• Title/Summary/Keyword: tumour

Search Result 320, Processing Time 0.023 seconds

Role of E-cadherin and cyclin D1 as predictive markers of aggression and clonal expansion in head and neck squamous cell carcinoma

  • Shergill, Khushdeep;Sen, Arijit;Pillai, Hari Janardanan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
    • /
    • v.44 no.4
    • /
    • pp.182-190
    • /
    • 2018
  • Objectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Inconsistency in various histopathologic features for predicting nodal metastasis and overall prognosis and a better understanding of molecular mechanisms of tumourigenesis have shifted the focus to a search for more definitive predictive markers. To identify the role of two immunohistochemical (IHC) markers, E-cadherin and cyclin D1, as predictive markers of aggressiveness in HNSCC and to assess clonal expansion of tumour cells. Materials and Methods: A total of 66 cases of HNSCC with neck node dissection were studied. IHC was performed on primary tumour sections and lymph nodes showing metastatic deposits. Histopathological parameters such as tumour grade and TNM stage together with nodal status were compared according to expression of the two markers. Fischer's chi-square test was used to assess the correlation between the two markers and histopathological parameters. Results: Out of 66 cases studied, 37 showed LN metastasis. Most of the patients were male, and the most common tumour site was buccal mucosa. We found a significant association between loss of E-cadherin and node metastasis (P<0.001) and higher TNM stage (P<0.001). Cyclin D1 overexpression was significantly associated with only nodal metastasis (P=0.007). No significant association with tumour grade was found for either marker. The subgroup of E-cadherin loss with cyclin D1 overexpression was associated with the maximum incidence of nodal metastasis and higher TNM stage, highlighting the importance of using a combination of these two markers. A significant association was noted between the expression of markers at the primary site and at nodal deposits, indicating clonal expansion. Conclusion: A combination of the two markers E-cadherin and cyclin D1 can predict prognosis in HNSCC, although tumour heterogeneity may affect this association in some cases.

Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression

  • Guo, Jie;Liao, Mengfan;Hu, Xianmin;Wang, Jun
    • Molecules and Cells
    • /
    • v.44 no.9
    • /
    • pp.647-657
    • /
    • 2021
  • As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno-regulatory mechanism by which Reg3A modulates tumour-promoting responses during pancreatic cancer (PC) progression. In an in vitro Transwell system that allowed the direct co-culture of human peripheral blood-derived dendritic cells (DCs) and Reg3A-overexpressing/ silenced human PC cells, PC cell-derived Reg3A was found to downregulate CD80, CD83 and CD86 expression on educated DCs, increase DC endocytic function, inhibit DC-induced T lymphocyte proliferation, reduce IL-12p70 production, and enhance IL-23 production by DCs. The positive effect of tumour-derived Reg3A-educated human DCs on PC progression was demonstrated in vivo by intraperitoneally transferring them into PC-implanted severe combined immunodeficiency (SCID) mice reconstituted with human T cells. A Reg3A-JAK2/STAT3 positive feedback loop was identified in DCs educated with Reg3A. In conclusion, as a tumour-derived factor, Reg3A acted to block the differentiation and maturation of the most important antigen-presenting cells, DCs, causing them to limit their potential anti-tumour responses, thus facilitating PC escape and progression.

Further Evidence of Linkage at the tva and tvc Loci in the Layer Lines and a Possibility of Polyallelism at the tvc Locus

  • Ghosh, A.K.;Pani, P.K.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.18 no.5
    • /
    • pp.601-605
    • /
    • 2005
  • Three lines of White Leghorn (WL) chickens (IWJ, IWG and IWC) maintained at Central Avian Research Institute, Izatnagar (UP), were used for chorioallantoic membrane (CAM) and liver tumour (LT) assay. Eleven-day-old embryos of each line were partitioned into three groups and inoculated with 0.2 ml of subgroup A, subgroup C and an equal mixture of subgroup A and C Rous sarcoma virus (RSV). Subgroup virus receptor on the cell surface membrane for subgroup A is coded for by tumour virus a (tva) locus and for subgroup C by tumour virus c (tvc) locus. The random association of the genes at the tva and tvc loci in IWJ and IWC line was assessed and the $x^2$-values for phenotypic classes were found to be significant, indicating the linkage between the tva and tvc loci. The linkage value was estimated to be 0.09 on pooled sex and pooled line basis. On the basis of four subclass tumour phenotypes a 4-allele model was proposed for tva locus having $a^{s1}$, $a^{s2}$, $a^{r1}$ and $a^{r2}$ alleles and the frequencies were calculated as 0.47, 0.13, 0.13 and 0.27 for IWJ line, 0.31, 0.33, 0.14 and 0.22 for IWG line and 0.44, 0.11, 0.21 and 0.24 for IWC line, respectively. Similarly, for tvc locus the frequencies of four alleles i.e. $c^{s1}$, $c^{s2}$, $c^{r1}$ and $c^{r2}$ were calculated as 0.42, 0.20, 0.21 and 0.17 for IWJ line, 0.42, 0.17, 0.27 and 0.14 for IWG line and 0.30, 0.21, 0.16 and 0.33 for IWC line, respectively. The $x^2$-values for all classes of observations were not significant (p>0.05), indicating a good fit to the 4-allele model for the occurrence of 4-subclass tumour phenotypes for tva and tvc loci. On the basis of the 2-allele model both tva and tvc locus carries three genotypes each. But, on the basis of the 4-allele model tva and tvc locus carries 10 genotypes each. The interaction between A-resistance and C-resistance (both CAM and LT death) was ascertained by taking the 10 genotypes of tva locus and 3 genotypes of tvc locus by pooling the lines and partitioning the observations into 3 classes. The $x^2$-values for the genotypic classes of CAM (-) LT (+) and CAM (-) LT (-) phenotypes to mixed virus (A+C) infection were found to be highly significant (p<0.01), indicating increased resistance, which indicates the joint segregation of $a^r$ and $c^r$ genes, suggesting the existence of close linkage between the tva and tvc loci. Therefore, an indirect selection approach using subgroup C viruses can be employed to generate stocks resistant to subgroup A LLV, obviating contamination with the most common agent causing LL in field condition.

CAD Scheme To Detect Brain Tumour In MR Images using Active Contour Models and Tree Classifiers

  • Helen, R.;Kamaraj, N.
    • Journal of Electrical Engineering and Technology
    • /
    • v.10 no.2
    • /
    • pp.670-675
    • /
    • 2015
  • Medical imaging is one of the most powerful tools for gaining information about internal organs and tissues. It is a challenging task to develop sophisticated image analysis methods in order to improve the accuracy of diagnosis. The objective of this paper is to develop a Computer Aided Diagnostics (CAD) scheme for Brain Tumour detection from Magnetic Resonance Image (MRI) using active contour models and to investigate with several approaches for improving CAD performances. The problem in clinical medicine is the automatic detection of brain Tumours with maximum accuracy and in less time. This work involves the following steps: i) Segmentation performed by Fuzzy Clustering with Level Set Method (FCMLSM) and performance is compared with snake models based on Balloon force and Gradient Vector Force (GVF), Distance Regularized Level Set Method (DRLSE). ii) Feature extraction done by Shape and Texture based features. iii) Brain Tumour detection performed by various tree classifiers. Based on investigation FCMLSM is well suited segmentation method and Random Forest is the most optimum classifier for this problem. This method gives accuracy of 97% and with minimum classification error. The time taken to detect Tumour is approximately 2 mins for an examination (30 slices).

Stimulation of Osteogenic Differentiation in Stromal Cells of Giant Cell Tumour of Bone by Zoledronic Acid

  • Yang, Tao;Zheng, Xiao-Fei;Li, Mei;Lin, Xi;Yin, Qing-Shui
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.9
    • /
    • pp.5379-5383
    • /
    • 2013
  • Therapeutic effects of zoledronic acid (ZOL) on giant cell tumour of bone (GCT) have been proven. Apoptosis induction was considered to be one of the mechanisms of ZOL tumour inhibition. In this study, we presented the possibility of an osteogenic differentiation stimulation mechanism of ZOL and further investigated dosage and time effects. We treated stromal cells of GCT (GCTSC) with ZOL for 48 hours at different concentrations ($0{\mu}M$, $0.01{\mu}M$, $0.1{\mu}M$, $1{\mu}M$, 5${\mu}M$, $30{\mu}M$) and assessed apoptotic and osteogenic differentiation markers with immunohistochemical techniques and real-time quantitative RT-PCR. Our results suggested that ZOL enhanced mRNA expression of Cbfa-1, osterix and osteocalcin genes with a maximum effect at $1{\mu}M$ in GCTSC. Time course experiments indicated a time dependent osteogenic differentiation effect. In conclusion, ZOL may be considered as an adjuvant in the treatment of GCT not only by inducing apoptosis but also by stimulating osteogenic differentiation of remaining tumor stromal cells after surgery.

RNases and their role in Cancer

  • Beeram, Eswari
    • The Korean Journal of Food & Health Convergence
    • /
    • v.5 no.2
    • /
    • pp.27-34
    • /
    • 2019
  • RNases plays a pivotal role in biological system and different RNases are known for their various functions like angiogenesis, immunological response, antiviral, antitumour activity and apoptosis. In which anti tumour activity of RNase is proved to improve genome stability in normal cells up to some extent. RNases like RNase L shows antiviral and antitumour activities against virus infected cells and cancer cells through 2'-5' oligo adenylate pathway and induces RNaseL dependent apoptosis where as RNase A modulates various proliferative pathways like MAP kinase, JNK, TGF-${\beta}$ and activates apoptosis in cancer cells and promotes immunological response through processing of Ags. IRE1 RNase acts as both tumour suppressor gene and oncogene in normal and cancer cells and involved in both antitumour and tumorigenic activities. RNase III upregulates miRNA in cancer cells there by acting via posttranscriptional level and proven to be effective against colorectal adeno carcinoma. In addition to this IRE1 RNase is a double edged sword through RIDD pathway in ER (18). To some of the cancers expressing c-myc IRE1 acts as tumour suppressor where as in cancers where myc is downregulated IRE1 acts as tumour provoking through RIDD pathway (18). Thus RNases play vital role in regulating the genome stability.

Correlation of Tumour Response with Starting Tumour Size and Dose of Tamoxifen in an N-Methyl-N-Nitrosourea (NMU)-Induced Rat Mammary Cancer Model

  • Yankuzo, Hassan Muhammad;Emilia, Sharifah Tuan Sheriff;Shaari, Rumaizi;Yaacob, Nik Soriani
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.16
    • /
    • pp.6721-6726
    • /
    • 2014
  • Background: The aim of this preliminary study was to address variations of responses observed with different starting tumor sizes of 10 and 15 mm, and the effects of different doses of tamoxifen (TAM) on experimental rat mammary tumors. Materials and Methods: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and $500{\mu}g/day$) groups of six animals each, and another group (n=6) treated with TAM $100{\mu}g/day$ at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice. Results: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups. Conclusions: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.

Tumour Markers in Peritoneal Washing Fluid - Contribution to Cytology

  • Yildirim, Mustafa;Suren, Dinc;Yildiz, Mustafa;Alikanoglu, Arsenal Sezgin;Kaya, Vildan;Doluoglu, Suleyman Gunhan;Aydin, Ozgur;Yilmaz, Necat;Sezer, Cem;Karaca, Mehmet
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.2
    • /
    • pp.1027-1030
    • /
    • 2013
  • Background: Peritoneal washing cytology (PWC) that shows the microscopic intra-peritoneal spread of gynaecologic cancers is not used in staging but is known as prognostic factor and effective in planning the intensity of the therapy. False negative or false positive results clearly affect the ability to make the best decision for therapy. In this study we assessed levels of tumour markers, carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125) and carbohydrate antigen (CA19-9), in peritoneal washing fluid to establish any possible contribution to the peritoneal washing cytology in patients operated for gynaecologic cancer. Materials and Methods: Preoperative tumour markers were studied in serum of blood samples obtained from the patients for preoperative evaluation of a gynaecologic operation. In the same group peritoneal tumour markers were studied in the washing fluid obtained for intraoperative cytological evaluation. Results: This study included a total of 94 patients, 62 with malignant and 32 with benign histopathology. The sensitivity of the cytological examination was found to be 21% with a specificity of 100%. When evaluated with CEA the sensitivity of the cytological examination has increased to 37%. Conclusions: In addition to examination of PWC, the level of CEA, a tumour marker, in peritoneal washing fluid can make a diagnostic contribution. Determining the level of CEA in peritoneal washing fluid will be useful in the management of gynaecologic cancers.

Exosomes from CIITA-Transfected CT26 Cells Enhance Anti-tumor Effects

  • Fan, Wen;Tian, Xing-De;Huang, E.;Zhang, Jia-Jun
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.2
    • /
    • pp.987-991
    • /
    • 2013
  • Aim: To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26 cells. Methods: In this study, we established an MHC class II molecule-expressing murine colon cancer cell line (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results in vivo were tested and monitored. Results: Exosomes from CT26-CIITA cells were found to contain a high level of MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantly increased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells. In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA-Exo enhanced splenocyte proliferation and IFN-${\gamma}$ production of CD4+T cells, while inhibiting IL-10 secretion. In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-${\alpha}$ and IL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantly inhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumour-bearing mice. Conclusion: Our findings indicate that CT26-CIITA-released exosomes are more efficient to induce anti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes as cancer vaccine candidates.

MicroRNA 449c Mediates the Generation of Monocytic Myeloid-Derived Suppressor Cells by Targeting STAT6

  • Han, Xiaoqing;Luan, Tao;Sun, Yingying;Yan, Wenyi;Wang, Dake;Zeng, Xianlu
    • Molecules and Cells
    • /
    • v.43 no.9
    • /
    • pp.793-803
    • /
    • 2020
  • Myeloid-derived suppressor cells (MDSCs) promote tumour progression by contributing to angiogenesis, immunosuppression, and immunotherapy resistance. Although recent studies have shown that microRNAs (miRNAs) can promote the expansion of MDSCs in the tumour environment, the mechanisms involved in this process are largely unknown. Here, we report that microRNA 449c (miR-449c) expression was upregulated in myeloid progenitor cells upon activation of C-X-C motif chemokine receptor 2 (CXCR2) under tumour conditions. MiR-449c upregulation increased the generation of monocytic MDSCs (mo-MDSCs). The increased expression of miR-449c could target STAT6 mRNA in myeloid progenitor cells to shift the differentiation balance of myeloid progenitor cells and lead to an enhancement of the mo-MDSCs population in the tumour environment. Thus, our results demonstrate that the miR-449c/STAT6 axis is involved in the expansion of mo-MDSCs from myeloid progenitor cells upon activation of CXCR2, and thus, inhibition of miR-449c/STAT6 signalling may help to attenuate tumour progression.