Studies of monkey complement: measurement of cynomolgus monkey CH50, ACH50, C4, C2 and C3

Abstract: Background: The cynomolgus monkey is commonly used as the recipient in transplantation experiments. However, study of the complement system of cynomolgus monkeys is lacking. In the present study, the complement system of cynomolgus monkeys was compared with that of humans, by checking hemolytic titers. Methods: Hemolytic titers of complement from cynomolgus monkeys were calculated using the same methods as are used in humans. The complement regulatory function of human decay accelerating factor (DAF, CD55) in cynomolgus monkey serum was next studied using erythrocytes from human DAF‐transgenic pigs. Results: The results indicated relatively high values, except for C4: CH50: 211.19 ± 42.78 units/ml, ACH50: 51.47 ± 12.43 units/ml, C4: 30 170 ± 14 300 SFU/ml C2: 33831 ± 7442 SFU/ml and C3: 93612 ± 30131 SFU/ml. Western blot experiments using antibodies for human complement components revealed similarities between the cynomolgus monkey and human complement systems. Human DAF inhibited pig erythrocyte lysis from approximately 60–70% to 17% in both human and cynomolgus monkey sera, indicating an almost identical complement regulatory function. Conclusion: The hemolytic titer of cynomolgus monkeys was greater than the titer measured in human serum. However, human DAF showed nearly the same complement regulatory function in both human and cynomolgus monkey sera.     

Depth of tumor invasion in locally advanced rectal cancer correlates with patients’ prognosis: The usefulness of elastic stain for its measurement

Purpose The relationship between the prognosis and the extent of colorectal carcinoma (CRC) is still unclear. As a simple parameter of the local invasion of CRC, we assessed the extent of tumor invasion beyond the outer border of the muscularis propria (MP). Methods We examined 147 cases of CRC using a slight modification of the procedure established by the Japanese Society for Cancer of the Colon and Rectum. For the statistical analysis, the patients were divided into two groups, namely, a “shallow” group and a “deep” group, using a specific cut-off value (COV). A multivariate analysis to identify independent prognostic factors was performed. Results Significant differences in the 5-year survival rate were observed between the “shallow” and “deep” groups in 39 cases of rectal carcinoma (COV 4 mm; 72.4% vs. 30.0%, hazard ratio = 3.204), but not observed in 147 cases of CRC. In addition, the outcome for patients with “deep” cancer in the lower rectum was markedly worse than that for patients with “shallow” cancer (COV 4 mm; 81.8% vs. 12.5%, hazard ratio = 5.371). Conclusions The depth of tumor invasion beyond the MP is thus considered to be an important prognostic factor for patients with T3/T4 rectal carcinoma, especially in the lower rectum. A careful follow-up is required for the patients with rectal carcinoma that has invaded more than 4 mm beyond the MP.     

Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations

Of 11 children with juvenile myelomonocytic leukemia (JMML) carrying RAS mutations (8 with NRAS mutations, 3 with KRAS2 mutations), 5 had a profound elevation in either or both the white blood cells and spleen size at diagnosis. Three patients had no or modest hepatosplenomegaly and mild leukocytosis at presentation but subsequently showed a marked increase in spleen size with or without hematologic exacerbation, for which nonintensive chemotherapy was initiated. The other three patients with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement has been observed during a 2- to 4-year follow up. In the third group, all hematopoietic cell lineages analyzed had the RAS mutations at the time of hematologic improvement, whereas DNA obtained from the nails had the wild type. Additionally, numbers of circulating granulocyte-macrophage progenitors were significantly reduced during the clinical course. Thus, some patients with JMML with specific RAS mutations may have spontaneously improving disease.     

Toll-like receptor 2 -196 to 174del polymorphism influences the susceptibility of Japanese people to gastric cancer

Toll like receptors (TLR) play important roles in the signaling of many pathogen-related molecules and endogenous proteins associated with immune activation. The –196 to –174del polymorphism affects the TLR2 gene and alters its promoter activity. We investigated the influence of the TLR2 –196 to –174del polymorphism on the occurrence of non-cardiac gastric cancer (NCGC) in a Japanese population. The study was carried out with 289 patients with NCGC, 309 non-cancer patients with abdominal discomfort and 146 healthy controls. The –196 to –174del TLR2 polymorphism was investigated using the allele-specific polymerase chain reaction method in all of the subjects. The –196 to –174del/del genotype of TLR2 showed a significantly higher frequency in NCGC patients than in healthy controls (adjusted odds ratio [OR] = 6.06; 95% confidence interval [CI] = 1.86–19.72). Similarly, the frequency of the –196 to –174del/del genotype was significantly higher among NCGC patients than in non-cancer patients (adjusted OR = 2.02; 95% CI = 1.22–3.34). The same genotype was associated with an increased risk of both intestinal (OR = 2.00, 95% CI = 1.12–3.60) and diffuse-type (OR = 2.05; 95% CI = 1.11–3.79) histopathology. There were no significant associations between TLR2 genotypes and tumor stage and anatomical location. Our data suggest that the –196 to –174del/del genotype of TLR2 may increase the risk of gastric cancer in the Japanese population. ( Cancer Sci 2007; 98: 1790–1794)     

Transcatheter arterial embolization for the continuous bleeding from duodenal carcinoma--a case report

We report a case of duodenal carcinoma with continuous bleeding that was successfully treated with transcatheter arterial embolization using gelatin sponge particles. The case was a woman in her 70's who had a curative surgical resection for sigmoid colon cancer with liver and lung metastases, hepatic arterial infusion chemotherapy and radiofrequency ablation for liver metastasis in the past. She was admitted to our hospital because of liver abscess and anemia. Upper gastrointestinal endoscopy revealed active bleeding from a duodenal tumor. The biopsy of the specimens was made and showed duodenal adenocarcinoma. The patient was considered to be inoperable because of the liver abscess and transcatheter arterial embolization of an anterior superior pancreaticoduodenal artery through an inferior pancreaticoduodenal artery was performed for the continuous bleeding from duodenal carcinoma not completely treated by endoscopic hemostasis or frequent transfusion. After the tumor embolization anemia was improved and partial response was obtained by systemic chemotherapy of mFOLFOX6. Transcatheter arterial embolization for a continuous bleeding from duodenal carcinoma is a feasible and effective method as a noninvasive therapy when it is unabled to be treated by surgical resection or endoscopic therapy.     

A case of multiple liver metastases from rectal cancer in poor performance status successfully treated with hepatic arterial infusion chemotherapy plus CPT-11

Hepatic arterial infusion (HAI) chemotherapy is one of the strategies for cases in poor performance status. This is a case report of multiple liver metastases from rectal cancer in poor performance status successfully treated with HAI plus CPT-11. A 59-year-old man who had rectal cancer, multiple liver metastases and para-aortic LN metastasis underwent a laparoscopic rectal anterior resection. He denied receiving postoperative chemotherapy and selected alternative therapy at another clinic. Four months later, he visited our hospital. His liver metastasis and performance status got worse, so HAI of 5-FU 1250 mg/m2 for 5-hour weekly (weekly high-dose 5-FU: WHF) was started at first. After 3 courses, his status improved, so systemic chemotherapy was added. HAI (WHF: 1000 mg/m2) plus CPT-11 (100 mg/m2) was effective, and liver metastases showed a significant reduction (PR) on abdominal CT. HAI plus CPT-11 was effective for a patient of the poor performance status with unresectable liver metastasis.     

The relationship between FDG uptake in PET scans and biological behavior in breast cancer

BACKGROUND: Positron emission tomography (PET) is a non-invasive imaging modality used in the diagnosis and staging of breast cancer. However, several factors can affect fluoro-deoxyglucose (FDG) uptake by a tumor. To clarify the parameters that most affect FDG accumulation in tumors, the relationship between standardized uptake values (SUVs) and clinicopathological factors and immunohistopathological analysis was investigated in breast cancer. MATERIAL AND METHODS: PET studies were performed preoperatively on 37 patients with breast carcinoma. SUVs were counted at one hour (early phase) and at two hours (delayed phase) after FDG injection. The relationships between SUVs and 13 clinical, pathological and immunohistchemical factors were studied. RESULTS: A significant association was found between FDG accumulation and early and delayed phase mitotic counts (p=0.0018 and 0.0010, respectively), Ki67 positive cell percentage (p=0.0098 and 0.0062, respectively), and nuclear grade (p=0.0232 and 0.0195, respectively). On the other hand, nodal status weakly correlated with the delayed phase (p=0.0907). However, other clinicopathological parameters and immunohistopathological status, which included tumor size, age, histology, estrogen receptor, progesterone receptor and Her2/neu overexpression, did not correlate significantly with FDG uptake. CONCLUSION: Mitotic count and Ki67 reflect cellular aggressiveness. These parameters were strongly correlated with tracer uptake. Thus our data suggested that the biological behavior of breast cancer is reflected in the variation of FDG uptake by the tumor. However, whether FDG uptake is a true prognostic and predictive factor remains to be confirmed in larger studies over an extended period of time.     

Use of the medical information on the internet by pregnant patients with a prenatal diagnosis of neonatal disease requiring surgery

Purpose  

The purpose of this study was to clarify the current status and the problems associated with using medical information on the internet during pregnancy in patients prenatally diagnosed with fetal abnormalities at a single Japanese institution.