Madridge Journal of Cancer Study & Research

ISSN: 2640-5180

2nd International Cancer Study & Therapy Conference

Feb 20-22, 2017, Baltimore, USA
Poster Session Abstracts
DOI: 10.18689/2640-5180.a2.003

Targeted anticancer drug discovery based on natural product derivitives

Gang Liu and Ao Zhang*

CAS Key Laboratory of Receptor Research, and Synthetic Organic and Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China

Anti-malaria natural product artemisinin (Qinghaosu) has been repositioned for the development of novel antitumor agents due to its unique structure and safety profile. Nevertheless, compared to the great success in the development of anti-malarial drugs, the majority of reported artemisinin analogues (artemalogues) only displayed limited in vitro and in vivo anticancer potency. In addition, the precise anticancer mechanism of these artemalogues) are also poorly understood. Therefore, chemical modification on artemisinin is highly needed both for the development of more potent anticancer artemalogues and for the understanding of the mode of actions. Most of the reported structural modifications focuse on the C10-carbonyl function with the aim to enhance the pharmacokinnetical properties. To generate structurally more diverse artemalogues, we conducted an alternative medicinal chemistry campaign by constructing various heterocyclic functionalities at the less explored sites including C-6 and -9 positions through 1,3-dipolar cycloaddition or click reaction, thus affording a series of structurally novel artemalogues. Several compounds demonstrated superior in vitro antiproliferative effects against cancer cell lines with IC50 values in nanomolar ranges. We further investigated the effects of artemisinin and three potent artemalogues on protein expression in whole A549 cells by using mass spectrometry-based global chemical proteomics approach, and systematically identified dozens of significantly up- and down-regulated proteins through quantitative proteomic analysis, some of which are involved in essential biological processes. These findings will shed light on the understanding of anticancer action mechanism of artemalogues.

Professor Zhang received the Ph.D. diploma in 2000, and did Postdoctoral research at Georgetown University and Harvard Medical School during 2002-2004. He was promoted to Instructor of Harvard Medical School in 2004 and received the Hundred Talent Project award from the Chinese Academy of Sciences, and became the Professor of Medicinal Chemistry at Shanghai Institute of Materia Medica (SIMM). In 2011, he was awarded the Distinguished Young Investigator Award from Chinese Natural Science Foundation. He has authored or co-authored over 110 publications and 40 patents. Several drug candidates from his research group are now under clinical or preclinical studies.

Assessment of selected transcription factors and neoplastic markers in stainless steel welders

Tadeusz Halatek1*, Magdalena Stanislawska1, Ewa Jablonska2, Edyta Reszka2, Monika Przybek2 and Wojciech Wąsowicz1

1Department of Biological and Environmental Monitoring; Nofer Institute of Occupational Medicine, Poland
2Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Poland

The exposure to toxic fumes generated during welding of stainless steel (SS) is toxic due to chromium content and the reduction of Cr (VI) to Cr (V), a cascade of reactions involving the production of reactive oxygen specis (ROS). Generation of ROS may be induced also by nickel, leading to cytotoxicity and apoptosis.

The study focused on two transcription factors: NF-kappa-B (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and AP-1 (activator protein 1). NF-kappa-B is encoded by one gene: NFKB1. AP-1 is a protein complex that consists mainly of two protooncogenic families: Jun (c-Jun, JunB, JunD) and Fos (c-Fos, FosB, Fra-1, Fra-2), encoded by eight genes: JUN, JUNB, JUND, FOS, FOSB, FOSL1 and FOSL2.

The study of SS welders was undertaken to observe the relationship between NF-kappa-B and AP-1 and some plasma neoplastic markers (carcinoembryonic antigen (CEA), cytokeratin fragment antigen 21-1 (CYFRA 21-1 and prostate specific antigen (PSA)). Study participants included controls (n=50) and exposed SS welders (n=50) from production departments, exposed to the welding fumes at 0.12-3.50 mg/m3 (inhalable fraction) and 0.12-1.65 mg/m3 (respirable fraction). Total concentration of metals (mg/m3) was Fe 264.0, Mn 42.2, Cr 83.3 and Ni 40.4. mRNA expression for JUNB, JUND, FOS, FOSB and FOSL2 was significantly increased in the exposed welders (as compared to controls). No significant changes were observed for NFKB1, JUN and FOSL1. Expression of majority of mRNA transcripts was inversely correlated with serum cyfra21 levels in controls but not in the exposed welders.

No correlation between mRNA expression of AP-1/ NF-kappa-B and CYFRA 21-1 in welders may indicate disrupted cytoprotective mechanisms associated with AP-1/ NF-kappa-B, specifically with respect to lung cancer development.

Tadeusz Hałatek studied at the Faculty of Pharmacy, Medical University of Lodz. In 1991 received Ph.D in pharmacy Medical University of Lodz,. In 1974 started working in the Department of Biochemistry, Nofer Institute of Occupational Medicine (NIOM) in Łódź as an assistant and then assistant professor in the Department of Toxicology and Carcinogenesis, NIOM (1991-2011). Since 2011 Professor in the Department of Biological and Environmental Monitoring, NIOM.
The main scientific interest of his work was identification of early biomarkers of critical effects of metals in occupational environmental for assessing the associated health risk. In studies on the respiratory biomarkers, he collaborated with the Catholic University of Louvain, Brussels, Belgium. in 1994-1995.

The clinical usefulness of anti-Mullerian hormone evaluation in breast cancer patients who are taking Tamoxifen

KANG Cheol Min1*, KO Beom Seok1, UM Eunhae1 and KIM Jinsung1

1Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Republic of Korea

In premenopausal, hormone receptor (+) breast cancer patients, anti-hormone therapy is very important therapy for preventing cancer recurrence. It is recommended for the patients, after taking Tamoxifen for five years, to either continue with Tamoxifen or change to the aromatase inhibiter, depending on their menopausal status. The important problem for clinicians is that a woman has no menses does not mean the women is no longer producing estrogen, which could compromise the effectiveness of the aromatase inhibitor. So it is needed to know whether the woman was really in menopausal state or not.

The elevated serum follicle stimulating hormone (FSH) level may be helpful in confirming menopause. Mean serum FSH level increases with age and be significantly higher in the 40 to 50 years, the period of initiation of menopause. However, it is known that a woman administered with Tamoxifen usually has a tendency of low serum FSH level. Serum anti-Mullerian hormone (AMH) level may be more accurate indicator of menopausal status than serum FSH level in perimenopausal, hormone receptor(+) breast cancer patients who were treated with Tamoxifen for 5 years and were considered additional anti-hormone therapy.

We evaluated the perimenopausal women who were visited the survivor clinic in breast cancer department of Asan Medical Center between December 2014 and January 2016. All the patients had a surgery and were recommended to take Tamoxifen 20mg. Totally 46 perimenopausal women were enrolled and analyzed. The relationship between the presence of menopause and serum FSH and AMH levels was assessed using Pearson Chi-square test. We compared the relationship of the patientʼs biological menopause and laboratory menopause (serum FSH>30mIU/mL, serum AMH<0.08ng/mL). Statistically, menopause compared to FSH levels has no significant relationship. (p value: 0.157) but menopause compared the AMH levels has significant relationship. (p value: 0.017).

We concluded anti-Mullerian hormone can beaaccurate predictor of menopause than follicular stimulating hormone in perimenopausal, hormone-receptor (+) breast cancer patients who were treated with Tamoxifen.

1999.03~2005.02 M.D., College of Medicine, University of Ulsan, Seoul, Korea
2005.03~2008.04 Public health physician, Yun-gi Gun public health center, Korea
2008.05~2009.02 Internship, Asan Medical Center and College of Medicine, University of Ulsan, Seoul, Korea
2012.03~2016.02 Residency in General Surgery, Asan Medical Center and College of Medicine, University of Ulsan, Seoul, Korea
2016.03~ Clinical fellow, Division of Breast and Endocrine surgery, Department of Surgery, Asan Medical Center and College of Medicine, University of Ulsan, Seoul, Korea.

Novel approaches based on immune checkpoints for cancer immunotherapy

Jorge Augusto Borin Scutti

MD Anderson Cancer Center (Houston-Texas), USA

Introduction: Cancer immunotherapy is one of the best therapies compared to traditional therapies that may cause potential toxicities such as chemotherapy and radiation. The potential use of immunotherapy is to restore the immune system of patients in attempt to stimulate it to reject and destroy cancer cells. With the recent approval of the monoclonal antibodies against CTLA-4 and PD-1 for the treatment of melanoma, renal carcinoma cancer and non-small cell lung have attracted wide interest for strategies that enhance T-cell-mediated response against cancer. A complex network of biological pathways governs interactions between the immune system and cancer cells. The balance of signaling via co-inhibitory or co-stimulatory molecules expressed on T cells has demonstrated to be a powerful approach to intensify antitumor immune responses. This approach has been used effectively for the generation of a new class of anticancer therapies called checkpoint-blocking antibodies. Exploiting on the success of CTLA-4 blockade, agents that target a second co-inhibitory receptor, PD-1 (Programmed cell death protein 1), or its ligand, PD-L1, are in clinical development.

Research: The presence of several inhibitory pathways that block T cell responses offers particular strategies for mobilizing the immune system to attack cancer cells. There are some strategies to modulate the microenvironment - targeting regulatory cells, blocking differentiation or recruitment, blocking immunosuppressive enzymes, regulatory cell depletion, re-programming immunosuppressive cells, modifying the chemokine and cytokine profile are some examples. The attractively of new strategies for immunotherapy is driven by immune response and microenvironment discovery. Usually, scientists have relied on conventional laboratory research tools to identify several biomarkers, for example, altered genes transcription factors changes in mRNA and protein expression. To put these cancer biomarkers in the context the researchers can use several strategies to find a good parameter to take care of patient and drug development. As more and more immunotherapies are made available, the overall goal will be to screen patients and determine which of the immunotherapies will be more effective for each cancer type and each patient, including the analysis of new immune cell population.

Results: Currently there are several Clinical Trials across more than 20 different cancers including, melanoma, ovarian, prostate, breast, lung, gastric, kidney, bladder, cervical, anal, colorectal and pancreatic cancers, as well as in leukemia, lymphoma, sarcoma and glioblastoma. Inhibitory molecules like CTLA-4, PD-1, LAG-3, TIM-3, VISTA and BTLA besides co-stimulatories molecules such as ICOS, OX40 and 4-1BB are potent agents for combination therapy in order to improve antitumor responses. The analysis of tissue and blood samples from cancer patients is being conducted with new technologies as Flow Cytometry (FACS) and mass cytometry (Cytof). Here, we will share some strategies in order to pursuit molecules that could help us to better understand cancer immunotherapy responses.

Conclusion: A harmonized struggle to assess the value biomarkers that address different aspects of the cancer-immunity cycle in T cell checkpoint blockade will allow us to integrate information on individual aspects of tumor-immune interaction.

Dr. Jorge Augusto Borin Scutti is currently Research Scientist of Immunotherapy Platform (Immunology Department) at the MD Anderson Cancer Center (Houston-Texas). As Research Scientist hisworks focuses onanalyzing the activity of innate and adaptive cell populations like T cells, B cells, tumor cells, Myeloid Derived Suppressor Cells (MDSC) and Natural Killer (NK) cells that are critical on immune response against cancer and then might regulate positively or negatively T-cell responses. Dr. Scutti earned his Master and PhD in Microbiology and Immunology Department at Federal University of São Paulo (UNIFESP) working on cancer vaccines and peptides derived proteins to stimulate immune system against melanoma. Postdoctoral at MD Anderson Cancer Center (MDACC) - Pediatrics Department, where he began evaluating pediatrics cancer - DIPG (Diffuse Intrinsic Glioma Pontine) its microenvironment, Natural killer cells and histone deacetylase inhibitors (iHDAC) as cancer immunotherapy tool. Experience in cancer immunology and immunotherapy in experimental studies and clinical research.

To perform chemotherapy or not, that is a question in elderly patients with pancreatic cancer

Ho Gak Kim, Dong Wook Lee and Jimin Han

Department of Internal Medicin, Catholic University of Daegu School of Medicine, South Korea

Background/Aims: Pancreatic cancer is a disease seen predominantly in elderly patients. Chemotherapy (CTx), which is one of the standard treatments for locally advanced and metastatic pancreatic cancer, is considered therapeutic modality with high risk in elderly patients. This study investigated the outcome and tolerability of chemotherapy in elderly patients with pancreatic cancer.

Methods: Between January 2010 to January 2016, 226 patients were diagnosed with pancreatic cancer. Among them, patients with over 70 years old were reviewed retrospectively and clinical parameters, survival rate from initial chemotherapy, and adverse events during chemotherapy were analyzed.

Results: Among 226 patients, 84 patients (34.7%) were older than 70 years of age and gemcitabine-based chemotherapy was performed in 57 patients (CTx group) and 27 patients were not received chemotherapy (non-CTx group). The overall median survival of total elderly patients was 8.2 months and the median survival of each group was 10.3 months in CTx group and 3.7 months in non-CTx group (p = 0.042). The incidence of adverse events such as bone marrow suppression (neutropenia, thrombocytopenia and anemia) was not different between younger patients (< 70 years) and older patients. The independent negative prognostic factors associated with survival were lower Karnofsky performance status (≤80) and presence of distant metastasis.

Conclusions: The survival benefit can be achieved through gemcitabine-based chemotherapy in elderly patients without frequent adverse event. Karnofsky performance status and distant metastasis are independent prognostic factors.

Professor Ho Gak Kim has completed his M.D. at the age of 26 years from Kyungpook National University School of Medicine, Taegu, South Korea. He is the Chief of Physician at Catholic University of Daegu School of Medicine, Daegu, South Korea since 2013. He has published more than 100 papers in reputed journals and has been serving as a president of Korean Pancreatobiliary Association since 2014, and editorial board member of Clinical Endoscopy.

Tumor-associated macrophages (TAMs) promote ovarian cancer cell migration/invasion via activation of the CCL7-CCR3 axis

Miran Jeong and Jung-Hye Choi

Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, South Korea

The tumor microenvironment is critical for cancer pathobiology and has been reported to play an important role in the development of cancer metastasis. In the tumor microenvironment, macrophages can be educated by a tumor may turn into tumor-associated macrophages (TAMs) that may promote tumor growth, migration, invasion, and metastasis. However, it has been poorly understood TAMs interact with ovarian cancer cells.

In the present study, we have demonstrated that the conditioned medium (CM) from TAMs (TAM-CM) significantly increased the migration and invasion of human ovarian cancer cells. To find out which cytokines are involved in the increase, we performed cytokine array and real time PCR in TAMs. The expression and production of CC chemokine ligand 7 (CCL7) was higher in TAMs than regularmacrophages. Moreover, CCL7, its receptor CCR3 was found to be highly expressed in human ovarian cancer cells. Inhibition of CCL7-CCR3axis markedly attenuated the TAM-CM-induced migration/invasion. Taken together, these data suggest that TAM promotes ovarian cancer cell migration/invasion through the CCL7-CCR3 pathway.

Ms. Miran Jeong is from the Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, South Korea. Her research interests are understanding tumor stromal interactions in ovarian tumor microenvironment that promote angiogenesis, ascites and peritoneal spread, and also to identifying target receptors to develop therapeutic strategies for complementing current treatment regimens in ovarian cancer.

Role of psychological support in cancer care and treatment

Shriya Shripad Ambhaikar

Dali Medical University, China

Cancer has a major impact on society across the world. It is among the leading causes of death worldwide. This examines the evidence for psychological factors and therapies that affects the patientʼs journey from diagnosis through treatment and long-term survivorship or end of life. Every disease is psychosomatic. Psychological therapies help to increase patientʼs quality of life, boost their immune system and help them live longer. Implementation of this study may decrease the number of deaths of cancer causing patients. Evidence is convincing that emotional distress, depression, anxiety, uncertainty, hopelessness and negative thoughts unite and interact with pain. This unrelieved pain can increase the desire for hastened death. A variety of psychological therapies and processes can reduce pain severity and interference with function, as indicated in multiple meta-analysis and high quality randomized controlled trials. The effective methods and therapies include healing, yoga, meditation, breathing techniques and one of the most powerful Sudarshan Kriya which was introduced by Sri Sri Ravishankar ji who is an Indian. His years of meditation gave birth to this process which significantly reduces stress, depression, anxiety, pain, and increases well-being both mentally and physically. Experimental work performed on various patients suffering from cancer and this process helped them to develop positive energy, will power and self Confidence to fight with the physiological treatments like radiation, chemotherapy, surgery and the patient wins in the battle of life and death and survives. This introduces the modern medical science with ancient Indian healing and Sudarshan Kriya. “Approach of psychology over physiology” and the results were very positive. Research also demonstrates that the effects of Sudarshan Kriya reach all the way down to the molecular level, to our DNA. Exercise study have evaluated outcome. This showed promising results like better diagnosis, responds well to treatment, recovery rate got increased, high and positive energy level, enjoying better state of health. Study has done in India and China. The survey was taken from hospitals and organizations in order to know about the psychological support provided till date for the cancer patients. This study may bring the awareness among doctors and patients for the importance of psychological support in cancer in present time. Evaluation of methods has been described and the data set is prepared for the same. There are also few case studies discussed which shows the positive results of these therapies. Multidisciplinary teams are essential in oncology settings to integrate analgesic care, expertise in psychological support, therapies in standard care for symptom management, better effect of treatment as well as exact diagnosis including pain relief.

Ms. Shriya Shripad Ambhaikar is Studying in 3rd year, Clinical Medicine, M.B.B.S. in Dali Medical University, Dali, Yunnan Province, China. She has cleared her previous exams in honors. She has received a prize for her performance in International Day Ceremony of Dali University on April 2015. She has given a seminar on Addisonʼs disease during clinical medicine seminar in china and received a Best Presentation Award on October 31st 2015. She has also received a best performance award in international competition in 2015. She has also received an award of Excellence on 6th January 2016 for her best performance. She has also published a research paper ‘Role of Information and communication technologies in medical science and research’ in an International Conference on Advances in Information technology and Management 2016 and her paper also published in International Journal IJCA. She is also doing her research in diabetes over artificial pancreas and preparing data bases on the same. She has a great interest in the field of research. She wants to contribute her study and knowledge for the better healthcare of society.

The 4th Dimension and Cancer

Raphael Michael Happy-Ikenwilo

Rahamis Ministry International

Encumbered with the Darwinian theory of evolution, Man is losing the battle against a being whose radiations falsify the decryption of its own genetic code developing “cancers”. Our ignorance of his modus operandi sustains its progression. Shall we consider our hollistic nature as tripartite beings (body, a soul and of a spirit) in research methodoloy and while seeking the help, validate Einstein and Michio Kaku, in the existence of “a mathematician God whose cosmic music resonnates through 11-dimension hyperspace.” (American News, 2016). Those strings, fused in one essence in our realm forms what I term: Alpha Rays radiations.

Godly inclined, I graduated from the 5th dimension as Dr in Spiritual Sciences in 2005. Loaded with the acumen to utilise the Alpha Rays, I travelled in 2012 to the USA to conduct 3 years of investigations about cancer. Their results, coupled with my encounter whith some beings responsible for some sicknesses amidst which childhood, breast, cervical, ovarain, brain and eosophagus cancers, prompts me to state without a doubt, that approximately 30% of our challenging cancers, may be birthed from the 4th dimension.

Having efficiently tested the Alpha Rays through the theory of quantum to detect and cure (without side effects) some patients, it is my firm belief that the cooperation with the 5th dimension and further researches may validate my hypothesis and sustain the creation of Epsilon; equipping any audio device will dispel the cancerous radiations before it manifests in the patientʼs body, to strike the sickness before it strikes the patient.