Join us   Log in   editor@cancercasereports.com  

Abstract


CANCER CASE REPORTS - Volume 1; Issue 2, (2020)

Pages: 1-15

Multidisciplinary Approaches to Minimally Invasive Cancer Treatment Using Colloidal Iodine: Twelve Case Reports in Digestive System

Norimasa Miura, Takehiko Wago, Ryusuke Fujiki

Category: Cancer Research

Download PDF

Abstract:

Background: Iodine is a substance with a long history of medical application to human bodies. In addition, when targeting a tumor, the microenvironment is essential to improve the efficacy of cancer therapy. We attempted to examine the synergistic effect of colloidal iodine mainly on gastroenterological malignancies using low-dose-chemotherapy, hyperthermotherapy, and/or hyperbaric oxygen therapy.

Materials and Methods: Colloidal iodine was administered to 12 patients with unresectable in stage IV have an outcome that is treated with palliative medicine. who had already been diagnosed with an incurable, intractable advanced neoplasm, including pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, colon cancer, and end-stage rectal cancer. The route of administration was oral for 5 patients, intravenous for 7 patients, and topical for 2 patients. The effect was estimated using a change of tumor markers or/and the findings of endoscopy or computed tomography.

Results: By each modality to evaluate the effect, the addition of iodine successfully reduced tumor size and inhibited the progression of complications in all cases, compared with cases in previous studies treated without iodine. We also confirmed that intravenous infusion was a safe route of administration without adverse effects.

Conclusions: In this pilot study, twenty patients with advanced cancer who received treatment with colloidal iodine in nanoparticle status successfully inhibited tumor progression and improved ADL without adverse effects. As a multidisciplinary approach for both the cancer itself and its microenvironment, the complementary use of colloidal iodine may increase the rate of improvement of cancer via a biomodulating mechanism. This formulations may be useful as one of the multidisciplinary therapeutic modalities and we expect outcomes from the further phase of clinical trials.

Keywords: Colloidal Iodine, Cancer, Biomodulation, Multidisciplinary Therapy, Tumor Microenvironment

References:

Aceves C, Anguiano B, Delgado G. The extrathyronine actions of iodine as antioxidant, apoptotic, and differentiation factor in various tissues. Thyroid 2013; 23: 938–946.

Aranda N, Sosa S, Delgado G, Aceves C, Anguiano B. Uptake and antitumoral effects of iodine and 6-iodolactone in differentiated and undifferentiated human prostate cancer cell lines. Prostate 2013; 73: 31–41.

Arroyo-Helguera O, Rojas E, Delgado G, Aceves C. Signaling Pathways Involved in the Antiproliferative Effect of Molecular Iodine in Normal and Tumoral Breast Cells: Evidence That 6-iodolactone Mediates Apoptotic Effects. Endocr Relat Cancer 2008; 15, 1003–1011.

Arvan P, Kim PS, Kuliawat R, Prabakaran D, Muresan Z, Yoo SE, Abu Hossain S. Intracellular protein transport to the thyrocyte plasma membrane: potential implications for thyroid physiology. Thyroid 1997; 7: 89–105.

Baraibar I, Melero I, Ponz-Sarvise M, Castanon E. Safety and Tolerability of Immune Checkpoint Inhibitors (PD-1 and PD-L1) in Cancer. Drug Saf 2019; 42: 281–294.

Benoist BD, Andersson M, Egli I, Takkouche B, Allen H. Iodine Status Worldwide. Geneva: World Health Organization 2004.

Bernet VJ. Thyroid hormone misuse and abuse. Endocrine 2019; 66: 79–86.

Beukelman CJ, van den Berg AJ, Hoekstra MJ, Uhl R, Reimer K, Mueller S. Anti-inflammatory properties of a liposomal hydrogel with povidone-iodine (Repithel) for wound healing in vitro. Burns 2008; 34: 845–855.

Bhatt AP, Redinbo MR, Bultman SJ. The Role of the Microbiome in Cancer Development and Therapy. CA Cancer J Clin 2017; 67: 326–344.

Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 2002; 23: 38–89.

Bigoni-Ordóñez GD, Ortiz-Sánchez E, Rosendo-Chalma P, Valencia-González HA, Aceves C, García-Carrancá A. Molecular iodine inhibits the expression of stemness markers on cancer stem-like cells of established cell lines derived from cervical cancer. BMC Cancer 2018; 26; 18: 928.

Bilal MY, Dambaeva S, Kwak-Kim J, Gilman-Sachs A, Beaman KD. A Role for Iodide and Thyroglobulin in Modulating the Function of Human Immune Cells. Front Immunol 2017; 15: 1573.

Bontempo A, Ugalde-Villanueva B, Delgado-González E, Rodríguez ÁL, Aceves C. Molecular iodine impairs chemoresistance mechanisms, enhances doxorubicin retention and induces downregulation of the CD44+/CD24+ and E-cadherin+/vimentin+ subpopulations in MCF-7 cells resistant to low doses of doxorubicin. Oncol Rep 2017; 38: 2867–2876.

Bosco G, Guizzon L, Yang Z, Camporesi E, Casarotto A, Bosio C, Mangar D, Chen C, Cannato M, Toniolo L, Garetto G, Nasole E, Bassi C. Effect of hyperbaric oxygenation and gemcitabine on apoptosis of pancreatic ductal tumor cells in vitro. Anticancer Res 2013; 33: 4827–4832.

Catalano V, Dentice M, Ambrosio R, Luongo C, Carollo R, Benfante A, Todaro M, Stassi G, Salvatore D. Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling. Cancer Res 2016; 76: 1237–1244.

Chaiyabutr N and Jakobsen PE. The influence of dietary iodine and enviromental temperature on the activity of mitochondria in liver and kidney. Z Tierphysiol Tierernahr Futtermittelkd 1978; 40: 225–235.

Cheng ML and Solit DB. Opportunities and Challenges in Genomic Sequencing for Precision Cancer Care. Ann Intern Med 2018; 168: 221–222.

Cheng Y, Weng S, Yu L, Zhu N, Yang M, Yuan Y. The Role of Hyperthermia in the Multidisciplinary Treatment of Malignant Tumors. Integr Cancer Ther 2019; 18: 1534735419876345.

Dentice M, Marsili A, Zavacki A, Larsen PR, Salvatore D. Version 2. The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation. Biochim Biophys Acta 2013; 1830: 3937–3945.

Evans SS, Repasky EA, Fisher DT. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol 2015; 15: 335–349.

Furth PA. Cancer prevention as biomodulation: targeting the initiating stimulus and secondary adaptations. Ann NY Acad Sci 2012; 1271: 1–9.

Galofré JC, Fernández-Calvet L, Ríos M, García-Mayor RV. Increased incidence of thyrotoxicosis after iodine supplementation in an iodine sufficient area. J Endocrinol Invest 1994a; 17: 23–27.

Galofré JC, García-Mayor RV, Fluiters E, Fernàndez-Calvet L, Rego A, Pàramo C, Andrade MA. Incidence of different forms of thyroid dysfunction and its degrees in an iodine sufficient area. Thyroidology 1994b; 6: 49–54.

Gulaboglu M, Yildiz L, Celebi F, Gul M, Peker K. Comparison of iodine contents in gastric cancer and surrounding normal tissues. Clin Chem Lab Med 2005; 43: 581–584.

Hays MT and Solomon DH. Influence of the gastrointestinal iodide cycle on the early distribution of radioactive iodide in man. J Clin Invest 1965; 44: 117.

Hegde PS and Chen DS. Top 10 Challenges in Cancer Immunotherapy. Immunity 2020; 52: 17–35.

Heimbuch BK, Harnish DA, Balzli C, Lumley A, Kinney K, Wander JD. Aerosol-phase activity of iodine captured from a triiodide resin filter on fine particles containing an infectious virus. J Appl Microbiol 2015; 118: 1315–1320.

Iwata A, Morrison ML, Roth MB. Iodide Protects Heart Tissue from Reperfusion Injury. PLoS One 2014; 9: e112458.

Kaushal N, Gupta Y, Goyal M, Khaiboullina SF, Baranwal M, Verma SC. Mutational Frequencies of SARS-CoV-2 Genome during the Beginning Months of the Outbreak in USA. Pathogens 2020; 9: 565.

Klotz KH and Benz R. Kinetics of the iodine- and bromine-mediated transport of halide ions: demonstration of an interfacial complexation mechanism. Biophys J 1993; 65: 2661–2672.

Kogai T, Schultz JJ, Johnson LS, Huang M, Brent GA. Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line. Proc Natl Acad Sci USA 2000; 97: 8519–8524.

Lee YS, Chin YT, Shih YJ, Shih YJ, Nana AW, Chen YR, Wu HC, S H Yang YC, Lin HY, Davis PJ. Thyroid Hormone Promotes β-Catenin Activation and Cell Proliferation in Colorectal Cancer. Horm Cancer 2018; 9: 156–165.

Leung AM and Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol 2014; 10: 136–142.

Lin Q, Li S, Jiang N, Shao X, Zhang M, Jin H, Zhang Z, Shen J, Zhou Y, Zhou W, Gu L, Lu R, Ni Z. PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation. Redox Biol 2019; 26: 101254.

Locy H, de Mey S, de Mey W, De Ridder M, Thielemans K, Maenhout SK. Immunomodulation of the Tumor Microenvironment: Turn Foe Into Friend. Front Immunol 2018; 9: 2909.

Mahmood J, Shukla HD, Soman S, Samanta S, Singh P, Kamlapurkar S, Saeed A, Amin NP, Vujaskovic Z. Immunotherapy, Radiotherapy, and Hyperthermia: A Combined Therapeutic Approach in Pancreatic Cancer Treatment. Cancers (Basel) 2018; 10: 469.

Miura N, Ishihara Y, Miura Y, Kimoto M, Miura K. miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives. BMC Cancer 2019; 19: 587.

Moen I and Stuhr LE. Hyperbaric oxygen therapy and cancer--a review. Target Oncol 2012; 7: 233–242.

Moreno-Vega A, Vega-Riveroll L, Ayala T, Peralta G, Torres-Martel JM, Rojas J, Mondragón P, Domínguez A, Obaldía RD, Avecilla-Guerrero C, Anguiano B, Delgado-González E, Zambrano-Estrada X, Cuenca-Micó O, Flores OD, Varela-Echavarría A, Aceves C . Adjuvant Effect of Molecular Iodine in Conventional Chemotherapy for Breast Cancer. Randomized Pilot Study. Nutrients 2019; 11: 1623.

Multhoff G, Habl G, Combs SE. Rationale of hyperthermia for radio(chemo)therapy and immune responses in patients with bladder cancer: Biological concepts, clinical data, interdisciplinary treatment decisions and biological tumour imaging. Int J Hyperthermia 2016; 32: 455–463.

Nava-Villalba M, Nuñez-Anita RE, Bontempo A, Aceves C. Activation of Peroxisome Proliferator-Activated Receptor Gamma Is Crucial for Antitumoral Effects of 6-iodolactone. Mol Cancer 2015; 14: 168.

Nicola JP, Basquin C, Portulano C, Reyna-Neyra A, Paroder M, Carrasco N. The Na+/I- Symporter Mediates Active Iodide Uptake in the Intestine. Am J Physiol Cell Physiol 2009; 296: C654–662.

Ohguri T, Imada H, Narisada H, Yahara K, Morioka T, Nakano K, Miyaguni Y, Korogi Y. Systemic chemotherapy using paclitaxel and carboplatin plus regional hyperthermia and hyperbaric oxygen treatment for non-small cell lung cancer with multiple pulmonary metastases: preliminary results. Int J Hyperthermia 2009; 25: 160–167.

Okamoto H, Nozaki M, Kanamoto H, Gomi M, Yano H. Inactivating Effects and Cytotoxicity of Oropharyngeal Medicines on Pharyngeal Infection Viruses. J Antibacterial and Antifungal Agents 2018; 46: 143–148.

Rosenholm JB, Peiponen KE, Gornov E. Materials Cohesion and Interaction Forces. Adv Colloid Interface Sci 2008; 141: 48–65.

Schubert J and Chanana M. Coating Matters: Review on Colloidal Stability of Nanoparticles with Biocompatible Coatings in Biological Media, Living Cells and Organisms. Curr Med Chem 2019; 25: 4556–4586.

Shelanski HA and Shelanski MV. PVP-iodine: history, toxicity, and therapeuticuses. J Int Coll Surg 1956; 25: 727–734.

Shimizu K, Iyoda T, Okada M, Yamasaki S, Fujii SI. Immune suppression and reversal of the suppressive tumor microenvironment. Int Immunol 2018; 30: 445–454.

Shimoda M, Mellody KT, Orimo A. Carcinoma-associated fibroblasts are a rate-limiting determiinant for tumor progression. Semin Cell Dev Biol 2010; 21: 19–25.

Spitzweg C, Heufelder AE, Morris JC. Thyroid iodine transport. Thyroid 2000; 10: 321–330.

St?pie? K, Ostrowski RP, Matyja E. Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours. Med Oncol 2016; 33: 101.

Supawat B, Udomtanakunchai C, Kothan S, Tungjai M. The Effects of Iodinated Radiographic Contrast Media on Multidrug-resistant K562/Dox Cells: Mitochondria Impairment and P-glycoprotein Inhibition. Cell Biochem Biophys 2019; 77: 157–163.

Venturi S, Venturi A, Cimini D, Arduini C, Venturi M, Guidi A. A new hypothesis: iodine and gastric cancer. Eur J Cancer Prev 1993; 2: 17–23.

Verheesen RH and Schweitzer CM. Iodine deficiency, more than cretinism and goiter. Med Hypotheses 2008; 71: 645–648.

Watanabe M. The Main Target of Carcinogenesis Is Not DNA. Gan To Kagaku Ryoho 2015; 42: 2409–2413.

Weir HK, Thompson TD, Soman A, Møller B, Leadbetter S. The past, present, and future of cancer incidence in the United States: 1975 through 2020. Cancer 2015; 12: 1827–1837.

Yokoyama M. Up-to-date Chemistry & Technological Application for Iodine (Popular Edition). CMC publishing 2018.

Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo E Drigo R, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nat Med 2018; 24: 39-49.

Zhou H, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ, Hei TK. Induction of a bystander mutagenic effect of alpha particles in mammalian cells. Proc Natl Acad Sci USA 2000; 97: 2099–2104.

DOI URL: http://dx.doi.org/10.47733/GJCCR.2020.1206