1Department of Cancer Systems Imaging, U.T.-M.D. Anderson Cancer Center, USA
2Department of Pediatric Radiology, Texas Childrenʼs Hospital, USA
3Department of Imaging Physics, U.T.-M.D. Anderson Cancer Center, USA
4Department of Gynecologic Oncology, U.T.-M.D. Anderson Cancer Center, USA
5Department of Bioengineering, University of California, USA
6Department of Radiology, U.T.-M.D. Anderson Cancer Center, USA
The degree of cytoreduction at surgery is one of the most important prognosticfactors for ovarian cancer. A multimodality agent that can be used with magnetic resonance (MR) for staging and pre-surgical planning, and with optical imaging to aid surgical removal of tumors, would present a new paradigm for ovarian cancer. We assessed whether a dual-mode, dual-Gadolinium (DM-Dual Gd-ICG) contrast agent can be used to visualize intraperitoneal ovarian tumors by multimodal MR and near infra-red (NIR) imaging. Intraperitoneal ovarian tumors (Hey-A8 or OVCAR3) in mice enhanced on MR two days after intravenous DM-Dual Gd-ICG injection compared to controls. As seen on open abdomen and excised tumors views and confirmed by radiant efficiency measurement, Hey-A8 or OVCAR3 tumors from animals injected with DM-Dual Gd-ICG had increased NIR fluorescence. As controls, increased MR signal was not seen by Gd-chelate alone nor was increased NIR signal seen by ICG alone 2 days after injection at doses similar to those given by DM-Dual Gd-ICG. This suggests clinical potential to localize ovarian tumors by MR for staging and surgical planning, and, by NIR at surgery for resection.
Vikas Kundra is Professor and Director of Molecular Imaging in the Department of Radiology, U.T.- M.D. Anderson Cancer Center with joint appointment in the Department of Cancer Systems Imaging. He received his M.D. and Ph.D. from Harvard University and completed his radiology training at Brigham and Womenʼs Hospital. He is a Fellow of the Society of Body Computed Tomography-Magnetic Resonance Imaging and a Distinguished Investigator of the Academy of Radiology Research. Clinical work focuses on Body Imaging particularly in cancer and research focuses on molecular imaging, including imaging of gene expression and nanotechnology.
University of Cincinnati Academic Health Center, Winkle College of Pharmacy, USA
In cancer, metastases manifest clinically at advanced disease stages. The dissemination of the transformed cells is an integral characteristic of malignancies and is absent from benign growths. While the major limiting factor in cancer spread is the death of the tumor cells before their implantation into target organs, a fraction of the released cells can survive in the circulation for extended periods of time. The molecular programs of metastasis act to promote tumor progression, not growth or extension of life span. Besides inducing directed migration and invasion, they support adhesion-independent survival. The cytokine Osteopontin is a metastasis gene product that supports the progression of over 30 aggressive tumors. The protein exists in three splice variants, dubbed Osteopontin-a (full-length), -b (lacking exon 5), and -c (lacking exon 4).
1. Untransformed non-hematopoietic cells undergo programmed cell deathconsecutive to losing contact with their substratum. Anchorage-deprivation causes impairment in glucose transport, a deficit in ATP availability and consecutiveanoikis. In cancer cells that have been shed from the primary tumor, metastasis gene products support enhanced energy generation and survival. Variant forms of Osteopontin act as autocrine inducers. Osteopontin-a increases the levels of glucose in deadherentbreast cancer cells. Osteopontin-c, upregulates peroxides as well as intermediates of the hexose monophosphate shunt and glycolysis, which utilize the available glucose and can feed into the tricarboxylic acid cycle. Consecutively, the cellular ATP levels are elevated and the cells can survive.
2. Osteopontin-c is present in 75-80% of breast cancers and 0% of normal breast tissues. It increases with tumor grade. In early breast cancer, high staining intensity of nuclear Osteopontin-c is strongly associated with mortality. Osteopontin-c is not correlated with proliferation markers, ER, PR, or HER2. Bya real-time RT-PCR test, the elevation in Osteopontin-c in the blood detectsa fraction of breast cancers, suggesting prognostic potential of a blood test. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome.In therapy responses, exon 4 is associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c falls short of being a significant predictor for sensitivity to the treatments investigated. The addition of Osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.
Acknowledgement: This research was supported by U.S. DOD grant BC095225 and the Marlene Harris-Ride Cincinnati/Pilot Program.
Georg F. Weber attended medical school in Würzburg, Germany. He worked at the Dana-Farber Cancer Institute, Harvard Medical School from 1990 through 1999 and is currently on the faculty at the University of Cincinnati. Georg F. Weber has published about 90 scientific reports, including many in the most respected professional journals, as well as various monographs, including textbooks on molecular oncology and anti-cancer drugs. He holds several U.S. and international patents.
University of Pittsburgh School of Medicine, USA
Accurate prediction of prostate cancer clinical courses remains elusive. In recent studies, we performed whole genome analysis on prostate cancers by combiningAffymetrix SNP6.0 chip, whole genome sequencing and transcriptome sequencing. Our result showed that combination of genome copy number variance and novel fusion transcripts specific for cancer achieved high accuracy in predicting prostate cancer outcomes. The prediction model was further improved when these molecular criteria were combined with Nomogram or Gleasonʼs grading. Interestingly, some of these fusion genes are also present in a variety of human malignancies. Treatment of cancers with drugs specific for fusion gene signaling pathways produced dramatic improvement of metastasis and survival rate of animals xenografted with cancers positive for fusion genes. Our analyses suggest that targeting therapy for fusion genes holds promise as an effective treatment for human cancers.
Dr. Luo been studying molecular pathology related to human malignancies in the last 24 years. Currently, he is a Professor of Pathology and Director of High Throughput Genome Center at University of Pittsburgh. In the last 16 years, Dr. Luo has been largely focusing on genetic and molecular mechanism of human prostate and hepatocellular carcinomas. In this period, his group has identified and characterized several genes that are related to prostate cancer and hepatocellular carcinoma, including SAPC, myopodin, CSR1, GPx3, ITGA7, MCM7, MT1h and GPC3. He has characterized several signaling pathways that play critical role in prostate cancer development, including Myopodin-ILK-MCM7 inhibitory signaling, myopodin-zyxin motility inhibition pathway, CSR1-CPSF3, CSR1-SF3A3 and CSR1-XIAP apoptotic pathways, MT1h-EHMT1 egigenomic signaling, ITGA7-HtrA2 tumor suppression pathway, GPx3-PIG3 cell death pathway, AR-MCM7 and MCM7-SF3B3 oncogenic pathways. He proposed prostate cancer field effect in 2002. He is one of the pioneers in utilizing high throughput gene expression and genome analyses to analyze field effects in prostate cancer and liver cancer. He is also the first in using methylation array and whole genome methylation sequencing to analyze prostate cancer. Recently, Dr. Luoʼs group found that patterns of copy number variants of certain specific genome loci are predictive of prostate cancer clinical outcomes, regardless tissue origin. His discovery of several novel fusion transcripts and their association with aggressive prostate cancer has brought significant new insight into the field of prostate cancer research. Overall, these findings advance our understanding onhow cancer develops and behaves, and lay down the foundation for better future diagnosis and treatment of human malignancies.
Adjunct Prof., Dept. of Family & Community Medicine, New York Medical College;
President, International College of Acupuncture & Electro-Therapeutics;
Former Director of Medical Research, Heart Disease Research Foundation, USA
A previous analysis of 500 breast cancer patientsʼ mammograms indicated that more than 90 percent of breast cancer tissue has human papillomavirus type-16 (HPV-16). Type-18 was found in less than a few percent. Human papillomavirus was measured non-invasively and rapidly using strong Electromagnetic Field (EMF) Resonance phenomenon between 2 identical substances with the same weight, for which US patent was given in 1993. Because of these findings, the relationship between HPV-16 and various cancers was studied. In various cancers including brain tumors, a significant infection of HPV-16 was detected in every cancer tissue evaluated. HPV-16 was found to be highly infectious, particularly when oral cavities have HPV-16 infection of more than 2000ng BDORT Units. In families where one member has a strong infection of HPV-16, other members of the family often have the same degree of infection. When one has a strong HPV-16 infection, there is a high tendency of developing cancers at the most infected organ. Even if the patient does not develop malignancies, when a strong infection of HPV-16 virus is present, β-amyloid (1-42), which is increased in Alzheimerʼs disease and autism, is also increased in the infected area of the body. When this is increased in cancer tissue, we found naturally existing molecules Vitamin D3 & its derivatives, Taurine (sulfur containing one type of amino acid) and PQQ were often reduced in the cancer tissue or infected areas. Therefore, we give these naturally existing substances, namely optimal doses of Vitamin D3 (400 I.U.), Taurine (~175mg), and PQQ (5-10mg). When these 3 substances are independently used, an optimal dose produces very significant anti-cancer effects and increases Acetylcholine and DHEA levels. In addition, viruses such as HPV-16 & CMV, bacteria such as Lyme Borrelia Burgdorferi spirochaete, & fungi like Candida Albicansare excreted through urine in very significant amounts. These effects are even more beneficial when used in a compatible combination of all 3, particularly when a compatible dose of Cilantro tablets is used together. We also found many atrial fibrillations are due to Lyme Burgdorferi infection of SA node and atrium areas. These infections can be effectively reduced without using anti-viral or anti-bacterial agents, but by simply using combination of compatible optimal doses of Vitamin D3, Taurine, and PQQ. Cancer is potentially transmitted by HPV-16 infection. The best treatment of cancer should have not only inhibition of cancer activities, but also simultaneous elimination of the viral infection using optimal doses of these naturalcomponents of our body mentioned, although other overdosed supplements (Vit. C, etc.) or certain medications can inhibit these beneficial effects. In order to give the best treatment combination, optimal doses and selection of combinations must be determined individually and prevent potential drug interactions with other medications or supplements.
Yoshiaki Omura received Oncological Residency training at Cancer Institute of Columbia University & Doctor of Science Degree through research on Pharmaco-Electro-Physiology of Single Cardiac Cells in-vivo and in-vitro from Columbia Uni. He researched EMF Resonance phenomenon between 2 identical molecules for non-invasive detection of molecules, at Graduate Experimental Physics Dept., Columbia Uni., for which he received U.S. patent. He is also the creator of Bi-Digital O-Ring Test. He published over 270 original research articles, many chapters, & 9 books. He is currently Adjunct Prof. of Family & Community Medicine, New York Medical College; President & Prof. of Intʼl College of Acupuncture & Electro-Therapeutics, NY; Editor in Chief, Acupuncture & Electro-Therapeutics Research, Intʼl Journal of Integrative Medicine, (indexed by 17 major intʼl Indexing Periodicals); Formerly, he was also Adjunct Prof. or Visiting Prof. in Universities in USA, France, Italy, Ukraine, Japan, Korea, & China.