Biomedical subjects

Andrew K Lee

Publications and source records attributed to Andrew K Lee.

27 records · Page 2Linked to original sources

PubMed2004

In vivo tumor imaging in mice with near-infrared labeled endostatin.

Endostatin is a potent inhibitor of angiogenesis currently in phase I clinical trials. Imaging technologies that use near-infrared fluorescent probes are well suited to the laboratory setting. The goal of this study was to determine whether endostatin labeled with a near-infrared probe (Cy5.5) could be detected in an animal and whether it would selectively localize to a tumor. Endostatin was conjugated to Cy5.5 monofunctional dye and injected into mice bearing Lewis lung carcinoma tumors (350 mm2). Mice were imaged at various time points while under sedation using a lightproof box affixed to a fluorescent microscope mounted with a filter in the near-infrared bandwidth consistent with Cy5.5 fluorescence. After i.p. injection, endostatin-Cy5.5 was absorbed producing a near-infrared fluorescent image within the tumors at 18 h reaching a maximum at 42 h after injection. No signal was emitted from mice injected with unlabeled endostatin or Cy5.5 dye alone or those that received no injection. Further results show that a dose response exists with injection of endostatin-Cy5.5. Mimicking the clinical route of administration, an i.v. injection had a peak signal emission at 3 h but also persisted to 72 h. Finally, to determine the intratumoral binding site for endostatin, we performed immunofluorescence on tumor specimens and demonstrated that endostatin binds to tumor vasculature and colocalizes with platelet/endothelial cell adhesion molecule 1 expression. This study demonstrates that endostatin covalently bound to Cy5.5 will migrate from a distant i.p. injection site to a tumor. These data indicate that endostatin-Cy5.5 is appropriate for selectively imaging tumors in uninjured experimental animals.

Animals↗

PubMed2004

An approach to the management of the patient with metastatic bone disease.

Patients with primary sarcomas of bone and soft tissue are generally treated on protocol by a multidisciplinary team at tertiary referral centers. Conversely, patients with metastatic disease to the skeleton are often evaluated by general orthopaedic surgeons in the community. Skeletal metastases affect a growing percentage of the elderly population and can contribute to a marked decrease in their quality of life. Treatment includes stabilization with the latest prosthetic implants and new devices. Advances in the field of radiation oncology and bisphosphonate use in patients with bone metastasis are other management approaches.

Arm↗

PubMed2003

Dosimetric consequences of using a surrogate urethra to estimate urethral dose after brachytherapy for prostate cancer.

PURPOSE: To assess the accuracy and dosimetric consequences of defining a surrogate urethra at the geometric center of the prostate in postimplant CT scans. METHODS AND MATERIALS: Eighty postimplant CT scans were obtained with a Foley catheter in place at Day 0 and at 1 month for 40 patients who had undergone (125)I prostate brachytherapy. The percentage of urethral volume receiving at least 275% of the prescribed dose (uV(275)), uV(250), uV(200), uV(150), maximal dose received by 90% of urethral volume (uD(90)), uD(70), uD(30), and uD(1) were measured for the Foley catheter and surrogate urethra. The distance between the Foley catheter and surrogate urethra was measured at the base, middle, and apex of the prostate. RESULTS: A statistically significant difference was found in all the above-listed dosimetric parameters between the Foley catheter and surrogate urethra at Day 0 (p <or= 0.001). At 1 month, the uD(90), uD(70), and uD(1) remained significantly different between the Foley catheter and surrogate urethra (p <or= 0.05). The difference in the uV(275) (p = 0.055) and uV(150) (p = 0.059) between the Foley catheter and surrogate urethra showed a trend toward statistical significance at 1 month. The uV(250), uV(200), and uD(30) were greater for the surrogate urethra than for the Foley catheter at 1 month, but were not significantly different statistically. The mean distance between the Foley catheter and the surrogate urethra was greatest at the base (1.2 cm) in the vertical axis at Day 0 and decreased substantially to 0.87 cm at 1 month (p = 0.0004). CONCLUSION: Using a surrogate urethra at the geometric center of the prostate may significantly overestimate the urethral dose at Day 0 and certain dosimetric parameters at 1 month. An alternative position for a surrogate urethra accounting for the difference in the location of the Foley catheter near the base of the prostate at Day 0 and 1 month could be considered in future studies.

Brachytherapy↗

PubMed2003

Bcl-2 is significantly overexpressed in localized radio-recurrent prostate carcinoma, compared with localized radio-naive prostate carcinoma.

PURPOSE: We set out to determine whether patients who underwent prostatectomy for recurrence after external-beam radiotherapy for prostate cancer had a higher incidence of alterations in the apoptotic pathway than did patients who underwent surgery as initial treatment. MATERIALS AND METHODS: Twenty patients who underwent unsuccessful full-dose external-beam radiotherapy for prostate cancer and subsequently underwent salvage radical surgery (radio-recurrent group), and 20 patients matched for various clinical parameters who underwent only radical prostatectomy for localized or locally advanced prostate cancer (radio-naive group), were studied. Tissue samples were examined for immunoreactivity for p53, p21, Bcl-2, and Ki-67 proteins. Statistically, the two groups were compared using exact logistic regression. RESULTS: Fifty-five percent of the tumors from patients initially treated with radiotherapy were noted to overexpress Bcl-2; whereas, in the radio-naive group, no patient had Bcl-2 overexpression (p = 0.0004). More patients who underwent salvage radical surgery were found to have a higher mean proliferative index (Ki-67 staining) (39.6%), compared with patients undergoing prostatectomy alone (22.1%), p = 0.0800. No significant difference was noted in immunohistochemical expression of p53 and p21 between the two groups. CONCLUSIONS: Patients undergoing radical prostatectomy after radiotherapy had a significantly higher rate of Bcl-2 overexpression than did patients who underwent surgery as the initial treatment. Alterations in the apoptotic pathway may be important in the development of local recurrence after radiation therapy.

Adenocarcinoma↗

PubMed2003

Current results of brachytherapy for soft tissue sarcoma.

Perioperative brachytherapy results in a better local control rate than surgery alone for extremity soft tissue sarcoma. Brachytherapy enables the delivery of a high radiation dose to a limited volume of tissue, allows the reduction of radiation treatment time, enables direct visualization of the tumor bed and surrounding critical structures, and costs less than external beam radiotherapy. The literature seems to regard the effectiveness of brachytherapy as comparable to that of external beam radiotherapy, and the side effect profile is acceptable. Traditional low-dose-rate brachytherapy methods require extended periods of patient isolation, but recent technologic advances may obviate this necessity. Newer high-dose-rate (HDR) brachytherapy delivery methods allow for the fractionation of radiation delivery and outpatient treatment in some cases. Furthermore, with HDR brachytherapy, the radiation dose distribution can be tailored around critical anatomic structures. Although the application of HDR brachytherapy to soft tissue sarcoma is relatively new, it seems to result in a satisfactory local control rate and may replace traditional low-dose-rate techniques.

Brachytherapy↗

PubMed2002

Prostate specific antigen bounce phenomenon after external beam radiation for clinically localized prostate cancer.

PURPOSE: We characterize the prostate-specific antigen (PSA) bounce in patients who underwent external beam radiation therapy for prostate cancer and correlate the PSA bounce with the development of biochemical disease progression. MATERIALS AND METHODS: In this study 964 patients received full dose radiation therapy alone. Followup PSA values were obtained 3 months after completion of radiotherapy and every 3 to 6 months thereafter. Median followup of the entire study group was 48 months. All time intervals were calculated from the completion date of radiation therapy. PSA bounce was defined as an initial increase in serum PSA of at least 0.5 ng./ml., followed by a decrease to pre-bounce baseline serum PSA values no more than 60 months after external beam radiation therapy. RESULTS: Of the 964 patients 119 (12%) had a PSA bounce. PSA bounce was unrelated to age, race, pretreatment PSA, Gleason score, clinical T stage or radiation dose. Mean time to PSA bounce was 9 months from the time of therapy. The respective 1 and 5-year biochemical disease-free survival rates were 100% and 82.1% for patients with PSA bounce and 93.9% and 57.7% for those without PSA bounce (p = 0.0001). CONCLUSIONS: Of men with prostate cancer treated with external beam radiation therapy 12% experienced a transient increase in PSA (PSA bounce) followed by a return to pre-bounce levels after radiation. The PSA bounce phenomenon was not predictive of time to biochemical recurrence.

Aged↗

PubMed2002

Percentage of core lengths involved with prostate cancer: does it add to the percentage of positive prostate biopsies in predicting postoperative prostate-specific antigen outcome for men with intermediate-risk prostate cancer?

OBJECTIVES: To evaluate whether the percentage of core lengths involved with prostate cancer added clinically significant information concerning the time to postoperative prostate-specific antigen (PSA) failure in the intermediate-risk patient beyond what is provided by the percentage of positive biopsies. METHODS: Cox regression multivariable analysis was performed to compare the ability of the two measurements of biopsy cancer volume to predict the time to PSA failure from a series of 184 surgically treated intermediate-risk patients. PSA outcome was estimated using the actuarial method of Kaplan and Meier, and comparisons were made using the log-rank test. RESULTS: Both the percentage of core lengths involved with prostate cancer (P = 0.01) and the percentage of positive biopsies (P = 0.002) were significant predictors of the time to PSA failure on univariable analysis. The 4-year PSA outcome was 83% versus 47% (P = 0.0008) and 83% versus 53% (P = 0.007) for the percentage of positive biopsies stratified by 50% or less versus greater than 50% and the percentage of core lengths involved with prostate cancer stratified by 25% or less versus greater than 25%, respectively. However, only the percentage of positive biopsies remained significant (P = 0.03) on multivariable analysis. CONCLUSIONS: The percentage of core lengths involved with prostate cancer did not provide additional clinically relevant information to the percentage of positive biopsies for patients with intermediate-risk prostate cancer. Therefore, the routine measurement of core involvement may not be necessary in this patient population.

Analysis of Variance↗

PubMedDate not supplied

Can the core length involved with prostate cancer identify clinically insignificant disease in low risk patients diagnosed on the basis of a single positive core?

Clinically insignificant prostate cancer, defined as at most microscopic foci of Gleason grade < or = 3 disease in the radical prostatectomy specimen, has been recognized in some low risk (PSA < 10, biopsy Gleason score < or = 6, clinical Tlc, 2a) patients with minimal biopsy cancer volume. The purpose of this study is to determine if the fraction of cancer in a single positive core biopsy could identify a subset of low risk prostate cancer patients with clinically insignificant disease. Of 1100 patients with Tlc,2 prostate cancer that consecutively underwent radical prostatectomy at Brigham and Women's Hospital between 1989 to 2000, 130 low risk patients whose diagnoses were made on the basis of a single positive core comprised the study cohort. The pathologic findings at radical prostatectomy were enumerated for men with < or = 5% of a single core involved with prostate cancer in order to determine the rate of clinically insignificant prostate cancer in this population. Estimates of PSA survival were calculated using the actuarial method of Kaplan and Meier. Pairwise comparisons were made using the log rank test. For patients with < or = 5% (n = 14) and > 5% (n = 116) involvement of a single positive core, the 4 year PSA failure free survivals were 100% vs. 89% (P = 0.048), respectively. Within the subset of patients with < or = 5% of a single core involved, 7% (1/14) met the criteria for clinically insignificant disease. However, of the remaining 93%, 3, 8, and 2 patients had pathologic stage T2a, T2b, and T3a, respectively. Eleven patients had prostatectomy Gleason scores < or = 3 + 3, two patients had pathologic Gleason scores of 3 + 4, and one patient had a positive surgical margin. Given that only 7% of low risk patients in this cohort with < or = 5% involvement of a single positive core had clinically insignificant disease, the involved core length alone cannot be used to identify patients with clinically insignificant disease. Further studies are needed in order to delineate which patients may not benefit from treatment.

Adult↗

PubMedDate not supplied

Uncertainties in physical and biological targeting with radiation therapy.

Advances in radiation therapy over the past decade have resulted from increased accuracy of imaging and highly conformal three dimensional treatment planning and delivery of radiation therapy. Three-dimensional conformal radiation therapy (3D CRT) with higher doses than previously considered tolerable is now standard for many types of cancer. Intensity modulated radiation therapy (IMRT) with x-rays, proton beam treatments and intensity modulated proton therapy (IMPT) are major areas of research. Tumor motion between and even during radiation treatments represents a major uncertainty. Tumor heterogeneity results in additional uncertainties affecting tumor control with radiation therapy. Imaging the heterogeneous targets within tumors offers new opportunities for tumor delineation. Molecular therapeutic agents enhance the effects of ionizing radiations in murine systems. Clinical trials combining molecular targeting agents with conformal radiation therapy are being initiated.

Animals↗