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ABSTRACT: This study was conducted to evaluate the correlation between color Doppler vascularity index (CDVI), clinical outcomes and five angiogenesis-related molecules including vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and calreticulin (CRT) in gastric cancer, and to develop an effective model selected from these five molecules to predict patient survival.
CDVI could be obtained preoperatively by transabdominal ultrasound from 30 patients. Enzyme immunoassay was adopted to determine protein level of VEGF and PlGF, and immunohistochemistry was used to detect COX-2, iNOS and CRT expression. Correlation between CDVI and five individual molecules was assessed. Multiple molecules model was developed using classification and regression tree (CART) analysis from five molecules, and was tested for patient survival in another 45 patients.
CDVI was significantly correlated with patient survival (P = 0.00907) and absolute number of metastatic lymph nodes (P = 0.01). There was no significant association between CDVI and any individual molecule. The model, developed by CART consisting of VEGF and PlGF, could differentiate high and low CDVI and survival in testing group (P = 0.00257).
CDVI was associated with lymph node metastasis, combined VEGF and PlGF expression status and patient survival in gastric cancer.
Journal of Surgical Oncology 07/2009; 99(7):402-8. · 2.10 Impact Factor
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ABSTRACT: Overexpression of eIF4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of growth-control gene products, which are normally translationally repressed. Overexpression of eIF4E was present in human breast carcinoma and human head and neck squamous cell carcinoma, and may be of prognostic value in breast carcinomas. In order to elucidate the clinical significance of eIF4E expression, this study was conducted to quantify expression of eIF4E in human gastric cancer tissue and correlate them with clinicopathological factors and patient survival.
Specimens from sixty-nine patients with gastric adenocarcinoma were analyzed and eIF4E overexpression was quantified by Western blot analysis. Quantification of eIF4E levels in cancer was expressed relative to controls from non-tumorous mucosa of the same patients. Confirmation of eIF4E overexpression at the cellular level was performed using immunohistochemical staining. The association of clinicopathologic factors and survival with eIF4E expression was analyzed.
In non-tumorous parts of specimens, overexpression of eIF4E was always present in gastric glands but not in gastric pits lining mucosa, and it was also expressed in the areas of intestinal metaplasia and dysplasia. In the 69 specimens, the mean eIF4E expression was 5.77 +/- 8.55-fold (mean +/- standard deviation), ranged from from 0.1-fold to 38-fold. The degree of eIF4E expression appeared to be independent of invasion depth of tumor, lymph node metastasis, Lauren classification, Borrmann types, and Helicobacter pylori infection. Marked overexpression of eIF4E (more than seven-fold) was correlated with tumor vascular invasion (P = 0.046, Fisher exact-test). The survival rate of the patients with underexpression or mild overexpression of eIF4E (less than sevenfold) was significantly higher than that with marked eIF4E overexpression (more than sevenfold) (P = 0.01734, log rank test).
Marked eIF4E overexpression in gastric cancer was found to be associated with vascular invasion. The prognosis for gastric cancer patients with marked overexpression of eIF4E was worse than those with underexpression. It may serve as an additional prognostic and therapeutic factor in gastric cancer, and deserves further investigation.
Journal of Surgical Oncology 05/2004; 86(1):22-7. · 2.10 Impact Factor
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Jin-Tung Liang,
Kuo-Chin Huang,
Hong-Shiee Lai,
Po-Huang Lee, Yung-Ming Cheng,
Hey-Chi Hsu,
Ann-Lii Cheng,
Chih-Hung Hsu,
Kun-Huei Yeh,
Shih-Ming Wang,
Chi Tang,
King-Jen Chang
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ABSTRACT: The influence of MSI on treatment outcome of colorectal cancers remains unclear and deserves further investigation. We recruited 244 patients with stage IV sporadic colorectal cancers for our study, based on appropriate eligibility criteria. Patients were nonrandomly allocated to 2 treatment groups of either with or without high-dose 5-FU plus leucovorin chemotherapy (HDFL, 5-FU 2,600 mg/m(2) leucovorin 300 mg/m(2) maximum 500 mg). Each treatment group was further divided into 2 subgroups according to high-frequency MSI (MSI-H) status. MSI-H was defined as the appearance of MSI in at least 2 of the 5 examined chromosomal loci (BAT-25, BAT-26, D5S346, D2S123, D17S250). We compared clinicopathologic parameters, p53 overexpression and overall survival between the groups. In addition, 4 subgroups were identified as follows: MSI-H(+)HDFL(+), n = 35; MSI-H(-)HDFL(+), n = 134; MSI-H(+)HDFL(-), n = 17; MSI-H(-)HDFL(-), n = 58. There was no significant difference of background clinicopathologic data between the HDFL(+) and HDFL(-) treatment groups (p > 0.05). Survival analyses indicated that the patients of subgroup MSI-H(+)HDFL(+) survived significantly longer than those of subgroup MSI-H(-)HDFL(+), with median survival times of 24 (95% CI 20.2-27.9) and 13 (95% CI 11.6-14.4) months, respectively (p = 0.0001, log-rank test). In contrast, in patients without chemotherapy, the prognosis was poor irrespective of MSI status, with median survival times of 7.0 (95% CI 4.6-9.4) and 7.0 (95% CI 6.1-7.9) months in the MSI-H(+)HDFL(-) and MSI-H(-)HDFL(-) subgroups, respectively (p = 0.8205, log-rank test). MSI-H cancers responded significantly better to HDFL (p = 0.001), with a mean response rate of 65.71% (95% CI 49.98-81.44%) in subgroup MSI-H(+)HDFL(+) compared to 35.07% (95% CI 26.99-43.15%) in subgroup MSI-H(-)HDFL(+). There appeared to be no preferential metastatic site where response to HDFL can be predicted based on the MSI status of the primary tumor. Toxicity to HDFL was similarly minimal between MSI-H(+) and MSI-H(-) patients (p > 0.05). Multivariate analysis of all patients further indicated that MSI-H and chemotherapy were independent favorable prognostic parameters (p < 0.05). Thus, the better prognosis of stage IV sporadic colorectal cancers with MSI-H may be associated with better chemosensitivity, rather than lower aggressiveness in biologic behavior.
International Journal of Cancer 11/2002; 101(6):519-25. · 5.44 Impact Factor
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ABSTRACT: It has been shown previously that proline-directed protein kinase F(A) (PDPK F(A)) is overexpressed in various human malignancies compared with its expression in normal controls, and the suppression of overexpressed PDPK F(A) is capable of inhibiting the growth of various types of human carcinoma cells, suggesting a role for this PDPK in human malignancies. In this report, the authors combine immunohistologic, molecular, cellular, and clinicopathologic studies to demonstrate further an essential critical role for overexpressed PDPK F(A) in bladder carcinoma invasion, chemoresistance, and poor prognosis.
The expression and localization of PDPK F(A) were analyzed by the immunohistochemical staining of specimens obtained from patients with primary transitional cell carcinoma (TCC) of the bladder. The stable antisense clones of human bladder carcinoma cells with specific suppression of overexpressed PDPK F(A) were established for invasion and chemosensitivity studies.
The immunohistochemical study revealed that PDPK F(A) was overexpressed preferentially in the invasive bladder carcinoma tissues. It was found that the stable antisense clones with specific suppression of overexpressed PDPK F(A) to approximately 40% of the parental control level were capable of inhibiting the invasive activity and simultaneously enhancing the chemosensitivity of bladder carcinoma cells to various therapeutic drugs, such as vinblastine, vincristine, paclitaxel, and bleomycin. Clinicopathologic studies also revealed a correlation between overexpressed PDPK F(A) and disease recurrence/survival in patients with primary TCC (P < 0.05).
Taken together, the results demonstrate an essential critical role of overexpressed PDPK F(A) in invasion, chemoresistance, and poor prognosis. Suppression of overexpressed PDPK F(A) may provide a new potential target for therapeutic intervention aimed at preventing chemoresistance, disease progression, and recurrence in patients with bladder carcinoma.
Cancer 09/2002; 95(4):775-83. · 4.77 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the clinical usefulness of microvessel density (MVD) and an in vivo angiogenesis parameter, color Doppler vascularity index (CDVI), in patients with gastric cancer.
Many studies have reported a significant association between the degree of MVD-evaluated angiogenesis with the clinicopathologic factors and prognosis of patients with various solid tumors. All these studies were accomplished on tissue sections retrospectively obtained from surgical specimens. However, an in vivo method to assess tumor angiogenesis for human malignancies is highly desirable for diagnostic purpose, treatment planning, and follow-up. The CDVI is a new ultrasound parameter for evaluating in vivo angiogenesis, has a good correlation with status of lymph node metastasis in cervical carcinoma, and can predict distant metastasis and survival in colon cancer patients. Therefore, the CDVI may also be useful to assess in vivo angiogenesis in human gastric cancer.
A total of 79 patients with gastric cancer were enrolled in this study, and microvessel density was evaluated by using immunohistochemical staining of surgical specimens with anti-CD-34 antibody. Tumors were sonographically visible in 31 patients. The CDVI of each tumor was determined using transabdominal color Doppler ultrasound. The CDVI was defined as the ratio of the number of the colored pixels within a tumor section to the number of total pixels in that specific tumor section, and was calculated by using Encomate software (Electronic Business Machine Co. Ltd., Taipei, Taiwan). Correlation between MVD, CDVI and clinicopathologic factors and patient survival was studied.
The MVD was significantly correlated with vascular invasion by multiple linear regression analysis. Although the survival of patients with high MVD (> 32) was significantly worse than those with low MVD (< 32) by univariate analysis, vascular invasion was an independent prognostic factor by Cox proportional hazard model. There was a linear correlation between CDVI and MVD (r =.495, P =.005). Moreover, in patients with a high CDVI (> 11%), the survival rate was significantly lower than that in those with low CDVI (< or = 11%, P =.005). None of the patients with high CDVI (> 11%) survived 2 years after curative resection. In addition to vascular invasion, the CDVI was another independent prognostic factor in the patients with stage III gastric cancer.
Vascular invasion was an important prognostic indicator in gastric cancer. The high CDVI was a good preoperative indicator of early death in stage III gastric cancer patients. Thus, the CDVI may be helpful in selecting patients with gastric cancer for neoadjuvant chemotherapy and/or anti-angiogenic therapy.
Annals of Surgery 04/2002; 235(4):512-8. · 7.49 Impact Factor
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ABSTRACT: Laparoscopy-assisted colectomy is technically feasible, but objective evidence of its benefits remains scarce. This study was done to evaluate the outcomes and operative stress of laparoscopy-assisted colectomy versus the traditional open method in the management of sigmoid complex polyps that cannot be safely or adequately removed by colonofibroscopy. Between January 1997 and December 1999, a total of 42 patients were equally randomized to the laparoscopy group and the laparotomy group by the blocked randomization method. Three patients randomized to the laparoscopy group did not complete the trial; therefore 18 patients treated by laparoscopy-assisted sigmoidectomy and the other 21 treated by the open method were prospectively evaluated. These two groups of patients were well matched in age, gender, symptoms, tumor location, localization method, tumor size, morphology, histopathology, and the accuracy of the clinical diagnosis. Two standardized surgical strategies, the lateral-to-medial and medial-to-lateral dissection sequences, were performed in 14 and 4 patients of the laparoscopy group, respectively, according to whether their tumors were located above or below 20 cm above the anal verge. After evaluating the surgical outcomes, we found that the laparoscopy group was significantly better than the laparotomy group in regard to parameters that included severity of postoperative pain, wound size, postoperative complication rate, and the duration of postoperative ileus, hospitalization, and disability. There was no significant difference in the operating times for these two groups. However, the costs of the laparoscopy group were significantly higher. To evaluate the surgical stress, we measured the serum C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), total lymphocyte count, and CD4+/CD8+ ratio 24 hours before and after surgery. We found that the postoperative serum CRP level and the ESR were significantly less elevated and the total lymphocyte counts and CD4+/CD8+ ratio were significantly less depressed in the laparoscopy group than in the laparotomy group. We thus concluded that laparoscopy-assisted sigmoidectomy can be safely performed with shorter convalescence and less operative stress but at a higher cost. We strongly recommended the use of this technique in the management of sigmoid complex polyps if the patient's economic status permits.
World Journal of Surgery 04/2002; 26(3):377-83. · 2.36 Impact Factor
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ABSTRACT: Laparoscopy-assisted colectomy istechnically feasible, but objective evidence of its benefits remainsscarce. This study was
done to evaluate the outcomes and operativestress of laparoscopy-assisted colectomy versus the traditional openmethod in the
management of sigmoid complex polyps that cannot besafely or adequately removed by colonofibroscopy. Between January 1997and
December 1999, a total of 42 patients were equally randomizedto the laparoscopy group and the laparotomy group by the blockedrandomization
method. Three patients randomized to the laparoscopygroup did not complete the trial; therefore 18 patients treated bylaparoscopy-assisted
sigmoidectomy and the other 21 treated by the openmethod were prospectively evaluated. These two groups of patients werewell
matched in age, gender, symptoms, tumor location, localizationmethod, tumor size, morphology, histopathology, and the accuracy
of theclinical diagnosis. Two standardized surgical strategies, thelateral-to-medial and medial-to-lateral dissection sequences,
wereperformed in 14 and 4 patients of the laparoscopy group, respectively,according to whether their tumors were located above
or below 20 cmabove the anal verge. After evaluating the surgical outcomes, we foundthat the laparoscopy group was significantly
better than the laparotomygroup in regard to parameters that included severity of postoperativepain, wound size, postoperative
complication rate, and the duration ofpostoperative ileus, hospitalization, and disability. There was nosignificant difference
in the operating times for these two groups.However, the costs of the laparoscopy group were significantly higher.To evaluate
the surgical stress, we measured the serum C-reactiveprotein (CRP) level, erythrocyte sedimentation rate (ESR), totallymphocyte
count, and CD4+/CD8+ ratio 24 hoursbefore and after surgery. We found that the postoperative serum CRPlevel and the ESR were
significantly less elevated and the totallymphocyte counts and CD4+/CD8+ ratio weresignificantly less depressed in the laparoscopy
group than in thelaparotomy group. We thus concluded that laparoscopy-assistedsigmoidectomy can be safely performed with shorter
convalescence andless operative stress but at a higher cost. We strongly recommended theuse of this technique in the management
of sigmoid complex polyps ifthe patient's economic status permits.
World Journal of Surgery 02/2002; 26(3):377-383. · 2.36 Impact Factor
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ABSTRACT: Our study aims to further clarify the prognostic significance of p53 overexpression in stage IV colorectal cancer. Between January 1994 and June 1997, we recruited 144 patients with stage IV colorectal cancers for our study, based on appropriate eligibility criteria. The patients were nonrandomly allocated to 2 treatment groups of either with or without high-dose 5-fluorouracil plus leucovorin chemotherapy (HDFL: 5-Fu: 2,600 mg/m(2) leucovorin 300 mg/m maximum 500 mg). Each treatment group was further divided into 2 subgroups according to the status of p53 overexpression. Therefore, 4 subgroups were allocated in our study and were designated as p53 (overexpression) HDFL (+), n = 65; p53 (normal) HDFL (+), n = 37; p53 (overexpression) HDFL (-), n = 27; and p53 (normal) HDFL (-), n = 15, respectively. All patients were prospectively followed until April 2001. There was no significant difference of the background clinicopathologic data of these 4 allocated subgroups of patients (p > 0.05). Multivariate analysis of various clinicopathologic factors of the whole group of patients indicated that age > or = 60 years, poor differentiation, mucin production, CEA > 100 ng/ml, p53 overexpression and without chemotherapy were the significant independent poor prognostic factors (p < 0.05). Survival analyses indicated that the patients of subgroup p53 (normal) HDFL (+) survived significantly longer than those of subgroup p53 (overexpression) HDFL (+), with mean survival time (95% confidence interval [CI]) of 20.24 (16.24-24.25) and 13.29 (10.98-15.60) months, respectively (p = 0.0043, log-rank test). In contrast, in patients without chemotherapy, the prognosis was poor regardless of their p53 status, with mean survival time (95% CI) of 6.85 (5.47-8.23) and 5.87 (4.48-7.26) months in p53 (overexpression) HDFL (-) and p53 (normal) HDFL (-) subgroups of patients, respectively (p = 0.2820, log-rank test). Cancers of normal p53 expression responded significantly better to HDFL (p < 0.05), with mean response rate (95% CI) being 65.57% (52.18-82.96%) in subgroup p53 (normal) HDFL (+) as compared to 35.38% (23.52-47.24%) in subgroup p53 (overexpression) HDFL (+). The toxicity to HDFL was similarly minimal between p53-normal and p53-overexpression patients (p > 0.05). We thus concluded that the poorer prognosis of stage IV colorectal cancers with p53 overexpression was associated with their poorer chemosensitivity rather than the more biologic aggressiveness.
International Journal of Cancer 02/2002; 97(4):451-7. · 5.44 Impact Factor
