Colorectal Carcinoma with Extremely Low CA19-9

Aim. The aim of this study is to determine the significance of postoperative sequential measurements of serum CA19-9 in patients with extremely low serum level. Patients and Methods. Serum level of CA19-9 of 1096 patients who underwent surgery was measured preoperatively and every three months after surgery for 5 years. Patients with CA19-9 level of less than 2 U/mL at the time of diagnosis were defined as Extremely Low CA19-9 (ELCA). Results. One hundred and seven patients (9.8%) were ELCA. Of these, 86 underwent surgery with curative intent. Serum levels of CA19-9 in patients who did not undergo curative resection (N = 12) and who developed recurrence (N = 10) were less than 2.0 U/mL in all occasions during followup. In all patients without recurrence, serum level of CA19-9 also remained less than 2.0 U/mL. Conclusion. In patients with extremely low CA19-9, who consist of 9.8% of colorectal carcinoma cases, postoperative sequential measurement of serum level of CA19-9 contributed neither to assessment of curability of surgical resection nor to detection of recurrence

Acute Pancreatitis Secondary to Duodenoduodenal Intussusception in Duodenal Adenoma

Duodenoduodenal intussusception is a rare condition that is in general caused by a tumor. We describe duodenoduodenal intussusception secondary to a tubulovillous adenoma that caused acute pancreatitis in a 31-year-old female. We resected a duodenal tumor from the submucosal layer and then simply closed the duodenal wall. To the best of our knowledge, this is the first description of acute pancreatitis secondary to duodenoduodenal intussusception by tubulovillous adenoma in the second part of the duodenum in an adult

Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites

The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism

DNA Methylation Profiles of Primary Colorectal Carcinoma and Matched Liver Metastasis

BACKGROUND: The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear. METHODS: We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers. RESULTS: Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency. CONCLUSIONS: Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis

Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer

Gastric cancer cells often show altered Ras signaling, though the underlying molecular mechanism is not fully understood. We examined the expression profile of eight ras-association domain family (RASSF) genes plus MST1/2 and found that RASSF2A is the most frequently downregulated in gastric cancer. RASSF2A was completely silenced in 6 of 10 gastric cancer cell lines as a result of promoter methylation, and expression was restored by treating the cells with 5-aza-2′-deoxycytidine. Introduction of RASSF2A into non-expressing cell lines suppressed colony formation and induced apoptosis. These effects were associated with the cytoplasmic localization of RASSF2A and morphological changes to the cells. Complementary DNA microarray analysis revealed that RASSF2A suppresses the expression of inflammatory cytokines, which may in turn suppress angiogenesis and invasion. In primary gastric cancers, aberrant methylation of RASSF2A was detected in 23 of 78 (29.5%) cases, and methylation correlated significantly with an absence of the lymphatic invasion, absence of venous invasion, absence of lymph node metastasis, less advanced stages, Epstein–Barr virus, absence of p53 mutations and the presence of the CpG island methylator phenotype-high. These results suggest that epigenetic inactivation of RASSF2A is required for tumorigenesis in a subset of gastric cancers

LARVAL DEVELOPMENT IN LABORATORY OF CANCER AMPHIOETUS RATHBUN, IN COMPARISON WITH THOSE OF SEVEN OTHER SPECIES OF CANCER (DECAPODA, BRACHYURA)

Recently the larval development has been described in detail successively in the following seven species of Cancer (Decapoda, Brachyura): Cancer magister Dana, C. productus Randall, C. gracilis Dana, C. antennarius Stimpson and C. anthonyi Rathbun from the Pacific coast of North America and C. irroratus Say and C. borealis Stimpson from the Atlantic coast of North America (Poole, 1966; Trask, 1970; Ally, 1975; Roesijadi, 1976; Sastry, 1977a, b; Anderson, 1978). Cancer amphioetus Rathbun used for the present study is a dweller on the Pacific coast of Hokkaido, North Japan. The first zoea of this species has been observed already under laboratory conditions (Iwata, 1973). In the present study, the complete larval development including five zoeal stages and a megalopa are described in detail and the larval characters in the present species are compared with those in seven Cancer species hitherto reported

女子尿道癌の2例

症例1， 74歳.初診， 1975年3月11日.主訴，外尿道口部の尽痛。外尿道口部に外観尿道小阜を思わせるアズキ大の腫瘤を認めた。電気切除された腫瘤は，組織学的にはadenocarcinomaであった。さらに尿道全周にわたりTUR，TUECを行なった。 1979年7月他施設にて死亡した。死因，その他は不明であった。 症例2，63歳。初診， 1980年5月14日。主訴，外尿道口部の腫瘤。尿道全摘術+膀胱痩造設術を施行。組織学的にはsquamous cell carcinomaであった。術後， 下腹部と両ソケイ部に4000radのコバルト照射を行なった。 1980年11月末現在，再発，転移の徴候は認めていない。1975年より6年間に経験した2例の原発性尿道癌を, 若干の文献的考察を加えて報告した。Primary carcinoma of the female urethra is uncommon. In a review of the literature In 1980 Yamazaki and colleagues found 234 cases. Herein we describe such 2 cases