• Title/Summary/Keyword: Cancer progression

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Anti-Oxidative Effect of Myrtenal in Prevention and Treatment of Colon Cancer Induced by 1, 2-Dimethyl Hydrazine (DMH) in Experimental Animals

  • Lokeshkumar, Booupathy;Sathishkumar, Venkatachalam;Nandakumar, Natarajan;Rengarajan, Thamaraiselvan;Madankumar, Arumugam;Balasubramanian, Maruthaiveeran Periyasamy
    • Biomolecules & Therapeutics
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    • v.23 no.5
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    • pp.471-478
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    • 2015
  • Colon cancer is considered as the precarious forms of cancer in many developed countries, with few to no symptoms; the tumor is often diagnosed in the later stages of cancer. Monoterpenes are a major part of plant essential oils found largely in fruits, vegetables and herbs. The cellular and molecular activities show therapeutic progression that may reduce the risk of developing cancer by modulating the factors responsible for colon carcinogenesis. Colon cancer was induced with DMH with a dose of (20 mg/Kg/body weight) for 15 weeks by subcutaneous injection once in a week. Myrtenal treatment was started with (230 mg/Kg/body weight) by intragastric administration, one week prior to DMH induction and continued till the experimental period of 30 weeks. The Invivo results exhibit the elevated antioxidant and lipid peroxidation levels in DMH treated animals. The Histopathological analysis of colon tissues well supported the biochemical alterations and inevitably proves the protective role of Myrtenal. Treatment with myrtenal to cancer bearing animals resulted in a remarkable increase in the inherent antioxidants and excellent modulation in the morphological and physiological nature of the colon tissue. It is thus concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of colon carcinoma in Wistar albino rats.

Significant Differences in the Clinicopathological Characteristics and Survival of Gastric Cancer Patients from Two Cancer Centers in China and Korea

  • Shen, Zhan Long;Song, Kyo Young;Ye, Ying Jiang;Xie, Qi Wei;Liang, Bin;Jiang, Kewei;Park, Cho Hyun;Wang, Shan
    • Journal of Gastric Cancer
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    • v.15 no.1
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    • pp.19-28
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    • 2015
  • Purpose: To compare the clinicopathological data and long-term survival of gastric cancer patients in China and Korea. Materials and Methods: Patients who had undergone gastrectomy for gastric cancer between 1998 and 2009 in 2 high-volume institutions in both China (n=1,637) and Korea (n=2,231) were retrospectively evaluated. Clinicopathological variables, overall survival (OS), progression-free survival (PFS), and surgery-related complications were assessed for all patients and compared between the 2 institutions. Results: Chinese patients included in the study were significantly older and had a significantly lower body mass index (BMI) than the Korean patients. Esophagogastric junction tumors were more frequent in Chinese patients. However, the number of patients with stage I gastric cancer, the number of harvested lymph nodes, and the number of total gastrectomies were significantly higher in the Korean population. Korean patients also presented with fewer undifferentiated tumors than Chinese patients. Furthermore, Korean patients had prolonged OS and PFS for stage III cancers only. BMI, tumor-node-metastasis (TNM) stage, tumor invasion, number of positive lymph nodes, and distant metastases were all independent factors affecting OS and PFS. Conclusions: Although China and Korea are neighboring Asian countries, the clinicopathological characteristics of Chinese patients are significantly different from those of Korean patients. Korean gastric cancer patients had longer OS and PFS than Chinese patients. Influencing factors included TNM stage, tumor invasion, and lymph node metastasis.

Classifying the Linkage between Adipose Tissue Inflammation and Tumor Growth through Cancer-Associated Adipocytes

  • Song, Yae Chan;Lee, Seung Eon;Jin, Young;Park, Hyun Woo;Chun, Kyung-Hee;Lee, Han-Woong
    • Molecules and Cells
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    • v.43 no.9
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    • pp.763-773
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    • 2020
  • Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach

  • Buddham, Richa;Chauhan, Sweety;Narad, Priyanka;Mathur, Puniti
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.365-377
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    • 2022
  • Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

Fractal dimension analysis as an easy computational approach to improve breast cancer histopathological diagnosis

  • Lucas Glaucio da Silva;Waleska Rayanne Sizinia da Silva Monteiro;Tiago Medeiros de Aguiar Moreira;Maria Aparecida Esteves Rabelo;Emílio Augusto Campos Pereira de Assis;Gustavo Torres de Souza
    • Applied Microscopy
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    • v.51
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    • pp.6.1-6.9
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    • 2021
  • Histopathology is a well-established standard diagnosis employed for the majority of malignancies, including breast cancer. Nevertheless, despite training and standardization, it is considered operator-dependent and errors are still a concern. Fractal dimension analysis is a computational image processing technique that allows assessing the degree of complexity in patterns. We aimed here at providing a robust and easily attainable method for introducing computer-assisted techniques to histopathology laboratories. Slides from two databases were used: A) Breast Cancer Histopathological; and B) Grand Challenge on Breast Cancer Histology. Set A contained 2480 images from 24 patients with benign alterations, and 5429 images from 58 patients with breast cancer. Set B comprised 100 images of each type: normal tissue, benign alterations, in situ carcinoma, and invasive carcinoma. All images were analyzed with the FracLac algorithm in the ImageJ computational environment to yield the box count fractal dimension (Db) results. Images on set A on 40x magnification were statistically different (p = 0.0003), whereas images on 400x did not present differences in their means. On set B, the mean Db values presented promising statistical differences when comparing. Normal and/or benign images to in situ and/or invasive carcinoma (all p < 0.0001). Interestingly, there was no difference when comparing normal tissue to benign alterations. These data corroborate with previous work in which fractal analysis allowed differentiating malignancies. Computer-aided diagnosis algorithms may beneficiate from using Db data; specific Db cut-off values may yield ~ 99% specificity in diagnosing breast cancer. Furthermore, the fact that it allows assessing tissue complexity, this tool may be used to understand the progression of the histological alterations in cancer.

Identification of Selective STAT1 Inhibitors by Computational Approach

  • Veena Jaganivasan;Dona Samuel Karen;Bavya Chandrasekhar
    • Journal of Integrative Natural Science
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    • v.16 no.3
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    • pp.81-95
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    • 2023
  • Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

Inhibition of Adrenergic Agonists-induced Metastatic Ability of Liver Cancer Cells by Ethanol Extract of Premature Citrus Unshiu Peel (청피 에탄올 추출물이 스트레스성 카테콜아민으로 유도한 간암세포의 전이를 억제하는 효과 및 기전 연구)

  • Shin-Hyung Park
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.38 no.1
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    • pp.10-15
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    • 2024
  • Previous studies have highlighted the pivotal role of the β-adrenergic receptor (β-AR) signaling pathway in stimulating cancer metastasis induced by chronic stress. According to the theory of traditional Korean medicine, chronic stress can induce Qi stagnation. Based on the traditional role of premature citrus unshiu peel in moving Qi, we hypothesized that an ethanol extract of premature citrus unshiu peel (EPCU) can attenuate chronic stress-induced cancer progression. In this study, we investigated the potential role of EPCU on modulating the adrenergic agonists-induced metastatic properties of liver cancer cells. Our findings revealed that adrenergic agonists, including norepinephrine (NE), epinephrine (E), and isoproterenol (ISO), augmented the migratory capacity of Hep3B human hepatocellular carcinoma cells, which was completely abrogated by EPCU treatment in a concentration-dependent manner. Consistently, EPCU inhibited the E-induced invasive property of Hep3B cells in a dose-dependent manner. These results suggest that EPCU efficiently attenuates adrenergic agonists-induced metastatic abilities of liver cancer cells. As a molecular mechanism, EPF suppressed the phosphorylation of major components of β-AR signaling pathway, including Src, signal transducer and activator of transcription 3 (STAT3) and ERK, induced by E treatment. Taken together, our results demonstrate that EPCU impedes the adrenergic agonists-driven metastatic potential of cancer cells by inhibiting β-AR signaling pathway. This study provides basic evidence supporting the probable use of premature citrus unshiu peel to prevent metastasis in liver cancer patients under chronic stress.

Growth inhibition and cell cycle phase-specific apoptosis induced by celecoxib in human NSCLC cells in vitro.

  • Choi, Kang-Eun;Kang, Jin-Hyoung;Kuh, Hyo-Jeong
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.244.1-244.1
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    • 2002
  • Cyclooxygenase-2 ( COX-2 ) is an inducible enzyme which produces prostanoids by various stimuli. Overexpression of COX-2 in many tumor types indicates its association with tumor progression, which has been a promising target for chemoprevention and chemomodulation. We studied conc- and time-dependency of COX-2 inhibition, growth inhibition, and cell cycle arrest induced by celecoxib, a selective COX-2 inhibitor, in human non-small cell lung cancer (NSCLC) A549 cells. (omitted)

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Are there Time-period-related Differences in the Prophylactic Effects of Bacille Calmette-Guérin Intravesical Instillation Therapy in Japan?

  • Okamura, Takehiko;Ando, Ryosuke;Akita, Hidetoshi;Hashimoto, Yoshihiro;Iwase, Yutaka;Naiki, Taku;Kawai, Noriyasu;Tozawa, Keiichi;Kohri, Kenjiro
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4357-4361
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    • 2012
  • Objective: The guidelines on indications for prophylactic use of Bacille Calmette-Gu$\acute{e}$rin (BCG) against non-muscle-invasive bladder cancer (NMIBC) have changed over the years. In order to assess the impact on outcome, the present retrospective comparison of BCG efficacy by time period with Japanese patients was conducted. Patients and Methods: A total of 146 cases of NMIBC treated with BCG since February 1985 were retrospectively evaluated. All patients received 80 mg of BCG (Tokyo 172 strain) six to eight times a week for prophylactic use. Comparison was made among three historical groups (Group A: 1980's, 39 cases; Group B: 1990's, 61 cases; Group C: 2000's, 46 cases). Results: In total, recurrence was seen in 55 of the 146 cases (37.7%), and progression in 14 (9.6%), 1 patient dying of cancer. These overall results were similar to those outlined in previous reports. However, the outcomes of this time-period-based analysis indicated a tendency for a shorter time to recurrence in patients after 2000, although a log-rank test showed no significance (P=0.229). Seven of the cases featuring progression (i.e., half of all such cases) were among the 46 Group C patients (15.2%). Excluding these progressive cases, there was no significant difference among the remaining 132 patients in the three groups. Conclusion: This study results revealed a tendency for a lower non-recurrence rate after 2000 in our series. This could stem from a number of factors, including changes in BCG indication criteria and the evolution of histopathological diagnostic criteria.