A variety of large bioreactor scales have been utilized ranging from pilot-scale 50L and production scale 200L and 1000L. The downstream process optimizations including chromatography, virus inactivation, tangential flow filtration and normal flow filtration are performed in parallel with upstream process optimization to expedite the timeline for the best benefit for Thai patients.
To elucidate mechanisms through which chemical and biological agents in the environment induce pathogenesis. To study the association between environmental and occupational exposures and effects of toxicants, particularly carcinogenic compounds in air and water, in selected populations. To study the effects of environmental pollutants and industrial chemicals as modifiers of physiological and pathological status, and the influence of host factors, such as nutritional status and disease states, on toxicity and carcinogenicity of chemicals.
Cholangiocarcinoma (CCA) is malignancy arising from cholangiocyte in the biliary tract and is the second most common type of primary liver cancer. This type of cancer is associated with poor prognosis and limited treatment options. The major risk factors of this cancer associate with chronic inflammation, cellular injury in the bile duct, and partial obstruction of bile flow caused by various conditions such as primary sclerosing cholangitis (PSC), hepatolithiasis and infestation by liver fluke (Opisthorchis viverrini) (Kubo, Kinoshita, Hirohashi, & Hamba, 1995; Sirica, 2005; Watanapa & Watanapa, 2002). Recent studies attempt to investigate the molecular pathogenesis of this disease, including etiology and molecular alterations. Genetics and epigenetics changes in cholangiocarcinoma have been identified from a number of studies. Alterations of several cellular functions including self-sufficiency and proliferation, apoptosis resistance, escape from senescence, and tumor invasiveness and metastasis, are proposed to contribute the onset of cholangiocarcinoma (Lazaridis & Gores, 2005). The uncontrolled proliferation of cells due to harboring of genes mutations causes cancer development. Cell cycle progression is a highly regulated process that involves several steps including DNA replication and cell mitosis. At present, understanding the mechanisms involved in cholangiocarcinoma cells development and finding the indicators of the response to cancer treatment is beneficial to the treatment option of this cancer. Recent research conducted by the Thailand Initiative in Genomics and...
Photodynamic therapy (PDT) has proven to be an effective and minimally invasive modality for cancer treatment, which can be used alone or together with other conventional treatments. PDT requires three harmless key components: photosensitizer, light and oxygen. The treatment protocol is based on the activation of a photosensitizer by using a suitable wavelength of light in the presence of tissue oxygen, which then results in the generation of singlet oxygen or other reactive oxygen species (ROS) to destroy cancer cells. PDT also offers significant benefits to overcome a variety of cancers. Many photosensitizers are hydrophobic and show tendency to aggregate in aqueous solutions, so that encapsulation in drug delivery system may improve their PDT performance. Recently, our laboratory successfully prepared polymer-lipid hybrid nanoparticles with good biocompatibility to deliver the hydrophobic photosensitizers that expand the therapeutic applications of PDT to multidrug resistant (MDR)lung cancer cells. The formulated nanoparticles have the potential to improve the solubility of photosensitizer. Also, nanoparticles may augment in vitro PDT efficacy by effectively increasing the accumulation of photosensitizer in MDR cells without being affected by the MDR mechanisms, leading to enhanced light-induced generation of singlet oxygen and superoxide anion, which finally causes apoptotic cell death. Cancer immunotherapy is another area of interest. Some cancer cells have partner proteins that bind to...
It is now widely accepted that the tumor microenvironment influences the fate and behavior of cancer cells and plays crucial roles in regulating tumor progression and therapeutic responses. The microenvironment of cells cultured in vitro on traditional plastic substrata does not account for cell interactions with the extracellular matrix (ECM) and is thus a less reliable approach to analyze cellular activity. However, most studies are performed with cancer cells grown in two-dimensions on plastic plates, leading to high failure rate of drug discovery and development. Culture conditions that recreate the appropriate microenvironment for cells should provide a better model for studying cellular activity and discovery of anticancer drugs. We thus developed cell culture models that more closely resemble in vivo tumor biology and investigated its consequences on cellular activity and responses to anticancer compounds. The results of an in vitro 3D model showed that 3D cultured cells on Matrigel showed cellular dormancy (G0/G1 cell cycle arrest), decreased cell migration and invasion, and were resistant towards a variety of chemotherapeutic agents.Further investigation of the molecular mechanisms implicated in tumor dormancy and drug resistance led to the identification of a key mediator involved in the development of chemoresistance in 3D cultures which may offer the potential of developing effective targeted therapies for cancer.
Metastasis and drug resistance of cancer cells are major problems in cancer therapy. Metastasis is the spread of cancer cells in the body, from primary tumor site to distant organs, where the cancer cells remain dormant for months to years as micrometastases, and then regrow to become recurrent tumors. We have explored the effect of chemicals and drugs on metastasis of cancer cell lines. A common environmental contaminant, perfluorooctanoic acid (PFOA), enhanced the metastatic potential of FTC133 thyroid cancer cells, while sub-lethal doses of the drug, doxorubicin, increased metastatic potential of low-invasive HepG2 liver cancer cells. On the other hand, vanillin, the vanilla flavoring agent, was found to reduce the metastatic potential of 4T1 mouse breast cancer cells and to suppress metastasis in an animal model, orally given vanillin for a month. Vanillin and its structure-related compound, apocynin, decreased metastatic potential of A549 lung cancer cells by inhibiting the PI3K/Akt signaling pathway. Homodimers of vanillin and apocynin were more potent than their monomers in inhibiting invasion of HepG2 liver cancer cells, and protein focal-adhesion kinase (FAK) was identified as a target of the dimeric compounds. Chrysin, found in Thai propolis, also showed anti-metastatic potential by reducing tumor recurrence, through suppressing growth of breast cancer micrometastases after spreading to the lungs of mice.With chrysin, STAT3 inhibition was the mechanism for inhibiting...
Many proteins are chemically modified after synthesis. These Post-Translational Modifications (PTMs), such as phosphorylation and O-GlcNAcylation, play an important role in regulating metabolic processes. Our studies show that the levels of O-GlcNAcylation and O-GlcNAc transferase (OGT), an enzyme catalyzing the addition of a single GlcNAc residue to target proteins, were up-regulated in breast and colon cancer tissues and cell lines. Using mass spectrometry, many O-GlcNAc-modified proteins were identified in these cancers, for example pyruvate kinase M2 (PKM2). O-GlcNAcylation of PKM2 affects its phosphorylation as well as its activity, thus indicating the crosstalk between these two PTMs. We also demonstrated that OGT knockdown led to a significant reduction of colony formation in breast and colon cell lines, suggesting it plays vital roles in tumor progression. Phosphorylation is another regulatory mechanism, but identification of phosphoproteins can sometimes be difficult due to possible digestion by phosphatase enzyme. We have therefore isolated exosomes, extracellular vesicles (EVs) of 30-100 nm size, from the conditioned media of isogenic cholangiocarcinoma cell lines with different metastatic potential. More than 40 phosphoproteins were identified with significant change in phosphorylation level. Heat Shock Protein 90 was confirmed as showing differential phosphorylation in relation to tumor invasiveness, so aberrant phosphorylation of exosomal proteins may be useful for development of a metastatic cancer biomarker. Indeed, since EVs contain many functional biomolecules, such...
Cancer is a disorder resulting from autonomous, uncontrolled cell growth and differentiation, and with malignant behavior, is capable of invasion and metastasis. Carcinogenesis is initiated by non-lethal genetic damage, followed by a multi-step process involving both phenotypic and genetic changes. Regulatory genes such as the proto- oncogenes, the tumor suppressor genes, and genes regulating apoptosis are important targets of genetic damage, as well as the DNA repair genes. Mutational damage to these genes will result in activation or inactivation of the functions of their gene products, resulting in uncontrolled proliferation with abnormal differentiation and acquisition of the capability for invasion or metastasis. Because of our longstanding interests in proteins, we are exploring the protein changes that occur in human cancer. Initially, we collaborated with the Department of Pathology, Phramongkutklao Hospital, Bangkok to analyze changes in protein in human cancer tissues, using surgical specimens of tumor tissue and normal tissue, characterized in terms of pathology. Our group was the first research group in Thailand to use the proteomic approach in 1997, at that time using two-dimensional gel electrophoresis to compare the proteome patterns (or the total protein present at any tissue at any given time) between normal and cancer tissue. Thus, study of thyroid disease demonstrated increased expression of certain proteins, such as cathepsin B and prohibitin, in neoplastic thyroid diseases...
Our early studies on genetic diseases, since 1987 and earlier, focused on the hemoglobinopathies, which occur frequently in Thailand and consist of two types. Thalassemia results from lack or decreased synthesis of one or more globin chains, while abnormal hemoglobins consist of mutations altering the amino acid sequence of globin chain(s). However, as research in the hemoglobinopathies developed in Thailand, we shifted our interest to Inborn Errors of Metabolism, which can cause severe clinical manifestations, such as mental retardation or developmental abnormalities. Generally, inborn errors arise from deficiencies in enzymes of various metabolic pathways, such as the urea cycle, pathways for degradation or synthesis of specific amino acids, or mucopolysaccharide degradation. Such disorders may be due to mutations leading to dysfunctional or poorly functioning enzyme or may result from lowered expression or absence of these enzymes. Such enzyme deficiencies are typically detected by an accumulation of the substrate of the enzyme reaction and/or a decrease in the level of metabolites, which occur after the enzyme reaction. Typically, each inborn error of metabolism occurs with low frequency, but there are many defects, so cumulatively, inborn errors of metabolism are significant problems. In many cases, the devastating effects can be avoided through proper treatment, such as in phenylketonuria, which may be treated with diets low in phenylalanine. So, it is important to...
Air pollution is a global issue with serious health impacts to the health and disease status of the public. WHO reported that air pollution is strongly linked to mortality and morbidity from effects on the respiratory and cardiovascular systems, as well as cancer. Thailand and other countries in the region are affected by problems associated with air pollution. Genotoxic air pollutants, in particular, have significant potential impacts on human health. Polycyclic aromatic hydrocarbons have been associated with lung cancer, while volatile organic compounds, such as benzene and 1,3-butadiene, have been associated with leukemia incidence. These pollutants have many sources, including combustion, as well as production and use in the industrial sector. CRI thus focuses on research on the effects of exposure to air pollution on the health of the public, using principles of molecular epidemiology and utilizing various biomarkers, including biomarkers of exposure and biomarkers of early biological effects, such as effects on DNA. The Laboratory of Environmental Toxicology has conducted molecular epidemiological studies on the impacts on health in exposed populations, i.e., those living in Bangkok, using biomarkers of exposure and early biological effects to assess health risks in these populations. Results showed that susceptible populations who are exposed to these genotoxic air pollutants from traffic-related sources (e.g., traffic policemen, street vendors and school children in Bangkok), from their...
Name: Mister Supachai Ritruechai Office address: Laboratory of Pharmacology, 4thFloor, Biomedical Science Building 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel: +66 2553 8555 (ext. 3160) E-mail: Position: Research Assistant Research Interests • Purification of phytochemical compounds from medicinal Plant Education • B.Sc. in Chemistry, Ramkhamhaeng University Area of expertise • Natural products and phytochemistry analysis by HPLC, LC-MS techniques and Spray dry Publications • Changes in the contents of four active diterpenoids at different growth stages inAndrographis paniculata(Burm.f.) Nees (Chuanxinlian). Pholphana N, Rangkadilok N, Saehun J,Ritruechai S, Satayavivad J. Chinese Medicine. 2013; 8:1-12.
Name: Miss Jittra Saehun Office address: Laboratory of Pharmacology, 4thFloor, Biomedical Science Building 54 Kamphaeng Phet 6 Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Tel: +66 2553 8555 (ext. 3163) E-mail: Position: Research Assistant Research Interests • Chemical and heavy metal analysis from medicinal plants, foods and environmental samples Education • Maejo University, B.Sc. in Fisheries Area of expertise • HPLC and ICP-MS technique, analytical chemistry and microwave digestion • Animal handling Publications Evaluation of trace elements in selected foods and dietary intake by young children in Thailand. Nookabkaew S, Rangkadilok N, Akib CA, Tuntiwigit N,Saehun J, Satayavivad J. Food Addit Contam B. 2013; 6:55-67. Changes in the contents of four active diterpenoids at different growth stages inAndrographis paniculata(Burm.f.) Nees (Chuanxinlian). Pholphana N, Rangkadilok N,Saehun J, Ritruechai S, Satayavivad J. Chinese Medicine. 2013; 8:1-12.
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