitro experiments. Collective research findings manifested that polysaccharide extracted from Pleurotus ostreatus bears anti-proliferative activity and thus influence tumor suppression in-vivo and in-vitro against hepatocellular carcinoma and can be used for therapeutic purposes as a potential anti-cancerous source in the future.
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Affiliation(s)
- Kavish Hasnain Khinsar
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Sattar Abdul
- Department of Biochemistry, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, 116044, China
| | - Akbar Hussain
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Riaz Ud Din
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Liu Lei
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Jing Cao
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Majid Abbasi
- Department of Biochemistry, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, 116044, China
- Department of Biochemistry, Ghulam Muhammad Mahar Medical College, SMBB Medical University Larkana, Larkana, Pakistan
| | - Ata Ur Rehman
- Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Nabeel Farooqui
- Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Xin Yi
- Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Huang Min
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China
| | - Liang Wang
- Stem Cell Clinical Research Centre, National Joint Engineering Laboratory, Regenerative Medicine Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 11601, China.
| | - Zhong Mintao
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.
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Petenyi FG, Garay T, Muhl D, Izso B, Karaszi A, Borbenyi E, Herold M, Herold Z, Szasz AM, Dank M. Modulated Electro-Hyperthermic (mEHT) Treatment in the Therapy of Inoperable Pancreatic Cancer Patients-A Single-Center Case-Control Study. Diseases 2021; 9:81. [PMID: 34842668 PMCID: PMC8628793 DOI: 10.3390/diseases9040081] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/03/2021] [Accepted: 10/30/2021] [Indexed: 02/05/2023] Open
Abstract
UNLABELLED Our present oncological treatment arsenal has limited treatment options for pancreatic ductal adenocarcinoma (PDAC). Extended reviews have shown the benefits of hyperthermia for PDAC, supporting the perspectives with the improvements of the treatment possibilities. METHODS A retrospective single-center case-control study was conducted with the inclusion of 78 inoperable PDAC patients. Age-, sex-, chemotherapy-, stage-, and ascites formation-matched patients were assigned to two equal groups based on the application of modulated electro-hyperthermia (mEHT). The EHY2030 mEHT device was used. RESULTS A trend in favor of mEHT was found in overall survival (p = 0.1420). To further evaluate the potential beneficial effects of mEHT, the presence of distant metastasis or ascites in the patients' oncological history was investigated. Of note, mEHT treatment had a favorable effect on patients' overall survival in metastatic disease (p = 0.0154), while less abdominal fluid responded to the mEHT treatment in a more efficient way (p ≤ 0.0138). CONCLUSION mEHT treatment was associated with improved overall survival in PDAC in our single-center retrospective case-control study. The outcome measures encourage us to design a randomized prospective clinical study to further confirm the efficiency of mEHT in this patient cohort.
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Affiliation(s)
- Flora Greta Petenyi
- Faculty of Information Technology and Bionics, Pazmany Peter Catholic University, 1083 Budapest, Hungary; (F.G.P.); (T.G.); (B.I.)
| | - Tamas Garay
- Faculty of Information Technology and Bionics, Pazmany Peter Catholic University, 1083 Budapest, Hungary; (F.G.P.); (T.G.); (B.I.)
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Dorottya Muhl
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Blanka Izso
- Faculty of Information Technology and Bionics, Pazmany Peter Catholic University, 1083 Budapest, Hungary; (F.G.P.); (T.G.); (B.I.)
| | - Adam Karaszi
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Erika Borbenyi
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Magdolna Herold
- Department of Internal Medicine and Hematology, Semmelweis University, 1088 Budapest, Hungary;
| | - Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Attila Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
| | - Magdolna Dank
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; (D.M.); (A.K.); (E.B.); (Z.H.); (A.M.S.)
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Herold Z, Szasz AM, Dank M. Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system. World J Gastrointest Oncol 2021; 13:1109-1120. [PMID: 34616516 PMCID: PMC8465447 DOI: 10.4251/wjgo.v13.i9.1109] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/29/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatopancreatobiliary tumors are challenging to treat, and the advanced or metastatic forms have a very low 5-year survival rate. Several drug combinations have been tested, and new therapeutic approaches have been introduced in the last decades, including radiofrequency and heat based methods. Hyperthermia is the artificial heating of tumors by various biophysical methods that may possess immunostimulant, tumoricidal, and chemoradiotherapy sensitizer effects. Both whole-body and regional hyperthermia studies have been conducted since the 1980s after the introduction of deep-seated tumor hyperthermia techniques. Results of the effects of hyperthermia in hepatocellular and pancreatic cancer are known from several studies. Hyperthermia in biliary cancers is a less investigated area. High local and overall responses to treatment, increased progression-free and overall survival, and improved laboratory and quality-of-life results are associated with hyperthermia in all three tumor types. With the evolution of chemotherapeutic agents and the introduction of newer techniques, the combination of adjuvant hyperthermia with those therapies is advantageous and has not been associated with an increase in alarming adverse effects. However, despite the many positive effects of hyperthermia, its use is still only known at the experimental level, and its concomitant utilization in routine cancer treatment is not certain because of the lack of thorough clinical studies.
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Affiliation(s)
- Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
| | - A Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
| | - Magdolna Dank
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest H-1083, Hungary
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14
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Alshaibi HF, Al-shehri B, Hassan B, Al-zahrani R, Assiss T. Modulated Electrohyperthermia: A New Hope for Cancer Patients. BIOMED RESEARCH INTERNATIONAL 2020; 2020:8814878. [PMID: 33274226 PMCID: PMC7683119 DOI: 10.1155/2020/8814878] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/14/2020] [Accepted: 10/31/2020] [Indexed: 12/26/2022]
Abstract
According to the World Health Organization, the prevalence of cancer has increased worldwide. Oncological hyperthermia is a group of methods that overheat the malignant tissues locally or systematically. Nevertheless, hyperthermia is not widely accepted, primarily because of the lack of selectivity for cancer cells and because the temperature-triggered higher blood flow increases the nutrient supply to the tumor, raising the risk of metastases. These problems with classical hyperthermia led to the development of modulated electrohyperthermia (mEHT). The biophysical differences of the cancer cells and their healthy hosts allow for selective energy absorption on the membrane rafts of the plasma membrane of the tumor cells, triggering immunogenic cell death. Currently, this method is used in only 34 countries. The effectiveness of conventional oncotherapies increases when it is applied in combination with mEHT. In silico, in vitro, and in vivo preclinical research studies have all shown the extraordinary ability of mEHT to kill malignant cells. Clinical applications have improved the quality of life and the survival of patients. For these reasons, many other research studies are presently in progress worldwide. Thus, the objective of this review is to highlight the capabilities and advantages of mEHT and provide new hopes for cancer patients worldwide.
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Affiliation(s)
- Huda F. Alshaibi
- Faculty of Science Biochemistry Department, King Abdulaziz University, Saudi Arabia P.O. Box 52502, Jeddah 21573
| | - Bashayr Al-shehri
- Faculty of Science Biochemistry Department, Undergraduate Students at King Abdulaziz University, Saudi Arabia
| | - Basmah Hassan
- Faculty of Science Biochemistry Department, Undergraduate Students at King Abdulaziz University, Saudi Arabia
| | - Raghad Al-zahrani
- Faculty of Science Biochemistry Department, Undergraduate Students at King Abdulaziz University, Saudi Arabia
| | - Taghreed Assiss
- Faculty of Science Biochemistry Department, Undergraduate Students at King Abdulaziz University, Saudi Arabia
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15
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Lee SY, Fiorentini G, Szasz AM, Szigeti G, Szasz A, Minnaar CA. Quo Vadis Oncological Hyperthermia (2020)? Front Oncol 2020; 10:1690. [PMID: 33014841 PMCID: PMC7499808 DOI: 10.3389/fonc.2020.01690] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 07/29/2020] [Indexed: 12/19/2022] Open
Abstract
Heating as a medical intervention in cancer treatment is an ancient approach, but effective deep heating techniques are lacking in modern practice. The use of electromagnetic interactions has enabled the development of more reliable local-regional hyperthermia (LRHT) techniques whole-body hyperthermia (WBH) techniques. Contrary to the relatively simple physical-physiological concepts behind hyperthermia, its development was not steady, and it has gone through periods of failures and renewals with mixed views on the benefits of heating seen in the medical community over the decades. In this review we study in detail the various techniques currently available and describe challenges and trends of oncological hyperthermia from a new perspective. Our aim is to describe what we believe to be a new and effective approach to oncologic hyperthermia, and a change in the paradigm of dosing. Physiological limits restrict the application of WBH which has moved toward the mild temperature range, targeting immune support. LRHT does not have a temperature limit in the tumor (which can be burned out in extreme conditions) but a trend has started toward milder temperatures with immune-oriented goals, developing toward immune modulation, and especially toward tumor-specific immune reactions by which LRHT seeks to target the malignancy systemically. The emerging research of bystander and abscopal effects, in both laboratory investigations and clinical applications, has been intensified. Our present review summarizes the methods and results, and discusses the trends of hyperthermia in oncology.
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Affiliation(s)
- Sun-Young Lee
- Department of Radiation Oncology, Chonbuk National University Hospital, Jeonbuk, South Korea
| | | | - Attila Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Gyula Szigeti
- Innovation Center, Semmelweis University, Budapest, Hungary
| | - Andras Szasz
- Biotechnics Department, St. Istvan University, Godollo, Hungary
| | - Carrie Anne Minnaar
- Department of Radiation Oncology, Wits Donald Gordon Medical Center, Johannesburg, South Africa
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16
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Besztercei B, Vancsik T, Benedek A, Major E, Thomas MJ, Schvarcz CA, Krenács T, Benyó Z, Balogh A. Stress-Induced, p53-Mediated Tumor Growth Inhibition of Melanoma by Modulated Electrohyperthermia in Mouse Models without Major Immunogenic Effects. Int J Mol Sci 2019; 20:ijms20164019. [PMID: 31426515 PMCID: PMC6720184 DOI: 10.3390/ijms20164019] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 08/09/2019] [Accepted: 08/13/2019] [Indexed: 02/07/2023] Open
Abstract
Modulated electrohyperthermia (mEHT), an innovative complementary technique of radio-, chemo-, and targeted oncotherapy modalities, can induce tumor apoptosis and contribute to a secondary immune-mediated cancer death. Here, we tested the efficiency of high-fever range (~42 °C) mEHT on B16F10 melanoma both in cell culture and allograft models. In vivo, mEHT treatment resulted in significant tumor size reduction when repeated three times, and induced major stress response as indicated by upregulated cytoplasmic and cell membrane hsp70 levels. Despite the increased PUMA and apoptosis-inducing factor 1, and moderate rise in activated-caspase-3, apoptosis was not significant. However, phospho-H2AX indicated DNA double-strand breaks, which upregulated p53 protein and its downstream cyclin-dependent kinase inhibitors p21waf1 and p27kip. Combined in vitro treatment with mEHT and the p53 activator nutlin-3a additively reduced cell viability compared to monotherapies. Though mEHT promoted the release of damage-associated molecular pattern (DAMP) damage signaling molecules hsp70, HMGB1 and ATP to potentiate the tumor immunogenicity of melanoma allografts, it reduced MHC-I and melan-A levels in tumor cells. This might explain why the number of cytotoxic T cells was moderately reduced, while the amount of natural killer (NK) cells was mainly unchanged and only macrophages increased significantly. Our results suggest that mEHT-treatment-related tumor growth control was primarily mediated by cell-stress-induced p53, which upregulated cyclin-dependent kinase inhibitors. The downregulated tumor antigen-presenting machinery may explain the reduced cytotoxic T-cell response despite increased DAMP signaling. Decreased tumor antigen and MHC-I levels suggest that natural killer (NK) cells and macrophages were the major contributors to tumor eradication.
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Affiliation(s)
- Balázs Besztercei
- Institute of Clinical Experimental Research, Semmelweis University, 1097 Budapest, Hungary
| | - Tamás Vancsik
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1097 Budapest, Hungary
| | - Anett Benedek
- Institute of Clinical Experimental Research, Semmelweis University, 1097 Budapest, Hungary
| | - Enikő Major
- Institute of Clinical Experimental Research, Semmelweis University, 1097 Budapest, Hungary
| | - Mbuotidem J Thomas
- Institute of Clinical Experimental Research, Semmelweis University, 1097 Budapest, Hungary
| | - Csaba A Schvarcz
- Institute of Clinical Experimental Research, Semmelweis University, 1097 Budapest, Hungary
| | - Tibor Krenács
- 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1097 Budapest, Hungary
| | - Zoltán Benyó
- Institute of Clinical Experimental Research, Semmelweis University, 1097 Budapest, Hungary
| | - Andrea Balogh
- Institute of Clinical Experimental Research, Semmelweis University, 1097 Budapest, Hungary.
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17
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Szasz O. Bioelectromagnetic Paradigm of Cancer Treatment—Modulated Electro-Hyperthermia (mEHT). ACTA ACUST UNITED AC 2019. [DOI: 10.4236/ojbiphy.2019.92008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Bender Ignacio RA, Lin LL, Rajdev L, Chiao E. Evolving Paradigms in HIV Malignancies: Review of Ongoing Clinical Trials. J Natl Compr Canc Netw 2018; 16:1018-1026. [PMID: 30099376 PMCID: PMC6109631 DOI: 10.6004/jnccn.2018.7064] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 07/23/2018] [Indexed: 12/19/2022]
Abstract
This review highlights current interventional clinical trials for HIV-associated malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic therapies; novel tumor-targeted and virally targeted therapies in both AIDS-defining and non-AIDS-defining cancers (NADC); and other screening or topical/ablative interventions. A search on ClinicalTrials.gov located 35 trials, including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials, 10 trials of therapies with tumor or viral molecular targets, and 7 trials evaluating screening interventions or topical or ablative therapies. Study drugs, mechanisms, and outcomes of interest, including future directions, are discussed. Targeted therapies and immunotherapies address not only the tumor but underlying viral oncogens, including possible benefits on HIV-specific immunologic control. The resulting science from the trials listed in this review will provide important translational breakthroughs for people living with HIV (PLWH) and cancer. We highlight disease-specific challenges that could be addressed in future studies, including testing the safety and efficacy of cutting-edge immunotherapy and targeted treatments used in the general cancer population, and improving gaps in knowledge and practice for cancer screening and its treatment, especially in low-resource regions. Additional important considerations include identification of novel therapies for virally mediated tumors that disproportionally present in PLWH, how to treat persons with HIVAM and advanced immunosuppression, and how to comanage both diseases in antiretroviral therapy-naïve persons and those receiving care in settings where supportive therapies for hematologic toxicities and infections are limited. Current and future clinical trials should address needs of both resource-replete and -limited regions, as well as cancers that are uncommon in or respond differently to HIV-negative populations (eg, Kaposi sarcoma or anal cancer), in addition to an increased focus on NADCs not traditionally linked with HIV, such as lung or gastrointestinal tumors.
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Affiliation(s)
| | - Lilie L. Lin
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | | | - Elizabeth Chiao
- Baylor College School of Medicine
- DeBakey Veterans Affairs Medical Center, Houston, Texas
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Fang Y, Ning A, Li S, Zhou S, Liu L, Joseph TP, Zhong M, Jiao J, Zhang W, Shi Y, Zhang M, Huang M. Polysaccharides Extracted from Rhizoma Pleionis Have Antitumor Properties In Vitro and in an H22 Mouse Hepatoma Ascites Model In Vivo. Int J Mol Sci 2018; 19:E1386. [PMID: 29735884 PMCID: PMC5983843 DOI: 10.3390/ijms19051386] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2018] [Revised: 04/23/2018] [Accepted: 04/24/2018] [Indexed: 02/06/2023] Open
Abstract
Malignant ascites is a highly severe and intractable complication of advanced or recurrent malignant tumors that is often immunotherapy-resistant. Rhizoma Pleionis is widely used in traditional medicine as an antimicrobial and anticancer agent, but its effectiveness in treating malignant ascites is unclear. In the current study, we investigated the effect of polysaccharides isolated from Rhizoma Pleionis (PRP) on murine hepatocarcinoma H22 cells in an ascites model. We have found that the main components of PRP, that presented a relative molecular weight of 383.57 kDa, were mannose and glucose. We also found that PRP reduced the occurrence of abdominal ascites and increased survival in our mouse model. An immune response in the ascites tumor model was observed by performing a lymphocytes proliferation experiment and an E-rosette test. The ratios of CD8+ cytotoxic T cells and NK cells in the spleen were examined by flow cytometry, and the mRNA expression of Foxp3+in CD4⁺CD25⁺ (T regulatory Tregs) was measured by RT-PCR (reverse transcription-polymerase chain reaction). The levels of the cytokines TNF-α (tumor necrosis factor), VEGF (vascular endothelial growth factor), IL-2 (interleukin), and IFN-γ (interferon) in the serum and ascites supernatants were measured by ELISA. The expression of Foxp3 and Stat3 in peritoneal cells in the mouse model was measured by immunocytochemistry. The results indicated that PRP increased H22 tumor cell apoptosis in vivo by activating and enhancing the immune response. Furthermore, the effects of PRP on the proliferation of H22 cells were assessed by the CCK8 assay, Hoechest 33258, and TUNEL staining in vitro. We found that PRP suppressed the proliferation of H22 tumor cells but had no effect on BRL (Big rat liver) -3A rat hepatoma normal cells in vitro. Next, we investigated the underlying immunological mechanism by which PRP inhibits malignant ascites. PRP induced tumor cell apoptosis by inhibiting the Jak1⁻Stat3 pathway and by activating Caspase-3 and Caspase-8 to increase the Bax/Bcl-2 ratio. Collectively, our results indicate that PRP exhibits significant antitumor properties in H22 cells in vivo and in vitro, indicating that PRP may be used as a new therapeutic drug for cancer treatment.
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Affiliation(s)
- Yukun Fang
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Anhong Ning
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Sha Li
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Shaozheng Zhou
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Lei Liu
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | | | - Mintao Zhong
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Jilong Jiao
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Wei Zhang
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Yonghui Shi
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Meishan Zhang
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
| | - Min Huang
- Department of Microbiology, Dalian Medical University, Dalian 116044, China.
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Roussakow SV. Clinical and economic evaluation of modulated electrohyperthermia concurrent to dose-dense temozolomide 21/28 days regimen in the treatment of recurrent glioblastoma: a retrospective analysis of a two-centre German cohort trial with systematic comparison and effect-to-treatment analysis. BMJ Open 2017; 7:e017387. [PMID: 29102988 PMCID: PMC5722101 DOI: 10.1136/bmjopen-2017-017387] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
OBJECTIVE To assess the efficacy and cost-effectiveness of modulated electrohyperthermia (mEHT) concurrent to dose-dense temozolomide (ddTMZ) 21/28 days regimen versus ddTMZ 21/28 days alone in patients with recurrent glioblastoma (GBM). DESIGN A cohort of 54 patients with recurrent GBM treated with ddTMZ+mEHT in 2000-2005 was systematically retrospectively compared with five pooled ddTMZ 21/28 days cohorts (114 patients) enrolled in 2008-2013. RESULTS The ddTMZ+mEHT cohort had a not significantly improved mean survival time (mST) versus the comparator (p=0.531) after a significantly less mean number of cycles (1.56 vs 3.98, p<0.001). Effect-to-treatment analysis (ETA) suggests that mEHT significantly enhances the efficacy of the ddTMZ 21/28 days regimen (p=0.011), with significantly less toxicity (no grade III-IV toxicity vs 45%-92%, p<0.0001). An estimated maximal attainable median survival time is 10.10 months (9.10-11.10). Cost-effectiveness analysis suggests that, unlike ddTMZ 21/28 days alone, ddTMZ+mEHT is cost-effective versus the applicable cost-effectiveness thresholds €US$25 000-50 000/quality-adjusted life year (QALY). Budget impact analysis suggests a significant saving of €8 577 947/$11 201 761 with 29.1-38.5 QALY gained per 1000 patients per year. Cost-benefit analysis suggests that mEHT is profitable and will generate revenues between €3 124 574 and $6 458 400, with a total economic effect (saving+revenues) of €5 700 034 to $8 237 432 per mEHT device over an 8-year period. CONCLUSIONS Our ETA suggests that mEHT significantly improves survival of patients receiving the ddTMZ 21/28 days regimen. Economic evaluation suggests that ddTMZ+mEHT is cost-effective, budget-saving and profitable. After confirmation of the results, mEHT could be recommended for the treatment of recurrent GBM as a cost-effective enhancer of ddTMZ regimens, and, probably, of the regular 5/28 days regimen. mEHT is applicable also as a single treatment if chemotherapy is impossible, and as a salvage treatment after the failure of chemotherapy.
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