The London College UCK, U.K.
The cancer is a phenomenon of special reaction mechanism, which is functioning against the threat of severely acted tissues in the body. It is only created to eliminate severe damages and dangerous that occur in the cells of the body, when the immune system fails to cure the damages.
The effect of the cancer could only be ended when a direct, right and simple treatment method should be applied to cure the previous diseases that have caused the cancer, but not to attempt to treat the cancer itself.
For the telomere matter, cancer cells have similar lengthening characteristics of the telomere, [in every DNA replication], to those of germ and stem cells. While in somatic cells the telomere is shortening in every DNA replication.
May be, a possible method to eliminate the cancer, is by applying a suitable amount and direction of a magnetic action on opposing the cancer cells. This method, could be, inhibited the lengthening of the telomere of the cancer cells, towards the somatic cells characteristics. Where, then, this application could be accepted as a method of vanishing the cancer.
Keywords: Cancer Natural Action, History of Old Diseases, Lengthening the Telomere, New Strategy to Treat the Cancer, Telomere Similarity of Cancer and Germ Cells, Treat Old Diseases before Cancer.
The London College UCK, U.K.
Breast cancer is the second most common cancer after lung cancer and contributes to 15% of total cancer death; being treated by surgery, radio and target therapy still it relapse after sometime. It has been found that angiogenesis plays central role in cancer and cancer cells with stem like properties are main culprit for relapse of cancer, thereby making them the new target of treatment. CD146, 113 KDa surface glycoprotein has been found to have key role in angiogenesis and cancer stem cells, thus we hypothesized that CD46 is playing a key role in regulating both angiogenesis and cancer stem cells thereby targeting growth and metastasis of breast cancer. Based on our hypothesis we have conducted our research on MDA MB 231 triple negative cell line by performing various in-vitro and in-vivo experiments and also inhibited the CD146 expression to study its effect. So we found that CD146 is key molecule which when targeted can inhibit breast cancer growth and metastasis.
Synergies Institute, Ghana
Cancer is rated one of the fastest growing causes of death in Ghana. Amidst the growing concern and pursuit for the cure, is a relationship between a hospital and the patient. A large part of this relationship is and ought to be governed by various regimes of law, such as: Law of Contract, Law of Tort, Criminal Law, Administrative Law, Human Rights,and Law Mental Health Law.
The purpose of this paper is to look at these various aspects of law and how they apply in the peculiar relationship between a cancer patient and the hospital; the expectations both parties have of each other; the expectations the state has of the doctor/hospital treating the patient; the expectations of the hospital, from the personnel treating the patient and the patient being treated; issues of negligence and vicarious liability. A qualitative study using a purposive sampling approach of 10 cancer patients receiving treatment, 5 clinicians and 2 administrative staff at the Trauma and Specialist Hospital were employed to assess the peculiar relationship. It was overwhelmingly evident that 90% of the patients had no idea of the varying facets of the application of laws in regards to their treatment, 60% of clinicians lacked appropriate insight into the laws that govern the patients and treatments, while 100% of the administrative staff could not relate to the ensuing relationship that was being assessed.
It was recommended that the general public, health institutions and facilities as in the Ghanaian landscape must be well educated and appropriately sensitized on issues of the law as applied to cancer, its treatment and the law with the hope of fostering a more balanced relationship, which looks at the rights and obligations between the hospital through its personnel and the patient.
Ogochukwu Chidiebere Nweke is an African from Nigeria. He is a lawyer, a social media consultant, a relationship consultant, a public speaker, a professional mediator and an ADR advocate. He is currently the Vice President of Synergies Institute–Ghana. His contributions to the use of social media in teaching and learning (on and off campus) won an award for the African University College of Communications (AUCC), in New York, USA, through a programme facilitated by AUCC and Simmons College, Boston, USA. He is also an associate director with the International Institute for ICT Journalism. Ogochukwu has received trainings in various areas of social relations (through Coursera and Edex), and has certificates in:
• Philosophy, from the University of Edinburgh
• Entrepreneurship, from the University of Maryland
• Creative Problem Solving, from the University of Minnesota
• Religious Literacy, from Harvard University
• Contract Law, from Harvard University
• Environmental Law, from the University of North Carolina
He also serves as a part-time law lecturer at Regent University College of Science and Technology and Kings University College, both in Accra-Ghana. He is on Linkedin as Ogochukwu Nweke and features on www.relationshiphealthcenter.org
The Chinese University of Hong Kong, China
Transcription factor FOXP3, a biomarker for regulatory T cells, can also express in several types of cancers but its function is debatable. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) has not been studied. In this study, the tumor samples and clinical information were collected from 115 HCC patients. 5 human cancer cell lines were used for various experiments. The sequence of FOXP3 was examined for mutation and the promoter activity was checked by luciferase assay. Mouse tumor model was employed to confirm in vitro results. We found that mutations in FKH domain of FOXP3 mRNA were detected in 33% HCC tumor tissues but none of the adjacent non-tumorous tissues. No prevalent mutations were identified at high frequency in the samples, indicating the mutations occurred randomly. Moreover, the mutations were not detected in corresponding regions of genomic DNA. Many mutations resulted in amino acid substitutions in FKH region, which could subsequently cause changes of FOXP3 subcellular localization. The delocalization of FOXP3 from nucleus to cytoplasm caused loss of its transcription regulation and xenograft tumor-suppressor capabilities and different cellular responses to HDAC inhibitors. In addition, more complicated FKH mutations appeared to be associated with worse prognosis in HCC patients. Collectively, mutations in FKH domain of FOXP3 mRNA frequently occurred in HCC. The mutations were most possibly caused by transcription errors but not derived from genomic DNA mutations. Our results have suggested for the first time that transcriptional mutagenesis of FOXP3 plays a suppressive role in HCC.(Supported by NSFC No.81472339)
George G Chen is an Emeritus Professor in the Department of Surgery, and Senior Research Fellow, Department of Otorhinolaryngology, Head and Neck Faculty of Medicine, the Chinese University of Hong Kong, China. He has extensive experience in cancer research. He has authored or co-authored 230 papers and has written a number of books or book chapters, with h-index: 45.
Wayne State University, USA
Impaired nuclear protein transport, often observed in cancer, causes mislocalization dependent inactivation of critical cellular proteins. Earlier we showed that nuclear exporter protein exportin 1 (XPO1) is over-expressed in metastatic castration resistant prostate cancer (mCRPC). We also showed that targeted inhibition of XPO1 by crispr/cas9 validated specific inhibitor of nuclear export compounds (SINE) selinexor or next generation compound eltanexor could suppress CRPC cellular proliferation and xenograft tumor growth. XPO1 inhibition reduces total androgen receptor (AR) levels, including AR variant 7 (ARv7), via eIF4E inhibition and may re-sensitize prostate cancer cells to androgen deprivation therapy. Selinexor, the first-in-class, orally bioavailable reversible covalent XPO1 inhibitor, showed anticancer activity in patients (pts) with solid tumors including mCRPC. Here we evaluate the combination of SINE with PARP inhibitors (rucaparib, veliparib and olaparib). SINE synergize with three PARPi (CI<1) at pharmacologically relevant concentrations. SINE-PARPi showed superior induction of apoptosis compared to single agent treatment. Molecular analysis using RT-PCR revealed that SINE-PARPi suppressed AR, PSA and AR targets UBE2C and FOXA1. SINE-PARPi caused down-regulation of pro-survival factor Bcl-2 with simultaneous activation of pro-apoptotic caspases. Western blot analysis revealed similar results with significant down-regulation of AR, Arv, UBE2C, SAM68 and FOXA1. Crispr/cas9 edited cells lacking SINE binding site were not responsive to SINE treatment confirming a XPO1 inhibition dependent synergy. Pre-clinical evaluation of the efficacy of SINE-PARPi in xenograft of CRPC are currently ongoing. Our studies bring forward a novel and effective combination regimen targeting prostate cancer at the nuclear pore.
Md. Hafiz Uddin is a postdoctoral fellow at the Department of Oncology, Wayne State University. He was awarded the prestigious Graduate Scholarship for Excellent Foreign Student (GSFS) fellowship for his Ph.D. program at Seoul National University, South Korea. During his Ph.D., he worked on the mechanism of carcinogen-parasite induced bile duct cancer in hamster model. In his postdoctoral research, he focused on the mechanism of chemoresistance and molecular targets in ovarian, breast and prostate cancer and their association with cancer stem cells, unfolded protein response,drug synergy, TRAIL,MAPK and DNA damage pathways.
University of Delhi, India
At cellular level, cancer is a disease of the cell that develops because of failures in the mechanisms that regulate cell growth. An individual cell multiplies without restrain until it and its progeny eventually overwhelm tissues and organs. Cancer development is a multistep process in which the summation of events is required to produce malignant tumor. Although there is tremendous progress in understanding the molecular events that lead to malignancy, progress in the development of clinically innovative drugs that can cure cancer is not moving at that pace.
A recent discovery that might challenge the existing knowledge of cancer and methods to treat it, researchers found that “cancer cells spread to organs much earlier than was thought.” In fact, cancer cells can spread even before a tumour develops, remain quiet for long periods of time and then awaken to form aggressive and fatal metastasis. The findings also offer an explanation for why some 5% of cancer patients have metastases but no original tumour. Cancer cells are able to spread from a nascent tumor much earlier than scientists long thought and are more adept than later emigrants at forming potentially lethal metastases at distant sites such as the brain and bones.
Chemotherapy with cytotoxic anticancer agents is still the main way of therapy targeted at specific cellular mechanisms in the malignant tissues. Some chemotherapeutic agents disrupt the crucial parts of the cell that are critical for cell division such as mitotic spindle. Most common cancers require combination of radiation and chemotherapy for the treatment.
Noscapine is a very safe cough suppressant (antitussive) which has been in use for many decades. In recent years, noscapineʼs anti-cancer effect has been demonstrated when taken at doses higher than those used for cough suppression. It is currently in off-label use by a number of physicians in treatment of cancers of the breast, lung, prostate, ovaries and brain, and lymphomas, to name but a few. It is being clinically studied in non-Hodgkinʼs lymphoma and chronic lymphocytic leukemia (CLL). Noscapine, a non-addictive derivative of opium, has also demonstrated outstanding clinical effectiveness in reducing death rates from strokes. Its long safety record, widespread availability and ease of administration make it an ideal candidate for fighting several life-threatening conditions.
Our laboratory established that noscapine inhibits the progression of cancer cells by interfering with microtubular functions at the cellular level and induces apoptosis as like taxanes and the vinca alkaloids. Noscapine binds to tubulin and alters its conformation, resulting in a disruption of the dynamics of microtubule assembly (by increasing the time that microtubules spend idle in a paused state) unlike other tubulin inhibitors such as taxanes and vinca alkaloids which affect microtubule polymerization. Perhaps more importantly, noscapine was able to inhibit cancer at doses (300mg/kg body weight) which produced little or no toxicity, including no adverse effects on the primary immune response. In addition, noscapine also demonstrated potential anti-angiogenic activity as an alternate anti-cancer mechanism.
In our novel analogues of noscapine as well as developed nanoformulations like 9-bromo-noscapine loaded human serum albumin nanoparticles, noscapine bearing rapid release solid lipid nanoparticles, noscapine and 9-bromo-noscapine loaded optimized liposomes and niosomes have shown promising consequences in in vitro and in vivo setup. Further, in depth in vivo investigations are needed on these optimized nanoformulations of noscapine and 9-bromo-noscapine, for translating in to the clinical viable anticancer products.
Prof. Ramesh Chandra is an outstanding scientist, revered teacher and an exceptionally successful administrator, who excels in institution building and eminently suited to provide leadership role in higher education. He is currently heading Department of Chemistry, University of Delhi, where he is serving as Professor for the last more than 26 years and Founder Director of Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, since March 1991. He has been Vice-Chancellor, Bundelkhand University, Jhansi for six years (1999-2005); Member, Planning Commission, Government of U.P, India as well as the President of the Indian Chemical Society (2004-2006).
Professor Chandra shows deep commitment to the cause of higher education and research and possess in ample measure, quality of dynamic leadership and a vision required for building academic institutions and first rate researcher in the field of Biomedical Science. Professor Chandra started his research career at the University of Delhi, thereafter he went to The New York Hospital-Cornell University Medical Center and the Rockefeller University, New York; State University of New York at Stonybrook, USA as Assistant Research Professor. He conducted advanced research at the Harvard University Medical School-Massachusetts General Hospital, jointly at MIT, Cambridge, USA. Over the last 38 years, Professor Chandra has contributed largely in the field of Chemical Sciences and particularly in New Drug Discovery and Development as well as Drug Metabolism. His research work is being used in the development of drugs for Physiological Jaundice/Neonatal Jaundice and development of naturally occurring chemotherapeutic agents for the treatment of Breast and Ovarian Cancers, and drugs for Diabetes and Hypertension. He has supervised large number of (84 Ph. D. and 10 M. Phil) Students, in all trained more than 100 research scholars, who are now occupying high positions internationally. He has to his credit several patents, published more than 300 original Scientific Research Papers/ Review Articles in International journals of repute and six of his internationally acclaimed scientific Books. He is sought after speaker at several top universities in the world.
Prof. Chandra is the recipient of several professional national/ international recognitions; these includes: Millennium Plaques of Honor (Life Time Achievement Award for Contribution in Science & Technology) by the Indian Science Congress Association (ISCA) for 2017-2018, Award of the Highest Honor of Soka University, Tokyo, Japan (2000); J William Fulbright Scholarship (1993); The Rockefeller Foundation USA-Biotechnology Career Award (1993); and several others.
University of Madras, India
Saliva is generated within the salivary glands by acinus cells, collected in small ducts, and subsequently released into the oral cavity. There are three major and numerous minor saliva-producing glands located in and around the mouth and throat. Saliva serves to initiate the breakdown of lipids and starches via endogenous enzymes. However, in recent years, what we have come to understand about salivary secretions and the oral cavity has changed dramatically. Studies have shown that saliva actually contains a variety of molecular and microbial analytes. Although proteomic and transcriptomic indicators have yielded the most promising results to date ,information obtained from oral microbes and immunologic factors remains one of the more intriguing aspects in the pursuit of salivary biomarkers. Although the mechanism by which these disease indicators come to exist in saliva has not been explained fully, these findings insinuate that oral fluids may represent a significant source of discriminatory biomarkers for local, systemic, and infectious disorders The use of saliva as a diagnostic fluid has yet to become a mainstream idea. This partially stems from work revealing that while most analytes detected in the blood serum are also found in saliva, their levels are substantially diminished. For example, in healthy adults, IgA levels are normally 2.5 to 5 mg/ml in serum and 250 to 500 µg/ml in saliva. Similarly, IgG (5 to 30 mg/ml versus 5 to 30 µg/ml) and IgM (0.5 to 1 mg/ml versus 5 to 10 µg/ml) levels in serum are severalfold higher than those found in saliva . (Even so, the correlation between salivary and blood-based constituents implies that while these two biofluids are separate and unique, they may be linked on a molecular level. Hence, it is imperative that we explore saliva as a potential alternative to blood- and tissue-based diagnostics. Salivary biomarkers are entities within the body capable of providing impartial information regarding the current physiologic state of a living organism.Salivary biomarkers exist in a variety of different forms, including antibodies, microbes, DNA, RNA, lipids, metabolites, and proteins. Alterations in their concentration, structure, function, or action can be associated with the onset, progression, or even regression of a particular disorder or result from how the body responds to it A collection of reliable and reproducible biomarkers unique to certain maladies is often referred to as a biomarker or molecular signature. Understanding and evaluating the significance of an individual's salivary biomarker signature can be useful in determining the presence, location, and even likelihood of disease. Thus,salivary biomarkers serve as a valuable and attractive tool in the detection, risk assessment, diagnosis, prognosis, and monitoring ofdisorders/ diseases, like cancer.
Keywords: Saliva, Biomarkers, Diseases, Disorders, Cancer, Techniqies.
Shemyakin - Ovchinnikov Institute of Bioorganic Chemistry, Russia
An important task of successful cancer diagnostics and therapy is the introduction into the arsenal of modern oncology of a wide range of compounds with different mechanisms of action on cancer cells.
Focusing on these goals, a multifunctional agent was created for targeted delivery of two toxic agents — radionuclides and biological toxin — to cancer cells. Specifically, we synthesized hybrid complex, including upconversion nanoparticles (UCNP) doped with beta-emitting radionuclide yttrium-90, and a pseudomonas exotoxin A fragment equipped with the targeted scaffold polypeptide DARPin9.29 specific to tumor receptor HER2. It was shown that the synergistic effect of the simultaneous use of a radionuclide and a toxin is 2200 times stronger than when used separately.
We also developed dual targeting-based HER2-directed cancer cell therapy with biocompatible and biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles and targeted immunotoxin. The PLGA nanoparticles were equipped with: i) HER2 recognizing scaffold protein ZHER2:342, ii) fluorescent dye for cell imaging and iii) chemotherapeutic drug doxorubicin for cell killing. The capabilities of these multifunctional PLGA nanoparticles for cancer cell theranostics was demonstrated in vitro and in vivo. In order to enhance the targeted cytotoxic effect, we used targeted nanoparticles and a targeted bifunctional immunotoxin DARPin9.29-LoPE. LoPE is low-immunogenic modification of Pseudomonas exotoxin A, which is promising for in vivo applications. We showed that such combined therapy with DARPin9.29-LoPE & PLGA*ZHER2:342 nanoparticles allows reducing the effective concentration of immunotoxin up to about 1000 times.
The results of our other studies on oncotheranostics will also be presented.
Prof. Sergey Deyev has completed his PhD from Engelhardt Institute of Molecular Biology, Russia. He is Head of Immunology Department in Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Moscow. He holds concurrent appointments as Professor in Lomonosov Moscow State University, the Faculty of Immunology. He is member of Russian Academy of Sciences and Academia Europaea, the recipient of numerous honors, including the Mechnikov Prize of Russian Academy of Sciences in the field of immunology and biotechnology. He has published more than more than 150 papers in reputed journals, including Nature Biotechnology, Nature Nanotechnology, ACS NANO, Proc. Natl. Acad. Sci. USA, Theranostics.