Molecular recognition of a single-chain Fv antibody specific for GA-pyridine, an advanced glycation end-product (AGE), elucidated using biophysical techniques and synthetic antigen analogues.

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by non-enzymatic reaction between reducing-sugar and Arg/Lys in proteins and are involved in various diabetic complications. GA-pyridine is derived from glycolaldehyde and is one of the most cytotoxic AGEs. Here, we established a single-chain Fv (scFv) antibody against GA-pyridine, 73MuL9-scFv, and examined the details of its specificity and antigen recognition by using various techniques involving biophysics, chemical biology and structural biology. We also synthesized several compounds that differ slightly in regard to the position and number of GA-pyridine substituent groups, and revealed that GA-pyridine was specifically bound to 73MuL9-scFv. Thermodynamic analysis revealed that the association of GA-pyridine to 73MuL9-scFv was an exothermic and enthalpy driven reaction, and thus that the antigen recognition involved multiple specific interactions. Crystallographic analysis of the Fv fragment of 73MuL9-scFv revealed that several CH-π and hydrogen bond interactions took place between the Fv-fragment and GA-pyridine, which was consistent with the results of thermodynamic analysis. Further studies using 73MuL9-scFv as a tool to clarify the relevance of GA-pyridine to diabetic complications are warranted.

[A case of unresectable cardiac gastric cancer patient who maintained a long-term QOL with chemotherapy and detention of metallic stent].

A case was a 66-year-old man. He visited our hospital for dysphagia, abdominal distention and body weight loss. He was underwent gastro-endoscopy and made a diagnosis of the advanced cardiac gastric cancer. The early esophageal and gastric cancer also detected. Furthermore, computed tomography was performed and detected multiple liver and spleen, para-aortic lymph-node metastases and the ascites (suspected for dissemination). We decided that curative resection was impossible. Therefore, we performed an abdominal puncture to remove the ascites and combination chemotherapy with S-1 and docetaxel. The combination therapy was effective. The main tumor and multiple metastatic lesions were reduced. But after six months, a tumor marker was increased. The anticancer drug was changed to S-1 and CDDP. After eight months from the first-line chemotherapy started, the stenosis was appeared at esophago-gastric junction. We performed balloon dilation, and a metallic stent was detention with gastroscopy and radiography at stenotic lesion. He improved swallowing and discharged from hospital. After eleven months from the first-line chemotherapy started, he was died of increased liver metastases and peritonitis carcinomatousa.

[A case of recurrence gastric cancer patient who was post operated and multi drug chemotherapy was effective for administration of S-1 and docetaxel combination therapy].

Recently, chemotherapy against gastric cancer has been diversified with an appearance of new agents such as S-1, capecitabine, CPT-11, oxaliplatin, paclitaxel and docetaxel. But a prognosis of advanced or recurrent gastric cancer patient, who was failure of first- and second-line chemotherapy, was poor. We reported that a case of recurrence gastric cancer patient who was post operated and multi drug chemotherapy was effective for administration of S-1 and docetaxel combination therapy. A case was a 50-year-old man. He underwent distal gastrectomy and administered of multi anticancer drugs until about eight years after operation. But multi lung and liver and lymph-node metastases were appeared. We administered S-1 and docetaxel combination chemotherapy. After two courses, multi metastatic lesions were reduced in size, and tumor markers were decreased. The same combination therapy was administered for six courses, but metastatic lesions were increased again. At one hundred four months after the operation, he died in the palliative care unit.

[A case report of un-resectable pancreas body carcinoma successfully treated by chemoradiotherapy].

We report a case of unresectable pancreatic cancer who survived for 29 months after a successful treatment by concurrent chemo-radiotherapy by gemcitabine and systemic administration of gemcitabine. A 65-year-old woman who was diagnosed as unresectable pancreas body cancer received concurrent chemo (gemcitabine 800 mg/body/w) -radiotherapy (1.8x30 Gy) and systemic chemotherapy (gemcitabine 1,000 mg/body/w) at an outpatient clinic. Twenty nine months after the initial treatment, she was died of peritoneal dissemination. Recently, there are some reports of synergistic effect for combined treatment of gemcitabine and radiation. Clinical course of our case supports the synergistic effect of radiation and gemcitabine.

[The colon cancer patient with multiple hepatic metastases and peritoneal disseminations was treated by hepatic arterial infusion chemotherapy and resection of the metastatic peritoneal dissemination with successive systemic chemotherapy--a case report of the long term survivor].

A 33-year-old man, who underwent ileo-cecal resection and sigmoidectomy for concomitant cecal cancer and sigmoid colon cancer which was diagnosed during the emergent operation for the perforated acute appendicitis, suffered simultaneous multiple hepatic metastases. Postoperative hepatic aerial infusion chemotherapy with 5-FU was done (total dose 63 g), and the metastases were successfully disappeared (CR). Although 16-month passed from the operation, locoregional recurrence at the colorectal anastomosis and peritoneal dissemination were occurred. Aggressive resections of the recurrent sites (anterior resection of the rectum, ileum, ascending colon and other recurrent sites) and successive systemic administration of FOLFOX4(9-course), FOLFIRI (20-course) and capecitabine (15-course) were achieved. The patient survived for 4.5 years after the initial treatment.

[Four cases of recurrent esophageal cancer with tracheal invasion treated by a placement of tracheal stent].

Frequently advanced or recurrent esophageal cancer was invasive trachea and occurred with hemoptysis or dyspnea. Occasionally, these cases were treated by a placement of tracheal stent for hemostasis and an establishment of airway for life saving. We experimented the four cases of recurrent esophageal cancer with tracheal invasion treated by a placement of tracheal stent. These 4 cases were for patients treated with no prior chemotherapy (CRT) had a better prognosis and quality of life (QOL) than the patient with a placement of tracheal stent after CRT. Therefore, the patient without CRT was a good indication to a placement of tracheal stent. However, even if the patient of previously performed CRT, it was important and effective treatment that a placement of tracheal stent was avoided the state of lethal condition with dyspnea.