Nintedanib effects on delaying cancer progression and decreasing COX-2 and IL-17 in the prostate anterior lobe in TRAMP mice

The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1–suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.

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The resistance to the tumor suppressive effects of COX inhibitors and COX-2 gene disruption in TRAMP mice is associated with the loss of COX expression in prostate tissue

Carcinogenesis ◽

10.1093/carcin/bgm226 ◽

2007 ◽

Vol 29 (1) ◽

pp. 120-128 ◽

Cited By ~ 7

Author(s):

X. Wang ◽

J. K.L. Colby ◽

P. Yang ◽

S. M. Fischer ◽

R. A. Newman ◽

...

Keyword(s):

Gene Disruption ◽

Prostate Tissue ◽

Cox Inhibitors ◽

Cox 2 ◽

Tramp Mice

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Steroidal hormone and morphological responses in the prostate anterior lobe in different cancer grades after Celecoxib and Goniothalamin treatments in TRAMP mice

Cell Biology International ◽

10.1002/cbin.10967 ◽

2018 ◽

Vol 42 (8) ◽

pp. 1006-1020 ◽

Cited By ~ 4

Author(s):

Rafael Sauce Silva ◽

Larissa Akemi Kido ◽

Fabio Montico ◽

Débora Barbosa Vendramini-Costa ◽

Ronaldo Aloise Pilli ◽

...

Keyword(s):

Anterior Lobe ◽

Steroidal Hormone ◽

Morphological Responses ◽

Tramp Mice

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Abstract 5119: Multiple drug resistance-associated protein 4 (MRP4) may contribute to breast cancer progression by exporting the COX-2 product PGE2.

10.1158/1538-7445.am2013-5119 ◽

2013 ◽

Cited By ~ 2

Author(s):

Tyler J. Kochel ◽

Jocelyn Reader ◽

Namita Kundu ◽

Yanchun Li ◽

Xinrong Ma ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cancer Progression ◽

Multiple Drug Resistance ◽

Breast Cancer Progression ◽

Multiple Drug ◽

Cox 2

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Abstract 5217: The role of miR-526b in COX-2 mediated breast cancer progression via EP4 signaling

10.1158/1538-7445.am2014-5217 ◽

2014 ◽

Cited By ~ 1

Author(s):

Erin O. Landman ◽

Mousumi Majumder ◽

Ling Liu ◽

Peeyush K. Lala

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Breast Cancer Progression ◽

Cox 2

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Pilot study of capecitabine combined with celecoxib (CapCel) for the treatment of far advanced metastatic breast cancer (MBC) patients (pts)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10680 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10680-10680 ◽

Cited By ~ 1

Author(s):

A. Fabi ◽

M. Milella ◽

P. Malaguti ◽

P. Papaldo ◽

G. Ferretti ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Liver Toxicity ◽

Metastatic Breast ◽

Hormonal Treatment ◽

Skin Toxicity ◽

Median Number ◽

Metastatic Setting ◽

Starting Dose ◽

Cox 2

10680 Background: COX-2 is overexpressed during cancer progression in several solid tumors, including breast cancer, and constitutes an attractive therapeutic target. Selective COX-2 inhibitors, such as Celecoxib, have been successfully combined with fluoropyrimidine-based regimens, resulting in a lower-than-expected hematologic, GI, and skin toxicity rate. Methods: MBC pts who had progressed after at least one chemotherapy regimen for metastatic disease were eligible for the study. Capecitabine was administered at the starting dose of 1500–2000 mg/m2 daily for 14 days q3 wks. Celecoxib was administered at 200 mg b.i.d., continuously, starting on day 1. Dose escalation to Capecitabine 2000 or 2500 mg/m2 was allowed in the absence of toxicity > G1. Results: To date, 22 pts (median age: 55 yrs, range 35–81; ECOG PS 0: 21 pts) have been accrued; all pts had MBC and the majority had received adjuvant chemotherapy and hormonal treatment in the adjuvant and/or metastatic setting; all pts had been exposed to anthracyclines and/or taxanes. CapCel was administered as 2nd-, 3rd-, or ≥ 4th-line chemotherapy in 3, 10, and 9 pts, respectively. Capecitabine starting dose was 1500 mg/m2 in 9 pts and 2000 mg/m2 in 13 pts. Median number of cycles administered was 5 (range: 1–15). Toxicity was negligible: 1 pt experienced G3 neutropenia, 2 pts G3 skin/nail toxicity, and 1 pt G3 liver toxicity; all other toxicities were of grade ≤2. No Celecoxib-related GI or cardiovascular toxicities were observed. Capecitabine dose was escalated from 1500 to 2000 mg/m2 in 3/9 pts and from 2000 to 2500 mg/m2 in 2/13 pts, respectively, and reduced from 2000 to 1500 mg/m2 in 4/13 pts. Twenty pts are currently evaluable for response: 2 pts had PR (duration 48 and 49 wks, respectively), 15 pts had SD (median duration: 20 wks, range 12–44), and 3 pts progressed on therapy, for an overall clinical benefit rate of 40%. Median survival has not been reached. Conclusions: Overall, these preliminary results indicate that CapCel is extremely well-tolerated and has significant anti-tumor activity in a population of far advanced MBC pts. The study will continue to reach the projected accrual of 45 pts. No significant financial relationships to disclose.

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Prognostic and predictive effect of COX-2 expression in appendiceal adenocarcinomas.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.526 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 526-526

Author(s):

Kanwal Pratap Singh Raghav ◽

Syed Mohammad Ali Kazmi ◽

Aditya V. Shetty ◽

Melissa W. Taggart ◽

Keith F. Fournier ◽

...

Keyword(s):

Cancer Progression ◽

Stable Disease ◽

Treatment Duration ◽

Current Data ◽

Rank Test ◽

Cancer Center ◽

Significant Prognostic Factor ◽

Similar Treatment ◽

Cox 2 ◽

And Migration

526 Background: Cyclooxygenase-2 (COX-2), an inducible isoenzyme, is upregulated in inflammation and involved in cancer progression by promoting angiogenesis, cell proliferation and migration and by inhibiting apoptosis. COX-2 is implicated in colorectal tumorigenesis and by extension COX-2 expression testing and therapeutic inhibition has been considered in appendiceal adenocarcinomas (AAs). However, its role in this setting has never been well studied. The purpose of our study was to investigate COX-2 expression in AAs and to evaluate its prognostic and predictive significance. Methods: We performed a retrospective review of 607 patients with AAs treated at MD Anderson Cancer Center between 2002 and 2010. Immunohistochemistry was performed for COX-2 expression (COX2 mAb Clone CX229, Cayman Chemical) in 49 (8%) patients. Thirty (61%) stained positive and 19 (39%) showed no staining. Kaplan-Meier product limit method and log-rank test were used to estimate overall survival (OS) and to determine association between OS, COX-2 expression and other characteristics. Results: Median age at diagnosis was 47 yrs (range 34-78 yrs). Grade (P = 0.003), completeness of cytoreduction score (P = 0.010) and stage (P = 0.023) were significantly associated with OS. Median OS for patients with COX-2 positive and COX-2 negative tumors was 58.3 and 42.8 months, respectively (P = 0.232). Nine COX-2 positive patients received celecoxib (selective COX-2 inhibitor) in combination with other chemotherapy. Mean treatment duration was 5.5 months with best radiographic response being stable disease in 7 patients. Reduction in tumor markers (CEA or CA19-9) was seen in 7 cases (median reduction of 30%). Similar treatment duration (6.6 months), rate of stable disease (6/8 pts) and tumor marker reduction (7/8 pts) was seen on the preceding non-celecoxib containing chemotherapy in these patients. Median OS, with and without COX-2 inhibition, was 55.7 and 57.6 months respectively (P = 0.57). Conclusions: In this cohort, COX-2 expression is not a significant prognostic factor in AAs. Benefit from COX-2 inhibition in COX-2 expressing AAs is unclear. Current data does not support the routine use of either COX-2 testing or COX-2 inhibition therapy in AAs.

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