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Biomedical subjects

M Craig Hall

Publications and source records attributed to M Craig Hall.

26 records · Page 2Linked to original sources
PubMed2003

Analysis of G/A polymorphism in the androgen response element I of the PSA gene and its interactions with the androgen receptor polymorphisms.

OBJECTIVES: To compare the in vitro functional activity of the prostate-specific antigen (PSA) androgen response element (ARE) I alleles alone or in combination with androgen receptor (AR) polymorphisms and to determine the association of ARE I alleles with serum PSA in men without clinical prostatic disease. Data are conflicting regarding the association of PSA promoter alleles with serum PSA in men. METHODS: In vitro functional analyses of ARE I and AR polymorphisms were conducted by luciferase reporter assays in LNCaP and PC-3 cells. Associations among serum PSA, ARE I, and AR genotypes were determined by genotyping 109 white and 71 African-American men determined to be free of clinical prostatic disease. RESULTS: We found no significant difference in the androgen responsiveness of the two alleles when cells were transfected with PSA promoter reporter constructs differing only in the ARE I single nucleotide polymorphism and treated with varying doses of androgen. The response to androgens of the ARE I alleles co-transfected with AR expression vectors of 9, 21, and 29 CAG repeat lengths were identical. No individual or combined effects of the ARE I genotype and the AR genotype on serum PSA were noted. CONCLUSIONS: Our data indicate that ARE I polymorphisms, alone or in combination with AR polymorphisms, have no functional effect on the activity of the PSA promoter in vitro and in vivo.

Adult↗
PubMed2003

Randomized prospective trial of a novel local anesthetic technique for extensive prostate biopsy.

OBJECTIVES: To determine the effectiveness of a novel technique of administering local anesthesia for extensive prostate biopsy. Little reported experience with local anesthesia for extensive prostate biopsy methods is available. METHODS: A prospective, randomized study was performed on 50 men undergoing transrectal ultrasound-guided prostate biopsy using the five-region technique. Patients were randomized into one of two groups. One group received 22 mL of a 1% lidocaine solution injected into the neurovascular bundles, the genitourinary diaphragm, and between the rectal wall and prostate. The second group received 10 mL of 2% intrarectal lidocaine jelly. A median of 12 biopsy cores was obtained from each patient. The patients were then asked by a urology nurse unaware of the anesthesia method to grade the discomfort using a 10-point linear visual analog pain scale. RESULTS: Twenty-three men received anesthesia with lidocaine jelly, and 27 received anesthesia with lidocaine infiltration. The mean pain scores were significantly different statistically between the lidocaine jelly and lidocaine infiltration groups with respect to overall pain (4.2 versus 0.5) and pain during the biopsy portion of the procedure (4.2 versus 0.5). CONCLUSIONS: Extensive biopsy techniques may be comfortably performed by the urologist in an office setting using local anesthesia. The administration of 22 mL of a 1% lidocaine solution, injected at the prostatic pedicles, the genitourinary diaphragm, and the space between the prostate and rectum, allows the patient to comfortably undergo an extensive biopsy protocol in an office setting.

Administration, Topical↗
PubMed2003

Bladder cancer.

Bladder cancer is a significant public health problem responsible for more than 130,000 deaths annually worldwide. Disease prevalence is also remarkable, with more than 500,000 patients carrying the diagnosis in the United States alone. Significant progress has been made in understanding the underlying molecular and genetic events in bladder cancer. However, there remains a great need for the development of reliable markers that can provide clinically useful information regarding diagnosis and prognosis and to facilitate the selection of appropriate therapy in the individual patient. Ongoing and future investigation is anticipated to refine treatment of patients with high-risk superficial disease, to determine the role of neoadjuvant and adjuvant chemotherapy for high-risk invasive disease, and to improve the efficacy of chemotherapy for patients with metastatic bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.

Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.

Aged↗
PubMed2002

Phase II trial of radio frequency ablation of renal cancer: evaluation of the kill zone.

PURPOSE: We report on the pathological evaluation of renal tumors after intraoperative radio frequency ablation performed immediately before surgical nephrectomy. MATERIALS AND METHODS: Ten patients with renal tumors were enrolled in a prospective, Institutional Review Board approved phase II trial of radio frequency ablation. Following surgical exposure of the kidney a single 12-minute radio frequency ablation of the tumor was performed using the Radionics Cool-tip RF Radio Frequency Ablation System (Radionics, Burlington, Massachusetts). The tumor was then excised via radical or partial nephrectomy. Gross and histological evaluations of the tumor were performed, including evaluation with nicotinamide adenine dinucleotide vital staining. RESULTS: All 10 tumors were confirmed histologically to be renal cell carcinoma. Mean tumor size was 3.2 cm. (range 1.4 to 8.0). Of the 10 tumors 8 were completely ablated with a mean treatment margin of 6.75 mm. (range 2 to 13). Of the 2 tumors that were incompletely treated 1 never attained a temperature sufficient for tissue destruction and the other measured 8 cm., far exceeding the expected ablation volume of treatment protocol. CONCLUSIONS: This study represents the initial report of the histological outcome of saline cooled radio frequency ablation of renal tumors. Our data indicate that it can completely destroy renal cancers while transmitting minimal collateral damage to surrounding renal parenchyma. Further investigation is required to determine long-term oncological outcome.

Adult↗
PubMed2002

Bladder cancer.

Bladder cancer is a common and chemotherapy-responsive tumor, related to tobacco smoking, environmental arsenic exposure, industrial dye exposure, and parasitic schistosomiasis exposure. Both reduction of carcinogen exposure and chemoprevention, possibly with cyclooxygenase 2 inhibitors, should reduce the incidence. The search for the ideal screening and monitoring test continues with some promising new candidates, including survivin. Although 10-year survival can be achieved in 87% of early-stage patients with muscle-invasive disease rendered T(0) and 57% of those rendered T(1) at second look after transurethral resection bladder tumor, most still require radical cystectomy. Continued improvements in surgical techniques permit gains in quality of life after the procedure. Ten-year survival can still be achieved with cystectomy in the face of grossly positive lymph nodes in 32% of T(2) and 10% of T(3) patients. A recent meta-analysis indicates that preoperative irradiation is unlikely to be beneficial, but definitive chemoradiation can produce significant 5-year survival rates in nonoperative candidates and those desiring bladder preservation. The Intergroup now has preliminary data from a Southwest Oncology Group-based trial showing a significant benefit for neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin. The regimen of gemcitabine and cisplatin is equally efficacious with less toxicity than methotrexate, vinblastine, doxorubicin, and cisplatin. It has been adopted as the standard arm in a phase III trial for advanced bladder cancer, comparing it with the triplet of gemcitabine, paclitaxel, and cisplatin. Other active agents in bladder cancer include ifosfamide, carboplatin, docetaxel, and vinorelbine, and various doublets of these agents are being tested in phase II trials, with promising results.

Antineoplastic Agents↗
PubMedDate not supplied

Prognostic significance of clinicopathologic and deoxyribonucleic acid flow cytometric variables in non-metastatic renal cell carcinoma in the modern era.

OBJECTIVE: The prognostic value of deoxyribonucleic acid (DNA) ploidy in renal cell carcinoma (RCC) is not well-defined among modern surgical nephrectomy series. We sought to determine which variables correlated with overall survival and recurrence-free survival in the modern era. METHODS: We reviewed all patients from 1992 to 2000, who prospectively had DNA ploidy analysis of their primary tumor determined at the time of nephrectomy for nonmetastatic RCC. Variables examined included age, gender, ethnicity, presentation (incidental vs. symptomatic), preoperative laboratory studies, American Society for Anesthesiology class, tumor size, tumor-nodes-metastasis stage, histology, Fuhrman grade, and diploid versus nondiploid tumor. Statistical analyses of overall survival and recurrence-free survival were performed using the Kaplan-Meier method, log-rank test, and Cox regression model using commercially available software. RESULTS: Sixty men and 41 women, median age 61 years (range, 23-85), were included. Pathologic stage included T1 (54 patients), T2 (14), and T3 (33). Eighty-four patients had conventional RCC. A total of 58 patients had well-differentiated (Fuhrman Grade 1 [12] or Grade 2 [46]), 28 had moderately differentiated (Grade 3), 12 had poorly differentiated tumors (Grade 4), and 3 were not specified. There were 52 patients who had diploid tumors, and 49 had aneuploid tumors. Median follow-up was 39 months (range, 0-109). Actuarial 5-year overall survival was 70%, and 5-year recurrence-free survival was 76%. Diploid tumors were significantly associated with better recurrence-free survival (P = 0.02) but not overall survival (P = 0.17). On multivariate analysis, the American Society for Anesthesiology class (P = 0.01), abnormal preoperative platelet count (P = 0.03), and tumor differentiation (P = 0.01) were independent predictors of overall survival, whereas only tumor differentiation (P = 0.05) was an independent predictor of recurrence-free survival. CONCLUSIONS: In the modern era, DNA ploidy is not an independent predictor of either overall survival or recurrence-free survival in patients with nonmetastatic RCC. The most important predictor of recurrence-free survival is tumor differentiation.

Adult↗