CD36 (Naka) sensitization with platelet-transfusion refractoriness in a liver transplant recipient.
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Biomedical subjects
Publications and source records attributed to Takashi Ogata.
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We report a case of primary amelanotic malignant melanoma of the esophagus, an extremely rare disease. A 58-year-old man was diagnosed as having middle esophageal cancer with lymph node metastasis, which was classified as esophageal cancer, Stage III:T3N1M0, by International Union Against Cancer (UICC) criteria. Preoperative chemotherapy was performed, but the response assessment was no change (NC). The patient underwent a subtotal esophagectomy via right thoracotomy and laparotomy. Reconstruction was performed by pulling up the stomach via the retrosternal route; the site of anastomosis was the neck. Adjuvant chemotherapy consisted of five courses of dacarbazine (DITC), nimustine (ACNU), vincristine (VCR), and interferon-beta. Eleven months after the surgery, computed tomography (CT) demonstrated recurrence in the upper mediastinum. The patient received chemoendocrine therapy, consisting of the first planned course of DITC, ACNU, and cisplatin (CDDP), given intravenously; and tamoxifen (TAM), given orally. Subsequently with a modified regimen of this therapy he attained a complete response (CR). In general, the prognosis of esophageal malignant melanoma is very poor. Although our patient had a recurrence, he is alive 4 years and 5 months after the surgery and 3 years and 6 months after the recurrence. The chemoendocrine therapy probably contributed to this outcome.
BACKGROUND: It has been controversial whether HLA antibodies cause hemolytic transfusion reactions (HTR) or shortened red blood cell (RBC) survival. A patient is reported who had two episodes of HTR, the latter of which was likely due to RBC-reactive HLA antibodies. CASE REPORT: A 77-year-old woman, admitted for gastric varix rupture, had no RBC-irregular antibodies detected before transfusion. On Hospital Day 12, after transfusion of 2 units of RBCs and 2 units of fresh-frozen plasma, the first delayed hemolytic episode occurred and anti-E, anti-c, anti-Jk(a), and unidentified RBC-reactive antibodies were detected in a serum sample from Day 14. Two additional units of matched RBCs were transfused with a leukoreduction filter on Days 19 and 22. After 4 hours of starting a transfusion on Day 22, the patient had fever, and a second hemolytic episode was recorded. Multireactive HLA antibodies (reactive against 20 of 20 donor panel lymphocytes) were detected in serum samples from Day 15 to Day 21. These HLA antibodies reacted strongly with HLA-A2 and HLA-B7 antigens, corresponding to Bg(c) and Bg(a) antigens on RBCs, respectively. RBCs transfused on Day 22 were found to be HLA-A2 by genotyping. CONCLUSION: Strong HLA alloantibodies in this recipient appear to have caused a HTR. It is suggested that HLA antibodies be considered in patients with unexplained HTRs.
DC (dendritic cells) vaccine therapy against cancer has attracted attention in recent years. However, the existence of the immunosuppressive state in cancer individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and DC migration to the target organ. It has been reported that injected intra-tumor DC is expected to work phagocytosis of the tumor as a localized effect, the consequent CTL induction in the tumor and the regional lymphnodes, resulting in a systemic effect. Two cases reported in this article were performed with intra-tumor DC injection therapy by means of EUS (endoscopic ultrasonography) which indicated interesting immunoreaction.
A 62-year-old man was revealed to have type 2 gastric cancer with synchronous liver metastasis. We considered liver metastasis to be a prognostic factor, and performed two courses of combination thermochemotherapy consisting of hepatic arterial infusion of MMC and TS-1 and thermotherapy. Partial response was observed in the liver metastases,but the primary lesion showed no changes; therefore, we performed four courses of combination thermochemotherapy consisting of TS-1/CDDP therapy and thermotherapy. By the end of three courses of this therapy,the primary lesion had cicatrized,and endoscopic biopsy revealed no cancer cells. These results suggest that gastric cancer,in which liver metastasis is considered to be a prognostic factor,can be effectively treated by combination therapy with hepatic arterial infusion therapy, followed by thermochemotherapy for the primary lesion.
This study evaluated a newly developed polyolefin bag, which has a 50%/m(2) higher oxygen permeability to extend the shelf-life of platelets. Single-donor aphaeresis platelets were pooled, separated equally into two bags, PO-80 (0.8 l capacity) and KBP-PO (1 l capacity) for control, and stored in plasma for up to 7 d. Platelet biochemical and functional parameters were monitored in bags containing high (4.2 x 10(11)/250 ml/bag, n = 9) and low (2.0 x 10(11)/200 ml/bag, n = 3) concentrations of platelets over the storage period. After 7 d of storage, the PO-80 bags containing high concentrations of platelets had a better pH (mean pH 6.74) than those stored in KBP-PO (pH 6.32, P < 0.01); none of the nine PO-80 bags with a high platelet concentration had a pH below 6.2, compared with four of nine controls (P < 0.05). Similarly, lactate values were 20.19 mmol/l and 28.09 mmol/l respectively (P < 0.05). Aerobic metabolism was maintained better with greater O(2) consumption and less lactate generation in high-platelet concentration PO-80 bags than in the control bags. A significant difference was also found in pH, pCO(2) and lactate levels between the two bags containing low concentrations of platelets during the 7-d period. The in vitro characteristics of platelets declined less over 7 d when stored in a higher oxygen permeable container than in a marketed bag.
This study was designed to seek for the optimal anticancer agents for a combination of chemotherapy and specific immunotherapy using dendritic cells (DC) in gastric cancer. We investigated the immuno-suppressive activity of anticancer agents on human peripheral blood mononuclear cells (PBMC), apoptosis inducing activity on gastric cancer cells and expression of Toll-like receptor (TLR)-4 mRNA on immatureDCs (iDCs) by paclitaxel (TXL) and docetaxel (TXT). We further compared the cytotoxicity of cytotixic T lymphocytes (CTLs) induced by DCs pulsed with tumor cell lysate and apoptotic cells induced by TXT. Although most of the anticancer agents demonstrated the suppression activity on proliferation of PBMC in a dose dependent manner, TXT, doxifluridine and irinotecan did not show the suppressive activity on PBMC even in the highest drug concentration. About 60% of gastric cancer cells demonstrated apoptosis after a 24-48 hour treatment with both TXL and TXT. Expression of TLR-4 mRNA in iDCs was up-regulated by TXT, not by TXL, and peaked at 2 hours after the treatment. CTLs induced by DCs pulsed with tumor cell lysate and apoptotic cells showed a similar killing activity to target cells. These results suggest that TXT appears to be an optimal anticancer agent for a combination therapy with chemotherapy and tumor specific immunotherapy using dendritic cells in gastric cancer.
Dendritic cells (DC) are powerful antigen-presenting cells, and have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of an immunosuppressive state in cancer individuals leads to anergy and failure in cytotoxic T cell (CTL) induction and DC migration to the target organ. It has been reported that injected intra-tumor DCs are expected to work phagocytosis of the tumor as a localized effect. Consequently CTL induction in the tumor and the regional lymphnodes results in a systemic effect. In this study, intra-tumor DC injection therapy was performed by means of endoscopic ultrasonography (EUS) in 2 gastric cancer cases. As a result, tumor markers and ascites of one case were on the decrease. The results indicate this method can be useful in advanced cancer patients.
BACKGROUND: Efficient collection of progenitor cells is essential for PBPC transplantation. Two apheresis machines (Amicus, Baxter Healthcare; and Spectra, Gambro BCT, software version 4.7) were compared prospectively by a crossover trial. STUDY DESIGN AND METHODS: Apheresis collections were performed for two consecutive days on patients for autologous and donors for allogeneic PBPC transplantation. The patients and donors, receiving a G-CSF, were randomized into two groups. In Group I, PBPCs were collected by the Amicus on the 1st day and the Spectra on the 2nd day, and the reverse order was used with Group II. A total of 60 apheresis procedures of 30 (16 in Group I and 14 in Group II) among 40 patients and donors enrolled were performed and evaluated. RESULTS: The nucleated cell counts, MNC counts, CD34+ PBPC counts, and amounts of CFU-GM collected per procedure were similar with the Amicus and the Spectra. On the other hand, the decrease of peripheral blood platelet counts of patients and donors was more prominent from using Spectra than Amicus (p < 0.0001). Components collected by the Amicus had fewer platelets than those collected by the Spectra (p < 0.0001). The efficiencies of collecting nucleated cells, MNCs, and CD34+ PBPCs were not different between the machines (p > 0.05). However, the efficiency of collecting platelets was significantly higher with Spectra than with Amicus (p < 0.0001). The Amicus took longer than the Spectra to process the same volume (p < 0.05). CONCLUSION: Amicus is superior to Spectra in avoiding apheresis-induced thrombocytopenia caused by platelets contaminating the collected samples. Therefore, the Amicus is useful for patients with thrombocytopenia or with a less-than-normal platelet count.
Dendritic cells (DC) are powerful antigen-presenting cells, and have attracted attention in recent years from the viewpoint of DC vaccine therapy against cancer. However, the existence of an immunosuppressive state in cancer individuals leads to anergy and immunotolerance, which has been reported to be caused by T cell and DC immunosuppressive subsets or cytokines such as Th2, Tc2, CD4+CD25+, DC2 and IL-10 against Th1, Tc1, DC1 and IL-12. Therefore, DC therapy could be incompatible with severe chemotherapy. Conversely, there are some reports that indicate tumor specific cytotoxicity in DC therapy could be augmentedly un exposure to tumor antigen caused by apoptosis in combination radiation or chemotherapy. In this study we examined the usefulness of DC therapy combined with chemotherapy and BRM (PSK) administration by analyzing the immunocyte subsets and cytokines as well as the combination effect. The results indicate this method can be useful in advanced cancer patients.
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BACKGROUND: Vaccine therapy targeting tumor antigens recognized by cytotoxic T cells (CTL) has been tried extensively. However, in a cancer-bearing state, the Th1/Th2 balance shifts to Th2 dominance, and this has been the obstacle to vaccine therapy to induce the CTL. DC1/DC2 subsets have also been reported to control the differentiation of Th subsets. The key to tumor immunotherapy is how to activate the DC1-Th1 lineage. PATIENTS AND METHODS: Six normal adults and 14 patients with gastric or colorectal cancers, who gave informed consent, were studied. The Th1/Th2 and DC1/DC2 ratios were determined by FACS. IL-12 and IL-10 production from PBMC were measured by ELISA. RESULTS: The Th1/Th2 and DC1/DC2 ratios were all significantly lower in the patients with gastric or colorectal cancers compared to normal adults. After protein-bound polysaccharide K (PSK) therapy in cancer patients, the Th1/Th2 balance shifted to Th1 dominance and the DC1/DC2 balance to DC1 dominance. IL-10 production was significantly decreased by PSK therapy. CONCLUSION: In the cancer-bearing state, the Th1/Th2 and DC/1/DC2 balance becomes Th2- and DC2-dominant. PSK therapy results in a shift of the Th1/Th2 and DC1/DC2 balance towards Th1 and DC1 dominance. We plan to examine whether combining dendritic cells (DC) vaccination therapy with oral PSK enhances the induction of T cell and DC differentiation in cancer patients.