Combination treatment with recombinant methioninase enables temozolomide to arrest a BRAF V600E melanoma in a patient-derived orthotopic xenograft (PDOX) mouse model

Kawaguchi, Koji; Igarashi, Kentaro; Li, Shukuan; Han, Qinghong; Tan, Yuying; Kiyuna, Tasuku; Murakami, Takashi; Chmielowski, Bartosz; Nelson, Scott D.; Russell, Tara A.; Dry, Sarah M.; Li, Yunfeng; Unno, Michiaki; Eilber, Fritz C.; Hoffman, Robert M.

doi:10.18632/oncotarget.20231

Cited by 67 publications

(72 citation statements)

References 52 publications

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“…The patient-derived orthotopic xenograph (PDOX) model has been developed for melanoma in order to individualize chemotherapy for individual patients with advanced melanoma. For example, effective therapy was identified for melanoma with/without BRAF-V600 mutation (206)(207)(208)(209)(210)(211)(212).…”

Section: Effects Of Vitamin D On Melanoma Cells In Vitromentioning

confidence: 99%

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

2019

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Melanoma is one of the most lethal types of skin cancer, with a poor prognosis once the disease enters metastasis. The efficacy of currently available treatment schemes for advanced melanomas is low, expensive, and burdened by significant side-effects. Therefore, there is a need to develop new treatment options. Skin cells are able to activate vitamin D via classical and non-classical pathways. Vitamin D derivatives have anticancer properties which promote differentiation and inhibit proliferation. The role of systemic vitamin D in patients with melanoma is unclear as epidemiological studies are not definitive. In contrast, experimental data have clearly shown that vitamin D and its derivatives have anti-melanoma properties. Furthermore, molecular and clinicopathological studies have demonstrated a correlation between defects in vitamin D signaling and progression of melanoma and disease outcome. Therefore, adequate vitamin D signaling can play a role in the treatment of melanoma. Skin cells are able to activate vitamin D via classical and nonclassical metabolic pathways (1-9). Vitamin D derivatives have anticancer properties and promote differentiation and inhibit proliferation of various cells, including melanoma, the most aggressive and lethal type of skin cancer. In this review, we provide an overview on the endogenous synthesis and activation of vitamin D via classical and non-classical pathways. We also present the association of vitamin D and melanoma based on epidemiological, experimental and clinical evidence, showing that defects in vitamin D signaling correlate with progression of melanoma and disease outcome. Therefore, restoration of the adequate vitamin D signaling can play a role in melanoma therapy. 473 This article is freely accessible online.

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Section: Effects Of Vitamin D On Melanoma Cells In Vitromentioning

confidence: 99%

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

2019

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“…In previous studies, we established patient-derived orthotopic xenograft (PDOX) nude mouse model of BRAF V600E-mutant melanoma [8][9][10][11][12]. In this model, we determine the efficacy of rMETase in combination with a first-line melanoma drug, temozolomide (TEM) [11]. The combination therapy of TEM, first-line therapy, and rMETase was significantly more efficacious than either mono-therapy [11].…”

Section: Introductionmentioning

confidence: 99%

“…In this model, we determine the efficacy of rMETase in combination with a first-line melanoma drug, temozolomide (TEM) [11]. The combination therapy of TEM, first-line therapy, and rMETase was significantly more efficacious than either mono-therapy [11].…”

Section: Introductionmentioning

confidence: 99%

Targeting methionine with oral recombinant methioninase (o-rMETase) arrests a patient-derived orthotopic xenograft (PDOX) model of BRAF-V600E mutant melanoma: implications for chronic clinical cancer therapy and prevention

Kawaguchi

Han

et al. 2018

Cell Cycle

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The elevated methionine (MET) use by cancer cells is termed MET dependence and may be the only known general metabolic defect in cancer. Targeting MET by recombinant methioninase (rMETase) can arrest the growth of cancer cells in vitro and in vivo. We previously reported that rMETase, administrated by intra-peritoneal injection (ip-rMETase), could inhibit tumor growth in a patient-derived orthotopic xenograft (PDOX) model of a BRAF-V600E mutant melanoma. In the present study, we compared ip-rMETase and oral rMETase (o-rMETase) for efficacy on the melanoma PDOX. Melanoma PDOX nude mice were randomized into four groups of 5 mice each: untreated control; ip-rMETase (100 units, i.p., 14 consecutive days); o-rMETase (100 units, p.o., 14 consecutive days); o-rMETase+ip-rMETase (100 units, p.o.+100 units, i.p., 14 consecutive days). All treatments inhibited tumor growth on day 14 after treatment initiation, compared to untreated control (ip-rMETase, p<0.0001; o-rMETase, p<0.0001; o-rMETase+ip-rMETase, p<0.0001). o-rMETase was significantly more effective than ip-rMETase (p = 0.0086). o-rMETase+ip-rMETase was significantly more effective than either mono-therapy: ip-rMETase, p = 0.0005; or o-rMETase, p = 0.0367. The present study is the first demonstrating that o-rMETase is effective as an anticancer agent. The results of the present study indicate the potential of clinical development of o-rMETase as an agent for chronic cancer therapy and for cancer prevention and possibly for life extension since dietary MET reduction extends life span in many animal models.

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“…Recently, PDOX models of sarcoma (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64), cervical cancer (65-67) as well as melanoma (68)(69)(70)(71)(72)(73)(74) have also been developed.…”

Section: Patient-derived Orthotopic Xenograft (Pdox) Mouse Models Of mentioning

confidence: 99%

Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse Models of Cancer

Suetsugu

Shimizu

Saji

et al. 2018

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Abstract. The tumor microenvironment (TME) contains stromal cells in a complex interaction with cancer cells. This relationship has become better understood with the use of fluorescent proteins for in vivo imaging cancer-cell or stromal-cell targeting by potential therapeutics can be visualized. Color-coded imaging enabled the visualization of apparent fusion of cancer and stromal cells. Color-coded imaging is a powerful tool visualizing the interaction of cancer and stromal cells during cancer progression and treatment.In vivo imaging with fluorescent proteins was pioneered by our laboratories and has been particularly useful for studying tumor growth, invasion, cancer-cell trafficking, metastasis, angiogenesis, and other aspects of tumor progression (1-5). Multicolored proteins have allowed the color-coding of cancer cells growing in vivo such as between highly-and poorly-metastatic cells, cancer stem and non-stem cells, and gene transfer between cancer cells (3, 4,(6)(7)(8)(9)(10)(11)(12)(13).The present review focuses on color-coded imaging of cancer and stromal cells in the tumor microenvironment (TME).Transgenic nude mice expressing fluorescent proteins for colorcode imaging of the TME. The green fluorescent protein (GFP)-expressing athymic nude mouse was obtained by crossing nontransgenic nude mice with the transgenic C57/B6 GFP mouse in which the β-actin promoter drives GFP. In the adult GFP nude mice, most organs brightly expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, duodenum, and the entire digestive system from the tongue to the anus; the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The bared skeleton also highly expressed GFP (14).

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Combination treatment with recombinant methioninase enables temozolomide to arrest a BRAF V600E melanoma in a patient-derived orthotopic xenograft (PDOX) mouse model

Cited by 67 publications

References 52 publications

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Targeting methionine with oral recombinant methioninase (o-rMETase) arrests a patient-derived orthotopic xenograft (PDOX) model of BRAF-V600E mutant melanoma: implications for chronic clinical cancer therapy and prevention

Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse Models of Cancer

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