• Journal of Digestive Cancer Research
• /
• 제5권1호
• /
• pp.5-15
• /
• 2017

Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related death in the world. The aggressive but not always predictable pattern of HCC causes the limited treatment option and poorer outcome. Many researches had already proven the heterogeneity of HCC is one of the major challenges for treatment option and prognosis prediction. Molecular subtyping of HCC and selection of patient based on molecular profile can provide the optimization in the treatment and prognosis prediction. In this review, we have tried to summarize the molecular classification of HCC proposed by different valuable researches presented in the logistic way.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권4호
• /
• pp.427-432
• /
• 1999

Although importance of intrapancreatic neurons containing gastrin-releasing peptide (GRP) in control of exocrine secretion has been raised, the nature of GRP in the pancreas is unclear. Thus, the present study was undertaken to see distribution, content and molecular heterogeneity of immunoreactive GRP in the rat pancreas. Content of immunoreactive GRP in the rat pancreas was $2.99\;{\pm}\;0.66$ ng/g wet tissues determined by radioimmunoassay. Immunoreactive GRP was most abundantly expressed in the duodenal part among 3 parts of the pancreas; duodenal, body and splenic part. Vagotomy failed to change the content of immunoreactive GRP in the pancreas. Three distinct forms of immunoreactive GRP, very identical to GRP-27, bombesin-24 and neuromedin C, were observed in the rat pancreas by using reversed phase $C_{18}$ HPLC and Sephadex G-50 superfine column chromatography. Cell bodies of neurons containing immunoreactive GRP were scattered in pancreatic connective tissues and their nerve fibers innervated pancreatic acini and large ducts as determined by immunohistochemistry. The present results suggest that three distinct forms of GRP exist in intrapancreatic GRPergic neurons, which exert a stimulatory role in pancreatic exocrine secretion in rats.

• Biomolecules & Therapeutics
• /
• 제26권1호
• /
• pp.10-18
• /
• 2018

Tumors are dynamic metabolic systems which highly augmented metabolic fluxes and nutrient needs to support cellular proliferation and physiological function. For many years, a central hallmark of tumor metabolism has emphasized a uniformly elevated aerobic glycolysis as a critical feature of tumorigenecity. This led to extensive efforts of targeting glycolysis in human cancers. However, clinical attempts to target glycolysis and glucose metabolism have proven to be challenging. Recent advancements revealing a high degree of metabolic heterogeneity and plasticity embedded among various human cancers may paint a new picture of metabolic targeting for cancer therapies with a renewed interest in glucose metabolism. In this review, we will discuss diverse oncogenic and molecular alterations that drive distinct and heterogeneous glucose metabolism in cancers. We will also discuss a new perspective on how aberrantly altered glycolysis in response to oncogenic signaling is further influenced and remodeled by dynamic metabolic interaction with surrounding tumor-associated stromal cells.

• 대한의용생체공학회:의공학회지
• /
• 제42권5호
• /
• pp.232-240
• /
• 2021

Heterogeneity in cancer is the major obstacle for precision medicine and has become a critical issue in the field of a cancer diagnosis. Many attempts were made to disentangle the complexity by molecular classification. However, multi-dimensional information from dynamic responses of cancer poses fundamental limitations on biomolecular marker-based conventional approaches. Cell morphology, which reflects the physiological state of the cell, can be used to track the temporal behavior of cancer cells conveniently. Here, we first present a hybrid learning-based platform that extracts cell morphology in a time-dependent manner using a deep convolutional neural network to incorporate multivariate data. Feature selection from more than 200 morphological features is conducted, which filters out less significant variables to enhance interpretation. Our platform then performs unsupervised clustering to unveil dynamic behavior patterns hidden from a high-dimensional dataset. As a result, we visualize morphology state-space by two-dimensional embedding as well as representative morphology clusters and trajectories. This cell morphology profiling strategy by hybrid learning enables simplification of the heterogeneous population of cancer.

• 대한임상검사과학회지
• /
• 제55권3호
• /
• pp.121-131
• /
• 2023

African breast cancer patients benefit less from classical pathology services owing to the complex molecular and clinicopathological nature of the disease, poor quality of laboratory supplies, and shortage of experts in the field. This review presents evidence and confirms the need for improving anatomic pathology services in Africa. Peer-reviewed international journal articles available in Medline, Scopus, PubMed, and Google scholars, describing the status of pathology services in Africa, were included. Besides the late presentation of patients, anatomic pathology laboratories are accountable for the escalated mortality of breast cancer patients in several parts of Africa. Conversely, molecular diversity and biological heterogeneity of breast cancers, which disprove the one-size-fits-all therapeutic approach, have been reported from different parts of the continent. Irrespective of the geographical background, the choice of therapeutic options and predicting disease outcome depends on the right identification of the molecular signature of the cancer type. In conclusion, we propose that upgrading and integrating anatomic pathology with molecular diagnostic pathology is essential in order to provide better diagnostic results that will profoundly impact curbing mortality from breast cancers.

• Elastomers and Composites
• /
• 제37권4호
• /
• pp.234-243
• /
• 2002

A general scheme of a rubber structure is proposed. Using the thermomechanical method(TMA), some changes in the molecular and topological structures for uncured and cured, and unfilled and filled rubbers during processing are shown. In our investigations as region it is understood a complex structure, which is expressed at the thermomechanical curve(TMC) as a zone differed from others in thermal expansion properties. This zone is between the noticed temperatures of relaxation transitions, usually on the level like those determined by DMTA at 1Hz. These regions, which shares, are not stable, and differ in molecular-weight distribution(MWD) of chain fragments between the junctions. Differences in dynamics of the formation of the molecular and topological structures of a vulcanizate are dependent on the rubber formulation, mixing technology and curing time. Some of characteristics of these regions correlate with mechanical properties of vulcanizates what is shown for NR rubbers containing ENR or CPE as a polymeric additive. It is well known that the state of order influences diffusivity of low-molecular substances into the polymer matrix. Because of this, the two topological amorphous regions should influence the distribution of the ingredients and resulting in rubber compounds' heterogeneity, and related properties of cured rubber. Investigation of this problem is expected to be, in the future, one of the essential factors in determining further improvement of polymeric materials properties by compounding with additives and in reprocessing of rubber scrap.

• Clinical and Experimental Pediatrics
• /
• 제64권7호
• /
• pp.355-363
• /
• 2021

Background: Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity. Purpose: This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes. Methods: Transcriptome profiles from immortalized human podocyte cell line exposed to the plasma of 8 subjects (steroid-sensitive nephrotic syndrome [SSNS], n=4; steroid-resistant nephrotic syndrome [SRNS], n=2; and healthy adult individuals [control], n=2) were generated using microarray analysis. Results: Unsupervised hierarchical clustering of global gene expression data was broadly correlated with the clinical classification of NS. Differential gene expression (DGE) analysis of diseased groups (SSNS or SRNS) versus healthy controls identified 105 genes (58 up-regulated, 47 down-regulated) in SSNS and 139 genes (78 up-regulated, 61 down-regulated) in SRNS with 55 common to SSNS and SRNS, while the rest were unique (50 in SSNS, 84 genes in SRNS). Pathway analysis of the significant (P≤0.05, -1≤ log2 FC ≥1) differentially expressed genes identified the transforming growth factor-β and Janus kinase-signal transducer and activator of transcription pathways to be involved in both SSNS and SRNS. DGE analysis of SSNS versus SRNS identified 2,350 genes with values of P≤0.05, and a heatmap of corresponding expression values of these genes in each subject showed clear differences in SSNS and SRNS. Conclusion: Our study observations indicate that, although podocyte injury follows similar pathways in different clinical subgroups, the pathways are modulated differently as evidenced by the heatmap. Such transcriptome profiling with a larger cohort can stratify patients into intrinsic subtypes and provide insight into the molecular mechanisms of podocyte injury.

• Journal of Korean Neurosurgical Society
• /
• 제61권3호
• /
• pp.292-301
• /
• 2018

Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.

• BMB Reports
• /
• 제51권2호
• /
• pp.65-72
• /
• 2018

The endothelial to mesenchymal transition (EndMT) is a newly recognized, fundamental biological process involved in development and tissue regeneration, as well as pathological processes such as the complications of diabetes, fibrosis and pulmonary arterial hypertension. The EndMT process is tightly controlled by diverse signaling networks, similar to the epithelial to mesenchymal transition. Accumulating evidence suggests that microRNAs (miRNAs) are key regulators of this network, with the capacity to target multiple messenger RNAs involved in the EndMT process as well as in the regulation of disease progression. Thus, it is highly important to understand the molecular basis of miRNA control of EndMT. This review highlights the current fund of knowledge regarding the known links between miRNAs and the EndMT process, with a focus on the mechanism that regulates associated signaling pathways and discusses the potential for the EndMT as a therapeutic target to treat many diseases.

• Advances in pediatric surgery
• /
• 제14권1호
• /
• pp.75-82
• /
• 2008

Neuroblastoma arises from the primitive neural crest cells, and is a common malignancy in childhood. The clinical features are characterized by biological heterogeneity. Neuronal degeneration and differentiation occur in some patients. However treatment in the high risk group accounting for approximately half, has not been satisfactory despite a multimodal approach. Therefore, effective treatment is determined by the risk group of prognostic factors, such as age at diagnosis, stage of disease, pathological finding and N-myc amplification. Neuroblastoma can be diagnosed prenatally, which suggests its origin during the normal embryogenesis. Recent knowledge of molecular biology, such as Trk genes, and the concept of cancer stem cells have given us some improved understanding on this disease. Currently, targeted therapies based on the molecular biology of neuroblastoma are under investigation and increasing survival rate and decreasing late complications could be appreciated.