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Joel W Slaton

Publications and source records attributed to Joel W Slaton.

At least 19 recordsLinked to original sources
PubMed2006

CK2 signaling in androgen-dependent and -independent prostate cancer.

Protein serine/threonine kinase casein kinase 2 (CK2) is a key player in cell growth and proliferation but is also a potent suppressor of apoptosis. CK2 has been found to be dysregulated in all the cancers that have been examined, including prostate cancer. Investigations of CK2 signaling in the prostate were originally initiated in this laboratory, and these studies have identified significant functional activities of CK2 in relation to normal prostate growth and to the pathobiology of androgen-dependent and -independent prostate cancer. We present a brief overview of these developments in the context of prostate biology. An important outcome of these studies is the emerging concept that CK2 can be effectively targeted for cancer therapy.

Androgens↗
PubMed2006

Risk factors for upper tract recurrence in patients undergoing long-term surveillance for stage ta bladder cancer.

PURPOSE: While the evidence is clear that patients with carcinoma in situ or high grade T1 TCC of the bladder are at higher risk for developing UUT tumors, the role of imaging the UUT in patients with Ta tumors remains controversial. We hypothesized that the number and frequency of recurrences in patients with Ta disease would allow us to identify a population who should undergo routine UUT surveillance. MATERIALS AND METHODS: We reviewed our database of 375 patients who underwent resection of a stage Ta TCC between 1975 and 1995. Median followup was 6 years. Patients were stratified according to the presence of an UUT occurrence, rate and timing of superficial recurrences, and grade of the initial bladder tumor. RESULTS: Among the 375 patients 50% had no bladder recurrence, 25% had 1 tumor, 15% had 2 tumors, and 10% had 3 or more tumors. Average time between tumors was 17 months. UUT tumor developed in 13 patients (3.4%) at an average of 22 months after their initial bladder tumor. A high risk group consisting of patients who had 2 or more bladder recurrences recurring within 12 months of each other were at 4.5-fold the risk of UUT tumor. CONCLUSIONS: Stage Ta bladder cancer patients with 2 or more recurrences of bladder tumors with a median of less than 12 months between recurrences are at higher risk for developing an UUT tumor and should be considered for more frequent UUT surveillance.

Carcinoma, Transitional Cell↗
PubMed2005

Downregulation of CK2 induces apoptosis in cancer cells--a potential approach to cancer therapy.

We have previously documented that naked antisense CK2alpha ODN can potently induce apoptosis in cancer cells in culture and in mouse xenograft human prostate cancer. The effects of the antisense CK2alpha are related to downregulation of CK2alpha message and rapid loss of the CK2 from the nuclear compartment. Here we demonstrate that downregulation of CK2 elicited by diverse methods leads to inhibition of cell growth and induction of apoptosis. The various approaches to downregulation of CK2 employed were transfection with kinase-inactive plasmid, use of CK2alpha siRNA, use of inhibitors of CK2 activity, and use of antisense CK2alpha ODN packaged in sub-50 nm nanocapsules made from tenascin. In all cases, the downregulation of CK2 is associated with loss in cell survival. We have also described preliminary observations on an approach to targeting CK2 in cancer cells. For this, sub-50 nm tenascin-based nanocapsules bearing the antisense CK2alpha ODN were employed to test that the antisense is delivered to the cancer cells in vivo. The results provide the first preliminary evidence that such an approach may be feasible for targeting CK2 in cancer cells. Together, our results suggest that CK2 is potentially a highly plausible target for cancer therapy.

Animals↗
PubMed2005

Elevation of dipeptidylpeptidase iv activities in the prostate peripheral zone and prostatic secretions of men with prostate cancer: possible prostate cancer disease marker.

PURPOSE: Dipeptidylpeptidase IV (DPIV) is a multifunctional type II plasma membrane glycoprotein with serine-type exopeptidase activity that is secreted by the prostate and increased in prostate cancer. We determined whether changes in DPIV activities in prostatic tissue zones and expressed secretions were associated with the presence of cancer. MATERIALS AND METHODS: Expressed prostatic secretion (EPS), and biopsy of the transition (TZ) and peripheral (PZ) zones were collected from men undergoing ultrasound guided prostate biopsy. DPIV activities were measured by glypro-p-nitroanalide hydrolysis. RESULTS: DPIV activities were significantly higher in TZ than in PZ tissues in men with no evidence of malignancy. However, activities in EPS were negatively associated with TZ volume and positively associated with PZ volume. Mean and median DPIV activities in EPS from men with biopsy determined cancer were significantly higher than in men with no evidence of malignancy. DPIV activities in TZ and PZ biopsies were higher in men with cancer but most markedly in the PZ. CONCLUSIONS: These data indicate that secreted DPIV originates from the TZ and PZ. Increased DPIV activities in cancer are strongly associated with the PZ, which is the zone most commonly involved with cancer. Measuring DPIV levels in expressed EPS or post-digital rectal prostate examination urine may be useful for evaluating men for prostate cancer.

Adenosine Deaminase↗
PubMed2004

Prognostic value of body mass index in patients undergoing nephrectomy for localized renal tumors.

OBJECTIVES: To identify whether the body mass index (BMI) has any adverse effect on the prognosis of patients with established renal cell carcinoma, given the increasing prevalence of obesity and the rising incidence of renal cell carcinoma in the United States. METHODS: We reviewed the records of patients who underwent nephrectomy for localized disease between 1985 and 1998 at our institution. Patients were grouped according to BMI as normal (less than 25 kg/m2), overweight (25 to 30 kg/m2), or obese (more than 30 kg/m2). Cox regression analysis was used to determine the significant predictors of metastasis and survival. RESULTS: A total of 400 patients met the inclusion criteria. On univariate analysis, normal BMI (P = 0.018), pathologic stage (P <0.0001), Fuhrman grade (P = 0.007), maximal tumor size (P = 0.005), and time to recurrence (P <0.0001) were significant predictors of disease-specific death. On multivariate regression analysis, the time to metastasis (P <0.0001) was the best predictor of disease-specific death, followed by BMI (normal versus overweight or obese; P = 0.006) and pathologic stage (P = 0.007). Patients with a normal BMI who had pathologic Stage pT3 or greater and developed metastasis within 19 months of surgery had the worst prognosis, with a disease-specific death rate of 52.0%. CONCLUSIONS: Our findings suggest that overweight and obese patients with renal cell carcinoma have a more favorable prognosis than patients with a normal BMI. If others confirm our finding that a high BMI confers a survival advantage to patients undergoing nephrectomy, BMI may prove to be an important prognostic factor in renal cell carcinoma.

Adult↗
PubMed2004

Tumor length and location of cancer on biopsy predict for side specific extraprostatic cancer extension.

PURPOSE: We studied preoperative variables in a contemporary series of men who underwent nonnerve sparing radical prostatectomy in an effort to establish criteria that would predict side specific extraprostatic extension (EPE) of cancer. MATERIALS AND METHODS: We reviewed the records of 430 patients who underwent radical prostatectomy for localized prostate cancer with no prior therapy between 1996 and 1998, and for whom we had at least sextant biopsy information. We evaluated biopsy data (Gleason score, maximum length of cancer in positive cores, percent of cancer per involved core, proportion of positive biopsy cores, tumor location and number of positive biopsy cores) and correlated these findings with EPE at the neurovascular bundle and posterior lateral (NVB/PL) region. RESULTS: We found that a higher number of positive cores, a higher biopsy Gleason score on a side, a positive core at the basal region, 50% or greater tumor in the core or a maximum tumor length of 7 mm or greater increased the likelihood that EPE was present at the NVB/PL region on the corresponding side of the prostate. On multivariate analysis maximum tumor length 7 mm or greater and positive basal core location were the strongest independent predictors of EPE at the NVB/PL region on a given side (p <0.0001 and 0.002, respectively). CONCLUSIONS: Excluding any patient with 1 positive biopsy core with a maximum tumor length of 7 mm or greater plus a positive basal core of any tumor length and grade can decrease the risk of EPE at the NVB/PL region to approximately 10%.

Biopsy↗
PubMed2004

Correlation of metastasis related gene expression and relapse-free survival in patients with locally advanced bladder cancer treated with cystectomy and chemotherapy.

PURPOSE: Patients with locally advanced (ie clinically extravesical) transitional cell carcinoma are at high risk for recurrence after cystectomy. Although randomized trials have established an incremental benefit from the addition of chemotherapy in this setting, many patients still have disease relapse, and therefore it is necessary to determine patient and tumor characteristics that correlate with outcome in this setting. We investigated the tumor expression of several metastasis related genes and the association of gene expression with disease specific survival of patients with locally advanced transitional cell carcinoma treated randomized to either neoadjuvant or adjuvant chemotherapy and radical cystectomy. MATERIALS AND METHODS: Archival paraffin embedded specimens were available for 64 patients enrolled in a clinical trial of the methotrexate, vinblastine, doxorubicin and cisplatin regimen and cystectomy. Only samples obtained before exposure to chemotherapy were studied. The expression of several metastasis related genes, including basic fibroblast growth factor, vascular endothelial growth factor (VEGF), interleukin-8, matrix metalloproteinase (MMP)-9, and E-cadherin were assayed on paraffin sections using a colorimetric in situ hybridization assay. RESULTS: Expression of basic fibroblast growth factor, interleukin-8 and MMP-9 did not correlate with outcome. Expression of VEGF and E-cadherin were strongly related to disease specific survival. In addition, the ratio of MMP-9-to-E-cadherin was strongly prognostic for disease specific survival. CONCLUSIONS: These data advance the hypotheses that VEGF expression and an "invasive phenotype" characterized by the ratio of MMP-9-to-E-cadherin expression are mechanistically relevant to clinically aggressive locally advanced bladder cancers that are not cured by currently available combined modality treatment. Thus, in our view there is a compelling rationale to target these aspects of the malignant phenotype in this patient population.

Adult↗
PubMed2004

Percutaneous renal stone extraction: in vitro study of retrieval devices.

PURPOSE: Traditionally, percutaneous stone extraction has relied on the use of 2-prong and 3-prong graspers, which are prone to causing trauma to the urothelium. We evaluate the efficiency of stone removal with a novel tipless stone basket designed specifically for percutaneous procedures. MATERIALS AND METHODS: A 3, 5 and 8 mm human calculus were placed in the calix of a percutaneous renal model. A 26Fr Storz nephroscope (27093B, Storz Medical AG, Kreuzlingen, Switzerland) was inserted through a 30Fr Amplatz sheath into the model with camera input from a Storz telecam SL-NTSC feeding to a 20-inch Sony Triniton monitor (Sony Corp of America, New York, New York). Operators were randomized to start stone extraction with a Storz 3-prong grasper (27090RB) or a Cook 12Fr Perc-NCircle (38 cm) (Cook Urological, Inc., Indianapolis, Indiana). Subsequent testing alternated between the 2 devices until 10 extraction attempts were conducted with each device. Time to extraction of all 3 calculi and number of inadvertent withdrawals of the sheath were recorded. Three experienced operators tested each device. RESULTS: Stone extraction times were shorter with the Cook Perc-NCircle than the 3-prong grasper for all operators. Mean time for stone extraction was 25.3 +/- 11.2 seconds for the Perc-NCircle compared to 35.1 +/- 18.5 seconds for the 3-prong grasper (p = 0.016). Loss of access by inadvertent removal of the Amplatz sheath occurred in 53% of the attempts with the 3-prong grasper compared to 7% of attempts with the Perc-NCircle. CONCLUSIONS: The Cook Perc-NCircle facilitates a more expeditious approach to percutaneous stone removal with less risk of sheath withdrawal.

Equipment Design↗
PubMed2004

Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model.

Protein serine/threonine kinase CK2 (formerly casein kinase 2) is a ubiquitous protein kinase that plays key roles in cell growth, proliferation, and survival. We have shown previously that its molecular down-regulation induces apoptosis in cancer cells in culture. Here, we have employed a xenograft model of prostate cancer to extend these studies to determine whether antisense CK2alpha evokes a similar response in vivo. A single dose of antisense CK2alpha oligodeoxynucleotide given directly into the PC3-LN4 xenograft tumor in nude mouse induced a dose- and time-dependent tumor cell death in vivo. The tumor was completely resolved at the higher tested dose of the antisense. Cell death was due to apoptosis and correlated with a potent down-regulation of the CK2alpha message and loss of CK2 from the nuclear matrix in the xenograft tissue as well as in cancer cells in culture. These observations accorded with several of the earlier studies indicating that loss of CK2 from the nuclear matrix is associated with induction of apoptosis. Comparison of the effects of antisense CK2alpha oligodeoxynucleotide on cancer versus normal or noncancer cells showed that the concentration of antisense CK2alpha that elicited extensive apoptosis in tumor cells in culture or xenograft tumors in vivo had a relatively small or minimal effect on noncancer cells in culture or on normal prostate gland subjected to orthotopic injection of antisense oligodeoxynucleotide in vivo. The basis for the difference in sensitivity of cancer versus noncancer cells to antisense CK2alpha is unknown at this time; however, this differential response under similar conditions of treatment may be significant in considering the potential feasibility of targeting the CK2 signal for induction of apoptosis in cancer cells in vivo. Although much further work will be needed to establish the feasibility of targeting CK2 for cancer therapy, to our knowledge, this is the first report to provide important new evidence as an initial "proof of principle" for the potential application of antisense CK2alpha in cancer therapy, paving the way for future detailed studies of approaches to targeting CK2 in vivo to induce cancer cell death.

Animals↗
PubMed2003

Repeated intravesical instillations of an adenoviral vector in patients with locally advanced bladder cancer: a phase I study of p53 gene therapy.

PURPOSE: We investigated the feasibility, safety, and biologic activity of adenovirus-mediated p53 gene transfer in patients with locally advanced bladder cancer. PATIENTS AND METHODS: Patients with measurable, locally advanced transitional-cell carcinoma of the bladder who were not candidates for cystectomy were eligible. On a 28-day cycle, intravesical instillations of INGN 201 (Ad5CMV-p53) were administered on days 1 and 4 at three dose levels (10(10) particles to 10(12) particles) or on either 4 or 8 consecutive days at a single dose level (10(12) particles). RESULTS: Thirteen patients received a total of 22 courses without dose-limiting toxicity. Specific transgene expression was detected by reverse transcriptase polymerase chain reaction in bladder biopsy tissue from two of seven assessable patients. There were no changes in p53, p21waf1/cip1, or bax protein levels in bladder epithelium evident from immunohistochemical analysis of 11 assessable patients. Outpatient administration of multiple courses was feasible and well tolerated. A patient with advanced superficial bladder cancer showed evidence of tumor response. CONCLUSION: Intravesical instillation of Ad5CMV-p53 is safe, feasible, and biologically active when administered in multiple doses to patients with bladder cancer. Observations from this study indicate that this treatment has an antitumor effect in superficial transitional-cell carcinoma. Improvements in the efficiency of gene transfer and the levels of gene expression are required to develop more effective gene therapy for bladder cancer.

Adenoviridae↗
PubMed2003

Laser prostatectomy versus transurethral resection for treating benign prostatic obstruction: a systematic review.

PURPOSE: We conducted a systematic review of randomized controlled trials evaluating the efficacy and safety of laser prostatectomy techniques compared to transurethral resection of the prostate for symptomatic benign prostatic obstruction. MATERIALS AND METHODS: We searched MEDLINE, the Cochrane library and reference lists of retrieved studies to identify randomized trials of 6 months or greater in duration with at least 10 subjects in each treatment arm. We extracted data on study design, subject and treatment characteristics, adverse events, urinary symptoms and urinary flow. RESULTS: A total of 16 studies involving 1,488 subjects were evaluated, including 8 comparisons of transurethral resection with contact lasers, 7 with noncontact lasers and 4 with hybrid techniques. Study duration ranged from 6 to 36 months. Mean patient age (67.4 years), baseline symptom score (20.2) and peak urinary flow (9.5 ml. per second) did not differ by treatment group. Transurethral resection of the prostate provided slightly greater improvement in urinary symptoms and flow. The pooled mean percentage improvement for urinary symptoms ranged from 59% to 68% with lasers and 63% to 77% with transurethral resection. Improvement for peak urinary flow ranged from 56% to 119% with lasers and 96% to 127% with transurethral resection of the prostate. Laser procedures resulted in fewer transfusions (less than 1% versus 7%) and strictures (0% to 7% versus 8%), and required shorter hospitalizations. Reoperation occurred more often (RR = 5.7) following laser procedures. CONCLUSIONS: Laser techniques are a useful alternative to transurethral resection of the prostate for treating benign prostatic obstruction. Small sample sizes and differences in study design limit any definitive conclusions regarding the preferred type of laser technique.

Aged↗
PubMed2003

Clinical presentation and outcome of high-grade urinary bladder leiomyosarcoma in adults.

OBJECTIVES: To determine the clinical presentation and outcome of patients with high-grade bladder leiomyosarcoma. METHODS: Between July 1986 and April 1998, 36 adult patients (mean follow-up 56 months) with a diagnosis of urinary bladder leiomyosarcoma were evaluated at the University of Texas M. D. Anderson Cancer Center. We retrospectively reviewed the records of these patients for information on clinical features, treatment, and outcome. RESULTS: The mean age of the patients was 63 years. Twenty-six patients were white men in their seventh decade. The most common symptom at presentation was gross hematuria (81% of patients), followed by increased urinary frequency (28%), and dysuria (19%). Thirty-five patients were treated surgically for bladder leiomyosarcoma; of these, 12 (34%) developed recurrent disease (5 with local recurrence and 7 with distant metastasis), with a median time to diagnosis of recurrent disease of 8.3 months. The most common site of distant failure was the retroperitoneum. The disease-specific survival rate at 1, 3, and 5 years was 88.6%, 62.0%, and 62.0%, respectively. Multivariate analyses demonstrated that only the Memorial Sloan-Kettering Cancer Center disease stage system was a significant predictor of survival of patients with bladder leiomyosarcoma (P = 0.018). CONCLUSIONS: In patients with high-grade leiomyosarcoma of the bladder, radical cystectomy in the face of localized disease, whether at the initial presentation or after neoadjuvant chemotherapy, can result in a 5-year, disease-specific survival rate of 62.0%.

Adult↗
PubMed2002

Maximizing ureteroscope deflection: "play it straight".

We studied simple maneuvers to optimize active deflection of the flexible ureteroscope. Up to 61 degrees of active deflection is lost if the ureteroscope is not kept in a straight alignment. Holding the ureteroscope taut, placing a super-stiff guidewire in the working channel, or using an access sheath maximizes active deflection.

Humans↗
PubMed2002

Prognostic factors and survival of patients with sarcomatoid renal cell carcinoma.

PURPOSE: Sarcomatoid renal cell carcinoma often has an aggressive clinical course characterized by rapid disease progression. We evaluate prognostic factors for patient survival and the effect of treatment on patient outcome. MATERIALS AND METHODS: Between 1987 and 1998, 108 patients were classified as having sarcomatoid renal cell carcinoma at our institution. We reviewed the records of these patients to identify clinical and pathological prognostic variables. The Kaplan-Meier method was used to determine differences in overall survival. RESULTS: A total of 96 (89%) patients were symptomatic at presentation. Sarcomatoid renal cell carcinoma was localized to the kidney in 25 (23%) patients, whereas metastasis was present in 83 (77%). The median overall survival of all patients was 9 months. The presence of clinically localized disease was associated with longer overall survival when compared to patients with metastasis (17 versus 7 months, respectively, p <0.004). Of 86 patients who received systemic therapy partial response was seen in 28, and no complete responses were noted. Patients who had a partial response had a median survival of 19 months and those with no response 7 (p <0.005). Those patients with metastatic disease who were treated with nephrectomy followed by systemic therapy survived a median time of 8.5 months, whereas those who received systemic therapy alone 5.3 (p = 0.08). CONCLUSIONS: Patients with sarcomatoid renal cell carcinoma have poor overall survival because of the aggressive biological behavior. Survival is longer for patients presenting with clinically localized disease, single metastatic site, and exhibiting a partial response to systemic therapy.

Carcinoma, Renal Cell↗
PubMed2002

Contemporary morbidity from lymphadenectomy for penile squamous cell carcinoma: the M.D. Anderson Cancer Center Experience.

PURPOSE: Inguinal lymphadenectomy can be curative in patients with small volume inguinal metastases and those with more significant adenopathy responding to combination chemotherapy. However, several series collected for 15 to 40 years attest to the significant morbidity associated with lymphadenectomy. We reviewed our recent experience with lymphadenectomy in patients with invasive penile cancer who were judged to require inguinal staging and therapeutic procedures to assess the incidence and magnitude of complications caused by this procedure, especially in those with no palpable adenopathy (prophylactic group). MATERIALS AND METHODS: A total of 106 lymphadenectomy procedures were performed in 53 patients. The indications for dissection were prophylactic in 66 (62%) patients in whom a superficial dissection alone was completed on the ipsilateral side, therapeutic in 28 (26%) in whom superficial, deep and ipsilateral pelvic dissections were performed, and palliative in 12 (11%) undergoing extensive resection of inguinal and abdominal wall tissue after chemotherapy. Minor postoperative complications included those requiring local wound débridement in the clinic, mild to moderate leg edema, seroma formation not requiring aspiration and minimal skin edge necrosis requiring no therapy. Major complications included severe leg edema interfering with ambulation, skin flap necrosis requiring a skin graft, rehospitalization, deep venous thrombosis, death, or reexploration or other invasive procedures performed in the operating room. The incidence and magnitude of complications were compared with prior reports from our center and other series. RESULTS: A total of 41 (68%) minor and 19 (32%) major complications occurred with the 106 dissections (31 of 53 patients, 58%). Prophylactic and therapeutic dissections were associated with a lower incidence of complications compared with palliative dissections (p = 0.017 to 0.049). The incidence of major complications also trended lower in the prophylactic group compared with other indications (p = 0.05). One patient in the palliative group died of sepsis on postoperative day 15. When compared with 3 prior series, the incidence of skin edge necrosis in our series was significantly lower (8% versus 45% to 62%, p <0.0001). Similarly, the incidence and severity of edema in our series were significantly lower than in a prior report from our institution (23% versus 50%, p <0.0001). CONCLUSIONS: For select patients undergoing prophylactic inguinal dissection to detect the presence of microscopic metastases, the incidence and magnitude of complications appeared acceptable in our contemporary experience. Similarly the morbidity of therapeutic lymphadenectomy appeared acceptable, considering the potential therapeutic benefit. However, significant complications, including death, can be associated with palliative groin dissection. Optimal candidates are those having a significant response to systemic chemotherapy whose groins are grossly uninfected.

Adult↗
PubMed2002

Inhibition of tumorigenicity and metastasis of human bladder cancer growing in athymic mice by interferon-beta gene therapy results partially from various antiangiogenic effects including endothelial cell apoptosis.

We determined whether the IFN-beta gene could suppress angiogenesis, tumor growth, and metastasis of human bladder transitional cell carcinoma. The highly tumorigenic and metastatic 253J B-V(R) human bladder transitional cell carcinoma (TCC) cell line (resistant to the antiproliferative effects of IFN-beta) was infected in vitro with adenoviral beta-galactosidase (Ad-LacZ), murine adenoviral IFN-beta (Ad-mIFN-beta), or human adenoviral IFN-beta (Ad-hIFN-beta) and implanted into the bladders of athymic nude mice. Ad-mIFN-beta and Ad-hIFN-beta were used because of the species specificity of IFN-beta. The transient production of mIFN-beta and hIFN-beta from the infected 253JB-V(R) tumor cells significantly inhibited tumorigenicity and spontaneous lymph node metastasis. Subsequently, the 253J B-V(R) cells were implanted into the subcutis of athymic nude mice, and established tumors were treated by direct intratumoral injection with Ad-mIFN-beta, Ad-hIFN-beta, Ad-LacZ, or PBS. By in situ hybridization (ISH) and immunohistochemical analysis (IHC), expression of hIFN-beta and mIFN-beta mRNA and protein within the tumors was demonstrated after Ad-hIFN-beta and Ad-mIFN-beta gene therapy, respectively. The therapy also induced necrosis in both the Ad-mIFN-beta- and Ad-hIFN-beta-treated tumors. IHC revealed decreased tumor cell proliferation and the sequestration of activated macrophages within the tumors after Ad-mIFN-beta therapy. In addition, the expression of the proangiogenic factors bFGF, and MMP-9 protein (by IHC) was significantly down-regulated by Ad-hIFN-beta gene therapy. Double-immunofluorescent IHC for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) and CD-31 demonstrated tumor and endothelial cell apoptosis in those tumors treated with Ad-hIFN-beta gene therapy. Tumor-induced angiogenesis, as determined by the microvessel density, was decreased in tumors treated with both Ad-mIFN-beta and Ad-hIFN-beta. These data suggest that the inhibition of tumorigenicity and the metastasis of the 253J B-V(R) cells after infection with Ad-IFN-beta is caused by the inhibition of angiogenesis and the activation of host effector cells.

Animals↗
PubMed2002

Inhibition of angiogenesis by the antiepidermal growth factor receptor antibody ImClone C225 in androgen-independent prostate cancer growing orthotopically in nude mice.

In human androgen-independent prostate cancer (PCa), epidermal growth factor receptor (EGFR) regulates angiogenesis, tumor growth, and progression. In this study, we evaluated whether the blockade of EGFR by the anti-EGFR antibody ImClone C225 (IMC-C225) inhibited tumor growth and metastasis by inhibiting angiogenesis, and whether paclitaxel enhanced the results of therapy in androgen-independent PCa. PC-3M-LN4 PCa cells were implanted orthotopically in athymic nude mice and treated with i.p. IMC-C225 (1 mg twice a week) and/or paclitaxel (200 microg once a week). In vitro treatment of PC-3M-LN4 with IMC-C225 inhibited EGFR autophosphorylation without any significant antiproliferative effect. In contrast, in vivo therapy with IMC-C225 alone (P < 0.05) or in combination with paclitaxel (P < 0.005) significantly inhibited PCa growth and metastasis. Serum levels of interleukin (IL) 8 were lower after therapy, and IL-8 mRNA expression was down-regulated within the tumors after therapy. The down-regulation of IL-8 correlated with reduced microvessel density. IMC-C225 reduced tumor cell proliferation, enhanced p27(kip1) expression, and induced tumor and endothelial cell apoptosis. These studies indicate that IMC-C225 has significant antitumor effect in this murine model, mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. The simultaneous administration of paclitaxel enhanced this effect.

Androgens↗