Phase I clinical trial of 99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults.

Objective: Technetium etarfolatide ((99m)Tc-EF) is a radioactive diagnostic imaging agent that was developed to assess the expression of folate receptors in tumors. Administering folic acid prior to the administration of (99m)Tc-EF has been shown to improve SPECT images. Here, we conducted a phase I clinical trial to assess the safety, pharmacokinetics, and radiation dosimetry of (99m)Tc-EF injection following pre-administration of folic acid in healthy Japanese male adults.

Clinical relevance of the number of interleukin-17-producing CD 8+ T cells in patients with gastric cancer.

Purpose: There is accumulating evidence that inflammation is linked to cancer development and progression. Interleukin-17 (IL-17), an inflammatory cytokine, is produced by CD 8+ T cells (Tc17 cells); however, the specific role of Tc17 cells in tumor immunity against gastric cancer remains unclear.

Methods: The prevalence of Tc17 cells in both peripheral blood mononuclear cells and gastric tissue was evaluated by multicolor flow cytometry and the concentration of IL-17 in sera was quantitated by an enzyme-linked immunosorbent assay.

Acquired resistance to gemcitabine and cross-resistance in human pancreatic cancer clones.

The efficacy of gemcitabine (GEM), a standard treatment agent for pancreatic cancer, is insufficient because of primary or acquired resistance to this drug. Patients with tumors intrinsically sensitive to GEM gradually acquire resistance and require a shift to second agents, which are associated with the risk of cross-resistance. However, whether cross-resistance is actually present has long been disputed.

Pathogenic mutation of ALK2 inhibits induced pluripotent stem cell reprogramming and maintenance: mechanisms of reprogramming and strategy for drug identification.

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder characterized by progressive ossification of soft tissues. FOP is caused by mutations in activin receptor-like kinase 2 (ALK2) that cause its constitutive activation and result in dysregulation of BMP signaling. Here, we show that generation of induced pluripotent stem cells (iPSCs) from FOP-derived skin fibroblasts is repressed because of incomplete reprogramming and inhibition of iPSC maintenance.

Prevalence and clinical relevance of Th17 cells in patients with gastric cancer.

Background: Th17 cells have recently been identified as a distinct T helper (Th) lineage in a cancer animal model and in human cancers. Their specific role in tumor immunity is unclear. We, therefore, sought to evaluate the role of Th17 cells in gastric cancer.

Effect of a combination of S-1 and gemcitabine on cell cycle regulation in pancreatic cancer cell lines.

In a previous study, we showed that a combination of an oral fluoropyrimidine anticancer agent (S-1) and gemcitabine (GEM) had synergistic effects on cell growth and cell cycle arrest in the pancreatic cancer cell line MIA PaCa-2. Therefore, we conducted further mechanistic studies using the pancreatic cancer cell lines MIA PaCa-2 and SUIT-2. The combined effect of S-1 and GEM in SUIT-2 cells was evaluated using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the effects of S-1, GEM and S-1 plus GEM on cell cycle regulation were assessed using flow cytometry.

Retrospective analysis of prognostic outcome of gastric cancer in young patients.

Background: It has been suggested that gastric cancer in young patients has a worse prognosis than in older patients, but this is controversial. This retrospective investigation was undertaken to understand the clinicopathological features and identify the prognostic factors of gastric cancer in young patients.

Methods: Patients included in this study were those treated and followed up for gastric cancer from 1989 to 2005.

Serum interleukin-6 and -10 levels in patients with gastric cancer.

Background: Interleukin-6 (IL-6) is known to be a multifunctional cytokine and IL-10 is an immunosuppressive factor. Both have been reported to be related to the disease prognosis in some human solid tumors. In the present study, we evaluated the clinical significance of preoperative serum IL-6 and IL-10 levels as new tumor markers in patients with gastric cancer (GC).

Experimental study of combination therapy with S-1 against pancreatic cancer.

Purpose: To determine the most effective combination chemotherapy with S-1 against pancreatic cancer and to clarify the mechanism of synergy between S-1 and the partner drug.

Methods: We tested a combination of S-1 with the following antitumor drugs in an in vitro MTT assay against pancreatic cancer cell line MIA PaCa-2: gemcitabine (GEM), cisplatin (CDDP), irinotecan (CPT-11), mitomycin C, adriamycin, and paclitaxel. The efficacy of S-1, GEM, and a combination of S-1 and GEM was also tested in vivo by administering S-1 (10 mg/kg) orally to nude mice five times a week for 3 weeks, and GEM (100 mg/kg) intravenously every 2-3 days for a total of six times.

Clinicopathologic characteristics of gastric cancer patients who underwent noncurative gastrectomy with long-term survival.

Purpose: To demonstrate clinicopathologic characteristics of gastric cancer patients who underwent noncurative gastrectomy with long-term survival.

Methods: We retrospectively reviewed 202 advanced gastric cancer patients who underwent noncurative gastrectomy.

Results: The long-term survivors who survived for more than 3 years comprised four of 65 patients with a residual tumor in the peritoneum, one of 50 patients with a residual tumor from lymph node metastasis, three of 41 patients positive for the resected margin (M-factor) and 17 of 153 patients with free intraperitoneal cancer cells (Cy-factor).

Pharmacokinetics and postoperative analgesia of epidural tramadol: A prospective, pilot study.

Background: Tramadol, a centrally acting analgesic drug, can be administered via multiple routes and is generally well tolerated.

Objective: This study was designed to assess the pharmacokinetics of epidural tramadol administered preoperatively in Japanese patients undergoing upper abdominal surgery.

Method: Japanese patients who were scheduled to undergo upper abdominal surgery in The Kitasato Institute Hospital, Tokyo, Japan, were included.

Laparoscopic resection for malignant lymphoma of the ileum causing ileocecal intussusception.

A 22-year-old man was admitted with right lower abdominal pain. Colonoscopy revealed a ball-like tumor at the ileum. Abdominal sonography and computed tomography showed ileocecal intussusception.

Prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in patients with advanced gastric cancer.

Background And Objectives: To determine the prognostic significance of the ratio between metastatic and dissected lymph nodes (n ratio) in gastric cancer patients.

Methods: We retrospectively reviewed 777 advanced gastric cancer patients who had undergone curative gastrectomy at our hospital.

Results: The n ratio was significantly greater in cases with a large tumor, undifferentiated tumor, lymphatic vessel invasion, or blood vessel invasion.

[Experimental chemotherapy against human esophageal carcinoma xenografts with TS-1, cisplatin and docetaxel].

Three strains of human esophageal carcinoma xenografts established in our institution were tested against combination chemotherapy in vivo and in vitro. TS-1 plus cisplatin (CDDP) was shown to be an effective combination against two carcinoma strains of moderately-differentiated type. Determination of the thymidylate synthase (TS) demonstrated a higher inhibition of the enzyme by adding CDDP to 5-FU, suggesting biochemical modulation.

TZT-1027 elucidates antitumor activity through direct cytotoxicity and selective blockade of blood supply.

Background: TZT-1027 is a newly developed antitumor agent derived from dolastatin 10.

Materials And Methods: The in vitro activity of TZT-1027 on MCF-7 and R-27 cells was evaluated by MTT assay. TZT-1027 1 mg/kg/week was administered i.