Mutsumi Nozue

Impaired Proliferative Response of Vα24 NKT Cells from Cancer Patients Against α-Galactosylceramide

Human invariant Vα24+ NKT cells are a relatively new subpopulation of lymphocytes. It has been reported that Vα24 NKT cells are significantly involved in some human diseases. We have evaluated the number and function of Vα24 NKT cells in both healthy volunteers and cancer patients. In this study we found that Vα24 NKT cells in unfractionated PBMCs obtained from cancer patients did not respond efficiently to α-galactosylceramide (α-GalCer) in vitro. Thus, their proportion after stimulation with α-GalCer was smaller than that found in healthy volunteers. However, the cancer patients’ Vα24 NKT cells retained cytotoxic activity against malignant target cells, and they could efficiently proliferate to α-GalCer when fractionated by sorting. Furthermore, we found that addition of G-CSF to the culture could restore the low proliferative response of Vα24 NKT cells from cancer patients. These results suggest that some functions of NKT cells in cancer patients are impaired, and this observation carries significant implications for immunotherapy-based cancer treatments.

NATURAL HISTORY OF A SPONTANEOUS DISSECTING ANEURYSM OF THE PROXIMAL SUPERIOR MESENTERIC ARTERY : REPORT OF A CASE

We report herein the case of a 44-year-old man in whom an asymptomatic dissecting aneurysm was found in the proximal part of the superior mesenteric artery (SMA) during a preoperative evaluation for colon cancer. The patient was managed conservatively with blood pressure control during the perioperative period of the colon resection as the false lumen of the dissecting aneurysm was revealed to be completely occluded by thrombus. The thrombus in the false lumen continued to be absorbed until 1 month after surgery. The patient is currently well 4 years after his operation without any evidence of recurrence of the aneurysm.

Expression of costimulatory molecules, B7-1 and B7-2 on human gastric carcinoma.

Abstract Costimulation of T cells via B7-1 and B7-2 molecules on a tumor has been shown to be important for eliciting cell-mediated antitumor immunity. We studied the surface expression of B7-1 and B7-2 in 24 cases of gastric carcinoma from the primary locus, 20 cases of metastatic carcinoma from malignant ascites, 20 cases of benign gastric mucosa and 7 gastric carcinoma cell lines by two-color flow cytometry with mAb CD80 and CD86. The B7-1 and B7-2 molecules were expressed by 6 cell lines, and 1 cell line showed the predominant expression of B7-2 but not B7-1. Almost all patients with primary gastric carcinoma and benign gastric mucosa showed high levels of expression of the B7-1 and B7-2, revealing approximately 40%–60% positive cells. However, the percentage of B7-1-positive cells of poorly differentiated primary carcinomas was significantly lower than that of well-differentiated carcinoma and normal mucosa (P<0.01). Furthermore, all of the metastatic carcinoma cells revealed consistently very low or undetectable levels of expression of the B7-1 molecule, only 8% (mean) of cells being positive, despite showing higher levels of B7-2 expression. Thus, it seems likely that decreased or deleted expression of B7-1 correlates with the grade of tumor differentiation, tumor progression and metastasis. These results suggest that the B7-1 molecule on the gastric carcinoma bearing CD80+CD86+ is abrogated during tumor invasion and/or metastasis, and the tumor finally acquires the CD80−CD86+ phenotype. Consequently, inadequate B7-1 costimulation may contribute to the escape of tumors from destruction by the hosts immune system.

Incarcerated Paraesophageal Hernia Associated with Perforation of the Fundus of the Stomach: Report of a Case

Abstract We report herein a case of incarcerated paraesophageal hernia associated with perforation of the fundus of the stomach. A 71-year-old woman was transferred to our hospital after a diagnosis of gastrointestinal tract perforation had been made at a local hospital. Her history included an esophageal hiatal hernia. A laparotomy was performed which revealed that the antrum of stomach and the duodenal bulb had prolapsed into the esophageal hiatus and become incarcerated. This prolapse had caused stenosis in the corpus of the stomach, resulting in distension of the oral side of the stomach and thinning of the wall. A perforation, 15 mm long, was recognized in the major curvature of the fundus. The patient suffered respiratory failure postoperatively, necessitating respiratory support for 1 week. She was discharged on postoperative day 40. This case report serves to demonstrate that because of the very serious complications that may result from an untreated paraesophageal hernia, elective repair should be performed wherever possible even in asymptomatic patients.

E-cadherin expression in the primary tumors and metastatic lymph nodes of poorly differentiated types of rectal cancer.

AbstractPurpose. Dysfunction of E-cadherin, a cell–cell adhesion molecule, correlates with the grade of dedifferentiation and/or invasiveness of rectal cancer. However, the relationship between E-cadherin expression in the primary tumor and the potential for metastasis has never been reported. Methods. E-cadherin expression in 43 primary rectal cancer, including 10 poorly differentiated type, and their associated metastatic lymph nodes (LN mets.) were immunohisto-chemically evaluated. Results. Heterogeneous immunostaining, suggestive of damage to the E-cadherin-mediated cell–cell adhesion system, was seen in 13 of the 28 LN mets positive primary lesions, but in 0 of the 15 LN mets negative primaries. Furthermore, the incidence of heterogeneous immunostaining differed significantly between poorly differentiated and differentiated cancers, being seen in 8 of 10 cases and 5 of 33 cases, respectively (P = 0.0003 by Fishers exact test). Interestingly, most of the LN mets. foci (25 of 28 cases) showed homogeneous staining regardless of the E-cadherin staining pattern of the primary lesion. Conclusion. Heterogeneous immunostaining of E-cadherin in poorly differentiated rectal cancer was associated with lymph node metastasis. Its staining pattern in metastatic lymph nodes were, however, generally homogenous.

Correlation among lung damage after radiation, amount of lipid peroxides, and antioxidant enzyme activities

The correlation between lipid peroxidation and morphologic changes was examined in Sprague-Dawley rat lungs after 30 Gy single thoracic radiation. The rats were sacrificed every week until the end of the fifth week after radiation. The left lungs were used for the measurement of lipid peroxides and antioxidant enzymes activities. The right lungs were examined by light and electron microscopy. Amounts of lung lipid peroxides were within normal limits, and no cellular degenerative changes were observed in the lungs except for subendothelial and interstitial edema 2 weeks after radiation. Lipid peroxides drastically increased and marked degenerative cellular changes such as edematous swelling, vacuolation, and destruction of cell membranes occurred in the alveolar septa following the third week after radiation. The activities of catalase were significantly higher during the period from the second to the fifth week and those of superoxide dismutase and glutathione peroxidase increased at the end of the fifth week. Our results demonstrated that the acceleration of lipid peroxidation was well correlated with the morphologic expression of cell injury in the irradiated lungs.

Ulcerative colitis associated with Weber-Christian panniculitis and musculitis: A case report

A case of 22-year-old man suffering from ulcerative colitis, in whom Weber-Christian panni culitis and musculitis occurred simultaneously, is reported. He had suffered from ulcerative colitis for 7 years and he again had bloody stools 1 month before being admitted. Two weeks before admission, large (2–4cm) subcutaneous tumors appeared. Weber-Christian panniculitis, musculitis, and active stage ulcerative colitis were diagnosed. All the symptoms went into remission after steroid therapy. The possibility of the existence of a common antigen in enterobacterial wall, colonic epithelium, and adipose tissue was suggested.

Microsatellite Instability and Frameshift Mutations in the Bax Gene in Hereditary Nonpolyposis Colorectal Carcinoma

We studied microsatellite instability (MI) and bax gene abnormalities in colorectal carcinomas from 36 patients diagnosed as having hereditary nonpolyposis colorectal cancers (HNPCC) according to the clinical criteria (12 with confirmed HNPCC in group A and 24 at high risk of HNPCC in group B) and from 20 randomly selected patients with other colorectal cancers. MI was examined at 4 dinucleotide microsatellite loci and one mononucleotide locus. Frameshift mutations in the bax gene were detected by polymerase chain reaction‐single strand conformation polymorphism analysis. MI was detected in 7 of the 12 patients in group A and 12 of the 24 in group B. Three MI patterns were identified: type 1, MI in both mono‐ and dinucleotide repeats; type 2, MI only in mononucleotide repeats and type 3, MI only in dinucleotide repeats. Most MI‐positive patients in group A showed type 1 MI, whereas in group B, 5 showed type 1, 3 showed type 2 and 4 showed type 3. Frameshift mutations in the bax gene correlated strongly with type 1 and type 2 MI. These results indicate that mutations of different DNA mismatch repair genes may cause several types of MI and result in several different clinical phenotypes of HNPCC. The bax gene may be one of the target genes which play a role in the tumorigenesis of HNPCC.

Selection of three out of 24 anti-cancer agents in poorly-differentiated gastric cancer cell lines, evaluated by the AUC/delta IC50 ratio.

The purpose of this study was to screen 24 anti-cancer drugs, either in use or in clinical study, using four cell lines, all of which originated from poorly-differentiated gastric cancers. The MTT assay was used at 1, 6, 24 or 72 h exposure times as the chemosensitivity test. We also examined P-glycoprotein expression, mdr-1 gene amplification and the modifier effect of verapamil. All four cell lines generally showed the same chemosensitivity pattern, while GCIY cells showed mdr-1 gene amplification and P-glycoprotein expression, and KATOIII cells showed the multidrug resistant pattern without P-glycoprotein expression. Both cell lines acquired higher chemosensitivity after verapamil addition. All IC50 data (with or without verapamil) were multiplied by exposure time (AIC50) and compared with the clinical ‘area under the concentration curve (AUC)’. SN-38 with/without verapamil, cisplatin with verapamil and pirarubicin with/without verapamil seemed to be the best candidates for poorly-differentiated gastric cancer chemotherapy. Plant alkaloids could also be candidates. With further experiments, we may be able to deduce commonly effective chemotherapy for poorly-differentiated gastric cancer from these drugs.