[Induction chemotherapy with S-1/oxaliplatin prevented colostomy in a patient with advanced rectal cancer].

A 72-year-old woman was admitted to our hospital with bloody stools and constipation. She was diagnosed with advanced lower rectal cancer with multiple liver and pulmonary metastases. Because the rectal cancer was located 2 cm from the anal verge, we suggested she undergo an abdominoperineal resection(Miles operation), but she refused to undergo a colostomy. Then, 6 courses of chemotherapy with S-1/oxaliplatin(SOX)were administered, and the local tumor, liver metastases, and pulmonary metastases were all significantly decreased in size(reduction rate 60%). After chemotherapy, she chose to undergo low anterior resection(LAR), D2. Postoperative recovery was uneventful, and she currently has stable disease with adjuvant SOX chemotherapy. Induction SOX chemotherapy was considered to be useful for maintaining the quality of life(QOL) in a patient with advanced rectal cancer.

Cancer gene therapy using in vivo electroporation of Flt3-ligand.

Dendritic cells (DCs) are potent antigen-presenting cells which play pivotal roles in immunological response. The clinical application of DCs induced from peripheral monocytes in vitro has been initiated as a promising immuno-logical therapy against cancer. If the same type of immuno-stimulator could be achieved without in vitro manipulation, it might be very convenient in clinical settings. In this study, we performed systemic gene transfer of Flt3L using in vivo electroporation of Flt3L plasmid DNA (Flt3L-IVE) in pretibial muscles in order to determine the effects on DCs in situ. After Flt3L-IVE, Flt3L was detected in the serum for 10 days after IVE at significant levels. The peak concentration of 5326+/-920 pg/ml in the serum was observed 4 days after Flt3L-IVE. The number of DCs was significantly increased and showed highly co-stimulatory molecule expressions both in spleen and bone marrow after Flt3L-IVE compared to those of control groups. Immunohistochemical evaluation revealed that not only DCs but also CD8 and CD4 positive cells were significantly infiltrated into the local tumor site compared with those of control and remained in the tumor 21 days after a single Flt3L-IVE. However, anti-tumor effects of Flt3L-IVE were not significant in the MCA205 established tumor. Most of the tumor infiltrating DCs had immature phenotype. Only a small number of DCs in the peripheral areas had the mature phenotype. These results suggest that Flt3L gene transfer using in vivo electroporation could mobilize DCs into tumor site. Additional means to induce maturation of these DCs could have a positive impact on anti-tumor effects of this strategy.

Platelet factor 4 gene transfection into tumor cells inhibits angiogenesis, tumor growth and metastasis.

Tumor growth and metastasis depend on angiogenesis, which is triggered by a chemical signal from the tumor cells to resting endothelial cells which then enter into a phase of rapid growth. Platelet Factor 4 (PF4) inhibits endothelial proliferation in vitro and angiogenesis in vivo. PF4 also inhibits tumor growth, however, as with other angiogenesis inhibitors, sustained tumor growth inhibition requires prolonged exposure to the recombinant protein. In this study, Lewis lung carcinoma (LLH) cells were transfected with the human PF4 via mammalian expression vectors and the ability of the transfected cells to form tumors and metastasis in vivo was evaluated. To evaluate the tumor growth rate of PF4-transfected (LLH/PF4) or control (LLH/neo) cells in vivo, we injected LLH/PF4 or LLH/neo cells subcutaneously (s.c.) or intravenously (i.v.). In the s.c. assay, LLH/PF4 had no significant effect on tumor growth. Conversely, in the i.v. assay, PF4 significantly reduced the number of lung metastasis (p=0.019) and weight (p=0.056). The inhibition of lung metastasis suggests that PF4 may inhibit tumor-associated neovascularization, and may prevent the affinity of tumor cells for the normal lung tissue.

Dendritic cells might be one of key factors for eliciting antitumor effect by chemoimmunotherapy in vivo.

In this study, we demonstrated that chemoimmunotherapy using S-1, a novel oral fluoropyrimidine anticancer drug, combined with lentinan (LNT), a beta (1 --> 3) glucan, was effective in vivo, and we clarified the augmentation of the function of dendritic cells (DCs) in vivo and in vitro. The survival period of Colon-26-bearing mice treated with S-1 + LNT was significantly more prolonged than that of mice treated with S-1 alone (P < 0.05). On the other hand, LNT did not prolong the survival period when combined with S-1 in Colon-26-bearing athymic mice. The frequency of CD86+ DCs infiltrated into Colon-26 was increased in mice treated with S-1 + LNT, and splenic DCs harvested from mice treated with S-1 + LNT showed more potent T-cell proliferation activity than that of DCs from mice treated with S-1 alone (P < 0.05). Furthermore, the activity of cytotoxic T lymphocytes (CTLs) in splenocytes of S-1 + LNT-treated mice was specific and more potent than that of CTLs from mice treated with S-1 alone (P < 0.05). These results suggest that modulation of specific immunity with LNT has a significant role in enhanced antitumor effects through the modification of DC function. We demonstrated that DCs might play an important role in chemotherapy, and the combination therapy of S-1 and LNT presents a promising chemoimmunotherapy, which might lead to better survival for cancer patients.

Modification of endoscopic aspiration mucosectomy (EAM) for early gastric cancer: EAM with pre-cutting.

BACKGROUND/AIMS: We have performed endoscopic aspiration mucosectomy for early gastric cancer since June 1993. In order to increase the complete resection rate, it is necessary to place the cancer in the center of the resection field. To facilitate complete resection, a circular incision to guide aspiration mucosectomy was made with a cutting knife (pre-cutting) before endoscopic aspiration mucosectomy, a procedure that we call endoscopic aspiration mucosectomy, with pre-cutting. METHODOLOGY: Eleven patients who had undergone endoscopic aspiration mucosectomy with pre-cutting for early gastric cancer at our department were included in this study. All resected specimens were examined macroscopically and histopathologically to assess the curative potential of this modified method of mucosectomy. RESULTS: The resected specimens ranged from 22 to 28 mm (mean: 25 mm) in maximum diameter, while the tumors ranged from 10 to 18 mm (mean: 12 mm) in size. Each resected specimen had the tumor at its center. The resection rating was EA in 10 (90.9%) of the 11 lesions and EC in 1 lesion (9.1%). CONCLUSIONS: For curative endoscopic surgery, there is no dispute that complete resection is essential. Thus, endoscopic aspiration mucosectomy with pre-cutting should contribute to the cure of early gastric cancer.