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Tatsuya Kanuma

Publications and source records attributed to Tatsuya Kanuma.

7 recordsLinked to original sources

Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy.

The present study was designed to clarify the expression and prognostic significance of activated Akt and mTOR in cervical cancer and their correlation with response to neoadjuvant chemotherapy (NAC). Immunohistochemical analysis for p-Akt and p-mTOR expression was performed on paraffin-embedded biopsy specimens from 25 patients with advanced cervical cancer (stage Ib2-IIb). We correlated this finding with various clinicopathological variables and prognosis by uni- and multivariate analyses. All patients received cisplatin-based NAC, and primary tumor response was evaluated by RECIST criteria and then classified as a positive or negative response. Activation of Akt was detected in the cytoplasm and nucleus of the cancer cells in 12 patients (48%), whereas p-mTOR was detected in the cytoplasm and membrane of the cancer cells in 13 patients (52%). Post NAC evaluation of the primary tumor revealed 68% (17/25) responsive tumors. The expression of p-mTOR and distant metastasis significantly correlated with the response to NAC (p = 0.0101 and p = 0.0107); however, there was no significant correlation between p-Akt and p-mTOR expression and any of the clinicopathological characteristics of the patients. In the univariate analysis, activated Akt and mTOR were found to be significant prognostic indicators (p < 0.05). In multivariate analysis, p-mTOR expression retained its significance as an independent poor prognostic marker (p = 0.0178). In summary, our present study showed that cervical cancer expressed Akt and mTOR activation. Moreover, the expression of phosphorylated mTOR may have a role as a marker to predict response to chemotherapy and survival of cervical cancer patients who are treated with cisplatin-based neoadjuvant chemotherapy. Our results suggest that the mTOR cascade may be a promising target for therapeutic intervention in cervical cancer.

Adult↗

Differential sensitivity of paclitaxel-induced apoptosis in human esophageal squamous cell carcinoma cell lines.

PURPOSE: Paclitaxel is a highly effective chemotherapy agent against adenocarcinomas and squamous cell carcinomas of the esophagus. However, its precise effects in human esophageal cancer cells are not well understood. This study was designed to examine the relationship between cell-cycle phases of paclitaxel-activated checkpoints and to elucidate the molecular pathway of the effect of paclitaxel in human esophageal squamous cell carcinoma (ESCC) cell lines. METHODS: The three human ESCC cell lines--TE-2, TE-13 and TE-14--were examined for their response to paclitaxel. ESCC cells were treated with various concentrations of paclitaxel for 1-3 days using MTT assay. The cell-cycle progression and apoptosis were examined by flow cytometry. DNA fragmentation assay was carried out to confirm the fragmented cells as hallmark for apoptotic cells. In additional, the expression of apoptosis-related proteins in ESCC-treated cells was then examined by Western blot analysis. RESULTS: TE-14 cells demonstrated the highest sensitivity among all cells. G2/M cell-cycle arrest occurs prior to paclitaxel-induced apoptosis in ESCC cells. The fragmentation of chromatin was observed in drug treated TE-13 and TE-14 cells by flow cytometry and DNA ladder formation. In contrast, the measurement for TE-2 cells was more suggestive of phenotype a resistant in response to paclitaxel treatment. Western blot analysis results showed that the mitochondrial pathway might be involved in paclitaxel-induced apoptosis in ESCC cell lines. CONCLUSION: Differential sensitivity was observed in human ESCC cell lines in response to paclitaxel treatment. G2/M arrest occurs with a prior to paclitaxel-induced apoptosis and might be mediated by the mitochondrial (intrinsic) apoptosis pathway in human ESCC cells.

Antineoplastic Agents, Phytogenic↗

A new, accurate and conventional five-point method for quantitative evaluation of ascites using plain computed tomography in cancer patients.

BACKGROUND: To assess the exact response of the malignant ascites to the treatment, the objective measurement of the volume of ascites is essential. We have developed a simple method to measure the volume of ascites by using standard abdomino-pelvic computed tomography (CT). The aim of the study is to validate the accuracy of the measurements by comparing them with the standard volume calculation by using 3D-CT. METHODS: Twelve consecutive patients with cancer who had measurable ascites underwent 15 helical CT examinations. On conventional CT images, the thickness of ascites in centimeters was measured in three planes such as the bilateral subphrenic space (A and B), the bilateral paracolic space (C and D) and the pre-bladder space (E), and the average thickness: (A + B + C + D + E)/5 was then multiplied by the area of standard abdominal cavity in the anterior projection, that was assumed to be 1000 cm(2), to yield the volume of ascites: (A + B + C + D + E) x 200 (ml). The volume of ascites was compared with the exact volume, that was obtained from 3D-CT with the volume rendering method. RESULTS: The volume of ascites measured by the present method and the volume rendering method ranged from 140 to 4040 ml and from 86 to 4279 ml, respectively. The correlation was statistically significant with a correlation coefficient of 0.956 (P < 0.01) using the Spearman's rank correlation. In 13 examinations with the exact volume > or =300 ml, the average ratio of the absolute difference in the volume was 12.9 +/- 13.9% as compared with 62.8 and 162.0% in two examinations with the exact volume < 300 ml. CONCLUSION: The preliminary study indicated that the present five-point method using a conventional CT was accurate in patients with the volume of ascites > or =300 ml. Because this procedure is simple and easy to perform, it should be feasible in many hospitals for the follow-up of ascites after treatment.

Adult↗

Diagnostic accuracy of FDG PET imaging for the detection of recurrent or metastatic gynecologic cancer.

PURPOSE: This study evaluated the diagnostic role and accuracy of positron emission tomography (PET) using 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) for the detection of tumor foci in patients with suspected recurrent or metastatic lesions of gynecologic cancers. MATERIALS AND METHODS: FDG PET imaging was performed on 51 patients with a previous history of gynecologic cancer who were referred for a clinical suspicion of recurrent disease. PET acquisition was started 50-60 min after the intravenous injection of 5-6 MBq/kg FDG in all patients. The PET images were interpreted visually, and tracer uptake was quantitated as the standardized uptake value adjusted to body weight (SUV) in the lesions showing FDG uptake. The accuracy of the PET results was assessed by a consensual verdict based on histology, cytology, other imaging and clinical follow-up. RESULTS: FDG PET correctly diagnosed 33 of 36 patients with recurrent disease and 12 of 15 patients without recurrence. On patient-based analysis, the sensitivity, specificity and accuracy of FDG PET were 91.7%, 80.0% and 88.2%, respectively, depending on the selected scheme for visual scoring of the lesions. The area index in receiver-operating characteristic analysis was 0.95 for patient detection. Malignant lesions accumulated significantly more FDG than the benign ones (the mean SUVs were 3.7 +/- 1.9 and 1.6 +/- 1.1, respectively, p = 0.004). The sensitivity and specificity in correct identification of tumor recurrence or metastases using a threshold SUV 1.9 were 88.8% and 66.7% in contrast to the visual analysis (sensitivity 96.4%, specificity 50%) on a lesion-based analysis. The partial volume effect of SUV in a few small lesions and the presence of bone lesions in which FDG uptake was relatively low might be the reason for the lower sensitivity in SUV analysis. FDG PET was valuable when CT/MRI was negative or inconclusive, and in patients with elevated tumor marker levels as well as with normal tumor marker levels when recurrence was suspected clinically. However, PET failed to visualize some small metastatic lesions in lung and bone, and showed falsely high FDG uptake in some benign lesions. CONCLUSION: The results indicated that FDG PET is a reliable and accurate diagnostic method for detecting recurrent or metastatic gynecologic cancer particularly lymph node metastases. Although the sensitivity of PET for detecting small metastases was relatively limited, the overall sensitivity of FDG PET was significantly higher than morphologic imaging.

Adult↗

[Oxytocin].

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Abortion, Threatened↗

Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing: a comparative study using simultaneously sampled histology materials.

BACKGROUND: In cervical lesions, the overexpression of p16 is reported to be closely associated with high-risk human papillomavirus (HPV) infection. The objective of the current study was to confirm the usefulness of liquid-based cervical specimens for p16 staining as well as tissue sections. METHODS: A total of 98 patients with cervical lesions were entered into the current study. After the cytologic examination using liquid-based cervical smears, the same slides were immunostained for p16 and were compared with slides of simultaneously obtained, immunohistologically stained tissue sections. Moreover, the status of the HPV infection was examined by polymerase chain reaction using residual cytologic samples. RESULTS: Using liquid-based Pap smears, 98 cases were diagnosed as atypical squamous cells of undetermined significance (38 cases), low-grade squamous intraepithelial lesion (12 cases), high-grade squamous intraepithelial lesion (HSIL) (33 cases), and invasive carcinoma (15 cases). The concordance rate between the cytologic and histologic diagnoses was found to be higher in high-grade lesions compared with low-grade lesions. Immunohistochemistry revealed that all HSIL and invasive carcinoma cases contained p16-positive cells in the liquid-based Pap smears and diffuse p16 staining was observed in all high-grade lesions with greater than CIN Grade 3 cervical intraepithelial neoplasia except for two adenocarcinoma cases. Of the 98 cases, 60 were found to be positive for high-risk HPV and 55 of these 60 HPV-positive cases were found to be p16 positive on cytologic examination. There were 16 cases that demonstrated marked discrepancies between the cytologic and histologic diagnoses. CONCLUSIONS: The results of the current study confirmed that the immunohistochemical detection of p16 was more sensitive and specific than HPV status in cervical lesions using a liquid-based method as well as tissue samples, suggesting that p16 should be used as a satisfactory biomarker for the primary screening of cervical cytology.

Adenocarcinoma↗