A Phase II Study of Celecoxib With Irinotecan, 5-Fluorouracil, and Leucovorin in Patients With Previously Untreated Advanced or Metastatic Colorectal Cancer

Chen, Emerson Y.; Blanke, Charles D.; Benson, Al B.; Dragovich, Tomislav; Lenz, Heinz Josef; Robles, Carlos; Li, Hong; Mori, Motomi; Mattek, Nora; Sanborn, Rachel E.; Lopez, Charles D.

doi:10.1097/coc.0000000000000465

Cited by 23 publications

(24 citation statements)

References 25 publications

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“…In addition, the therapeutic effect of COX-2-inhibitors such as celecoxib has already been studied in other cancer types extensively [63]. However, COX-2 is not a routine target in modern oncology due to controversial results, e.g., for colorectal [64][65][66] and lung cancer [67,68]. For MPM on the contrary COX-2-inhibitors achieved promising results in vitro [35,57,69,70] and in vivo [36,71].…”

Section: Cox-2mentioning

confidence: 99%

Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

Vogl

Rosenmayr

Bohanes

et al. 2021

Cancers

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Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient’s outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome.

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Section: Cox-2mentioning

confidence: 99%

Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

Vogl

Rosenmayr

Bohanes

et al. 2021

Cancers

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“…There are several other drugs, such as leucovorin and irinotecan, which are used in the treatment of CRC-PC. 42 When combined with HFD treatment, the dose of these drugs could be reduced, and side effects could also be limited.…”

Section: Discussionmentioning

confidence: 99%

Dietary fats suppress the peritoneal seeding of colorectal cancer cells through the TLR4/Cxcl10 axis in adipose tissue macrophages

Xiang

Shi

Zhang

et al. 2020

Sig Transduct Target Ther

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Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is a terminal phase of malignancy with no effective strategies for the prevention of this condition. Here we established PC models in mice by intraperitoneal engraftment of CRC cells and revealed an unexpected role for a high-fat diet (HFD) in preventing metastatic seeding in the visceral fat. Mechanistically, the HFD stimulated the activation of adipose tissue macrophages (ATMs) toward an M1-like phenotype and enhanced ATM tumor phagocytosis in a TLR4-dependent manner. Furthermore, the TLR4–Cxcl10 axis in ATMs promoted T cell recruitment, and M1-like macrophages stimulated T cell activation in tumor-seeded fats. The inhibitory effect of the HFD on tumor seeding was abolished with the ablation of macrophages, inactivation of T cells, or blockade of the TLR4–Cxcl10 axis in macrophages. Finally, we showed that a HFD and conventional chemotherapeutic agents (oxaliplatin or 5-fluorouracil) synergistically improved the survival of tumor-seeded mice. Collectively, our findings demonstrate that peritoneal seeding of CRC can be suppressed by short-term treatment with a HFD in the early phase, providing a novel concept for the management of these patients in the clinic.

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“…Although VEGF inhibitors and other chemotherapeutic reagents are widely used in clinical treatment, drug resistance is still the major obstacle for CRC therapy. For example, insensitivity to 5-FU, a front-line chemo drug for colon cancer treatment, has been reported in many colon cancer studies [4,9]. Therefore, there is an urgent need to develop a combination treatment with 5-FU in order to improve 5-FU’s efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…It can also reduce the risk of recurrence in patients with high-risk colon cancer findings at surgery. 5-Fluorouracil (5-FU) and salinomycin (Sal) are common chemotherapeutic agents used to treat with CRC or recurrence after CRC surgery [4–7]. However, these drugs usually lead to severe side effects, including hand-foot syndrome, neuropathy, and allergic or sensitivity reactions [8,9].…”

Section: Introductionmentioning

confidence: 99%

Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer

Gao

Zhou

Pang

et al. 2019

Free Radical Research

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The thunder god vine (Tripterygium wilfordii Hook. F) is traditionally used for inflammationrelated diseases in traditional Chinese medicine. In recent years, celastrol (a natural compound from the root of the thunder god vine) has attracted great interest for its potential anticancer activities. The free radical nitric oxide (NO) is known to play a critical role in colorectal cancer growth by promoting tumour angiogenesis. However, how celastrol influences the NO pathway and its mechanism against colorectal cancer is largely unknown. In this study, we investigated the effects and mechanism of celastrol on nitric oxide synthase (NOS) and the angiogenesis pathway in colorectal cancer. Our data show that celastrol inhibited HT-29 and HCT116 cell proliferation, migration, and NOS activity in the cytoplasm. The antiproliferation activity of celastrol was associated with the inhibition of iNOS and eNOS in colorectal cancer cells. Treatment with celastrol inhibited colorectal cancer cell growth and migration, and was associated with suppression of the expression of key genes (TYMP, CDH5, THBS2, LEP, MMP9, and TNF) and proteins (IL-1b, MMP-9, PDGF, Serpin E1, and TIMP-4) involved in the angiogenesis pathway. In addition, combinational use of celastrol with 5-fluorouracil, salinomycin, 1400 W, and L-NIO showed enhanced inhibition of colorectal cancer cell proliferation and migration. In sum, our study suggests that celastrol could suppress colorectal cancer cell growth and migration, likely through suppressing NOS activity and inhibiting the angiogenesis pathway.

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A Phase II Study of Celecoxib With Irinotecan, 5-Fluorouracil, and Leucovorin in Patients With Previously Untreated Advanced or Metastatic Colorectal Cancer

Abstract: Celecoxib plus IFL chemotherapy for patients with metastatic CRC is tolerable, but does not appear to increase the efficacy of IFL.

Cited by 23 publications

References 25 publications

Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

Dietary fats suppress the peritoneal seeding of colorectal cancer cells through the TLR4/Cxcl10 axis in adipose tissue macrophages

Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer

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