The ECAS system can superselectively administer anticancer drugs to numerous feeding arteries from the superficial temporal artery: A case report and literature review.

Superselective intra-arterial chemoradiotherapy (SSIACRT) is one of the curative treatments for advanced oral cancer. SSIACRT can reportedly treat cervical lymph node metastases in the level I-IIA area by super selectively catheterizing the facial artery (FA) and infusing drugs. However, since advanced oral cancer lesions involve a number of feeding vessels, retrograde treatment requires the placement of catheters from the superficial temporal artery (STA) and occipital artery (OA). Furthermore, in the case of level IIB lymph node metastasis, the catheter must be changed because it is necessary to administer anticancer drugs to more than three routes, including the OA, when the feeding arteries of the primary tumor are combined. The external carotid artery sheath (ECAS) system used in the present study involves the insertion of a microcatheter or steering catheter from one route of the STA, allowing selection of numerous feeding vessels, including the OA. The ECAS system can facilitate the administration of chemotherapy via the STA simultaneously to the maxillary artery, lingual artery, FA and OA. The present study describes cases of maxillary gingival cancer and tongue cancer with cervical lymph node metastasis, which were treated with the ECAS system via the STA; the treatment successfully controlled both the primary tumor and cervical lymph node metastasis. In the two cases described in the present study, metastatic lymph nodes were found in the level ⅠB and ⅡB region, but were successfully treated by administering cisplatin via the OA, in addition to the primary lesion. To date, to the best of our knowledge, there is no case report clearly referring to the treatment of lymph node metastasis using the ECAS system. In conclusion, SSIACRT using ECAS may be considered a useful treatment for oral cancer with cervical lymph node metastasis.

An In Vivo Study of Local Administration of Low-dose Anti-PD-1 Antibody Using an Oral Cancer Cell Line.

BACKGROUND/AIM: The immunotherapy approach using anti-programmed cell death 1 (PD-1) antibody has been demonstrated in oral cancer treatment. However, serious immune-related adverse events (irAE) have been reported. If local administration of small doses of anti-PD-1 antibody via intraarterial chemoradiotherapy could have the same antitumor effect of systemic administration, this can reduce irAE and medical expenses. In this study, we investigate the antitumor effects of local and systemic administration of a small amount of anti-PD-1 antibody, the overall survival (OS), and the immune environment around cancer. MATERIALS AND METHODS: A mouse buccal mucosal oral squamous cell carcinoma cell line (Sq-1979) was used, and anti-mouse PD-1 was used as the drug. The cell line was transplanted to mouse, and the drug was locally (30 mg/body) and systemically (300 mg/body) administered in a dose. The tumor shrinkage rate and antitumor effect were examined 21 and 29 days after the start of administration. The OS was also compared in each of the groups. Furthermore, the subcutaneous growth of the tumors was inhibited, and the expressions of PD-L1, CD8T cells, perforin, and granzyme B were examined. RESULTS: We found that the local low-dose and systemic groups had the same antitumor effect, OS also showed a significant prolongation. In addition, indicated that the expression of granzyme B was higher in the local low-dose group. CONCLUSION: Local low-dose administration of anti-PD-1 antibody showed the same antitumor effect and OS as systemic normal-dose administration. Therefore, local low-dose administration in oral cancer can be useful.

Study of the Acquisition of Sensitivity to Paclitaxel Plus Cetuximab by the Addition of Low-dose Proteasome Inhibitor.

BACKGROUND/AIM: Although paclitaxel plus cetuximab for recurrent/metastatic oral squamous cell carcinoma (OSCC) has a relatively high success rate, many cases are refractory. We investigated the change in nuclear factor-kappa B (NF-B) expression after this combination therapy using microcollagen 3D cell culture. We also investigated changes in antitumor efficacy using low doses of paclitaxel-cetuximab combined with the proteasome inhibitor bortezomib on a cell line with low sensitivity to paclitaxel plus cetuximab. MATERIALS AND METHODS: Eight human OSCC cell lines were cultured in 3D and exposed to paclitaxel-cetuximab. real-time polymerase chain reaction was used to evaluate NF-B mRNA expression in OSCC cell lines in vivo and in vitro after exposure to anticancer agents. Activity at the protein level was confirmed using western blotting. Bortezomib (0.002-0.4 µg/ml) was added to paclitaxel-cetuximab and its effects assessed in OSCC cell lines with low paclitaxel-cetuximab sensitivity. RESULTS: mRNA and protein expression of NF-B was significantly reduced after treatment with paclitaxel-cetuximab in cell lines sensitive to this combination. In contrast, both mRNA and protein expression significantly increased in the cell lines with low sensitivity to paclitaxel plus cetuximab. The addition of low concentrations of bortezomib to cell lines with low sensitivity to paclitaxel-cetuximab was found to enhance antitumor efficacy. CONCLUSION: Increased NF-B expression strongly contributes to resistance to paclitaxel-cetuximab, suggesting that the administration of small doses of bortezomib, which inhibits NF-B, combined with paclitaxel-cetuximab may enhance antitumor efficacy against cancer cells with low sensitivity to the combination therapy.

PTEN Is Activated by the Addition of Cetuximab to Paclitaxel in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: The mechanisms through which cetuximab (cMab) coadministration with paclitaxel (PTX) enhances antitumor efficacy remain unclear. We examined the mechanism of the antitumor enhancing effect of cMab by determining changes in gene expression in the PI3K-AKT pathway. MATERIALS AND METHODS: Eight human oral squamous cell carcinoma (OSCC) cell lines were cultured three-dimensionally and exposed to PTX + cMab. The expression levels of PTEN mRNA in OSCC cell lines after anticancer drug treatment were assessed using real-time PCR. PTEN mRNA expression levels were also confirmed after administration of PTX + cMab in vivo. Western blot analysis was used to confirm the results at the protein level. RESULTS: PTEN mRNA and protein expression were significantly increased only in the cell lines with high sensitivity to PTX + cMab, and similar results were observed in vivo. CONCLUSION: PTEN activation may enhance the antitumor effect of PTX + cMab.

Optimal Contact Concentration of Paclitaxel in the Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test for Human Oral Squamous Cell Carcinoma and Evaluation of Combination with Cetuximab.

OBJECTIVE: A combination of the taxane anticancer drug paclitaxel (PTX) and molecular target drug cetuximab (cMab) is effective for the treatment of head and neck squamous cell carcinoma (HNSCC). However, its use is associated with serious side effects, such as neuropathy and myelosuppression. In addition, it is administered regardless of patient sensitivity because biomarkers indicating its efficacy are unavailable. Therefore, we investigated the usefulness of setting the indicated contact concentration of PTX and predicted the antitumor effect of combined contact with cMab using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). METHOD: Twelve human oral squamous cell carcinoma (OSCC) cell lines (i.e., SAS, HSC-2, HSC-3, HSC-4, OSC-19, OSC-20, KON, HO-1-N-1, HO-1-u-1, SAT, SCC-4, and Nialym) were used. Using the CD-DST, we calculated the optimal contact concentration of the cells with PTX based on the clinical response rate of HNSCC and evaluated the combined contact with cMab. Furthermore, nude mice were treated with standalone PTX and PTX + cMab, and the results were compared with those of the CD-DST. RESULTS: Based on the CD-DST, 0.1 µg/mL was the optimal contact concentration of PTX, to which the cells showed dose-dependent sensitivity. Moreover, the CD-DST method was used to evaluate the antitumor effects on OSCC even when PTX was used in combination with cMab. The antitumor effects in the CD-DST and nude mice were correlated (p < 0.05). CONCLUSION: The CD-DST results suggested that it was possible to predict the clinical effects of single-contact PTX and the enhancing effect of cMab + PTX.