Analysis of patients with colorectal cancer shows a specific increase in serum anti-ING1 autoantibody levels.

Colorectal cancer (CRC) is the third most prevalent cancer in the world, yet the sensitivity and specificity of biomarkers for CRC diagnosis are insufficient. In the present study, we performed a protein microarray screening method to identify antibody markers for CRC. Inhibitor of growth family 1 (ING1) was identified as a candidate tumor antigen for CRC using protein microarrays (ProtoArray). Subsequent amplified luminescence proximity homogeneous assay-linked immunosorbent assay using recombinant ING1 protein showed that the serum levels of anti-ING1 antibodies were increased not only in patients with CRC but also in those with esophageal cancer (EC), gastric cancer (GC), breast cancer (BrC), and pancreatic cancer (PC) compared with those of healthy donors (HDs). Antibodies against the ING1 amino acids between 239 and 253 were present at significantly higher levels in patients with CRC than in those with EC, GC, BrC, or PC. Anti-ING1 antibody levels were significantly higher in the patients with CRC at any stages than in the HDs. Immunohistochemical staining revealed higher expression of ING1 protein in CRC cells than in the adjacent normal tissues. In luciferase reporter assays using a CRC cell line, ING1 augmented p53-mediated NOXA promoter activity but attenuated p53-stimulated Bax, p21, and PUMA promoter activities. Consequently, serum anti-ING1 antibodies can be used for sensitive and specific diagnoses of CRC.

Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

Identification of specific and common diagnostic antibody markers for gastrointestinal cancers by SEREX screening using testis cDNA phage library.

The present study was planned to identify novel serum antibody markers for digestive organ cancers. We have used screening by phage expression cloning and identified novel fourteen antigens in this experiment. The presence of auto-antibodies against these antigens in serum specimens was confirmed by western blotting. As for auto-antibodies against fourteen antigens, AlphaLISA (amplified luminescence proximity homogeneous assay) assay was performed in the sera of gastrointestinal cancers patients to confirm the results. Serum antibody levels against these fourteen recombinant proteins as antigens between healthy donors (HD) and esophageal squamous cell carcinoma (ESCC) patients, gastric cancer (GC), or colon cancer (CC) were compared. The serum levels of all fourteen auto-antibodies were significantly higher in ESCC and GC than those of HD. Among those auto-antibodies, except ECSA2 and CCNL2, were also detected significantly higher levels in CC than those of HD. Receiver operating curve (ROC) revealed similar results except CCNL2 in CC. AUC values calculated by ROC were higher than 0.7 in auto-antibodies against TPI1, HOOK2, PUF60, PRDX4, HS3ST1, TUBA1B, TACSTD2, AKR1C3, BAMBI, DCAF15 in ESCC, auto-antibodies against TPI1, HOOK2, PUF60, PRDX4, TACSTD2, AKR1C3, BAMBI, DCAF15 in GC, and auto-antibodies against TPI1, HOOK2, PUF60 in CC. AUC of the combination of HOOK2 and anti-p53 antibodies in ESCC was observed to be as high as 0.8228. Higher serum antibody levels against ten antigens could be potential diagnostic tool for ESCC. Higher serum antibody levels against eight antigens could be potential diagnostic tool for GC, and serum antibody levels against three antigens could be potential diagnostic tool for CC.

[D2 Lymph Node Dissection in Mini-Laparotomy Transverse Colectomy Using Non-Contrast Simulation CT Colonography].

BACKGROUND AND PURPOSE: It is reported that simulation computed tomography colonography(S-CTC), which combines CTC and 3-dimensional(3D)vascular imaging, is useful in colorectal cancer surgery. However, it is difficult to create 3D vascular images using non-contrast CT. Laparoscopic transverse colectomy is said to be technically difficult. Mini-laparotomy surgery for mid-transverse colon cancer is quite easy to perform. However, exact D2 lymph node dissection is very difficult. We present a case of D2 lymph node dissection during mini-laparotomy transverse colectomy performed using S-CTC, which involves the creation of 3D vascular images using non-contrast CT. PATIENT AND METHOD: The patient was a 77-year-old man with transverse colon cancer located in the mid-transverse colon, cT2N0M0, Stage Ⅰ. He had coexisting chronic renal failure. Non-contrast CT was performed prior to surgery, and the images were processed using workstation Zaiostation2. RESULTS: Both the artery and the vein created from non-contrast CT could be visualized clearly until the marginal vessels. Using noncontrast S-CTC in combination with CTC and 3D artery imaging, it was identified that the dominant artery was the left branch of the middle colic artery(MCA Lt), while the right branch of the MCA(MCA Rt)and accessory MCA(AMCA)were 10 cm or more apart. The fusion of 3D artery and vein imaging made it evident that the vein accompanying MCA Lt branched from the superior mesenteric vein. Using non-contrast S-CTC, D2 lymph node dissection, dissection of the branching root of MCA Lt and the vein at the same level was simulated. Thus, mini-laparotomy transverse colectomy was performed through a 7 cm incision, in accordance with the simulation. CONCLUSION: Non-contrast S-CTC was useful for performing D2 lymph node dissection during mini-laparotomy transverse colectomy.

Incidence and risk factor of outlet obstruction after construction of ileostomy.

There are several reports on the usefulness of diverting ileostomy for decreasing the incidence of anastomotic leakage and the severity of pelvic peritonitis. However, a number of complications induced by ileostomy itself have also been reported, including a special condition induced by obstruction at the outlet of the stoma known as "outlet obstruction." In this study, we examined the frequency and risk factors of this complication based on the data of ileostomy cases in our institution. METHODS: One hundred and seven patients who received ileostomy creation at our department from January 2010 to December 2015 were included. The incidence of outlet obstruction and risk factors were analyzed. RESULTS: Outlet obstruction occurred in 18 cases (16.8%). The incidence was significantly higher in total colectomy or proctocolectomy cases as well as in those with left side construction and laparoscopic surgery than in other patients in a univariate analysis. However, in a multivariate analysis, no risk factors were extracted. CONCLUSIONS: To determine the true cause of this disease, a prospective study with a large number of cases is needed. Since multiple terms are used for this condition, resulting in confusion, a consensus on the appropriate terms is also important.

Comparison of Efficacy of Self-Expandable Metallic Stent Placement in the Unresectable Esophageal Cancer Patients.

This is a retrospective study to evaluate the prevention of complications of metallic stent placement in patients with unresectable advanced esophageal cancer. A total of 87 patients were treated with 4 types of metal stents in the esophagus over a period of 18 years. Stent placement was technically successful. The most common prior treatment was chemoradiotherapy. There were no significant differences in the rate of patients with no complications among the prior treatments. Approximately, 30% of patients had the most common chest pain in complications. Stent placement within one month after the completion of chemoradiotherapy should be avoided for the prevention of the chest pain. There was no significant difference in the rate of patients with no complications by lesion location. The rate of no complications was higher for the Niti-S stent than the Gianturco Z-stent or Ultraflex stent. Of note, no complications were noted for the Niti-S ultrathin stent at all. Among cases of stent-related death, the most common type of complication was respiratory disorder caused by the stent that seems to be thick and hard. Therefore, the stent with thin and flexible characteristics like the Niti-S ultrathin stent will solve the various problems of esophageal stent placement.

Endoscopic occlusion with silicone spigots for the closure of refractory esophago-bronchiole fistula after esophagectomy.

A 65-year-old man with cT1bN0M0 stage I middle thoracic esophageal cancer underwent subtotal esophagectomy and gastric tube reconstruction through the posterior mediastinal route after preoperative carbon-ion radiotherapy and chemotherapy in a clinical trial. Anastomotic leakage occurred, but it spontaneously improved. At six months after the operation, he was rehospitalized with a cough and dysphagia. An esophago-bronchiole fistula and stenosis of the gastric tube were observed. He first underwent stent placement in the gastric tube. Two weeks later, the syringeal epithelium was burned by argon plasma coagulation after stent removal. Endoscopic occlusion was then performed for the fistula with two guidewire-assisted silicone spigots. Two weeks later, he was discharged on an oral diet, and he has not developed recurrence of the fistula or cancer for three years. This is the first report of endoscopic occlusion with a guidewire-assisted silicone spigot through the esophagus.

Drill needle aspiration biopsy for submucosal tumors in an experimental study.

BACKGROUND AND AIMS: EUS-guided FNA biopsy has been widely performed to aid in the diagnosis of submucosal tumors (SMTs). However, in cases of small tumors, the diagnostic yield of EUS-FNA is poor. Therefore, it is necessary to develop a new needle for the diagnosis. We developed a device with a new mechanism that we refer to as a drill needle aspiration biopsy (DNAB). The aim of this study was to evaluate the use of DNAB in resected gastric SMT specimens. METHODS: A drill needle with a sharp tip and wide ditch was inserted into a catheter for angiography. Continuous suction is enabled through the catheter at the tip. DNAB was performed with one pass and one stroke in 13 gastric SMTs resected by operation. Similarly, FNA was performed by one pass and ten strokes. These gastric tumors included nine diagnosed gastrointestinal stromal tumors and four undiagnosed SMTs by preoperative examinations. The tissue quantity between DNAB and FNA was macroscopically and microscopically examined. RESULTS: All 13 drill biopsy specimens were obtained. Additionally, all 13 gastric SMTs, including 4 undiagnosed tumors, could be diagnosed by DNAB. The quantity of each specimen obtained by DNAB was macroscopically and microscopically much greater than that by FNA. In particular, for tumors <25 mm in the longer axis, the ratio of microscopic diagnosable cases was 100 % (7/7) for DNAB and 42.9 % (3/7) for FNA. CONCLUSIONS: DNAB is a novel method that can obtain more tissue than FNA for small gastric SMT.

[Optimal Dissection of the Intestinal Tract and Preservation of Vascular Supply in Left Hemicolectomy Using Simulation Computed Tomography Colonography].

Left hemicolectomy is a standard surgical method for cancer of the descending colon. Resection involves the region from the left side of the transverse colon to the sigmoid colon. Although laparoscopic hemicolectomy is widely used, it is difficult to determine an appropriate resection range during surgery because of the limited visual field. Simulation computed tomography colonography(S-CTC), which combines CTC and 3-dimensional vascular imaging, enables the surgeon to clearly identify the position of the primary lesion and dominant vessel. We present 3 cases of cancer of the descending colon with different affected sites and lesion grades, in which appropriate dissection of the large intestine and treatment of the vessels was simulated by S-CTC, enabling laparoscopic surgery in accordance with the simulation. Case 1: Splenic flexure, cT1bN0M0, Stage I . The dominant vessels were identified by S-CTC as accompanying vessels branching from the accessary middle colic artery(A-MCA)and inferior mesenteric vein(IMV). The left branch of the MCA and the left colic artery(LCA)were 10 cm or more apart. A D2-type dissection was performed, and simulation was conducted for dissection of the branching root of the vein and the same level of the A-MCA. Case 2: Mid-descending colon, cT3N0M0, Stage II . The dominant A-MCA and LCA were identified with S-CTC. The intestinal tract was dissected to 5 cm from the dominant artery, and D3-type dissection was simulated with a retained inferior mesenteric artery(IMA)for preservation of the sigmoid colon. Case 3: Site adjacent to the sigmoid colon, cT3N0M0, Stage II . S-CTC identified the first sigmoid artery(S1)as the dominant artery, and revealed that the LCA and IMV were defective and that the A-MCA was 10 cm or more apart. Simulation of S1 selective resection was conducted such that D3-type dissection was performed, with a retained IMA for preservation of the sigmoid colon. In all 3 cases, laparoscopic surgeries were performed in accordance with the simulation. S-CTC was useful for optimal preservation of the intestinal tract and vascular supply in laparoscopic surgery for descending colon cancer.

Assessment for diagnosis of lymph node metastasis in esophageal cancer using endoscopic ultrasound elastography.

BACKGROUND: We performed endoscopic ultrasound real-time tissue elastography to more accurately diagnose lymph node metastasis of esophageal cancer. The aim of this study was to evaluate the ability of EUS elastography to distinguish benign from malignant lymph nodes in esophageal cancer patients. METHODS: The present study had two steps. As the first step (study 1), we developed diagnostic criteria for metastatic lymph nodes using elastography and verified the validity of the criteria. Three hundred and twenty-two lymph nodes from 35 patients treated by surgical resection were included in the study. As the second step (study 2), we preoperatively examined the lymph nodes of esophageal cancer patients with EUS elastography and compared its diagnostic performance with that of the conventional B-mode EUS images. A total of 115 lymph nodes from 31 patients were included. RESULTS: In study 1, lymph nodes were considered malignant if 50 % or more of the node appeared blue, or if the peripheral part of the lesion was blue and the central part was red/yellow/green. The sensitivity and specificity of the elastography were 79.7 and 97.6 % with an accuracy of 93.8 %, which was significantly higher than the values for conventional B-mode imaging. In study 2, the sensitivity and specificity of the EUS elastography were 91.2 and 94.5 % with an accuracy of 93.9 %, which was also significantly higher than the values for conventional B-mode EUS imaging. CONCLUSIONS: The present study demonstrated that EUS elastography is useful for diagnosing lymph node metastasis of esophageal cancer.

[Perioperative Steroid Administration for Colorectal Cancer with Synchronous Unresectable Hepatic Metastases].

PURPOSE: In our institution, steroids are administered before resection of primary colorectal cancer lesions with synchronous unresectable hepatic metastases in order to avoid severe postoperative complications and hepatic failure. We herein report the results of the treatment. PATIENTS AND METHODS: Thirty-eight colorectal cancer patients with synchronous unresectable hepatic metastases were divided into 2 groups: Group S (patients who received steroids in the perioperative period) and Group N (other patients). The clinicopathological features, post-operative course, and survival were compared between the 2 groups. Hydrocortisone sodium succinate was administered twice a day from immediately before laparotomy until the second postoperative day. RESULTS: The number of patients with severe hepatic metastases and extra-hepatic metastases was significantly higher in Group S. No significant differences were observed between the 2 groups regarding the incidence of severe postoperative complications or the overall survival. Among 25 patients with liver dysfunction, the complication rate was significantly lower and survival was significantly longer in Group S compared to Group N. CONCLUSIONS: The perioperative administration of steroids to colorectal cancer patients with synchronous unresectable hepatic metastases may reduce the complication rate and may thus improve survival, especially in patients with liver dysfunction.

[Surgical Simulation-CT Colonography for Laparoscopic Assisted Sigmoid Colectomy Preserving the Inferior Mesenteric Artery and Vein].

D2 lymph node dissection in laparoscopic surgery for early colon cancer requires selective vessel dissection, making it technically very difficult. Using surgical simulation-CT colonography (simulation-CTC), we could perform laparoscopic assisted sigmoid colectomy preserving the inferior mesenteric artery (IMA) and vein (IMV) more accurately and safely. The case described here was a type 0-Ip sigmoid colon cancer with a tumor size of 13 mm. Endoscopic mucosal resection was performed to confirm a pathological diagnosis of pT1b (4,000 mm) and v1. Sigmoid colectomy was planned, and simulation-CTC was performed, which demonstrated that the cancer was located in the proximal sigmoid colon and supplied by the first sigmoid colon artery (S1). To maintain the blood flow to the distal sigmoid colon, selective S1 resection preserving the IMA and IMV was planned. At the operation, S1, which branches off from the IMA near the bifurcation of the abdominal aorta, was dissected, and the vein accompanying S1, which branches from the IMV in the same area as S1, was dissected. The operation was performed accurately according to the plan, showing that simulation-CTC can be very useful.

[Long-term survival in a case of recurrent gastrointestinal stromal tumor treated with intermittent or low-dose imatinib].

A 65-year-old woman with a gastrointestinal stromal tumor(GIST)underwent a total gastrectomy in 1999. In 2004, she was diagnosed with an intra-abdominal recurrence and was treated with 300mg/day of imatinib. Because of the side effects of imatinib, we interrupted the treatment and were forced to reduce the dose from 300mg/day to 100mg/day. However, at present, the tumor remains controlled. In conclusion, this case suggested that, even if given irregularly or at a low-dose, continuous treatment with imatinib might contribute to long-term survival in patients with GIST.

Identification of a novel SEREX antigen family, ECSA, in esophageal squamous cell carcinoma.

BACKGROUND: Diagnosis of esophageal squamous cell carcinoma (SCC) may improve with early diagnosis. Currently it is difficult to diagnose SCC in the early stage because there is a limited number of tumor markers available. RESULTS: Fifty-two esophageal SCC SEREX antigens were identified by SEREX (serological identification of antigens by recombinant cDNA expression cloning) using a cDNA phage library and sera of patients with esophageal SCC. Sequence analysis revealed that three of these antigens were similar in amino acid sequences, and they were designated as ECSA (esophageal carcinoma SEREX antigen)-1, -2 and -3. The ECSA family was also similar to an EST clone, hepatocellular carcinoma-associated antigen 25a (HCA25a). Serum antibody levels to ECSA-1, -2 and -3 were significantly higher in patients with esophageal SCC than in healthy donors. Based on the conserved amino acid sequences, three peptides were synthesized and used for enzyme-linked immunosorbent assays (ELISA). The serum antibody levels against one of these peptides were significantly higher in patients with esophageal SCC. This peptide sequence was also conserved in FAM119A, GOSR1 and BBS5, suggesting that these are also ECSA family members. Reverse transcription followed by quantitative PCR analysis showed that the mRNA expression levels of ECSA-1, -2 and -3 and FAM119A but not of HCA25a, GOSR1 and BBS5 were frequently elevated in esophageal SCC tissues. CONCLUSIONS: We have identified a new gene family designated ECSA. Serum antibodies against the conserved domain of the ECSA family may be a promising tumor marker for esophageal SCC.

Salivary amylase activity is useful for assessing perioperative stress in response to pain in patients undergoing endoscopic submucosal dissection of gastric tumors under deep sedation.

BACKGROUND: Although endoscopic submucosal dissection (ESD) for patients with gastric tumors under the conditions of unconsciousness is considered to be minimally invasive, no objective assessment of the perioperative stress of ESD has yet been conducted. Today, stress levels can be easily and objectively assessed by monitoring salivary amylase activity (sAMY). We evaluated the perioperative changes in the sAMY in patients undergoing ESD and identified the causes of such changes. METHODS: A total of 40 patients with gastric cancers/adenomas removed by ESD under general anesthesia (GA; n = 20) and under deep sedation (DS; n = 20) were enrolled. sAMY was measured using the enzyme analysis equipment, sAMY Monitor (NIPRO, Osaka, Japan) during the perioperative period of the ESD. Also, all patients were interviewed to determine their subjective stress level, using a questionnaire asking "How did you feel during ESD?", with the choice of responses ranging from "did not wake up at all" to "I was awake and ESD was extremely stressful". RESULTS: The sAMY of the DS group increased soon after the start of ESD. Meanwhile, that of the GA group decreased just after the ESD started and was maintained at a stable level throughout the ESD. In response to the stress level questionnaire, all of the patients in the GA group and a majority of the patients in the DS group responded, "did not wake up at all". CONCLUSION: Sympathetic agitation, expressed as an increase of sAMY, was absent in the GA group. Meanwhile, in the DS group, some patients showed high levels of sAMY which went down following the administration of an analgesic agent, thus suggesting that pain caused an elevation in the level of the stress and thereby induced an increase in sAMY. The measurement of sAMY is therefore considered to be useful for the assessment of analgesic status under DS.

Identification of Makorin 1 as a novel SEREX antigen of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (SCC) represents one of the most malignant tumors. To improve the poor prognosis, it is necessary to diagnose esophageal SCC at early stages using new tumor markers. SEREX (serological identification of antigens by recombinant cDNA expression cloning) is suitable for large-scale screening of tumor antigens and has been applied for various types of human tumors. METHODS: Tumor markers of esophageal squamous cell carcinoma (SCC) were screened by SEREX method. The presence of serum anti-makorin 1 (MKRN1) antibodies (s-MKRN1-Abs) was examined by Western blotting using bacterially expressed MKRN1 protein. The expression levels of MKRN1 mRNA in tissues were examined by RT-PCR. The biological activity of MKRN1 was examined by transfection of ras-NIH3T3 mouse fibroblasts with MKRN1 cDNA. Major ubiquitinated proteins in MKRN1-transfected cells were identified by immunoprecipitation with anti-ubiquitin antibody followed by mass spectrometry. RESULTS: MKRN1 was identified as a novel SEREX antigen of esophageal SCC. Although a total of 18 (25%) of 73 patients with esophageal SCC had s-MKRN1-Abs, none of the 43 healthy donors had a detectable level of s-MKRN1-Abs. There was no correlation between the presence of s-MKRN1-Abs and clinicopathological variables other than histological grading. Well-differentiated tumors were associated significantly with the presence of s-MKRN1-Abs in the patients. The mRNA levels of MKRN1 were frequently higher in esophageal SCC tissues than in the peripheral normal esophageal mucosa. Stable transfection of ras-NIH3T3 cells with MKRN1 cDNA induced prominent morphological changes such as enlargement of the cell body and spreading. Ubiquitination of 80- and 82-kDa proteins were clearly observed in MKRN1-transfected cells but not in the parental cells, which were identified as L-FILIP (filamin A interacting protein 1). CONCLUSION: MKRN1 is a novel SEREX antigen of esophageal SCC, and s-NKRN1-Abs can be a candidate of diagnostic markers of esophageal SCC with high specificity. It is plausible that MKRN1 is involved in carcinogenesis of the well-differentiated type of tumors possibly via ubiquitination of L-FILIP.

Detection of anti-CUEC-23 antibodies in serum of patients with esophageal squamous cell carcinoma: a possible new serum marker for esophageal cancer.

BACKGROUND: Serological identification of antigens by recombinant cDNA expression cloning (SEREX) is an established method for detecting new tumor-specific antigens. Antibodies to SEREX antigens may be useful for the detection of esophageal squamous cell carcinoma (SCC). METHODS: A phage cDNA library of a human esophageal SCC cell line was screened using sera of patients with esophageal SCC. The presence and levels of serum antibodies to SEREX antigens were established by Western blotting and enzyme-linked immunosorbent assay (ELISA) using purified recombinant antigen proteins, respectively. RESULTS: The newly identified esophageal SCC antigen is encoded by a novel gene located on chromosome 1, here designated CUEC-23. Serum CUEC-23-antibodies (s-CUEC-23-Abs) were detected in 14 of 54 patients with esophageal SCC (26%) by Western blot analysis. Esophageal SCCs were positive for s-CUEC-23-Abs together with CEA, SCC-Ag or CYFRA21-1 in 44, 41 and 52% of cases, respectively. There was no detectable association between the presence of s-CUEC-23-Abs and clinicopathological variables. ELISA showed that the levels of s-CUEC-23-Abs were significantly higher in patients with esophageal SCC than in healthy volunteers (17% in the former using the mean+3 SD of s-CUEC-23-Abs in healthy controls as the cutoff). CONCLUSION: A new tumor antigen, CUEC-23, was identified by SEREX screening. s-CUEC-23-Abs might be a useful serum marker to detect esophageal SCC.

Decrease in chemosensitivity against anticancer drugs by an esophageal squamous cell carcinoma SEREX antigen, AISEC.

We performed SEREX (serological identification of antigens by recombinant cDNA expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and examined whether some of the SEREX antigens can affect chemosensitivity against anticancer drugs. We isolated a novel gene which was designated as AISEC (antigen identified by SEREX for esophageal carcinoma). RT-PCR analysis showed that the mRNA expression levels of AISEC were higher in esophageal SCC tissues than in their normal counterparts. By transfection into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts, we isolated a clone, FAISEC-3, which stably expressed AISEC. FAISEC-3 cells were more resistant to anticancer drugs, such as mitomycin C, ifosfamide, vincristine, camptothecin and etoposide, than parental ras-NIH cells. Luciferase reporter assay after a transient transfection with AISEC cDNA or the control vector revealed that the transactivity of p53 was suppressed by AISEC in a dose-dependent manner. These results suggested that esophageal SCC tissues produce AISEC in increased amounts, which can reduce the chemosensitivity against anticancer drugs possibly by suppressing the p53 transactivation ability.

Sensitization against anticancer drugs by transfection with UBE2I variant gene into ras-NIH3H3 mouse fibroblasts.

We previously performed SEREX (serological identification of antigens by recombinant expression cloning) using the sera of patients with esophageal squamous cell carcinoma (SCC), and isolated a variant clone (AK093616) of ubiquitin-conjugating enzyme E21 (UBE2I). This clone was tentatively designated as UBE2I-v5 and analyzed for biological function by transient transfection of the cDNA into activated Ha-ras-transformed NIH3T3 (ras-NIH) mouse fibroblasts. Chemosensitivity to 92 cytotoxic drugs was compared between UBE2I-v5-transfected cells and the parental ras-NIH cells. The UBE2I-v5-transfected cells were more sensitive than the parental cells to anticancer drugs such as vincristine (VCR), mitoxantrone (MIT) and etoposide (VP16). The regression analysis of the total chemosensitivity pattern of UBE2I-vS-transfected cells revealed that the function of UBE2I-v5 was positively related to RPA2 (replication protein A2), Rho-GDI (Rho guanine nucleotide dissociation inhibitor a), FUS (putative tumor suppressor) and TKT (transketolase) but negatively related to Per-1 (period-I), Ran (nuclear Ras-related protein), PTEN (phosphatase and tensin homolog), C/EBPalpha (CCAAT/enhancer binding protein a) and the tumor suppressor p53. Thus, it is possible that UBE21-v5 plays a role in carcinogenesis by suppressing the function of CIEBPa and/or p53 via RPA2-like activity.

[A case of stage IV gastric cancer previously treated with TS-1 completely responding to second-line chemotherapy with weekly paclitaxel therapy].

We report herein a case with stage IV gastric cancer previously treated with TS-1 completely responding to second-line chemotherapy with weekly paclitaxel therapy. A 65-year-old female was diagnosed as having type 3 gastric cancer with para-aortic lymph node metastases. She underwent total gastrectomy with extended lymph node dissection on March 2003. Histopathological examination revealed that the tumor was poorly-differentiated adenocarcinoma with para-aortic lymph nodes metastases and completely resected. After the operation,she was treated by adjuvant chemotherapy with TS-1. In March of 2004, she suffered from hematuria, and a CT scan revealed para-aortic lymph nodes metastases and left kidney metastasis. Then, she was treated by a weekly infusion of paclitaxel as second-line chemotherapy. After 3 courses, the tumor disappeared and efficacy was judged as CR. Moreover, CR was maintained after 7 courses. At this writing in January of 2005, she is well and has been treated with paclitaxel without any severe adverse events. Therefore, weekly paclitaxel therapy was considered to be one of the promising second-line chemotherapies for advanced or recurrent gastric cancer previously treated by TS-1.