An investigation of the role of C-terminal tensin-like (Cten) gene in colorectal cancer

The C-terminal tensin-like (Cten) gene is a member of the tensin family and is localised at the cytoplasmic tail of β-integrin. It is involved in various biological events although the role of in the development of colorectal cancer (CRC) is uncertain. In order to study this, the expression of Cten during the development of CRC was initially evaluated using immunohistochemistry (IHC) on colorectal adenomas and carcinomas. Positive immunoreactivity for Cten was observed in 317/342 (92.6%) of CRC and 19/20 (90%) of colorectal adenoma. High Cten expression was significantly associated with advance Dukes stage (p=0.001), lymph node metastasis (p<0.001), extra-mural vascular invasion (p=0.001) and distant metastases (p=0.008). Survival analysis demonstrated that patients with high Cten expression had significantly shorter disease free survival (DFS) on univariate analysis (p<0.001) a trend towards Cten expression as an independent predictor of DFS on multivariate analysis (p=0.071). To further test the association with metastasis, the role of Cten in metastasis was tested by (a) intrasplenic injection of CRC cells stably transfected with Green Fluorescent Protein (GFP) tagged Cten into nude mice and (b) testing a series of primary CRCs and their metastases by IHC. Compared with control mice (injected with cells transfected with GFP empty vector), mice injected with cells expressing Cten developed larger tumours in the spleen (p=0.03) and liver (p=0.05). Compared with primary tumours, the metastatic deposits had a significantly higher frequency of nuclear localisation of Cten (p=0.002). To further investigate the potential role of Cten in metastasis, in-vitro models were used to investigate Cten function. Ectopic expression of Cten in the HCT116 CRC cell line (which expresses low levels of Cten) caused changes in cell morphology and increased cell motility (both migration and invasion). Conversely, the reciprocal Cten knock-down experiments in SW620 CRC cell line (which expresses high levels of Cten) resulted in inhibition of both cell migration and invasion. Since Cten is in complex with integrins at focal adhesions, its interactiosn with integrin-linked kinase (ILK), focal adhesion kinase (FAK) and CD24 were tested. Cten was shown to regulate ILK, FAK and CD24. Moreover, inhibition of CD24 after forced expression of Cten abrogated the Cten-mediated effects on both cell motility and protein levels of ILK and FAK. The studies were expanded and Cten expression was tested by IHC in another cancer model i.e. breast cancer (BC).Consistent with the data from CRC, increased Cten expression in BC was found to be associated with poor prognostic variables and shorter disease free survival. In conclusion, Cten expression is associated with poor prognosis in CRC and BC. This may be consequent to an ability to enhance metastasis which is related to promotion of cell motility. The activities of Cten are probably consistent across different tumour models

An investigation of the role of C-terminal tensin-like (Cten) gene in colorectal cancer

The C-terminal tensin-like (Cten) gene is a member of the tensin family and is localised at the cytoplasmic tail of β-integrin. It is involved in various biological events although the role of in the development of colorectal cancer (CRC) is uncertain. In order to study this, the expression of Cten during the development of CRC was initially evaluated using immunohistochemistry (IHC) on colorectal adenomas and carcinomas. Positive immunoreactivity for Cten was observed in 317/342 (92.6%) of CRC and 19/20 (90%) of colorectal adenoma. High Cten expression was significantly associated with advance Dukes stage (p=0.001), lymph node metastasis (p<0.001), extra-mural vascular invasion (p=0.001) and distant metastases (p=0.008). Survival analysis demonstrated that patients with high Cten expression had significantly shorter disease free survival (DFS) on univariate analysis (p<0.001) a trend towards Cten expression as an independent predictor of DFS on multivariate analysis (p=0.071). To further test the association with metastasis, the role of Cten in metastasis was tested by (a) intrasplenic injection of CRC cells stably transfected with Green Fluorescent Protein (GFP) tagged Cten into nude mice and (b) testing a series of primary CRCs and their metastases by IHC. Compared with control mice (injected with cells transfected with GFP empty vector), mice injected with cells expressing Cten developed larger tumours in the spleen (p=0.03) and liver (p=0.05). Compared with primary tumours, the metastatic deposits had a significantly higher frequency of nuclear localisation of Cten (p=0.002). To further investigate the potential role of Cten in metastasis, in-vitro models were used to investigate Cten function. Ectopic expression of Cten in the HCT116 CRC cell line (which expresses low levels of Cten) caused changes in cell morphology and increased cell motility (both migration and invasion). Conversely, the reciprocal Cten knock-down experiments in SW620 CRC cell line (which expresses high levels of Cten) resulted in inhibition of both cell migration and invasion. Since Cten is in complex with integrins at focal adhesions, its interactiosn with integrin-linked kinase (ILK), focal adhesion kinase (FAK) and CD24 were tested. Cten was shown to regulate ILK, FAK and CD24. Moreover, inhibition of CD24 after forced expression of Cten abrogated the Cten-mediated effects on both cell motility and protein levels of ILK and FAK. The studies were expanded and Cten expression was tested by IHC in another cancer model i.e. breast cancer (BC).Consistent with the data from CRC, increased Cten expression in BC was found to be associated with poor prognostic variables and shorter disease free survival. In conclusion, Cten expression is associated with poor prognosis in CRC and BC. This may be consequent to an ability to enhance metastasis which is related to promotion of cell motility. The activities of Cten are probably consistent across different tumour models

First Case Report of Primary Testicular Diffuse Large B-Cell Lymphoma from the Western Region of Saudi Arabia

Primary testicular lymphoma (PTL) represents 1-2% of all types of non-Hodgkin lymphomas (NHLs) and 1-10% of testicular neoplasms. Up to the best of my knowledge, this is the first case of PTL of the diffuse large B-cell lymphoma (DLBCL) in a 60-year-old man presented with a painless mass in the left testis as revealed by physical examination in a tertiary care hospital in Al-Madinah Al-Munwarah in the western region of the Kingdom of Saudi Arabia (KSA). Radiological examination revealed a large well-defined heterogeneous predominantly hypo-echoic mass with increased vascularity in the upper portion of the testis. On the other hand, histopathological examination revealed a tumor involving the whole left testis, which was large (measuring 6 3.5 &nbsp;3.3 cm), solid and dark red with focal areas of hemorrhage and epididymal infiltration. Immunohistochemistry showed positivity of leucocyte common antigen (LCA), pan B-cell marker (CD20) and negativity of pan T-cell marker (CD3). Other immunohistochemical markers such as CD10, placental alkaline phosphatase (PLAP), cytokeratin, vimentin, desmin and S100 protein were also negative. However, there was a marked expression of Ki67 and Bcl2 markers. Accordingly, the diagnosis of DLBCL was established. The tumor was classified as stage I according to the Ann Arbor system. The case was treated by orchiectomy followed by prophylactic anthracycline-based chemotherapy and irradiation of the contralateral testis and central nervous system

Cten Is Targeted by Kras Signalling to Regulate Cell Motility in the Colon and Pancreas

CTEN/TNS4 is an oncogene in colorectal cancer (CRC) which enhances cell motility although the mechanism of Cten regulation is unknown. We found an association between high Cten expression and KRAS/BRAF mutation in a series of CRC cell lines (p = 0.03) and hypothesised that Kras may regulate Cten. To test this, Kras was knocked-down (using small interfering (si)RNA) in CRC cell lines SW620 and DLD1 (high Cten expressors and mutant for KRAS). In each cell line, Kras knockdown was mirrored by down-regulation of Cten Since Kras signals through Braf, we tested the effect of Kras knockdown in CRC cell line Colo205 (which shows high Cten expression and is mutant for BRAF but wild type for KRAS). Cten levels were unaffected by Kras knockdown whilst Braf knockdown resulted in reduced Cten expression suggesting that Kras signals via Braf to regulate Cten. Quantification of Cten mRNA and protein analysis following proteasome inhibition suggested that regulation was of Cten transcription. Kras knockdown inhibited cell motility. To test whether this could be mediated through Cten, SW620 cells were co-transfected with Kras specific siRNAs and a Cten expression vector. Restoring Cten expression was able to restore cell motility despite Kras knockdown (transwell migration and wounding assay, p<0.001 for both). Since KRAS is mutated in many cancers, we investigated whether this relationship could be demonstrated in other tumour models. The experiments were repeated in the pancreatic cancer cell lines Colo357 & PSN-1(both high Cten expressors and mutant for KRAS). In both cell lines, Kras was shown to regulate Cten and forced expression of Cten was able to rescue loss of cell motility following Kras knockdown in PSN-1 (transwell migration assay, p<0.001). We conclude that, in the colon and pancreas, Cten is a downstream target of Kras and may be a mechanism through which Kras regulates of cell motility

An investigation of the role of C-terminal tensin-like (Cten) gene in colorectal cancer

The C-terminal tensin-like (Cten) gene is a member of the tensin family and is localised at the cytoplasmic tail of β-integrin. It is involved in various biological events although the role of in the development of colorectal cancer (CRC) is uncertain. In order to study this, the expression of Cten during the development of CRC was initially evaluated using immunohistochemistry (IHC) on colorectal adenomas and carcinomas. Positive immunoreactivity for Cten was observed in 317/342 (92.6%) of CRC and 19/20 (90%) of colorectal adenoma. High Cten expression was significantly associated with advance Dukes stage (p=0.001), lymph node metastasis (p<0.001), extra-mural vascular invasion (p=0.001) and distant metastases (p=0.008). Survival analysis demonstrated that patients with high Cten expression had significantly shorter disease free survival (DFS) on univariate analysis (p<0.001) a trend towards Cten expression as an independent predictor of DFS on multivariate analysis (p=0.071). To further test the association with metastasis, the role of Cten in metastasis was tested by (a) intrasplenic injection of CRC cells stably transfected with Green Fluorescent Protein (GFP) tagged Cten into nude mice and (b) testing a series of primary CRCs and their metastases by IHC. Compared with control mice (injected with cells transfected with GFP empty vector), mice injected with cells expressing Cten developed larger tumours in the spleen (p=0.03) and liver (p=0.05). Compared with primary tumours, the metastatic deposits had a significantly higher frequency of nuclear localisation of Cten (p=0.002). To further investigate the potential role of Cten in metastasis, in-vitro models were used to investigate Cten function. Ectopic expression of Cten in the HCT116 CRC cell line (which expresses low levels of Cten) caused changes in cell morphology and increased cell motility (both migration and invasion). Conversely, the reciprocal Cten knock-down experiments in SW620 CRC cell line (which expresses high levels of Cten) resulted in inhibition of both cell migration and invasion. Since Cten is in complex with integrins at focal adhesions, its interactiosn with integrin-linked kinase (ILK), focal adhesion kinase (FAK) and CD24 were tested. Cten was shown to regulate ILK, FAK and CD24. Moreover, inhibition of CD24 after forced expression of Cten abrogated the Cten-mediated effects on both cell motility and protein levels of ILK and FAK. The studies were expanded and Cten expression was tested by IHC in another cancer model i.e. breast cancer (BC).Consistent with the data from CRC, increased Cten expression in BC was found to be associated with poor prognostic variables and shorter disease free survival. In conclusion, Cten expression is associated with poor prognosis in CRC and BC. This may be consequent to an ability to enhance metastasis which is related to promotion of cell motility. The activities of Cten are probably consistent across different tumour models.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Clinicopathologic patterns of adult renal tumors

Background and Aim: Adult renal tumors (ARTs) are rare as compared with tumors of other organs and systems; however, it is important to have demographic and pathology data of rare tumors, including ART. No such data are available from the Kingdom of Saudi Arabia (KSA). Therefore, we aimed to study the demographic and pathological data of ART from King Fahad Hospital, Al-Madinah, KSA. Materials and Methods: This is a retrospective study of computerized data from the histopathology laboratory of King Fahad Hospital during a 10-year period (January 2006–September 2015). Results: There were 42 cases of ART, comprising 28 males and 14 females (male:female ratio of 2:1). The study group ranged in age from 17 to 83 years, with a mean of 54.5 years. In the study cohort, 93% of the patients had malignant tumors and 7% had benign lesions. Renal cell carcinoma (RCC) accounted for 85.8% of cases, followed by squamous cell carcinoma and sarcoma. The benign tumors recorded in our series were oncocytoma (4.7%) and angiomyolipoma (2.4%). The tumor size of RCC ranged from 4 to 17 cm, with a mean of 7.4 cm. The majority of patients (68%) had Fuhrman Grade II tumor. Gross capsular invasion, renal vein invasion and lymph node metastases were present in one case each. Conclusion: We conclude that the pathological findings of ART from the Madinah region are in concordance with studies in national and international literature