Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer

2009 ◽  
Vol 101 (04) ◽  
pp. 741-747 ◽  
Author(s):  
Konstantina Mathioudaki ◽  
Panagiotis Prezas ◽  
Dimitra Alexopoulou ◽  
Eleftherios Diamandis ◽  
Dimitris Xynopoulos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Stratum Corneum ◽  
Human Tissue ◽  
Serine Proteases ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Normal Colonic Mucosa ◽  
Tissue Kallikrein ◽  
Human Cancer Cell Lines

SummaryHuman tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum and resembles a chymotryptic endopeptidase originally called stratum corneum chymotryptic enzyme (SCCE). In this study, we examined for the first time, the prognostic value of KLK7 mRNA expression, using a semi-quantitative RT-PCR method, in 105 colorectal cancer tissues for 54 of which, paired normal colonic mucosa were available. Furthermore, we analysed the expression of KLK7 in 10 adenomas, in 18 biopsies of inflamed colon mucosa, as well as in 22 human cancer cell lines of various origin, four of them being of colon. A defined number of colon cancer samples were also examined by immunohisto-chemistry. KLK7 expression was higher in cancerous than in normal tissues. Less differentiated tumors of more advanced stage showed higher KLK7 expression. Follow-up analysis revealed that KLK7 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). In addition, selected colon cancer samples highly expressing KLK7 gene, showed intense immunohistochemical staining for KLK7, enhancing RTPCR results. Present data suggest that KLK7 gene is up-regulated in colon cancer and its expression predicts poor prognosis for colon cancer patients.

scholarly journals Recurrence of sigmoid colon carcinoma in the retained urethra after cystectomy: A case report and review of the literature

2015 ◽  
Vol 87 (2) ◽  
pp. 167
Author(s):  
Yusuke Yagihashi ◽  
Yoshitaka Arakaki
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Sigmoid Colon ◽  
Colorectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Sigmoid Colon Cancer ◽  
Review Of The Literature ◽  
Free Survival ◽  
Urethral Recurrence ◽  
Disease Free

Urethral recurrence arising from a primary colorectal adenocarcinoma is rare. Here, we report a case of urethral recurrence of sigmoid colon cancer, which developed after cysto-prostato-sigmoidectomy for sigmoid colon cancer invading the bladder. The patient underwent urethrectomy successfully and is currently tumor-free. Surgeons who follow patients with colorectal cancer invading the bladder should be aware of this case. The early detection of recurrence improves the chances for disease-free survival.

Evaluation and prognostic significance of human tissue kallikrein-related peptidase 10 (KLK10) in colorectal cancer

Tumor Biology ◽  
2012 ◽  
Vol 33 (4) ◽  
pp. 1209-1214 ◽  
Author(s):  
Constantina Petraki ◽  
Youssef M. Youssef ◽  
William Dubinski ◽  
Zsuzsanna Lichner ◽  
Andreas Scorilas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Human Tissue ◽  
Prognostic Significance ◽  
Tissue Kallikrein

Irinotecan Fluorouracil Plus Leucovorin Is Not Superior to Fluorouracil Plus Leucovorin Alone As Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803

2007 ◽  
Vol 25 (23) ◽  
pp. 3456-3461 ◽  
Author(s):  
Leonard B. Saltz ◽  
Donna Niedzwiecki ◽  
Donna Hollis ◽  
Richard M. Goldberg ◽  
Alexander Hantel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Metastatic Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Patient Characteristics ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
First Line Therapy ◽  
Weekly Bolus

Purpose Randomized studies have shown that irinotecan (CPT-11) extends survival in metastatic colorectal cancer patients when administered in second-line and when added to fluorouracil (FU) plus leucovorin (LV) in first-line therapy of metastatic colorectal cancer. When this study was initiated, FU plus LV was standard adjuvant treatment for stage III colon cancer. We evaluated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with completely resected stage III colon cancer. Methods A total of 1,264 patients were randomly assigned to receive either standard weekly bolus FU plus LV regimen or weekly bolus CPT-11 plus FU plus LV. The primary end points of the study were overall survival (OS) and disease-free survival (DFS). Results Treatment arms were well-balanced for patient characteristics and prognostic variables. There were no differences in either DFS or OS between the two treatment arms. Toxicity, including lethal toxicity, was significantly higher on the CPT-11 plus FU plus LV arm. Conclusion The addition of CPT-11 to weekly bolus FU plus LV did not result in improvement in DFS or OS in stage III disease, but did increase both lethal and nonlethal toxicity. This trial demonstrates that advances in the treatment of metastatic disease do not necessarily translate into advances in adjuvant treatment, and it reinforces the need for randomized controlled adjuvant studies.

Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy

2007 ◽  
Vol 156 (5) ◽  
pp. 875-883 ◽  
Author(s):  
N. Komatsu ◽  
K. Saijoh ◽  
C. Kuk ◽  
F. Shirasaki ◽  
K. Takehara ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Human Tissue ◽  
Tissue Kallikrein

Regulation of human tissue kallikrein-related peptidase expression by steroid hormones in 32 cell lines

2008 ◽  
Vol 389 (11) ◽  
Author(s):  
Julie L.V. Shaw ◽  
Eleftherios P. Diamandis
Keyword(s):  
Cervical Cancer ◽  
Steroid Hormones ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Tissue ◽  
Hormonal Regulation ◽  
Serine Proteases ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Tissue Kallikrein

AbstractHuman tissue kallikrein-related peptidases (KLK), which are secreted serine proteases, are encoded by 15 genes located on chromosome 19q13.4. Previous studies have shown thatKLKexpression is regulated by steroid hormones and many KLKs are dysregulated in hormone-dependent malignancies. Some KLKs are proposed biomarkers for these cancers. We have characterized KLK hormonal regulation patterns using a large number of human cell lines. KLK levels were quantified in supernatants from 32 cell lines, each subjected to four hormonal stimulations (dexamethasone, norgestrel, dihydrotestosterone or estradiol), using ELISAs. Cell lines included breast, prostate, ovarian, lung, pancreatic, colon, and cervical cancer cells, T-lymphocytes, keratinocytes and a non-cancerous epithelial breast cell line. KLKs were regulated in several cell lines not previously studied, such as keratinocytes (KLK5, 6, and 7), ovarian cancer (KLK5 and 9) and cervical cancer (KLK3, 5, 6, 7, 8, 10, 11, and 13) cells. Many KLKs were regulated by the synthetic glucocorticoid dexamethasone; specifically, KLK5, 6, 8, 10 and 11 were upregulated in several breast cancer cell lines and downregulated in several cervical cancer cell lines. Knowledge of KLK hormonal regulation patterns will help to shed further light on their potential use as biomarkers and therapeutic targets for hormone-related malignancies.

Colon Cancer Survival Is Associated With Decreasing Ratio of Metastatic to Examined Lymph Nodes

2005 ◽  
Vol 23 (34) ◽  
pp. 8706-8712 ◽  
Author(s):  
Adam C. Berger ◽  
Elin R. Sigurdson ◽  
Thomas LeVoyer ◽  
Alexandra Hanlon ◽  
Robert J. Mayer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Survival ◽  
Regional Lymph Node ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
The United States ◽  
Cancer Specific Survival ◽  
End Points ◽  
The Impact

Purpose Colorectal cancer is the second leading cause of cancer deaths in the United States, with poor survival predicted by regional lymph node (LN) metastasis. The impact of LN ratio (LNR) on survival is unknown in this disease. Patients and Methods We analyzed data from Intergroup trial 0089 of adjuvant chemotherapy for stage II and III patients with colon cancer, in which all patients received fluorouracil-based therapy. Survival was similar for all arms of the study, allowing us to evaluate all patients together. End points included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Multivariate analyses were performed on all patients and on groups according to LNR quartiles (LNR: < 0.05, 0.05 to 0.19, 0.2 to 0.39, and 0.4 to 1.0). Covariates included in the models were age, sex, tumor stage, grade, histology, number of positive LNs, number of LNs removed, and LNR. Results The median age was 63.7 years, and the median number of LNs removed was 11. In the multivariate analysis, LNR was a significant factor for OS, DFS, and CSS in patients with 10 to 15 LN and more than 15 LN removed but not for patients with less than 10 LN removed. Using quartiles, LNR maintained its significance for all three end points when patients were grouped by node status. Conclusion After curative resection for colorectal cancer, the LNR is an important prognostic factor and should be used in stratification schemes for future clinical trials investigating adjuvant treatments.

scholarly journals Interleukin-11 is a Marker for Both Cancer- and Inflammation-Associated Fibroblasts that Contribute to Colorectal Cancer Progression

2020 ◽  
Author(s):  
Takashi Nishina ◽  
Yutaka Deguchi ◽  
Wakami Takeda ◽  
Masato Ohtsuka ◽  
Daisuke Ohshima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Human Cancer ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Reporter Mice ◽  
Stat3 Phosphorylation ◽  
Colorectal Cancer Progression ◽  
Cancer And Inflammation

SUMMARYInterleukin (IL)-11 is a member of the IL-6 family of cytokines and involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells appeared in the colon of three murine tumor models, and a murine acute colitis model. Il11ra1 or Il11 deletion attenuated the development of colitis-associated colorectal cancer. IL-11+ cells expressed fibroblast markers, and genes associated with cell proliferation and tissue repair. IL-11 induced STAT3 phosphorylation in colonic fibroblasts, suggesting the activation of IL-11+ fibroblasts. Analysis using the human cancer database revealed that genes enriched in IL-11+ fibroblasts were elevated in human colorectal cancer, and correlated with reduced disease-free survival. Together, our results suggested that tumor cells induced IL-11+ fibroblasts, and that a feed-forward loop between IL-11 and IL-11+ fibroblasts might contribute to tumor development.

Forkhead-box A3 (FOXA3) represses cancer stemness and partially potentiates chemosensitivity by targeting metastasis-associated in colon cancer 1 (MACC1) signaling pathway in colorectal cancer cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Na Li ◽  
Yun Li ◽  
Hongbo Gao ◽  
Jing Li ◽  
Xiaoping Ma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Transcriptional Repression ◽  
Xenograft Model ◽  
Disease Free Survival ◽  
Luciferase Reporter ◽  
Cancer Stemness ◽  
Tumor Sphere ◽  
Forkhead Box ◽  
Colorectal Cancer Cells

Background: The major challenge to the treatment of advanced colorectal cancer (CRC) is persistent occurrence of chemoresistance. One of the established etiologies is the existence of cancerstem-like cells (CSCs) using which tumors resist to external therapeutic challenges. Objective: The forkhead-box A3 (FOXA3) is a potent transcription factor that potentiates the acquisition and maintenance of stemness fate in many physiological systems. However, its effect on cancer stemness, particularly treatment, has not been explored in CRC, forming the basis of the current study. Methods: FOXA3 expression in oxaliplatin-resistant CRC tissues and cells was evaluated using RT-qPCR. Effects of FOXA3 manipulation on sensitivity to oxaliplatin were assessed using WST-1, apoptotic ELISA, colony formation and xenograft model. Effects of FOXA3 alteration on CSCs were determined using tumor sphere assay and CD44 staining. Transcriptional regulation of MACC1 by FOXA3 was studied using ChIP, Co-IP and luciferase reporter assay. Results: FOXA3 expression was significantly reduced in tumor samples from oxaliplatin-non-responsive patients compared with that in tumor samples from oxaliplatin-sensitive patients. This downregulation of FOXA3 expression predicted a poor post-chemotherapy overall- or disease-free survival in our 117-patient cohort. FOXA3 down-regulation significantly enhanced cell survival and stem-like properties, thus rendering the CRC cells unresponsiveness to oxaliplatin-induced cell death. Mechanistically, the anti-neoplasic effect of FOXA3 was mediated mainly through transcriptional repression of metastasis-associated in colon cancer 1 (MACC1) in oxaliplatin-resistant CRC cells. Conclusion: Our findings establish FOXA3 as a potent tumor suppressor in CRC, which may disrupt the maintenance of stemness and modulate sensitivity to oxaliplatin by inhibiting the transcription of MACC1 within CRC cells.

scholarly journals Synthesis and potential cytotoxic activity of some new benzoxazoles, imidazoles, benzimidazoles and tetrazoles

2013 ◽  
Vol 63 (2) ◽  
pp. 253-264 ◽  
Author(s):  
Subramaniyan Arulmurugan ◽  
Helen P. Kavitha
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Colon Cancer ◽  
Heterocyclic Compounds ◽  
Human Cancer ◽  
Assay Method ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Ht 29 ◽  
Mcf 7

2 The present work deals with the synthesis of some novel heterocyclic compounds such as benzoxazoles , 7, 13 and 19, imidazoles 3, 8, 14 and 20, benzimidazoles 4, 9, 15 and 21, and tetrazoles 10, 16, and 22. The synthesized compounds were characterized by IR, 1H NMR, mass spectrometry and elemental analysis. The compounds were evaluated for cytotoxicity against human cancer cell lines such as MCF-7 (breast cancer) and HT-29 (colon cancer) by the MTT assay method. Among the tested compounds, 4,4’-sulfonylbis(N-(2-(1H-benzo[d]imidazol- -2-yl)ethyl)aniline (9), N-bis(2-(benzo[d]oxazol-2-yl)-ethyl)- 6-phenyl-1,3,5-triazine-2,4-diamine (13), N-bis(2-(1H-benzo[ d]imidazol-2-yl)ethyl)-6-phenyl-1,3,5-triazine-2,4-diamine (15) and N-tris(2-1H-benzo[d]imidazol-2-yl)ethyl)- 1,3,5-triazine-2,4,6-triamine (21) showed potent cytotoxicity.

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