Sertac Yazici - Academia.edu (original) (raw)

Papers by Sertac Yazici

Research paper thumbnail of Klinik Evre I Non-Seminomatöz Germ Hücreli Testis Tümörlerinin Tedavisi

Turkiye Klinikleri Journal of Urology Special Topics, 2008

Research paper thumbnail of Predictors of prostate cancer in ultrasound-guided transperineal saturation biopsy in Turkish men with multiple prior negative biopsies

Rivista Urologia, 2015

Transperineal prostate biopsy (STPB) is associated with an improved cancer detection rate and an ... more Transperineal prostate biopsy (STPB) is associated with an improved cancer detection rate and an increase in anterior and apical prostate cancers compared to standard transrectal biopsy. A total of 48 men with at least two sets of prior prostate biopsies underwent transrectal ultrasound-guided STPB. Prostate rebiopsy indications were serum prostate-specific antigen (PSA) levels greater than 2.5 ng/mL and/or abnormal digital rectal examination and/or presence of high-grade prostatic intraepithelial neoplasia (HGPIN; ≥2 cores) or atypical small acinar proliferation (ASAP) at previous biopsies. The procedure was performed at dorsal lithotomy position under general anesthesia using a perineal 0.5 cm brachytherapy template attached to the transrectal ultrasound probe. Specimens from each zone were sent separately for pathological examination. Mean PSA level at STPB was 15.9 ng/mL (range 4.03 to 59.57). An average of 54.5 cores was obtained. Prostate adenocarcinoma was detected in 15 of 48 (31%) patients. Mean percentage of malignant cores was 11.9%. Multivariate logistic regression analysis revealed that age and presence of ASAP or HGPIN at previous biopsies were independent predictors of prostate cancer (p<0.05). No major complications, including sepsis and severe urinary or rectal bleeding, were observed in any of the patients. Five patients (10%) developed acute urinary retention after the procedure requiring urethral catheterization. Considerable number of patients with negative multiple biopsies were diagnosed with prostate cancer. STPB is a well-tolerated procedure with minimal morbidity, which can be considered for the diagnosis of prostate cancer in patients with previous negative biopsies.

Research paper thumbnail of Ürolojik Malignitelerde Lazer Kullanımı

Turkiye Klinikleri Journal of Urology Special Topics, 2010

Research paper thumbnail of Inhibition of Platelet-Derived Growth Factor Receptor Signaling Restricts the Growth of Human Breast Cancer in the Bone of Nude Mice

Clinical Cancer Research an Official Journal of the American Association For Cancer Research, 2005

Purpose: Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF... more Purpose: Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFR) are involved in the regulation of bone resorption. This study examined the effects of STI571 (imatinib mesylate), which inhibits PDGFR tyrosine kinase signaling, on the growth of human breast cancer cells in the bone of nude mice with consequent osteolysis.

Research paper thumbnail of Böbrek Kanserlerinde Tanı Yöntemleri, Evrelendirme ve Prognostik Faktörler

Turkiye Klinikleri Uroloji Ozel Dergisi, 2011

Research paper thumbnail of Lev, D.C. et al. Inhibition of platelet-derived growth factor receptor signaling restricts the growth of human breast cancer in the bone of nude mice. Clin. Cancer Res. 11, 306-314

Clinical Cancer Research

Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDG... more Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFR) are involved in the regulation of bone resorption. This study examined the effects of STI571 (imatinib mesylate), which inhibits PDGFR tyrosine kinase signaling, on the growth of human breast cancer cells in the bone of nude mice with consequent osteolysis. Human breast cancer MDA-MB-435 cells were injected into the tibia of female nude mice. Two weeks later the mice were treated with p.o. and injected water (control), daily p.o. STI571, weekly injection of paclitaxel, or daily STI571, plus weekly paclitaxel, for up to 8 weeks. Growth of tumors in bones and osteolysis were monitored by digital radiography and tumors were collected for histochemical analysis. Mice treated with STI571 or STI571 plus paclitaxel had smaller bone tumors with less lytic bone destruction than did mice treated with water or paclitaxel alone. The results of treatment with paclitaxel plus STI57...

Research paper thumbnail of 1016 Does radiologic stage predict pathologic stage and cancer specific survival according to revised 7th TNM version in renal cancer?

European Urology Supplements, 2012

Research paper thumbnail of Detection of prostate cancer and changes in prostate-specific antigen (PSA) six months after surgery for benign prostatic hyperplasia in patients with elevated PSA

Urologia internationalis, 2003

To evaluate early postoperative results of patients with elevated prostate-specific antigen (PSA)... more To evaluate early postoperative results of patients with elevated prostate-specific antigen (PSA) levels who underwent surgery due to benign prostatic hyperplasia (BPH). 64 patients who had lower urinary tract symptoms (LUTS), normal digital rectal examinations (DRE), elevated PSA levels and prostate biopsies reported as being benign pathologically in specimens obtained by transrectal ultrasound (TRUS)-guided biopsies, were included in the study. Patients were assessed in accordance with PSA density, free/total PSA ratio and uroflowmetric studies. Patients had no cancer pre- and postoperatively (according to operative specimens). Six months postoperatively, 32 patients were accepted for re-evaluation for all PSA parameters, routine tests and prostatic biopsies. 64 patients with a mean age of 66.8 (SD 6.72) were included in the study. Total PSA average value was 14.38 (SD 7.49) ng/ml. Free PSA average value was 2.11 (SD 1.43) ng/ml. Average PSA density and free/total PSA ratio were 2...

Research paper thumbnail of Expression of glutathione-S-transferases isoenzymes and p53 in exfoliated human bladder cancer cells

Urologic Oncology: Seminars and Original Investigations, 2011

This study investigates the usefulness of glutathione-S-transferases (GST) isoenzymes and p53 imm... more This study investigates the usefulness of glutathione-S-transferases (GST) isoenzymes and p53 immunostaining as a marker of malignancy in urinary cytology, and evaluates their potential effect in increasing diagnostic accuracy in a series of urine cytologic samples. They are also correlated with cytopathology diagnosis and histopathologic diagnosis. In this study, the slides from 124 bladder carcinoma patients prepared by the cytocentrifugation method were observed. The cytomorphologic properties of these cancer cells were determined. Moreover, the immunocytochemical distributions of GST alpha (GSTA), pi (GSTP), mu (GSTM4), theta (GSTT1) isoenzymes and p53 protein were studied for the patients. The urothelial cancer cells had small cytoplasm and rough nuclear membrane. The chromatin granules were heterogeneously distributed in each malignant cell's nucleus. There was a pleomorphism of the malignant cells' nuclei. According to immunocytopathologic observations, the urothelial cancer cells had stronger staining intensity than the benign cells had in 48% of cases for GSTA, 46% of cases for GSTP, 38% of cases for GSTM4, and 42% of cases for GSTT1. For all papillary cases, the malignant cells were stained negative, while the benign cells were positive. For 83% of patients, the malignant cells were stained positive for p53. There was a significant difference in GSTA (P = 0.006), GSTT1 (P = 0.004), GSTP (P = 0.000) and p53 (P = 0.000) expressions for benign cells whereas, a non-statistical difference in the malignant cells for GSTA, GSTT1, GSTP, GSTM4, and p53 expressions (P > 0.05). GST isoenzymes and p53 immunostaining were not found to be markers of malignancy in urinary cytology.

Research paper thumbnail of Therapy of multidrug resistant human prostate tumors in the prostate of nude mice by simultaneous targeting of the epidermal growth factor receptor and vascular endothelial growth factor receptor on tumor-associated endothelial cells

The Prostate, 2006

BACKGROUND. Inhibiting epidermal growth factor receptor (EGF-R) and vascular endothelial growth f... more BACKGROUND. Inhibiting epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) activation with AEE788 can decrease prostate cancer (CaP) growth/progression. We determined whether tumor cells or tumor-associated endothelial cells were the primary target by treating multidrug-resistant (MDR) CaP growing in the prostate of nude mice. METHODS. MDR human CaP cells with 30-fold increased taxane-resistance were implanted into nude mouse prostates. After 2 weeks, mice were randomized to control, paclitaxel, AEE788, and AEE788/paclitaxel for 10 weeks. Mice were necropsied and tumors stained. RESULTS. AEE788 or AEE788 plus paclitaxel significantly reduced tumor incidence and tumor weight, and eradicated lymph node metastasis. Inhibiting VEGF-R and EGF-R phosphorylation induced apoptosis of tumor-associated endothelial cells causing a second apoptotic wave of surrounding tumor cells. CONCLUSION. Inhibiting VEGF-R and EGF-R activation on tumor-associated endothelial cells with AEE788 combined with paclitaxel can bypass CaP cell resistance and prevent lymph node metastasis.

Research paper thumbnail of Dual inhibition of the epidermal growth factor and vascular endothelial growth factor phosphorylation for antivascular therapy of human prostate cancer in the prostate of nude mice

The Prostate, 2005

BACKGROUND. Androgen-independent prostate cancer (PCa) may be susceptible to modulation of the tu... more BACKGROUND. Androgen-independent prostate cancer (PCa) may be susceptible to modulation of the tumor microenvironment. We determined whether a dual tyrosine kinase inhibitor (AEE788) of the epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) combined with chemotherapy can produce therapy of human PCa in nude mice. METHODS. PC-3MM2 human PCa cells were injected into the prostate of nude mice. Three days later, the mice were randomized into four groups: saline control, paclitaxel, AEE788, and AEE788 and paclitaxel. The mice were treated for 5 weeks and necropsied. Tumor incidence, weight, and incidence of lymph node metastasis were recorded. Tumor tissue was analyzed immunohistochemically. RESULTS. Treatment of mice with AEE788 or AEE788 plus paclitaxel significantly decreased tumor incidence, total tumor weight, and incidence of lymph node metastasis. AEE788 treatment alone or in combination with paclitaxel inhibited the phosphorylation of EGF-R and VEGF-R on tumor cells and tumor-associated endothelial cells. Therapeutic efficacy correlated with an increase in apoptosis of tumor cells and tumor-associated endothelial cells. CONCLUSION. Blockade of EGF-R and VEGF-R signaling pathways coupled with chemotherapy suppressed the progressive growth and metastasis of human PCa cells growing orthotopically in nude mice.

Research paper thumbnail of Induction of Apoptosis in Tumor-Associated Endothelial Cells and Therapy of Orthotopic Human Pancreatic Carcinoma in Nude Mice

Neoplasia, 2005

Although gemcitabine has been accepted as the firstline chemotherapeutic reagent for advanced pan... more Although gemcitabine has been accepted as the firstline chemotherapeutic reagent for advanced pancreatic cancer, improvement of response rate and survival is not sufficient and patients often develop resistance. We hypothesized that the inhibition of phosphorylation of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) on tumor cells and tumor-associated endothelial cells, combined with gemcitabine, would overcome the resistance to gemcitabine in orthotopic pancreatic tumor animal model. L3.6pl, human pancreatic cancer cells growing in the pancreas, and tumor-associated endothelial cells in microorgan environment highly expressed phosphorylated EGFR, VEGFR, and Akt, which regulates antiapoptotic mechanism. Oral administration of AEE788 (dual tyrosine kinase inhibitor against EGFR and VEGFR) inhibited the phosphorylation of EGFR, VEGFR, and Akt on tumor-associated endothelial cells as well as tumor cells. Although intraperitoneal (i.p.) injection of gemcitabine showed limited inhibitory effect on tumor growth, combination with AEE788 and gemcitabine produced nearly 95% inhibition of tumor growth in parallel with a high level of apoptosis on tumor cells and tumor-associated endothelial cells, and decreased microvascular density and proliferation rate. Collectively, these data indicate that dual inhibition of phosphorylation of EGFR and VEGFR, in combination with gemcitabine, produces apoptosis of tumor-associated endothelial cells and significantly suppresses human pancreatic cancer in nude mice. Neoplasia (2005) 7, 696 -704

Research paper thumbnail of A NEW DEVICE FOR THE TREATMENT OF POST- PROSTATECTOMY INCONTINENCE: ADJUSTABLE PERINEAL MALE SLING

The Journal of Urology, 2008

Research paper thumbnail of 527 A PREOPERATIVE PROGNOSTIC MODEL PREDICTING RECURRENCE FREE SURVIVAL FOR PATIENTS WITH KIDNEY CANCER: A MULTI-CENTER STUDY BY THE SOCIETY OF UROONCOLOGY

The Journal of Urology, 2011

Research paper thumbnail of In Vivo Imaging of Luciferase-Labeled Human Prostate Cancer Cells, PC-3MM2, in Orthotopic Nude Mouse Models

The Journal of Urology, 2008

Research paper thumbnail of CCR7 and CXCR4 as Novel Biomarkers Predicting Axillary Lymph Node Metastasis in T1 Breast Cancer

Clinical Cancer Research, 2005

The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metast... more The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metastasis. We therefore studied the differential expression of CCR7 and CXCR4, along with that of the biomarker HER2-neu, to evaluate whether these biomarkers could predict axillary lymph node metastasis in breast cancer. Biomarker expression levels were evaluated using paraffin-embedded tissue sections of lymph node-negative (n = 99) and lymph node-positive (n = 98) T1 breast cancer by immunohistochemical staining. Lymph node-positive tumors showed higher rates of high cytoplasmic CCR7 staining (21.5% versus 8.5%, P = 0.013) and HER2-neu overexpression (21.5% versus 9.3%, P = 0.019) than did lymph node-negative tumors. Similarly, high cytoplasmic CXCR4 expression occurred more commonly in lymph node-positive tumors (11.2% versus 5.1%, P = 0.113). In contrast, predominantly nuclear CXCR4 staining was more likely to be found in lymph node-negative tumors (54.5% versus 37.8%, P = 0.018). Furthermore, cytoplasmic CXCR4 coexpressed with HER2-neu was the only factor associated with involvement of four or more lymph nodes (16.7% versus 1.2%, P = 0.04) among lymph node-positive tumors. When all three biomarkers (CCR7, CXCR4, HER2-neu) were utilized together, 50.0% of lymph node-positive tumors highly expressed one of these biomarkers compared with 18.8% of the lymph node-negative tumors (P < 0.0001). Our results suggest that the chemokine receptor CCR7 is a novel biomarker that can predict lymph node metastases in breast cancer. Utilization of additional markers, such as CXCR4 and HER2-neu, further improves the prediction of the presence and extent of lymph node involvement.

Research paper thumbnail of Antivascular Therapy for Orthotopic Human Ovarian Carcinoma through Blockade of the Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptors

Clinical Cancer Research, 2005

Purpose: We determined whether the administration of the tyrosine kinase inhibitor, AEE788, which... more Purpose: We determined whether the administration of the tyrosine kinase inhibitor, AEE788, which targets the epidermal growth factor receptor and the vascular endothelial growth factor receptor, alone or in combination with paclitaxel, can inhibit progressive growth of human ovarian carcinoma in the peritoneal cavity of female nude mice. Experimental Design:Western blot analysis and immunohistochemical analysis identified the optimal dose and schedule of AEE788 therapy. In several different experiments, paclitaxelsensitive and paclitaxel-resistant human ovarian carcinoma cells were injected into the peritoneal cavity of nude mice. Seven days later, treatment with saline (control), AEE788 alone, paclitaxel alone, or a combination of AEE788 and paclitaxel began and continued for 45 days when the mice were necropsied. In independent survival experiments, the mice were necropsied when they became moribund. Results: Oral administration of AEE788 inhibited phosphorylation of the epidermal growth factor receptor and vascular endothelial growth factor receptor for up to 48 hours. Treatment with AEE788 plus paclitaxel significantly reduced tumor weight and increased survival of mice implanted with paclitaxel-sensitive cell lines compared with control mice or mice treated with AEE788 alone or paclitaxel alone. In mice implanted with paclitaxel-resistant cells, the combination therapy also significantly reduced tumor weight but did not prolong survival.The combination therapy induced apoptosis of both tumor cells and tumor-associated endothelial cells. Conclusions: The administration of AEE788 and paclitaxel inhibits the progression of human ovarian carcinoma in the peritoneal cavity of female nude mice, in part, by inducing apoptosis of tumor-associated endothelial cells.

Research paper thumbnail of Dual Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation by AEE788 Reduces Growth and Metastasis of Human Colon Carcinoma in an Orthotopic Nude Mouse Model

Cancer Research, 2005

We studied growth factors and their receptors in tumor cells and tumor-associated endothelial cel... more We studied growth factors and their receptors in tumor cells and tumor-associated endothelial cells as the therapeutic targets in colon cancer.

Research paper thumbnail of Simultaneous Blockade of Platelet-Derived Growth Factor-Receptor and Epidermal Growth Factor-Receptor Signaling and Systemic Administration of Paclitaxel as Therapy for Human Prostate Cancer Metastasis in Bone of Nude Mice

Research paper thumbnail of Management of High-Risk Localised Prostate Cancer

a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w... more a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m

Research paper thumbnail of Klinik Evre I Non-Seminomatöz Germ Hücreli Testis Tümörlerinin Tedavisi

Turkiye Klinikleri Journal of Urology Special Topics, 2008

Research paper thumbnail of Predictors of prostate cancer in ultrasound-guided transperineal saturation biopsy in Turkish men with multiple prior negative biopsies

Rivista Urologia, 2015

Transperineal prostate biopsy (STPB) is associated with an improved cancer detection rate and an ... more Transperineal prostate biopsy (STPB) is associated with an improved cancer detection rate and an increase in anterior and apical prostate cancers compared to standard transrectal biopsy. A total of 48 men with at least two sets of prior prostate biopsies underwent transrectal ultrasound-guided STPB. Prostate rebiopsy indications were serum prostate-specific antigen (PSA) levels greater than 2.5 ng/mL and/or abnormal digital rectal examination and/or presence of high-grade prostatic intraepithelial neoplasia (HGPIN; ≥2 cores) or atypical small acinar proliferation (ASAP) at previous biopsies. The procedure was performed at dorsal lithotomy position under general anesthesia using a perineal 0.5 cm brachytherapy template attached to the transrectal ultrasound probe. Specimens from each zone were sent separately for pathological examination. Mean PSA level at STPB was 15.9 ng/mL (range 4.03 to 59.57). An average of 54.5 cores was obtained. Prostate adenocarcinoma was detected in 15 of 48 (31%) patients. Mean percentage of malignant cores was 11.9%. Multivariate logistic regression analysis revealed that age and presence of ASAP or HGPIN at previous biopsies were independent predictors of prostate cancer (p<0.05). No major complications, including sepsis and severe urinary or rectal bleeding, were observed in any of the patients. Five patients (10%) developed acute urinary retention after the procedure requiring urethral catheterization. Considerable number of patients with negative multiple biopsies were diagnosed with prostate cancer. STPB is a well-tolerated procedure with minimal morbidity, which can be considered for the diagnosis of prostate cancer in patients with previous negative biopsies.

Research paper thumbnail of Ürolojik Malignitelerde Lazer Kullanımı

Turkiye Klinikleri Journal of Urology Special Topics, 2010

Research paper thumbnail of Inhibition of Platelet-Derived Growth Factor Receptor Signaling Restricts the Growth of Human Breast Cancer in the Bone of Nude Mice

Clinical Cancer Research an Official Journal of the American Association For Cancer Research, 2005

Purpose: Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF... more Purpose: Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFR) are involved in the regulation of bone resorption. This study examined the effects of STI571 (imatinib mesylate), which inhibits PDGFR tyrosine kinase signaling, on the growth of human breast cancer cells in the bone of nude mice with consequent osteolysis.

Research paper thumbnail of Böbrek Kanserlerinde Tanı Yöntemleri, Evrelendirme ve Prognostik Faktörler

Turkiye Klinikleri Uroloji Ozel Dergisi, 2011

Research paper thumbnail of Lev, D.C. et al. Inhibition of platelet-derived growth factor receptor signaling restricts the growth of human breast cancer in the bone of nude mice. Clin. Cancer Res. 11, 306-314

Clinical Cancer Research

Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDG... more Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFR) are involved in the regulation of bone resorption. This study examined the effects of STI571 (imatinib mesylate), which inhibits PDGFR tyrosine kinase signaling, on the growth of human breast cancer cells in the bone of nude mice with consequent osteolysis. Human breast cancer MDA-MB-435 cells were injected into the tibia of female nude mice. Two weeks later the mice were treated with p.o. and injected water (control), daily p.o. STI571, weekly injection of paclitaxel, or daily STI571, plus weekly paclitaxel, for up to 8 weeks. Growth of tumors in bones and osteolysis were monitored by digital radiography and tumors were collected for histochemical analysis. Mice treated with STI571 or STI571 plus paclitaxel had smaller bone tumors with less lytic bone destruction than did mice treated with water or paclitaxel alone. The results of treatment with paclitaxel plus STI57...

Research paper thumbnail of 1016 Does radiologic stage predict pathologic stage and cancer specific survival according to revised 7th TNM version in renal cancer?

European Urology Supplements, 2012

Research paper thumbnail of Detection of prostate cancer and changes in prostate-specific antigen (PSA) six months after surgery for benign prostatic hyperplasia in patients with elevated PSA

Urologia internationalis, 2003

To evaluate early postoperative results of patients with elevated prostate-specific antigen (PSA)... more To evaluate early postoperative results of patients with elevated prostate-specific antigen (PSA) levels who underwent surgery due to benign prostatic hyperplasia (BPH). 64 patients who had lower urinary tract symptoms (LUTS), normal digital rectal examinations (DRE), elevated PSA levels and prostate biopsies reported as being benign pathologically in specimens obtained by transrectal ultrasound (TRUS)-guided biopsies, were included in the study. Patients were assessed in accordance with PSA density, free/total PSA ratio and uroflowmetric studies. Patients had no cancer pre- and postoperatively (according to operative specimens). Six months postoperatively, 32 patients were accepted for re-evaluation for all PSA parameters, routine tests and prostatic biopsies. 64 patients with a mean age of 66.8 (SD 6.72) were included in the study. Total PSA average value was 14.38 (SD 7.49) ng/ml. Free PSA average value was 2.11 (SD 1.43) ng/ml. Average PSA density and free/total PSA ratio were 2...

Research paper thumbnail of Expression of glutathione-S-transferases isoenzymes and p53 in exfoliated human bladder cancer cells

Urologic Oncology: Seminars and Original Investigations, 2011

This study investigates the usefulness of glutathione-S-transferases (GST) isoenzymes and p53 imm... more This study investigates the usefulness of glutathione-S-transferases (GST) isoenzymes and p53 immunostaining as a marker of malignancy in urinary cytology, and evaluates their potential effect in increasing diagnostic accuracy in a series of urine cytologic samples. They are also correlated with cytopathology diagnosis and histopathologic diagnosis. In this study, the slides from 124 bladder carcinoma patients prepared by the cytocentrifugation method were observed. The cytomorphologic properties of these cancer cells were determined. Moreover, the immunocytochemical distributions of GST alpha (GSTA), pi (GSTP), mu (GSTM4), theta (GSTT1) isoenzymes and p53 protein were studied for the patients. The urothelial cancer cells had small cytoplasm and rough nuclear membrane. The chromatin granules were heterogeneously distributed in each malignant cell's nucleus. There was a pleomorphism of the malignant cells' nuclei. According to immunocytopathologic observations, the urothelial cancer cells had stronger staining intensity than the benign cells had in 48% of cases for GSTA, 46% of cases for GSTP, 38% of cases for GSTM4, and 42% of cases for GSTT1. For all papillary cases, the malignant cells were stained negative, while the benign cells were positive. For 83% of patients, the malignant cells were stained positive for p53. There was a significant difference in GSTA (P = 0.006), GSTT1 (P = 0.004), GSTP (P = 0.000) and p53 (P = 0.000) expressions for benign cells whereas, a non-statistical difference in the malignant cells for GSTA, GSTT1, GSTP, GSTM4, and p53 expressions (P > 0.05). GST isoenzymes and p53 immunostaining were not found to be markers of malignancy in urinary cytology.

Research paper thumbnail of Therapy of multidrug resistant human prostate tumors in the prostate of nude mice by simultaneous targeting of the epidermal growth factor receptor and vascular endothelial growth factor receptor on tumor-associated endothelial cells

The Prostate, 2006

BACKGROUND. Inhibiting epidermal growth factor receptor (EGF-R) and vascular endothelial growth f... more BACKGROUND. Inhibiting epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) activation with AEE788 can decrease prostate cancer (CaP) growth/progression. We determined whether tumor cells or tumor-associated endothelial cells were the primary target by treating multidrug-resistant (MDR) CaP growing in the prostate of nude mice. METHODS. MDR human CaP cells with 30-fold increased taxane-resistance were implanted into nude mouse prostates. After 2 weeks, mice were randomized to control, paclitaxel, AEE788, and AEE788/paclitaxel for 10 weeks. Mice were necropsied and tumors stained. RESULTS. AEE788 or AEE788 plus paclitaxel significantly reduced tumor incidence and tumor weight, and eradicated lymph node metastasis. Inhibiting VEGF-R and EGF-R phosphorylation induced apoptosis of tumor-associated endothelial cells causing a second apoptotic wave of surrounding tumor cells. CONCLUSION. Inhibiting VEGF-R and EGF-R activation on tumor-associated endothelial cells with AEE788 combined with paclitaxel can bypass CaP cell resistance and prevent lymph node metastasis.

Research paper thumbnail of Dual inhibition of the epidermal growth factor and vascular endothelial growth factor phosphorylation for antivascular therapy of human prostate cancer in the prostate of nude mice

The Prostate, 2005

BACKGROUND. Androgen-independent prostate cancer (PCa) may be susceptible to modulation of the tu... more BACKGROUND. Androgen-independent prostate cancer (PCa) may be susceptible to modulation of the tumor microenvironment. We determined whether a dual tyrosine kinase inhibitor (AEE788) of the epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) combined with chemotherapy can produce therapy of human PCa in nude mice. METHODS. PC-3MM2 human PCa cells were injected into the prostate of nude mice. Three days later, the mice were randomized into four groups: saline control, paclitaxel, AEE788, and AEE788 and paclitaxel. The mice were treated for 5 weeks and necropsied. Tumor incidence, weight, and incidence of lymph node metastasis were recorded. Tumor tissue was analyzed immunohistochemically. RESULTS. Treatment of mice with AEE788 or AEE788 plus paclitaxel significantly decreased tumor incidence, total tumor weight, and incidence of lymph node metastasis. AEE788 treatment alone or in combination with paclitaxel inhibited the phosphorylation of EGF-R and VEGF-R on tumor cells and tumor-associated endothelial cells. Therapeutic efficacy correlated with an increase in apoptosis of tumor cells and tumor-associated endothelial cells. CONCLUSION. Blockade of EGF-R and VEGF-R signaling pathways coupled with chemotherapy suppressed the progressive growth and metastasis of human PCa cells growing orthotopically in nude mice.

Research paper thumbnail of Induction of Apoptosis in Tumor-Associated Endothelial Cells and Therapy of Orthotopic Human Pancreatic Carcinoma in Nude Mice

Neoplasia, 2005

Although gemcitabine has been accepted as the firstline chemotherapeutic reagent for advanced pan... more Although gemcitabine has been accepted as the firstline chemotherapeutic reagent for advanced pancreatic cancer, improvement of response rate and survival is not sufficient and patients often develop resistance. We hypothesized that the inhibition of phosphorylation of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) on tumor cells and tumor-associated endothelial cells, combined with gemcitabine, would overcome the resistance to gemcitabine in orthotopic pancreatic tumor animal model. L3.6pl, human pancreatic cancer cells growing in the pancreas, and tumor-associated endothelial cells in microorgan environment highly expressed phosphorylated EGFR, VEGFR, and Akt, which regulates antiapoptotic mechanism. Oral administration of AEE788 (dual tyrosine kinase inhibitor against EGFR and VEGFR) inhibited the phosphorylation of EGFR, VEGFR, and Akt on tumor-associated endothelial cells as well as tumor cells. Although intraperitoneal (i.p.) injection of gemcitabine showed limited inhibitory effect on tumor growth, combination with AEE788 and gemcitabine produced nearly 95% inhibition of tumor growth in parallel with a high level of apoptosis on tumor cells and tumor-associated endothelial cells, and decreased microvascular density and proliferation rate. Collectively, these data indicate that dual inhibition of phosphorylation of EGFR and VEGFR, in combination with gemcitabine, produces apoptosis of tumor-associated endothelial cells and significantly suppresses human pancreatic cancer in nude mice. Neoplasia (2005) 7, 696 -704

Research paper thumbnail of A NEW DEVICE FOR THE TREATMENT OF POST- PROSTATECTOMY INCONTINENCE: ADJUSTABLE PERINEAL MALE SLING

The Journal of Urology, 2008

Research paper thumbnail of 527 A PREOPERATIVE PROGNOSTIC MODEL PREDICTING RECURRENCE FREE SURVIVAL FOR PATIENTS WITH KIDNEY CANCER: A MULTI-CENTER STUDY BY THE SOCIETY OF UROONCOLOGY

The Journal of Urology, 2011

Research paper thumbnail of In Vivo Imaging of Luciferase-Labeled Human Prostate Cancer Cells, PC-3MM2, in Orthotopic Nude Mouse Models

The Journal of Urology, 2008

Research paper thumbnail of CCR7 and CXCR4 as Novel Biomarkers Predicting Axillary Lymph Node Metastasis in T1 Breast Cancer

Clinical Cancer Research, 2005

The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metast... more The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metastasis. We therefore studied the differential expression of CCR7 and CXCR4, along with that of the biomarker HER2-neu, to evaluate whether these biomarkers could predict axillary lymph node metastasis in breast cancer. Biomarker expression levels were evaluated using paraffin-embedded tissue sections of lymph node-negative (n = 99) and lymph node-positive (n = 98) T1 breast cancer by immunohistochemical staining. Lymph node-positive tumors showed higher rates of high cytoplasmic CCR7 staining (21.5% versus 8.5%, P = 0.013) and HER2-neu overexpression (21.5% versus 9.3%, P = 0.019) than did lymph node-negative tumors. Similarly, high cytoplasmic CXCR4 expression occurred more commonly in lymph node-positive tumors (11.2% versus 5.1%, P = 0.113). In contrast, predominantly nuclear CXCR4 staining was more likely to be found in lymph node-negative tumors (54.5% versus 37.8%, P = 0.018). Furthermore, cytoplasmic CXCR4 coexpressed with HER2-neu was the only factor associated with involvement of four or more lymph nodes (16.7% versus 1.2%, P = 0.04) among lymph node-positive tumors. When all three biomarkers (CCR7, CXCR4, HER2-neu) were utilized together, 50.0% of lymph node-positive tumors highly expressed one of these biomarkers compared with 18.8% of the lymph node-negative tumors (P < 0.0001). Our results suggest that the chemokine receptor CCR7 is a novel biomarker that can predict lymph node metastases in breast cancer. Utilization of additional markers, such as CXCR4 and HER2-neu, further improves the prediction of the presence and extent of lymph node involvement.

Research paper thumbnail of Antivascular Therapy for Orthotopic Human Ovarian Carcinoma through Blockade of the Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptors

Clinical Cancer Research, 2005

Purpose: We determined whether the administration of the tyrosine kinase inhibitor, AEE788, which... more Purpose: We determined whether the administration of the tyrosine kinase inhibitor, AEE788, which targets the epidermal growth factor receptor and the vascular endothelial growth factor receptor, alone or in combination with paclitaxel, can inhibit progressive growth of human ovarian carcinoma in the peritoneal cavity of female nude mice. Experimental Design:Western blot analysis and immunohistochemical analysis identified the optimal dose and schedule of AEE788 therapy. In several different experiments, paclitaxelsensitive and paclitaxel-resistant human ovarian carcinoma cells were injected into the peritoneal cavity of nude mice. Seven days later, treatment with saline (control), AEE788 alone, paclitaxel alone, or a combination of AEE788 and paclitaxel began and continued for 45 days when the mice were necropsied. In independent survival experiments, the mice were necropsied when they became moribund. Results: Oral administration of AEE788 inhibited phosphorylation of the epidermal growth factor receptor and vascular endothelial growth factor receptor for up to 48 hours. Treatment with AEE788 plus paclitaxel significantly reduced tumor weight and increased survival of mice implanted with paclitaxel-sensitive cell lines compared with control mice or mice treated with AEE788 alone or paclitaxel alone. In mice implanted with paclitaxel-resistant cells, the combination therapy also significantly reduced tumor weight but did not prolong survival.The combination therapy induced apoptosis of both tumor cells and tumor-associated endothelial cells. Conclusions: The administration of AEE788 and paclitaxel inhibits the progression of human ovarian carcinoma in the peritoneal cavity of female nude mice, in part, by inducing apoptosis of tumor-associated endothelial cells.

Research paper thumbnail of Dual Inhibition of Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Phosphorylation by AEE788 Reduces Growth and Metastasis of Human Colon Carcinoma in an Orthotopic Nude Mouse Model

Cancer Research, 2005

We studied growth factors and their receptors in tumor cells and tumor-associated endothelial cel... more We studied growth factors and their receptors in tumor cells and tumor-associated endothelial cells as the therapeutic targets in colon cancer.

Research paper thumbnail of Simultaneous Blockade of Platelet-Derived Growth Factor-Receptor and Epidermal Growth Factor-Receptor Signaling and Systemic Administration of Paclitaxel as Therapy for Human Prostate Cancer Metastasis in Bone of Nude Mice

Research paper thumbnail of Management of High-Risk Localised Prostate Cancer

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