Potentiation of Paclitaxel Cytotoxicity by Inostamycin in Human Small Cell Lung Carcinoma, Ms-1 Cells

In the present study, we found that inostamycin increased the ability of paclitaxel to induce apoptosis in Ms-1 cells. A considerably higher concentration of paclitaxel was required for the induction of apoptosis in Ms-1 cells than in other cell lines tested. Treatment of Ms-1 cells with inostamycin, an inhibitor of phosphatidylinositol (PI) synthesis, reduced the dosage of paclitaxel required to induce cell death by apoptosis. This effect of inostamycin is specific to Ms-1 cells, and inostamycin did not increase the cytotoxicity of other antitumor drugs such as adriamycin, vinblastine, methotrexate, cisplatin, etoposide, or camptothecin in Ms-1 cells. Addition of inostamycin to paclitaxel-treated cells caused a significant increase in the sub G1 peak, representing apoptosis, which was accompanied by a decrease in the G2/M peak seen in paclitaxel-treated Ms-1 cells, without affecting paclitaxel-inhibited tubulin depolymerization. Moreover, paclitaxel did not enhance inostamycin-inhibited PI synthesis. The expression levels of Bcl-2, Bax, and Bcl-X_L were not changed following the co-treatment with inostamycin plus paclitaxel, whereas the activated form of caspase-3 was markedly increased. Thus, inostamycin is a chemosensitizer of paclitaxel in small cell lung carcinoma Ms-1 cells.     

Sequential T Cell Response Involved in Tumor Rejection of Sarcoma, Meth A, in Syngeneic Mice

We investigated the type of T cell response involved in Meth A tumor rejection in primary immune and hyperimmune syngeneic mice. It was found that a CD4⁺ T cell-mediated delayed-type hypersensitivity (DTH) response activating non-specific killer cells such as macrophages, NK and LAK cells, without a specific CD8⁺ cytotoxic T lymphocyte (CTL) response, was the major immune response leading to Meth A tumor rejection in primary immune mice. In contrast, the specific CD8⁺ CTL response was the major response leading to the tumor rejection, in addition to CD4⁺ T cell-mediated DTH response, in hyperimmune mice. Analysis of CD4⁺ T cell clones established from primary immune and hyperimmune spleen cells indicated that a CD4⁺ T cell clone (C9) of primary immune mice (although only one clone was established) was of Th1 type, and induced cytotoxicity in accessory cells by classic DTH in vitro. Eight CD4⁺ T cell clones were established from hyperimmune spleen cells. Six out of the eight clones were of the Th2 type and two were Th0-like. However, no Th1-type CD4⁺ T cell clone was established from hyperimmune spleen cells. All of these CD4⁺ T cell clones, even the Th2-type clones, were capable of inducing cytotoxicity in vitro in T cell-depleted accessory cells, as in an in vitro DTH response. We postulate on the basis of these results that the T cell response leading to Meth A tumor rejection in vivo sequentially changed from a CD4⁺ T cell-mediated classic DTH response to a CD8⁺ CTL response, in addition to a cellular response mediated probably by Th2-type cells, during the process of repeated immunization.     

CT图像中噪声产生机理与维修

本文重点阐述和分析了CT图像中的几种噪声产生的原因和对图像的影响,并结合笔者多年的维修经验,从理论和实际相结合,介绍了几种实用的维修方法,提出了减小噪声提高图像质量的有效措施。     

Nephrolithiasis associated with autosomal dominant polycystic kidney disease: contemporary urological management

PURPOSE: We evaluate the role of contemporary urological intervention in patients with nephrolithiasis associated with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: Intervention for upper tract stones associated with autosomal dominant polycystic kidney disease was performed in 5 women and 2 men 29 to 65 years old (mean age 47). Indications for intervention consisted of flank pain in 6 patients and/or hematuria in 2. A total of 12 procedures (mean 1.7 per patient) were performed, including shock wave lithotripsy in 6 patients, percutaneous nephrolithotomy in 2, retrograde endoscopy or manipulation in 3 and extended pyelonephrolithotomy in 1. RESULTS: All patients were rendered stone-free or had only residual "dust." Hospital stay for 5 patients was 1 night or less and there were no complications. Renal function for each patient was stable or improved as measured by serum creatinine. CONCLUSIONS: Most patients with autosomal dominant polycystic kidney disease who require intervention for nephrolithiasis can be safely and effectively treated with essentially any or all contemporary, minimally invasive techniques. The choice of intervention can be based primarily on size and location of the upper tract stones rather than the associated presence of polycystic kidneys.     

Variation in clinical outcome following shock wave lithotripsy

PURPOSE: We measure and compare operator specific success rates of extracorporeal shock wave lithotripsy (ESWL) performed by 12 urologists in 1 unit to determine interoperator variation. MATERIALS AND METHODS: From January 1, 1994 to September 1, 1997 a total of 5,769 renal and ureteral stones received 9,607 ESWL treatments by 15 urologists with a Dornier MFL 5000 lithotriptor. The 3-month followup data are available for 4,409 stones. Outcome measures consisted of patient demographics, stone characteristics, technical details of lithotripsy, and stone-free and success rates by treating urologists. RESULTS: Treatment results were analyzed for 12 urologists (surgeons A to L) who treated more than 100 stones each, totaling 4,244 with followup information available. Mean stone-free and success rates were 50.6% and 72.3%, respectively. Surgeon A had significantly higher stone-free and success rates of 56.2% and 76.7%, respectively (p<0.05), with treatment results from 877 stones, which was a significantly higher number than others (p<0.05). Significant differences existed in mean number of shocks delivered among urologists (p = 0.0001), with surgeons A and J delivering the highest mean numbers (2,317 and 2,801, respectively). There was no difference in treatment duration (p = 0.75) but variation existed among urologists in terms of mean maximum treatment voltage (p = 0.0001). Mean fluoroscopy time at 4.1 minutes was higher for surgeon A than others (p<0.05). Mean complication rate following ESWL was 4.9% with no difference among urologists (p = 0.175). Re-treatment was required in 21.7% of cases and surgeon A had the lowest rate (15.9%, p<0.05). CONCLUSIONS: We demonstrated clinically and statistically significant intra-institutional differences in success rates following ESWL. The best results were obtained by the urologist who treated the greatest number of patients, used a high number of shocks and had the longest fluoroscopy time. Accurate targeting is crucial when using a lithotriptor, such as the Dornier MFL 5000, with a narrow focal zone of 6.5 mm. in diameter. Other centers should be encouraged to develop similar programs of outcome analysis in an attempt to improve performance.     

Quality of life outcomes after brachytherapy for early stage prostate cancer

PURPOSE: We compare general and disease specific health related quality of life in men undergoing brachytherapy for early stage prostate cancer to those undergoing radical prostatectomy and age matched healthy controls. MATERIALS AND METHODS: Cohorts consisted of 48 men treated with brachytherapy with and without pretreatment external beam radiation therapy (brachytherapy group), 74 who underwent radical prostatectomy (prostatectomy group) and age matched healthy controls from the literature. The RAND 36-item general health survey, University of California Los Angeles Prostate Cancer Index, American Urological Association symptom index, validated Cancer Interference with Life and Family Scales, and sociodemographic and co-morbidity questionnaires were completed 3 to 17 months after treatment. RESULTS: General health related quality of life did not differ greatly among the 3 groups. Urinary function (leakage) was worse in the brachytherapy group than in controls but better than in the prostatectomy group. Brachytherapy group patients had more irritative urinary symptoms and worse bowel function than controls. Sexual function and bother were worse in prostatectomy and brachytherapy groups than in healthy controls. Physical function, bodily pain, urinary function, and bother and American Urological Association symptom index scores improved with time after brachytherapy. Patients who underwent brachytherapy after external beam radiation performed worse in all general and disease specific health related quality of life domains compared to those who did not undergo pretreatment radiation therapy. CONCLUSIONS: At an average of 7.5 months after treatment the general health related quality of life of patients undergoing brachytherapy with and without pretreatment external beam radiation was similar to age matched controls, although urinary, bowel and sexual problems were reported. These problems appeared to improve during the first year after treatment. Much of the impairment in disease specific health related quality of life among patients undergoing brachytherapy may be attributed to pretreatment radiation.     

Nephron sparing surgery for central renal tumors: experience with 33 cases

PURPOSE: Nephron sparing surgery is standard treatment for small, peripherally located renal cell carcinoma. In patients with a solitary kidney, bilateral tumors or impaired renal function nephron sparing surgery provides the only option to nephrectomy and subsequent hemodialysis or transplantation. We retrospectively investigated the value of nephron sparing surgery for centrally located renal cell carcinoma. MATERIALS AND METHODS: Between 1969 and 1997, 311 renal tumor enucleations were performed at our institution. The tumor was centrally located in 33 cases. The indication for enucleation was elective in 7 cases and imperative in 26, including bilateral tumor in 16 (metachronous in 9 and synchronous in 7), chronic renal failure in 4 and solitary kidney in 6. Four patients had metastasis at enucleation. RESULTS: Convalescence was unremarkable in 28 cases. Hemorrhage occurred in 1 patient, a urinary fistula in 2 and a local abscess secondary to a urinary fistula in 1. One patient died postoperatively of heart failure. Average serum creatinine was 1.25, 1.63 and 1.33 mg./dl. preoperatively, at hospital discharge and at a mean followup of 33 months, respectively. Hemodialysis was necessary transiently during convalescence in 1 patient and permanently starting 6 years after enucleation in another. Definitive histology revealed oncocytoma in 4 cases and renal cell carcinoma in 29. Disease was stages pT1 to pT3 in 9, 18 and 2 cases, and grades 1 to 3 in 6, 18 and 5, respectively. Local recurrence developed in 2 patients. Mean followup was 5.2 years (range 0.3 to 16.7). At a mean followup of 6.2 years (range 0.7 to 16.7) 20 patients were free of disease. In addition to the patient who died postoperatively, 9 died of renal cell carcinoma at a mean of 1.6 years (range 0.3 to 5.3) and 3 died of other causes at 5, 11 and 12 years postoperatively, respectively. No patient who underwent elective enucleation died. CONCLUSIONS: Nephron sparing surgery for centrally located kidney tumors is technically feasible and associated with an acceptable complication rate. Local tumor control is excellent, and the overall prognosis depends on contralateral disease and metastasis. Benign tumors may be diagnosed and removed without loss of the kidney. By avoiding hemodialysis quality of life is improved.     

Dramatic suppression of plasma and urinary prostate specific antigen and human glandular kallikrein by antiandrogens in male-to-female transsexuals

PURPOSE: Prostate specific antigen (PSA) and human glandular kallikrein (hK2) are mainly produced by the prostate and their genes are regulated by androgens through the androgen receptor. We determine whether PSA and hK2 change significantly in plasma and urine after antiandrogen treatment in male-to-female transsexuals. MATERIALS AND METHODS: Plasma and urine PSA and hK2 were measured with highly sensitive immunofluorometric procedures capable of detecting within 1 or 6 ng./l. PSA or hK2, respectively. Study groups consisted of 10 men treated with cyproterone acetate only (group 1), 15 transdermal estradiol plus cyproterone acetate (group 2) and 31 ethinyl estradiol plus cyproterone acetate (group 3). Plasma and urine samples were collected before initiation of treatment as well as after 4 months of hormonal therapy. For a subset of group 3 patients blood and urine samples were also obtained after 12 months of treatment. RESULTS: Cyproterone acetate, a steroidal antiandrogen, alone or with estradiol was able to suppress greater than 90% of plasma and urinary PSA and hK2 concentration after 4 or 12 months of therapy. CONCLUSIONS: Cyproterone acetate therapy causes dramatic suppression of plasma and urinary PSA and hK2 in men without prostate cancer. Since cyproterone acetate is used for prostate cancer treatment, suppression of PSA after hormonal therapy may not accurately reflect therapy success in reducing tumor burden.     

Immunobiologic, cytogenetic and drug response features of a newly established cell line (SCRC-1) from renal small cell carcinoma

PURPOSE: We describe the establishment and preliminary characterization of a cell line designated SCRC-1, which was derived from a primary renal small cell carcinoma. MATERIALS AND METHODS: Continuous cultures of a primary stage IVa renal small cell carcinoma and a xenograft in nude mice derived therefrom were characterized by immunohistology, electron microscopy, immunofluorescence/flow cytometry, cytogenetic analysis, and an in vitro drug resistance assay. RESULTS: SCRC-1 cells were reactive with antibodies to NSE, chromogranin-A, bombesin, Bcl-2, CD44s, CD44v6, CD44v7 to 8, vimentin and S100 protein (predominantly beta-subunit), and were unreactive with antibodies to EMA, CD54, EGFR(R1), URO-5, URO-7, URO-8 and URO-10. A similar immunoprofile was also found in both the primary tumor and the xenograft. Cytogenetic analysis revealed the following common clonal aberrations in all 50 metaphases analyzed: 45, XX, t (X;10;18) (p11;p11;q11), -der(18)t(X;10;18), indicating the clonal nature of this neoplasm. SCRC-1 cells showed low drug resistance to cyclophosphamide, doxorubicin, gemcitabine and fluorouracil, intermediate resistance to carmustine and mitomycin-C, and extreme resistance to cisplatin. CONCLUSION: We have documented the initial characterization of SCRC-1, which may be the first cell line reported to be derived from a primary small cell carcinoma of the kidney. This cell line can be used for further studies uncovering the biology and histogenesis of this rare cancer and delineating differences among small cell carcinomas of the kidney and other histological types.