Polymorphisms in Pharmacogenetics of Personalized Cancer Therapy

Therapy process of personalized cancer management covers surgery, chemotherapy, radiation therapy and targeted therapies. The choice of cancer chemotherapeutic agents and doses depends upon the location and stage of tumor, as well as the general state of the patient. On the chemotherapy, radiotherapy, and targeted therapy processes, pharmacogenetics offers customized solutions according to the personal genetic information. Especially for clinicians, genetic information obtained from polymorphism-based pharmacogenetic tests is highly crucial for the better prediction ability of drug response and life-threatening toxic reactions due to the narrow therapeutic index of cancer chemotherapeutic agents. Pharmacogenotyping utilizes different examination strategies, such as single nucleotide polymorphism analysis, somatic/germline mutation analysis and partial/full genome sequencing. The promising effect of pharmacogenetics on the solving of the individual variability in drug response and toxic reactions is being observed with the accumulation of the information that unravel the human genomic variations from large-scale population and multi-parameter-based pharmacogenetic studies of the post-genomic era. Polymorphisms contribute wide variations in human genome and may define how individuals respond to medications, either by changing the pharmacokinetics and pharmacodynamics of drugs or by altering the cellular response to therapeutic agents. To define the effect of polymorphisms on the targets of chemotherapeutics is necessary for the prediction of altered pharmacokinetics of therapeutic agents

Immunopharmacogenomics in Cancer Management

With the unavoidable progress of genomics technologies, “one size fits all” strategy has switched to individual-specific treatment approaches. Hence pharmacogenomics-based personalized cancer medicine has emerged. Promising treatment option immunotherapy includes either “take the brakes off immune system (i.e., checkpoint blockade therapy) or the use of immune cells expanded in an in vitro tumor-free environment’’. Both options have been varied and included unpredictable results. Combination of cancer immunotherapy and pharmacogenomics applications may contribute to solve the complexity of outcome prediction and variations between individuals receiving the same immunotherapeutic treatment. To enhance the tumor immunity and determine cancer patients who response to immunotherapy, classification based on gene polymorphisms in key immunoregulatory molecules including antigen-presenting molecules, immunoglobulins and their receptors, cytokine/chemokines and their receptors, adhesion and costimulatory molecules, toll-like receptors, and intracellular signaling molecules plays a vital role in redirecting or modulating the function of immune cells. Therefore, polymorphisms in immunoregulatory molecules and their impact on immunotherapeutic outcome should be considered in cancer management

MicroRNAs (miRNAs) in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer in the world and third leading cause of cancer-related deaths in men and women as well. While early screening procedures and removal of small polyps improve the survival rates among the patients, there is still need for new diagnostic and therapeutic approaches for developing more effective treatments. MicroRNAs (miRNAs) are short noncoding RNA fragments, which involve in posttranscriptional regulation of gene expression, and they are shown to involve in tumorigenesis either targeting oncogenes or tumor suppressor genes. Based on the current studies, miRNAs are now suggested as potential biomarkers for CRC diagnosis, prognosis, and therapeutic responses. In this chapter, the latest findings on the role of miRNA in CRC in many aspects are reviewed: diagnosis (role of circular miRNAs in blood and miRNAs from tissue biopsies and their potential role in pathophysiology and diagnosis of CRC), prognosis (miRNAs related with metastasis, recurrence, and survival rates in CRC), and therapeutic responses (role of miRNAs both in chemotherapies and/or in targeted therapies in CRC). In conclusion, miRNAs are promising molecules for diagnosis, prognosis, and therapeutic responses of CRC

DPYD, TYMS and MTHFR Genes Polymorphism Frequencies in a Series of Turkish Colorectal Cancer Patients.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadFluoropyrimidine-based chemotherapy is extensively used for the treatment of solid cancers, including colorectal cancer. However, fluoropyrimidine-driven toxicities are a major problem in the management of the disease. The grade and type of the toxicities depend on demographic factors, but substantial inter-individual variation in fluoropyrimidine-related toxicity is partly explained by genetic factors. The aim of this study was to investigate the effect ofDokuz Eylul University Research Foundatio

Early changes in apoplast composition associated with defence and disease in interactions between Phaseolus vulgaris and the halo blight pathogen Pseudomonas syringae pv. phaseolicola

The apoplast is the arena in which endophytic pathogens such as Pseudomonas syringae grow and interact with plant cells. Using metabolomic and ion analysis techniques, this study shows how the composition of Phaseolus vulgaris leaf apoplastic fluid changes during the first six hours of compatible and incompatible interactions with two strains of Pseudomonas syringae pv. phaseolicola (Pph) that differ in the presence of the genomic island PPHGI-1. Leaf inoculation with the avirulent island-carrying strain Pph 1302A elicited effector-triggered immunity (ETI) and resulted in specific changes in apoplast composition, including increases in conductivity, pH, citrate, γ-aminobutyrate (GABA) and K+, that are linked to the onset of plant defence responses. Other apoplastic changes, including increases in Ca2+, Fe2/3+ Mg2+, sucrose, β-cyanoalanine and several amino acids, occurred to a relatively similar extent in interactions with both Pph 1302A and the virulent, island-less strain Pph RJ3. Metabolic footprinting experiments established that Pph preferentially metabolizes malate, glucose and glutamate, but excludes certain other abundant apoplastic metabolites, including citrate and GABA, until preferred metabolites are depleted. These results demonstrate that Pph is well-adapted to the leaf apoplast metabolic environment and that loss of PPHGI-1 enables Pph to avoid changes in apoplast composition linked to plant defences

A Novel High-Affinity Sucrose Transporter Is Required for Virulence of the Plant Pathogen Ustilago maydis

A novel, high-affinity sucrose transporter identified in the plasma membrane of the plant pathogen Ustilago maydis is essential for fungal virulence and successful infection of maize

Mechanistic Studies of Ethylene Hydrophenylation Catalyzed by Bipyridyl Pt(II) Complexes

This article discusses mechanistic studies of ethylene hydrophenylation catalyzed by bipyridyl Pt(II) complexes

The Yuan dynasty through the eyes of western travellers

YÖK Tez: 690106Kubilay Han'ın, başkent Pekin olmak üzere kurduğu Yuan Hanedanlığı, Çin tarihinin en dikkat çekici hanedanlıklarından biridir. 1260 – 1368 yılları arasında varlığını sürdüren bu etkin devlet, siyasi arenada bulunduğu süreç boyunca birçok seyyahın ve maceraperestin dikkatini çekmiştir. Biraz da "Moğol Barışı" siyaseti sayesinde ticaret yollarını daha kolay aşan seyyahlar nihayet Çin'e, o dönemki ismiyle Cathay'a varmışlardır. Moğol yönetimindeki Çin hakkında bilgi veren Batılı seyyahlar sırasıyla; Marco Polo, Giovanni da Montecorvino, Odorico da Pordenone, Giovanni de'Marignolli, Pregrine, Perugialı Andreas, Jordanus Catalani, Sir John Mandeville ve Francesco Balducci Pegolotti'dir. Bahsi geçen seyyahlar Moğol yönetimindeki Çin hakkında izlenimlerini de kaydetmişlerdir. Çalışmamızda Yuan Hanedanlığı içerisindeki dinamiklerin Batılı seyyahların gözünden nasıl anlaşıldığı ve bu unsurlara seyyahların nasıl bir açıklama getirdiği yönünde detaylı bir inceleme yapılmıştır.Yuan Dynasty, which was established by Kublai Khan with Beijing as its capital, is one of the most dominate dynasties in the history of China. Existed around 1260 – 1368, this dominate dynasty attracted the attentions of many travellers, pilgrims and adventurers throughout its political history. Because of "Pax Mongolica", travellers eventually would travel trade nodes around Asia and arrive at China, which is recorded by those travellers as Cathay, more easily than before. The persons who provided information about China under Mongol rule are; Marco Polo, John of Montecorvino, Odoric of Pordenone, John of Marignolli, Pregrine, Andrew of Perugia, Jordanus Catalani, Sir John Mandeville and Francesco Balducci Pegolotti. Those aforementioned travellers also recoreded their opinions about China under Mongol rule. In our research, a detailed study has been done about these travellers' personal understanding and explainations of them about Yuan Dynasties' dynamics