Expression and Prognostic Significance ofO 6-Methylguanine-DNA Methyltransferase in Hepatocellular, Gastric, and Breast Cancers

Background: O⁶-Methylguanine-DNA methyltransferase MGMT is an enzyme that repairs O⁶-methylguanine, a promutagenic DNA base damaged by endogenous and environmental alkylating agents. There are few reports that describe whether or not abnormal MGMT expression correlates with the prognosis in human solid cancers.Methods: The expression of MGMT was immunohistochemically evaluated in 60, 62, 105, and 46 paraffin-embedded samples from patients with curatively resected hepatocellular, gastric, colorectal, and breast cancers, respectively.Results: The expression of MGMT was a positive predictive factor for overall survival in hepatocellular P = .005 and gastric cancers P < .001 and for relapse-free survival in breast cancers P < .001. MGMT-positive gastric tumors n = 42 were correlated with the absence of serosal invasion P = .045, lymph node metastasis P = .006, intestinal type P = .018, and low pathological tumor, node, metastasis stage P < .001. All breast tumors that recurred locally after operation were MGMT negative P = .004. The clinicopathologic characteristics of colorectal cancers with respect to MGMT expression did not significantly differ.Conclusions: The expression of MGMT is a predictive prognostic marker in patients with hepatocellular, gastric, and breast cancers. These findings may help to establish therapeutic strategies for patients with these types of solid cancer.     

Inhibitory effect of SM-20550, an Na+/H+ exchange inhibitor, on accumulation of leukocytes in ischemia and reperfusion

The effect of an Na+/H+ exchange inhibitor, SM-20550, on the adhesion, emigration and accumulation of leukocytes was studied in ischemia and reperfusion injury models using rat mesenteric venules or rabbit heart. Anesthetized rats underwent occlusion of the superior mesenteric artery (20 min) followed by reperfusion (60 min). After ischemia and reperfusion, the numbers of adherent and emigrated leukocytes increased significantly. Bolus intravenous administration of SM-20550 reduced the numbers of adherent and emigrated leukocytes in a dose-dependent manner, with statistical significance at dosages >0.1 mg/kg. Anesthetized rabbits underwent occlusion of the coronary artery (30 min) followed by reperfusion (5 h). Intravenous administration of SM-20550 before ischemia significantly reduced the neutrophil accumulation in the area-at-risk by 46% and reduced the infarct size by 38%. These results suggest that the inhibitory effect of SM-20550 on the neutrophil accumulation could be one of the mechanisms by which this drug limits the severity of infarctions.     

Epidemiology of Visceral Mycoses: Analysis of Data in Annual of the Pathological Autopsy Cases in Japan

The data on visceral mycoses that had been reported in the Annual of the Pathological Autopsy Cases in Japan from 1969 to 1994 by the Japanese Society of Pathology were analyzed epidemiologically. The frequency of visceral mycoses among the annual total number of pathological autopsy cases increased noticeably from 1.60% in 1969 to a peak of 4.66% in 1990. Among them, the incidences of candidiasis and aspergillosis increased the most. After 1990, however, the frequency of visceral mycoses decreased gradually. Until 1989, the predominant causative agent was Candida, followed in order by Aspergillus and Cryptococcus. Although the rate of candidiasis decreased by degrees from 1990, the rate of aspergillosis increased up to and then surpassed that of candidiasis in 1991. Leukemia was the major disease underlying the visceral mycoses, followed by solid cancers and other blood and hematopoietic system diseases. Severe mycotic infection has increased over the reported 25-year period, from 6.6% of the total visceral mycosis cases in 1969 to 71% in 1994. The reasons for this decrease of candidiasis combined with an increase of aspergillosis or of severe mycotic infection might be that (i) nonsevere (not disseminated) infections were excluded from the case totals, since they have become controllable by antifungal drugs such as fluconazole, but (ii) the available antifungal drugs were not efficacious against severe infections such as pulmonary aspergillosis, and (iii) the number of patients living longer in an immunocompromised state had increased because of developments in chemotherapy and progress in medical care.     

Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. The individual target dosage on the basis of daily medical examination.     

Comparative survey on current status and the differences of treatment using modified FOLFOX6 regimen in patients with colorectal cancer in two general hospitals

We surveyed the current status and the differences of treatment of colorectal cancer using modified FOLFOX6 regimen, in two general hospitals, Sakai City Hospital (A hospital) and Takarazuka Municipal Hospital (B hospital) between April 2005 and November 2006, retrospectively. The numbers of examined patients were 33 and 17 in A and B hospitals, respectively. The grade of myelosuppression and peripheral neuropathy were evaluated according to Common Terminology Criteria for Adverse Events v 3.0(CTCAE v 3.0)and Neurotoxicity Criteria of DEBIOPHARM(DEB-NTC). The setting of dosage was differed in two hospitals. In A hospital, the dosages of oxaliplatin, 5-FU bolus and 5-FU continuous infusion were more than 90% of the standard one at first time, and were reduced with almost same degree in the appearance of adverse effects. On the other hand, in B hospital, the dosages of these drugs were reduced about 20% even at first administration and, especially, the dose of 5-FU bolus tended to be remarkable reduction. Of adverse events, the rates of the appearance of neutropenia more than grade 3 was 21.2% and 47.1%, in A and B hospitals, respectively. No difference in peripheral neuropathy was detected at both hospitals. In conclusion, the differences in these two hospitals were detected in the dosage setting and myelosuppression, not in non-hematological adverse effects.     

Identification of side population cells (stem-like cell population) in pediatric solid tumor cell lines

Purpose

Recent evidence has supported the cancer stem cell theory that cancer contains a small number of cancer stem cells (CSC) as a reservoir of cancer cells. Only the CSC, but not most of the remaining constituent cancer cells, are thought to be responsible for tumorigenesis, progression, and metastasis as well as cancer relapse, suggesting that the CSC should be targeted to eradicate the cancer. Side population (SP) cells isolated by fluorescence-activated cell sorting (FACS) using Hoechst dye are known to be enriched in stem cells in various normal tissues as well as cancers. The authors investigated whether such stem-like SP cells may exist in pediatric solid tumors (PSTs).

Materials and Methods

Sixteen pediatric tumor cell lines including 7 neuroblastomas, 4 rhabdomyosarcomas, and 5 Ewing's sarcomas were used for FACS analysis. Analysis of SP cells based on the exclusion of the DNA binding dye, Hoechst 33342, with and without verapamil using FACS was performed.

Results

One Ewing's sarcoma cell line did not show an SP fraction, and only a small fraction of SP cells (0.12%-14.6%) was detected in the other 15 cell lines. These SP cells were all sensitive to verapamil.

Conclusions

This study suggested that most PSTs would contain a small fraction of SP cells (possible stem-like population). Targeting the CSC will provide a novel treatment strategy to eradicate refractory PSTs.     

Volumetric computed tomography analysis for gastroduodenal and pancreaticoduodenal artery aneurysm formation: A retrospective single-center study

Gastroduodenal artery aneurysms (GDAA) and pancreaticoduodenal artery aneurysms (PDAA) are rare, have high rupture risks, and are located in the arcade between the celiac artery and the superior mesenteric artery. Pancreaticoduodenal artery aneurysms are associated with celiac artery stenosis, and it is hypothesized that these celiac lesions might contribute to the formation of aneurysms. In contrast, a few studies have reported an association between a gastroduodenal artery aneurysm and celiac lesions. This study aimed to investigate the potential differences between patients with gastroduodenal and pancreaticoduodenal artery aneurysms and better understand their pathogenesis.We selected patients with GDAA and PDAA who were admitted to our department between January 2010 and December 2020. Aortic wall volume, aortic wall calcification, and pancreaticoduodenal arcade volume of computed tomography images were calculated semi-manually using Horos 3.3.5.Eight GDAAs and 11 PDAAs were analyzed. Celiac lesions were found in all PDAA patients, with none in GDAA cases. Volumetry demonstrated that aortic wall volume and calcification were more prominent in the GDAA group than in the PDAA group (P = .026 and P = .049, respectively). The pancreaticoduodenal arcade volume was larger in the PDAA group (P = .002).In our study, celiac artery lesions were strongly correlated with PDAA. The volume of the pancreaticoduodenal arcade was larger in the PDAA group, and aortic wall volume and calcification were larger in the GDAA group.