Biomedical subjects

Yasuhiro Tsubosa

Publications and source records attributed to Yasuhiro Tsubosa.

9 recordsLinked to original sources

PubMed2006

Expression profiling of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy: clinical implications.

In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy (CRT) has a curative potential even in cases of locally advanced carcinoma. However, only about half of the patients benefit from CRT, and an accurate prediction of sensitivity to CRT is eagerly awaited. Using microarrays, we analyzed gene-expression patterns of pretreatment biopsy specimens from 33 patients with CRT alone including long-term survivors, more than 3 years (14 cases) and short-term survivors, less than 1 year (11 cases). The expression patterns of about 12,600 genes were used to identify genes correlated with survival terms. Fifty-seven genes correlating with short-term survival and 120 genes with long-term survival were identified. The genes involved in the immune response were characteristically upregulated in the long-term survivors, and an immunohistochemical staining confirmed an increased CD8-positive T cell number in the long-term survivors over that in the short-term survivors. In the short-term survivors, on the other hand, increased expression of the genes involved in drug resistance was observed. Our gene list should contribute to the elucidation of the mechanisms of CRT response and contains useful markers for predicting the prognosis of individual ESCC patients treated with CRT alone.

Adult↗

PubMed2005

Effects of degenerate oligonucleotide-primed polymerase chain reaction amplification and labeling methods on the sensitivity and specificity of metaphase- and array-based comparative genomic hybridization.

Degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) is often applied to small amounts of DNA from microdissected tissues in the analyses of chromosomal copy number with comparative genomic hybridization (CGH). The sensitivity and specificity in CGH analyses largely depend on the unbiased amplification and labeling of probe DNA, and the sensitivity and specificity should be high enough to detect one-copy changes in aneuploid cancer cells when accurate assessment of chromosomal instability is needed. The present study was designed to assess the effects of DOP-PCR and labeling method on the sensitivity of metaphase- and array-based CGHs in the detection of one-copy changes in near-tetraploid Kato-III cells. By focusing on several chromosomes whose absolute copy numbers were determined by FISH, we first compared the green-to-red ratio profiles of metaphase- and array-based CGH to the absolute copy numbers using the DNA diluted with varying proportions of lymphocyte DNA, with and without prior DOP-PCR amplification, and found that the amplification process scarcely affected the sensitivity but gave slightly lower specificity. Second, we compared random priming (RP) labeling with nick translation (NT) labeling and found that the RP labeling gave fewer false-positive gains and fewer false-negative losses in the detection of one-copy changes. In array CGH, locus-by-locus concordance between the DNAs with and without DOP-PCR amplification was high (nearly 100%) in the gain of three copies or more and the loss of two copies or more. This suggests that we could pinpoint the candidate genes within large-shift losses-gains that are detected with array CGH in microdissected tissues.

Cell Line, Tumor↗

PubMed2005

Esophagectomy with three-field lymph node dissection for esophageal carcinoma with a nonrecurrent inferior laryngeal nerve.

In rare cases, the inferior laryngeal nerve branches directly from the vagus trunk. A 58-year-old man with carcinoma of the thoracic esophagus was referred to our hospital. A nonrecurrent anomaly of the right recurrent laryngeal nerve associated with an aberrant right subclavian artery was detected preoperatively by computed tomography and magnetic resonance imaging. This artery ran on the right side between the esophagus and the vertebral column. Recognition of this nerve before upper mediastinal lymph node dissection was thought to be important for avoiding unexpected neural injuries. For a successful esophagectomy with three-field lymph node dissection in patients associated with this anomaly, a cervico-abdominal procedure followed by a thoracic procedure, which is the reverse of the usual process, could be useful for a safe operation. However, this anomaly made it difficult to dissect lymph node along the left recurrent laryngeal nerve.

Carcinoma, Squamous Cell↗

PubMed2004

Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings.

Peritoneal wash cytology plays a pivotal role in the decision for gastric cancer treatment because advanced gastric cancer often turns out incurable with peritoneal metastasis. Molecular detection of minimal cancer cells from peritoneal washings may overcome the sensitivity boundary of conventional cytology and contribute to the prediction of the disease outcome. To select marker candidates out of ten thousands of genes, we performed microarray analyses in 12 gastric cell lines and 8 peritoneal washings of early stage cases. With 40 candidates selected by the above expression profiling, RT-PCR in 16 representative peritoneal wash samples was performed to identify genes specific to cytology positive samples. The finally selected five genes, CK20, FABP1, MUC2, TFF1, and TFF2, were then evaluated for their utility as a marker for minimal residual disease in 99 peritoneal wash samples. Nested RT-PCR using the five genes showed positive results highly specific to incurable cases (91-100%). With a high specificity, the combination of these five genes succeeded in identifying 6 out of 20 (30%) additional patients with all types of early recurrence that could not be predicted by the conventional method. The six newly identified recurrences included four non-peritoneal ones, showing that RT-PCR using the five genes without a real-time quantitative PCR technique contributes to the detection of minimal residual disease.

Ascitic Fluid↗

PubMed2003

Alterations of chromosomal copy number during progression of diffuse-type gastric carcinomas: metaphase- and array-based comparative genomic hybridization analyses of multiple samples from individual tumours.

The application of comparative genomic hybridization (CGH) has led to the rapid accumulation of cytogenetic information on gastric carcinoma (GC), but there is little information on the time sequence of cytogenetic changes. In the present study, degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) and CGH were applied to multiple samples microdissected from 19 diffuse-type GCs including eight early cancers. Recurrent gains were detected at 8q, 3q, 7q, and 8p, and loss at 17p (in more than 50% of the cancers), the frequencies of which were fairly similar between the samples with (SIG) and those without (POR) abundant signet ring cells. Earlier stemline changes (8q+, 8p+, 1q+, 17p-, etc), with breakpoints that were common to all the samples, were discriminated from later sideline changes (2q+, 11q+, 17q-, 21q-, etc) in individual tumours. The changes were generally common to early and advanced cancers, except for 7p+, 15q+, 3p-, and 18q-, which were largely sideline changes and more frequently detected in advanced cancers (p<0.05). Because the samples with 7p+ had a greater number of copy-number changes than those without 7p+ (p<0.01), 7p+ may play a role in tumour progression by acceleration of chromosomal instability. Fifteen different chromosomal loci with amplification were detected in ten cases, mostly as sideline changes in advanced cancers. By microarray-based CGH, KRAS, MDM2, and FGFR2 were confirmed in the amplicons at 12p, 12q, and 10q, and FES at 15q26, for the first time in GC. These results support the notion that SIG and POR are of a genetically single lineage in both early and advanced diffuse-type GC and that the majority of advanced cancers derive from early cancers through the accumulation of various sideline changes in addition to stemline changes.

Adenocarcinoma↗

PubMed2003

Cytogenetic heterogeneity and progression of esophageal squamous cell carcinoma.

It is widely believed that most human tumors, including esophageal squamous cell carcinoma (ESCC), arise through multistep genetic and cytogenetic alterations. The time sequence of these alterations, however, is still unknown. The present study was designed to differentiate common early changes from uncommon later ones with combined comparative genomic hybridization (CGH) and ploidy analyses in multiple or single samples of 12 ESCCs. We first demonstrated that the mean copy numbers of chromosomes 3 and 11, determined directly by fluorescence in situ hybridization, showed linear correlation with the mean copy numbers calculated from the G/R ratio of CGH and DNA ploidy (R(2)=0.714, P<0.0001). On this basis, we estimated the absolute copy numbers of chromosomal parts by applying the ploidy-dependent threshold criteria to the G/R ratio data after the criteria were corrected by the percentage of tumor cells in each sample. One-copy changes in the DNA-diploid stage may give large shifts of the G/R ratio, even after tetraploidization, whereas those after tetraploidization undergo small shift. Using the tumors with multiple samples, it was actually demonstrated that most of the gains common to the samples in individual tumors showed the large shifts. Though early changes varied from tumor to tumor in the nine informative cases, it was found that gains of 3q (5/7: number of cases with large-shift 3q+/total number of cases with 3q+), 8q (3/4), 11q13 (4/5), and 14q (3/4) were early events, while losses of 3p (2/8), 5q (1/5), 13q (1/5), and 21q (1/5), and gains of 1p (1/4) and Xq (1/4) were later events in progression of individual tumors.

Aged↗

PubMed2003

Magnitude of serosal changes predicts peritoneal recurrence of gastric cancer.

BACKGROUND: Peritoneal dissemination is the most frequent mode of recurrence in patients with gastric cancer. We tried to identify factors that predict peritoneal recurrence with high sensitivity. STUDY DESIGN: Clinical and pathologic data from 587 consecutive patients with gastric cancer were reviewed retrospectively. The stepwise Cox proportional hazards regression model was used to assess the prognostic significance of the magnitude of serosal changes. Multiple stepwise logistic regression analysis was used to determine factors associated with peritoneal recurrence in 375 patients who underwent curative resection. RESULTS: The 5-year survival rate of patients with S2 disease (greatest dimension of macroscopic serosal changes >/= 2.5 cm) was 18%, which was worse than S0 (no serosal changes) and S1 disease (macroscopic serosal changes < 2.5 cm)(p < 0.001). Patients with S0 tumors who underwent curative resection had the best 5-year survival rate. Multivariate analyses indicated that the magnitude of serosal changes was an independent prognostic factor for survival both overall and after curative resection. Logistic regression analysis showed that peritoneal recurrence was more than four times as likely with S2 than with S0 or S1 tumors. The sensitivity for predicting peritoneal recurrence was 79%; the sensitivity of cytologic examination was 38%. CONCLUSIONS: Magnitude of serosal changes is easy to measure intraoperatively and predicts peritoneal recurrence of gastric cancer with greater sensitivity than conventional peritoneal lavage cytology.

Gastrectomy↗

PubMed2002

Enzyme histochemistry is useful to assess viability of tumor tissue after microwave coagulation therapy (MCT): metastatic adenocarcinoma treated by lateral segmentectomy after MCT.

We report on a case of metastatic adenocarcinoma of liver that was removed and examined histochemically after microwave coagulation therapy (MCT). The patient was a 65-year-old woman who had a metastatic tumor in the liver (S3) after high anterior resection due to a rectal adenocarcinoma and received MCT against the tumor. One month after MCT, multiple metastatic tumors were detected by abdominal computed tomography (CT) scan. As it was difficult to control them by MCT alone, we performed lateral segmentectomy. To assess the effects of microwave ablation on cellular viability of metastatic tumor, we used enzyme histochemistry for acid phosphatase (AcP), which is positive in macrophages infiltrating in the tumor. In a part of the ablated area of resected liver, there was remaining neoplastic tissue of which the morphology was maintained in H&E staining. This was found to be microwave-fixed non-viable tissue because no enzyme activity of AcP was detected in the infiltrating macrophages. This case report suggests that enzyme histochemistry was useful to assess the effect of MCT, enabling us to distinguish fixed cells from viable cells.

Acid Phosphatase↗

PubMed2002

[Multidisciplinary therapy for peritoneal dissemination using peritonectomy].

An aggressive approach to peritoneal dissemination involves peritonectomy procedures combined with preoperative intraperitoneal chemotherapy, intraoperative chemo-hyperthermia, and postoperative systemic chemotherapy. We have been performing multimodal therapy consisting of peritonectomy plus perioperative chemotherapy for the treatment of patients with peritoneal dissemination. Fifty-seven patients with established peritoneal dissemination from gastric cancer (n = 32), colon cancer (n = 17), ovarian cancer (n = 7), and mesothelioma (n = 1) have been treated with peritonectomy and intraoperative chemo-hyperthermia. Five-year survival rates of patients with gastric and colon cancer were 18% and 38%, respectively. Among various clinical factors, complete tumor resection was the most significant prognostic factor, and the prognosis of patients who underwent complete cytoreduction was significantly better than those who received incomplete cytoreduction. A multimodal therapy consisting of perioperative chemotherapy and peritonectomy with complete cytoreduction may be the most powerful method to treat patients with established peritoneal dissemination.

Colonic Neoplasms↗