Phase III Randomized Trial Assessing Rofecoxib in the Adjuvant Setting of Colorectal Cancer: Final Results of the VICTOR Trial

2010 ◽  
Vol 28 (30) ◽  
pp. 4575-4580 ◽  
Author(s):  
Rachel S. Midgley ◽  
Christopher C. McConkey ◽  
Elaine C. Johnstone ◽  
Janet A. Dunn ◽  
Justine L. Smith ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinogenesis ◽  
Phase Iii ◽  
Adjuvant Setting ◽  
Case Control Studies ◽  
Curative Surgery ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Cox 2

Purpose Laboratory and case-control studies suggest a pivotal role for the cyclooxygenase-2 (COX-2) pathway in colorectal carcinogenesis. The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer (CRC). Patients and Methods Patients who had undergone potentially curative surgery and completion of adjuvant therapy for stage II and III CRC were randomly assigned to receive rofecoxib (20 mg daily) or placebo. The primary end point was overall survival (OS). Where formalin-fixed paraffin-embedded tumor tissue samples were available, COX-2 expression was evaluated by immunohistochemistry and correlated with clinical outcome. Results Two thousand four hundred thirty-four patients were entered onto the study. The trial was terminated early because of the worldwide withdrawal of rofecoxib. At this point, 1,167 patients had received rofecoxib and 1,160 patients had received placebo for median treatment durations of 7.4 and 8.2 months, respectively. For the rofecoxib and placebo arms, median follow-up times were 4.84 and 4.85 years, with 241 and 246 deaths and 297 and 329 recurrences, respectively. No difference was demonstrated in OS (hazard ratio [HR] = 0.97; 95% CI, 0.81 to 1.16; P = .75) or recurrence (HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) comparing the two groups. Tumor COX-2 expression by immunohistochemistry was assessed for 871 patients, but neither prognostic nor predictive effects were observed. Conclusion In this study of abbreviated therapy in the adjuvant setting of CRC, rofecoxib did not improve OS or protect from recurrence in unselected patients. In addition, COX-2 expression did not correlate with prognosis overall or predict effectiveness of COX-2 inhibitors.

scholarly journals Pks+ Escherichia Coli More Prevalent in Benign than Malignant Colorectal Tumors

2021 ◽  
Author(s):  
Carmina Villariba Tolentino ◽  
Ana Maria Cariño ◽  
Kin Israel Notarte ◽  
Imee Macaranas ◽  
Allan Fellizar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Malignant Tumors ◽  
Colorectal Tumors ◽  
Tissue Samples ◽  
E Coli ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Abstract Background: Some E. coli strains that synthesize the toxin colibactin within the 54-kb pks island are being implicated in colorectal cancer (CRC) development. Here, the prevalence of pks+ E. coli in malignant and benign colorectal tumors obtained from selected Filipino patients was compared to determine the association of pks+ E. coli with CRC in this population. Methods and Results: A realtime qPCR protocol was developed to quantify uidA, clbB, clbN, and clbA genes in formalin fixed paraffin embedded colorectal tissues. The number of malignant tumors (44/62; 71%) positive for the uidA gene was not significantly different (p=0.3428) from benign (38/62; 61%) tumors. Significantly higher number of benign samples (p<0.05) were positive for all three colibactin genes (clbB, clbN, and clbA) compared with malignant samples. There was also higher prevalence of pks+ E. coli among older females and in tissue samples taken from the rectum. Conclusion: Hence, pks+ E. coli may not be associated with CRC development among Filipinos.

scholarly journals INHIBITION OF COX-2 EXPRESSION BY LUNASIN-RICH SOYBEAN EXTRACT ON COLORECTAL CANCER

2019 ◽  
pp. 116-121
Author(s):  
KUSMARDI KUSMARDI ◽  
VANNESSA KARENINA ◽  
ARI ESTUNINGTYAS ◽  
ARYO TEDJO
Keyword(s):  
Colorectal Cancer ◽  
Distal Colon ◽  
Negative Control Group ◽  
Negative Control ◽  
Colorectal Carcinogenesis ◽  
Control Group ◽  
Tissue Samples ◽  
Cell Counts ◽  
Soybean Extract ◽  
Cox 2

Objective: The incidence of colorectal cancer has been growing faster than most other cancers in the past decade, especially in developing countries. One of the substances that is currently being investigated as potential chemopreventive agent is lunasin, which is contained in soybeans. This research explored the effect of lunasin on COX-2 expression in the distal colons of mice in which colorectal carcinogenesis was induced with azoxymethane (AOM) and dextran sodium sulfate (DSS). Methods: A total of 30 Swiss Webster mice were separated into six groups. In five of the groups—a negative control group, positive control group, and three intervention groups—carcinogenesis was induced with AOM and DSS; the sixth group received no interventions. Lunasin-rich soybean extracts were given in doses of 250, 300, and 350 mg/kgBW for 6 w to the intervention groups Immunohistochemical staining of COX-2 was then carried out on tissue samples from the distal colons of mice that had been sacrificed. The samples were microscopically assessed and photographed, and cell counts were performed using the Image J application. COX-2 expression is reported in the form of an optical density score (ODS). Results: Significant differences between the negative control and the intervention groups were found at the 300 mg/kgBW (p = 0.047) and 350 mg/kgBW (p = 0.016) lunasin dosage levels. Conclusions: This demonstrates that administration of lunasin-rich soy extracts can inhibit COX-2 expression in cryptic epithelial cells of the distal colon in mice with carcinogenesis induced by AOM and DSS.

scholarly journals Evaluation of Merkel Cell Polyomavirus DNA in Tissue Samples from Italian Patients with Diagnosis of MCC

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 61
Author(s):  
Carla Prezioso ◽  
Raffaella Carletti ◽  
Francisco Obregon ◽  
Francesca Piacentini ◽  
Anna Maria Manicone ◽  
...  
Keyword(s):  
Point Mutations ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
Tissue Samples ◽  
Metastatic Lesions ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Metastatic Sites ◽  
Archived Specimens ◽  
Coding Control

Because the incidence of Merkel cell carcinoma (MCC) has increased significantly during the last 10 years and it is recognized that Merkel cell polyomavirus (MCPyV) and ultraviolet (UV) radiation represent two different etiological inputs sharing clinical, histopathological, and prognostic similar features, although with different prognosis, this study investigated the detection of MCPyV in skin and lymph nodes with histological diagnosis of MCC. Formalin-fixed paraffin-embedded tissue (FFPE) were retrieved from archived specimens and MCPyV non-coding control region (NCCR) and viral capsid protein 1 (VP1) sequences were amplified and sequenced. Results provide an interesting observation concerning the discrepancy between the MCPyV DNA status in primary and metastatic sites: in fact, in all cases in which primary and metastatic lesions were investigated, MCPyV DNA was detected only in the primary lesions. Our data further support the “hit-and-run” theory, also proposed by other authors, and may lead to speculation that in some MCCs the virus is only necessary for the process of tumor initiation and that further mutations may render the tumor independent from the virus. Few point mutations were detected in the NCCR and only silent mutations were observed in the VP1 sequence compared to the MCPyV MCC350 isolate. To unequivocally establish a role of MCPyV in malignancies, additional well-controlled investigations are required, and larger cohorts should be examined.

scholarly journals TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features

2021 ◽  
Vol 147 (4) ◽  
pp. 1125-1135
Author(s):  
Sang Kyum Kim ◽  
Jang-Hee Kim ◽  
Jae Ho Han ◽  
Nam Hoon Cho ◽  
Se Joong Kim ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Malignant Neoplasm ◽  
Clinicopathologic Features ◽  
Ki 67 ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Tert Promoter Mutations ◽  
Formalin Fixed Paraffin Embedded ◽  
Penile Squamous Cell Carcinoma ◽  
Promoter Mutations

Abstract Purpose Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features. Methods In this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. Results Recurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis. Conclusion Our study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

scholarly journals Immunohistochemical expression of β-catenin, Ki67, CD3 and CD18 in canine colorectal adenomas and adenocarcinomas

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Kristin M. V. Herstad ◽  
Gjermund Gunnes ◽  
Runa Rørtveit ◽  
Øyvor Kolbjørnsen ◽  
Linh Tran ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Colorectal Adenomas ◽  
Colorectal Carcinogenesis ◽  
Positive Staining ◽  
Colonic Tissue ◽  
Retrospective Case ◽  
Tissue Samples ◽  
Colonic Cells ◽  
Control Samples

Abstract Background Inflammation is believed to influence human colorectal carcinogenesis and may have an impact on prognosis and survival. The mucosal immunophenotype in dogs with colorectal cancer is poorly described. The aim of this study was to investigate whether the density, distribution and grade of tumor-infiltrating immune cells (TIIs) are different in normal colonic tissue vs benign stages (adenomas) and malignant stages (adenocarcinomas) of canine colorectal carcinogenesis, and thus, whether they can be considered as prognostic factors in dogs. This retrospective case-control study was performed on formalin-fixed, paraffin-embedded tissue samples from dogs with histologically confirmed colorectal adenoma (n = 18) and adenocarcinoma (n = 13) collected from archived samples. The samples had been collected by colonoscopy, surgery or during postmortem examination. Healthy colonic tissue obtained post mortem from dogs euthanized for reasons not involving the gastrointestinal tract served as control tissue (n = 9). Results The tumor samples had significantly lower numbers of CD3+ T-cells in the epithelium compared to controls (adenocarcinoma vs control, Kruskal-Wallis test, p = 0.0004, and adenoma vs control, p = 0.002). Adenomas had a significantly lower number of CD18+ cells in the lamina propria, compared to control samples (Kruskal-Wallis test, p = 0.008). Colonic samples from control dogs had uniform staining of β-catenin along the cell membrane of epithelial cells. Compared to normal colonic cells, the expression levels of cytoplasmic β-catenin were significantly higher in adenomas and adenocarcinomas (adenoma vs control Kruskal-Wallis test, p = 0.004, and adenocarcinoma vs control, p = 0.002). None of the control samples showed positive staining of β-catenin in the nucleus of colonic cells. In contrast, adenocarcinomas and adenomas showed moderate to strong staining of the cell nucleus. The nuclear β-catenin expression (signal strength and distribution) was significantly higher in adenomas compared to adenocarcinomas (Kruskal-Wallis test, p < 0.05). Conclusions β-catenin and Ki67 were not useful markers for demonstrating tumor progression from adenomas to adenocarcinomas. The lower presence of CD18 and CD3+ cells in colorectal tumors compared to controls indicates a reduced presence of histiocytes and T-cells, which may have implications for the pathogenesis and progression of colorectal cancer in dogs.

scholarly journals The Dutch National TissueArchive Portal enables efficient, consistent, and transparent procurement of diagnostic tissue samples for scientific use

2021 ◽  
Author(s):  
Robin Verjans ◽  
Annette H. Bruggink ◽  
Robby Kibbelaar ◽  
Jos Bart ◽  
Aletta Debernardi ◽  
...  
Keyword(s):  
The Netherlands ◽  
Tissue Sample ◽  
Ffpe Tissue ◽  
Tissue Samples ◽  
Internet Portal ◽  
Formalin Fixed Paraffin ◽  
Practical Support ◽  
Formalin Fixed Paraffin Embedded ◽  
The Rich ◽  
Formalin Fixed

AbstractBiobanks play a crucial role in enabling biomedical research by facilitating scientific use of valuable human biomaterials. The PALGA foundation—a nationwide network and registry of histo- and cytopathology in the Netherlands—was established to promote the provision of data within and between pathology departments, and to make the resulting knowledge available for healthcare. Apart from the pathology data, we aimed to utilize PALGA’s nationwide network to find and access the rich wealth of Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples for scientific use.  We implemented the Dutch National TissueArchive Portal (DNTP) to utilize PALGA’s nationwide network for requesting FFPE tissue samples. The DNTP consists of (1) a centrally organized internet portal to improve the assessing, processing, harmonization, and monitoring of the procurement process, while (2) dedicated HUB-employees provide practical support at peripheral pathology departments. Since incorporation of the DNTP, both the number of filed requests for FFPE tissue samples and the amount of HUB-mediated support increased 55 and 29% respectively. In line, the sample procurement duration time decreased significantly (− 47%). These findings indicate that implementation of the DNTP improved the frequency, efficiency, and transparency of FFPE tissue sample procurement for research in the Netherlands. To conclude, the need for biological resources is growing persistently to enable precision medicine. Here, we access PALGA’s national, pathology network by implementation of the DNTP to allow for efficient, consistent, and transparent exchange of FFPE tissue samples for research across the Netherlands.

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