Clinical Significance of Folate Receptor β–expressing Tumor-associated Macrophages in Pancreatic Cancer

Kurahara, Hiroshi; Takao, Sonshin; Kuwahata, Taisaku; Nagai, Taku; Ding, Qiang; Maeda, Koki; Shinchi, Hiroyuki; Mataki, Yuko; Maemura, Kosei; Matsuyama, Tomohiko; Natsugoe, Shoji

doi:10.1245/s10434-012-2263-0

Cited by 84 publications

(91 citation statements)

References 32 publications

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“…The fluorescence measured in the noncancerous lymph nodes was likely due to OTL38 binding to activated macrophages, which express FRb (27)(28)(29)(30). However, the formation of OTL38 aggregates and Clinical Cancer Researchnonspecific uptake by lymph nodes is unlikely, as dissolving the agent at 7.5 mmol/L in 5% dextrose did not lead to the formation of measurable aggregates.…”

Section: Discussionmentioning

confidence: 95%

A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian Cancer

Hoogstins

Tummers

Gaarenstroom

et al. 2016

Clinical Cancer Research

227

236

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Purpose: Completeness of cytoreductive surgery is a key prognostic factor for survival in patients with ovarian cancer. The ability to differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is often difficult and can lead to incomplete tumor removal. Near-infrared fluorescence imaging has the potential to improve the detection of malignant tissue during surgery, significantly improving outcome. Here, we report the use of OTL38, a near-infrared (796 nm) fluorescent agent, that binds folate receptor alpha, which is expressed in >90% of epithelial ovarian cancers.Experimental Design: We first performed a randomized, placebo-controlled study in 30 healthy volunteers. Four single increasing doses of OTL38 were delivered intravenously. At fixed times following drug delivery, tolerability and blood/skin pharmacokinetics were assessed. Next, using the results of the first study, three doses were selected and administered to 12 patients who had epithelial ovarian cancer and were scheduled for cytoreductive surgery. We measured tolerability and blood pharmacokinetics, as well as the ability to detect the tumor using intraoperative fluorescence imaging.Results: Intravenous infusion of OTL38 in 30 healthy volunteers yielded an optimal dosage range and time window for intraoperative imaging. In 12 patients with ovarian cancer, OTL38 accumulated in folate receptor alpha-positive tumors and metastases, enabling the surgeon to resect an additional 29% of malignant lesions that were not identified previously using inspection and/or palpation.Conclusions: This study demonstrates that performing realtime intraoperative near-infrared fluorescence imaging using a tumor-specific agent is feasible and potentially clinically beneficial.

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Section: Discussionmentioning

confidence: 95%

A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian Cancer

Hoogstins

Tummers

Gaarenstroom

et al. 2016

Clinical Cancer Research

227

236

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“…folate receptor beta (FR-β) and VEGF and that mainly resided perivascularly and in the invasive front of the tumor [122].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment

Lahmar

Keirsse

Laoui

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

113

117

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“…(69,72) Clinical research has confirmed that M2-polarized TAMs are associated with poor prognoses in several cancers, including classical Hodgkin's lymphoma (CHL), (73) lung adenocarcinoma, (74) and pancreatic cancer. (75) Ding, et al (76) found a significant correlation between the expression of CD68 or CD163 protein with a tumor size, lymph node metastasis, and vascular invasion in patients with pancreatic cancer consistent with the role of TAM in ltration in pancreas and the promotion of pancreatic cancer development.…”

Section: Tumor Metastasismentioning

confidence: 76%

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica

Sun

Gao

et al. 2017

Chin. J. Integr. Med.

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Infiltration of the tumor microenvironment (TME) by immune and inflammatory cells is involved in promoting tumorigenesis, tumor progression, local invasion and metastasis.(1) Tumor-associated macrophages (TAMs), a prominent and abundant inflammatory component of solid and hematological malignancies, express a pro-and anti-tumor effect in all stages of carcinogenesis. Asian region. According to the theory of Chinese medicine (CM) and its practice, some Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we brie y summarize the pivotal remodeling the tumor microenvironment (TME). Here we brie y summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antiand immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, tumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy. and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.

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Clinical Significance of Folate Receptor β–expressing Tumor-associated Macrophages in Pancreatic Cancer

Cited by 84 publications

References 32 publications

A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian Cancer

A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian Cancer

Tissue-resident versus monocyte-derived macrophages in the tumor microenvironment

Targeting tumor-associated macrophages by anti-tumor Chinese materia medica

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