• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2575-2580
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• 2015

Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies.

• Korean Journal of Veterinary Research
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• v.56 no.3
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• pp.177-181
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• 2016

Mini-pigs have been widely employed in preclinical studies to explore new therapeutic strategies for diseases of the human urinary system; however, the normal reference of the renal artery has not been clearly investigated in the mini-pig model. Therefore, we aimed to establish a normal reference of the radiological morphology of the renal artery in mini-pigs by renal angiography via catheterization of the carotid artery. The renal angiographies obtained from 15 mini-pigs were evaluated to determine the orifice from the aorta, facing direction, size and the number of branches of renal arteries. Cranio-laterally facing renal arteries with 2 distal branches were mainly observed in the renal artery of mini-pigs. Both sides of the renal artery presented symmetrical sizes; however, the right renal artery orifice from the aorta was located more cranially than the left counterpart. The results of this study will contribute to radiological diagnosis of the renal artery as well as preclinical studies of mini-pigs.

• Current Optics and Photonics
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• v.3 no.1
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• pp.54-65
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• 2019

To develop a biomarker predicting tumor treatment efficacy is helpful to reduce time, medical expenditure, and efforts in oncology therapy. In clinics, microvessel density using immunohistochemistry has been proposed as an indicator that correlates with both tumor size and metastasis of cancer. In the preclinical study, we hypothesized that vascular morphometrics using optical coherence tomography angiography (OCTA) could be potential indicators to estimate the treatment efficacy of breast cancer. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber which was applied to a nude mouse, and the change in vascular morphology was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily OCTA maximum intensity projection map, multiple vessel parameters (vessel skeleton density, vessel diameter index, fractal dimension, and lacunarity) were compared with the tumor size in no tumor, treated tumor, and untreated tumor cases. Although each case has only one animal, we found that the vessel skeleton density (VSD), vessel diameter index and fractal dimension (FD) tended to be positively correlated with tumor size while lacunarity showed a partially negative correlation. Moreover, we observed that the changes in the VSD and FD are prior to the morphological change of the tumor. This feasibility study would be helpful in evaluating the tumor vascular response to treatment in preclinical settings.

• Journal of Yeungnam Medical Science
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• v.38 no.1
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• pp.27-33
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• 2021

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.49-55
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• 2023

Tumors are encircled by various non-cancerous cell types in the extracellular matrix, including fibroblasts, endothelial cells, immune cells, and cytokines. Fibroblasts are the most critical cells in the tumor stroma and play an important role in tumor development, which has been highlighted in some epithelial cancers. Many studies have shown a tight connection between cancerous cells and fibroblasts in the last decade. Regulatory factors secreted into the tumor environment by special fibroblast cells, cancer-associated fibroblasts (CAFs), play an important role in tumor and vessel development, metastasis, and therapy resistance. This review addresses the development of FAP inhibitors, emphasizing the first, second, and latest generations. First-generation inhibitors exhibit low selectivity and chemical stability, encouraging researchers to develop new scaffolds based on preclinical and clinical data. Second-generation enzymes such as UAMC-1110 demonstrated enhanced FAP binding and better selectivity. Targeted treatment and diagnostic imaging have become possible by further developing radionuclide-labeled fibroblast activation protein inhibitors (FAPIs). Although all three FAPIs (01, 02, and 04) showed excellent preclinical and clinical findings. The final optimization of these FAPI scaffolds resulted in FAPI-46 with the highest tumor-to-background ratio and better binding affinity.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.249-255
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• 2022

Alzheimer's disease (AD) represents a major public health concern and has been identified as a research priority. Clinical research evidence supports that the core cerebrospinal fluid (CSF) biomarkers for AD, including amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau), reflect key elements of AD pathophysiology. Nevertheless, advances in the clinical identification of new indicators will be critical not only for the discovery of sensitive, specific, and reliable biomarkers of preclinical AD pathology, but also for the development of tests that facilitate the early detection and differential diagnosis of dementia and disease progression monitoring. The early detection of AD in its presymptomatic stages would represent a great opportunity for earlier therapeutic intervention. The chance of successful treatment would be increased since interventions would be performed before extensive synaptic damage and neuronal loss would have occurred. In this study, the importance of developing an early diagnostic method using cognitive decline biomarkers that can discriminate between normal, mild cognitive impairment (MCI), and AD preclinical stages has been emphasized.

• Journal of Korean Neurosurgical Society
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• v.61 no.5
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• pp.539-547
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• 2018

Traumatic spinal cord injury (SCI) research has recently focused on the use of rat and mouse models for in vivo SCI experiments. Such small rodent SCI models are invaluable for the field, and much has been discovered about the biologic and physiologic aspects of SCI from these models. It has been difficult, however, to reproduce the efficacy of treatments found to produce neurologic benefits in rodent SCI models when these treatments are tested in human clinical trials. A large animal model may have advantages for translational research where anatomical, physiological, or genetic similarities to humans may be more relevant for pre-clinically evaluating novel therapies. Here, we review the work carried out at the University of British Columbia (UBC) on a large animal model of SCI that utilizes Yucatan miniature pigs. The UBC porcine model of SCI may be a useful intermediary in the pre-clinical testing of novel pharmacological treatments, cell-based therapies, and the "bedside back to bench" translation of human clinical observations, which require preclinical testing in an applicable animal model.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3751-3755
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• 2012

Aim: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis. For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted to investigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelial cells (EC cells) and adhesion molecule expression in vitro. Methods: The expression of CD44 or CD54 in the PG cells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopy double fluorescence staining. Results: The results showed that tea polyphenols: (1) inhibited the expression of CD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantly blocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influenced CD44 and CD54 expression during the adhesion process of PG cells to EC cells. Conclusions: The data indicated that the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54. The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibiting adhesion molecule expression to block cancer cell adhesion.

• Toxicological Research
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• v.17
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• pp.201-203
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• 2001

The Japan Pharmaceutical Manufacturers Association. with the cooperation of the Japan Association of Contract Laboratories for Safety Evaluation. launched a collaborative study with 38 companies aimed at elucidating the correlation between histopathological/hematological findings and immune function. Seven substances were individually administered to Crj : CD (SD)IGS rats for 14 or 28 days. Their immunotoxicity was assessed by histopathology. hematology. plaque-forming cell assay. enzyme-linked immunosorbent assay of serum antibody to sheep red blood cells. and flow cytometry. Appropriate procedures for immunotoxicology evaluation of pharmaceuticals were considered.

• Biomedical Science Letters
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• v.17 no.2
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• pp.95-104
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• 2011

The development of a general appreciation for the central role of angiogenesis in cancer growth and metastasis and other disease status has led to a wide range of new therapeutic strategies. This paper reviews the domestic and international trends through technology, marketing and patent information analysis dealing with anti-angiogenic agents. This analytical research has led to the identification of new targets associated with angiogenesis, leading to the development of an extensive number of preclinical screening of antiangiogenetic agents.