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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676

Phase I/II trial of carbon-ion therapy for patients with locally recurrent rectal cancer

Background: The rate of local recurrence(LR) for rectal cancer ranges from 10 to 40%. Most patients are referred for radiotherapy. Radiotherapy is generally considered palliative treatment. The purpose of this study is to evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients locally recurrent rectal cancer. Methods: Between April 2001 and September 2003, 33 lesions at 32 patients were enrolled onto this study. Criteria for trial eligibility were confirmation of locally recurrent rectal cancers without distant metastases by CT, MRI and PET findings and ECOG performance score 0,1,2. Contraindications for trial entry included pelvic bone destruction or infiltration into the bladder. Carbon beams of 290, 350 and 400 MeV/nucleon energy were generated in the HIMAC synchrotron. The dose was determined as 67.2GyE and escalated to 70.4GyE,73.6GyE. Of the 32 eligible patients, 16 were male and 16 female. Median age was 62.8 years. The predominant sites of relapse were 13 presacral, 11 lymph nodes. Toxicity on organs were assessed according to the NCI-CTC and RTOG/EOTRC classification. Tumor response was defined by the RESIST scoring system. Local recurrence was defined in terms of lesions occurring in the tumor bed. Survival curves were estimated by the Kaplan and Meier method. Results: Ten patients received radiation dose at 67.2GyE, fourteen at 70.4GyE and nine at 73.6GyE. All toxicities in the 33 lesions at 32 patients were relatively few and mild in these patients. No grade 3 to 5 acute and late toxicity was observed. Tumor response was evaluated in 33 lesions patients. CR was observed in 5 lesions and PR in 11. The local control rates in 33 lesions are 84.9% at one year and 81.5% at two years. Local control rates at one year were 70% at 67.2GyE, 85% at 70.4GyE and 100% at 73.6GyE. The one and two year overall survival rate were 90.3% and 72.0% respectively. In the literature, the reported two-year survival rates for locally recurrent rectal cancer treated with radiation were 20 to 40%. Conclusions: : Carbon ion radiotherapy seems to be a safe and effective modality in the management of locally recurrent rectal cancer, providing good local control and offering a survival advantage without acceptable morbidity

Effects of carbon-ion beams on human pancreatic cancer cell lines that differ in genetic status.

The relative biologic effectiveness (RBE) of carbon-ion beams at 3 different linear energy transfer (LET) values (13, 50, and 80 keV/microm) accelerated by the Heavy Ion Medical Accelerator in Chiba on human pancreatic cancer cell lines differing in genetic status was determined. The RBE values were calculated as D10, the dose (Gy) required to reduce the surviving fraction to 10%, relative to X-rays. We also investigated apoptosis and the relationship between D10 and the cell cycle checkpoint using morphologic examination and flow cytometry analysis, respectively. The RBE values calculated by the D10 values ranged from 1.16 to 1.77 for the 13-keV/microm beam and from 1.83 to 2.46 for the 80-keV/microm beam. A correlation between the D10 values of each cell line and intensity of G2/M arrest was observed. In contrast, LET values did not clearly correlate with induction of apoptosis. These results suggest that carbon-ion beam therapy is a promising modality. Elucidation of the mechanisms of G2/M arrest and apoptosis may provide clues to enhancing the effects of radiation on pancreatic cancer