Biomedical subjects

Mark F Munsell

Publications and source records attributed to Mark F Munsell.

At least 19 recordsLinked to original sources

PubMed2006

Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.

The mTOR complex 2 (mTORC2) containing mTOR and rictor is thought to be rapamycin insensitive and was recently shown to regulate the prosurvival kinase AKT by phosphorylation on Ser473. We investigated the molecular effects of mTOR inhibition by the rapamycin derivatives (RDs) temsirolimus (CCI-779) and everolimus (RAD001) in acute myeloid leukemia (AML) cells. Unexpectedly, RDs not only inhibited the mTOR complex 1 (mTORC1) containing mTOR and raptor with decreased p70S6K, 4EPB1 phosphorylation, and GLUT1 mRNA, but also blocked AKT activation via inhibition of mTORC2 formation. This resulted in suppression of phosphorylation of the direct AKT substrate FKHR and decreased transcription of D-cyclins in AML cells. Similar observations were made in samples from patients with hematologic malignancies who received RDs in clinical studies. Our study provides the first evidence that rapamycin derivatives inhibit AKT signaling in primary AML cells both in vitro and in vivo, and supports the therapeutic potential of mTOR inhibition strategies in leukemias.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Relevance of extracapsular extension of pelvic lymph node metastasis in patients with bladder cancer treated in the contemporary era.

BACKGROUND: Previous reports have suggested that extracapsular extension (ECE) is a prognostic factor in patients with urothelial carcinoma who have positive lymph nodes at the time of radical cystectomy. In the current study, the relevance of ECE in patients treated in the contemporary era was evaluated. METHODS: A database search from 1993 to 2003 revealed 150 patients with pN+M0 disease detected after radical cystectomy; of these, 108 patients did not receive neoadjuvant chemotherapy and form the basis of the current report. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) data were analyzed by the Kaplan-Meier method, with log-rank tests used to evaluate associations between survival and variables studied. RESULTS: Five-year OS, DSS, and RFS rates were 30.9%, 45.5%, and 29.7%, respectively. Adjuvant chemotherapy was administered to 70% of patients. On multivariate analysis, adjuvant chemotherapy was significantly associated with prolonged OS, DSS, and RFS (P </= .01). For patients overall and when stratified by pN status, the presence of ECE of lymph node metastasis was not found to be significantly associated with OS (P = .52), DSS (P = .43), or RFS (P = .83). CONCLUSIONS.: The current study suggests that ECE is not an independent prognostic factor in a contemporary series of patients with positive lymph nodes at radical cystectomy. This might be reflective of a paradigm shift that encompasses the adoption of multimodal therapy.

Aged↗

PubMed2006

Survival in cancer patients undergoing in-hospital cardiopulmonary resuscitation: a meta-analysis.

INTRODUCTION: Cardiopulmonary resuscitation is thought to be a low-yield intervention in cancer patients. In patients with metastatic disease the procedure is thought to be futile. Comprehensive data on survival to discharge in subsets of cancer patients undergoing in-hospital cardiopulmonary resuscitation, however, are lacking. OBJECTIVE: To determine the rate of survival to discharge for adult cancer patients undergoing in-hospital cardiopulmonary resuscitation. METHOD: A systematic search of MEDLINE and our primary sources' references was performed for studies involving in-hospital cardiac arrest, in clearly defined subsets of adult cancer patients, with outcomes that included survival to hospital discharge. RESULTS: Forty-two studies from 1966-2005, comprising 1707 patients met our minimal inclusion criteria. Overall survival to discharge was 6.2%. Survival in patients with localized disease was 9.5%, and in patients with metastatic disease was 5.6%. Analysis of data reported since 1990 reveals a narrowing of the survival gap, with survival rates in patients with localised disease of 9.1%, and in patients with metastatic disease of 7.8%. Survival in patients resuscitated on the general medical/surgical wards was 10.1%, while survival in patients resuscitated on intensive care units (ICUs) was 2.2%. CONCLUSIONS: Overall survival of CPR to hospital discharge in cancer patients compares favorably to survival rates in unselected inpatients. Improved outcomes in recent years in patients with metastatic disease are likely to reflect more selective use of CPR in cancer patients, with the sickest patients deselected.

Cardiopulmonary Resuscitation↗

PubMed2006

Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome.

BACKGROUND: Women with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have a 40 to 60 percent lifetime risk of endometrial cancer and a 10 to 12 percent lifetime risk of ovarian cancer. The benefit of prophylactic gynecologic surgery for women with this syndrome has been uncertain. We designed this study to determine the reduction in the risk of gynecologic cancers associated with prophylactic hysterectomy and bilateral salpingo-oophorectomy in women with the Lynch syndrome. METHODS: Three hundred fifteen women with documented germ-line mutations associated with the Lynch syndrome were identified. Women who had undergone prophylactic hysterectomy (61 women) and women who had undergone prophylactic bilateral salpingo-oophorectomy (47 women) were matched with mutation-positive women who had not undergone the procedure in question (210 women for the analysis of endometrial cancer and 223 for the analysis of ovarian cancer). Women who had undergone prophylactic surgery and their matched controls were followed from the date of the surgery until the occurrence of cancer or until the data were censored at the time of the last follow-up visit. RESULTS: There were no occurrences of endometrial, ovarian, or primary peritoneal cancer among the women who had undergone prophylactic surgery. Endometrial cancer was diagnosed in 69 women in the control group (33 percent), for an incidence density of 0.045 per woman-year, yielding a prevented fraction (the proportion of potential new cancers prevented) of 100 percent (95 percent confidence interval, 90 to 100 percent). Ovarian cancer was diagnosed in 12 women in the control group (5 percent), for an incidence density of 0.005 per woman-year, yielding a prevented fraction of 100 percent (95 percent confidence interval, -62 to 100 percent). CONCLUSIONS: These findings suggest that prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective strategy for preventing endometrial and ovarian cancer in women with the Lynch syndrome.

Adult↗

PubMed2006

Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas. METHODS: Fifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma--women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI-high) secondary to methylation of MLH1 (n = 26). RESULTS: Nearly one-fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, 'undifferentiated' histology that was not observed in HNPCC or the young group. CONCLUSION: Data suggest a genotype-phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or 'undifferentiated' endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Partial cystectomy for muscle invasive urothelial carcinoma of the bladder: a contemporary review of the M. D. Anderson Cancer Center experience.

PURPOSE: Partial cystectomy is a surgical option for select patients diagnosed with urothelial carcinoma. We review our experience with partial cystectomy for muscle invasive urothelial carcinoma to assess local control and survival rates. MATERIAL AND METHODS: From 1982 to 2003 a total of 37 patients with muscle invasive urothelial carcinoma underwent partial cystectomy with curative intent. Reviewed data included history of superficial tumors, presence of variant histology, tumor location, clinical stage, pathological stage, presence of carcinoma in situ, adjuvant therapy and disease status. RESULTS: The 5-year overall, disease specific and recurrence-free survival rates were 67%, 87% and 39%, respectively. Mean followup was 72.6 months (range 6 to 217). Of the 37 patients 19 (51%) did not have tumor recurrence, 9 (24%) had superficial recurrence in the bladder that was treated successfully and 9 (24%) had recurrence with advanced disease. A total of 24 patients (65%) had an intact bladder with no evidence of disease after a median of 53 months. There were 6 patients (16%) who died of bladder cancer, 3 of whom died of late recurrence of muscle invasive cancer (41, 44 and 138 months after partial cystectomy). On multivariate analysis higher pathological stage (HR 3.4, p = 0.04) was associated with shorter recurrence-free survival. A history of superficial tumors (p <0.01) and clinical stage (p = 0.01) was associated with advanced recurrence-free survival. The use of adjuvant chemotherapy (HR 0.18, p = 0.03) was associated with prolonged advanced recurrence-free survival, however adjuvant chemotherapy did not impact overall survival. CONCLUSIONS: Partial cystectomy provides adequate local control of muscle invasive bladder cancer in select patients. Because late recurrence is not uncommon and is potentially life threatening, lifelong followup with cystoscopy is recommended.

Adult↗

PubMed2006

Evaluation of the relevance of lymph node density in a contemporary series of patients undergoing radical cystectomy.

PURPOSE: Lymph node density, that is the ratio of positive nodes to the total number of nodes excised, has been suggested to better stratify patients with bladder cancer who have nodal metastasis. We evaluated its relevance in a contemporary series of patients treated with radical cystectomy and in the context of adjuvant chemotherapy. MATERIALS AND METHODS: From 1993 to 2003, 150 patients had pN+M0 disease at cystectomy, of whom 108 who did not receive neoadjuvant chemotherapy form the basis of this report. Statistical analyses were performed using standard methodology. RESULTS: Five-year overall, disease specific and recurrence-free survival rates were 30.9%, 45.5% and 29.7%, respectively. The median number of lymph nodes removed was 12 and the median number of positive nodes was 2. Of the patients 70% received adjuvant chemotherapy. Patients with a lymph node density of 25% or less had 5-year overall and recurrence-free survival rates of 37.3% and 38.1% compared with 18.7% and 10.6%, respectively in those with a lymph node density of greater than 25% (p = 0.02). In the context of adjuvant chemotherapy, which was associated with prolonged overall, disease specific and recurrence-free survival (p < or =0.01), lymph node density still remained prognostic for recurrence-free survival (HR 1.69, p = 0.047). The total number of nodes removed and the number of positive nodes were not prognostic. CONCLUSIONS: Our results support the relevance of lymph node density in a contemporary series of patients with bladder cancer treated with radical cystectomy. Lymph node density remains a significant prognostic factor for recurrence-free survival even when adjuvant chemotherapy is used.

Aged↗

PubMed2006

Modeling the impact of treatment and screening on U.S. breast cancer mortality: a Bayesian approach.

BACKGROUND: Breast cancer mortality (BCM) in the United States declined from 33.1 per 100,000 women in 1990 to 26.6 per 100,000 women in 2000, yielding a 19.6% relative decline in BCM since 1990. Our goal is to apportion this decline between screening and therapy and to be able to state with some certainty that these interventions affected this decline. METHODS: We started with an age-appropriate population of 2,000,000 women in 1975 and monitored these women through 2000. On the basis of population data each year, we assigned screening and breast cancer to women. If a woman was diagnosed with breast cancer, we simulated a lifetime for her with death from breast cancer, and we modified this lifetime depending on the use of adjuvant therapy and whether the cancer was screen-detected. A woman's lifetime was taken as the minimum of her lifetime with death from breast cancer and her simulated natural lifetime. We used Bayesian simulation modeling, which allows for associating probability distributions with our estimates. RESULTS: We calculated the probabilities that screening mammography and adjuvant therapy contributed to the observed decline in BCM to be 90% and 99%, respectively. The posterior mean reduction in BCM due to screening is 10.6% +/- 5.7% and due to therapy is 19.5% +/- 5.4%. The decrease in the hazard of BCM due to tamoxifen use for ER-positive tumors is 37% +/- 14% and that due to adjuvant (nontaxane) chemotherapy is 15% +/- 14%. DISCUSSION: The spread in our posterior distributions reflect the uncertainty present in the data sources available to us. However, despite this uncertainty we conclude a high probability that both screening and improvements in therapy contributed to the reduction in BCM observed in the United States from 1990 to 2000.

Age Distribution↗

PubMed2006

Nephroureterectomy for treating upper urinary tract transitional cell carcinoma: Time to change the treatment paradigm?

OBJECTIVE: To evaluate factors associated with disease recurrence and survival in patients undergoing nephroureterectomy for upper urinary tract transitional cell carcinoma (UUT-TCC) in one centre over an 18-year period. PATIENTS AND METHODS: The records of patients who had a nephroureterectomy for UUT-TCC at our institution from 1986 to 2004 were reviewed for clinical, pathological and treatment period data. Cox's proportional hazards regression model was used to test the statistical significance of several potential prognostic factors for recurrence and survival. RESULTS The median overall duration of follow-up was 2.5 years for 184 patients. Significant prognosticators for disease-specific survival (DSS) by univariate analysis were tumour stage (P < 0.01), tumour grade (P < 0.01), node-positive disease (P < 0.01), multifocality (P = 0.03), previous cystectomy (P < 0.01) and synchronous bilateral UUT-TCC (P = 0.02). On multivariate analysis, only tumour stage (P = 0.03) and grade (P = 0.01) correlated with DSS. The median recurrence-free survival duration was 2.4 years. In 44 patients, the disease recurred outside the bladder; 15 (8.2%) had local recurrence, 20 (10.9%) distant metastasis, and nine (4.9%) both local and distant recurrence. Bladder tumours occurred in 40 (26.1%) patients with no previous cystectomy. The evaluation of treatment outcome during three periods of the study showed no significant effect on DSS. CONCLUSION: Tumour stage and grade correlated with DSS in this cohort, with no improvement in outcome over the 18-year period assessed. Patients with high-stage and high-grade disease continue to fare poorly, suggesting a need for changing the treatment protocol. Judiciously applying a multimodal approach to the management of high-risk patients by incorporating neoadjuvant chemotherapy and surgical resection might provide, for the first time, the opportunity to improve patient outcome.

Aged↗

PubMed2006

Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2-overexpressing breast cancer cells.

HER2 overexpression is one of the most recognizable molecular alterations in breast tumors known to be associated with a poor prognosis. In the study described here, we explored the effect of HER2 overexpression on the sensitivity of breast cancer cells to the growth-inhibitory effects of 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), a synthetic triterpenoid, both in vitro and in vivo in a xenograft model of breast cancer. Both cell growth and colony formation in the soft agar assay, a hallmark of the transformation phenotype, were preferentially suppressed in HER2-overexpressing cell lines at low concentrations of CDDO, whereas growth-inhibitory effects at high concentrations did not correlate with the expression level of HER2. CDDO dose-dependently inhibited phosphorylation of HER2 in HER2-overexpressing cells and diminished HER2 kinase activity in vitro. CDDO induced the transactivation of the nuclear receptor peroxisome proliferator-activated receptor-gamma in both vector control and HER2-transfected MCF7 cells. Dose-response studies showed that the growth inhibition seen at lower concentrations of CDDO correlated with induction of the tumor suppressor gene caveolin-1, which is known to inhibit breast cancer cell growth. CDDO also reduced cyclin D1 mRNA and protein expression. In vivo studies with liposomally encapsulated CDDO showed complete abrogation of the growth of the highly tumorigenic MCF7/HER2 cells in a xenograft model of breast cancer. These findings provide the first in vitro and in vivo evidence that CDDO effectively inhibits HER2 tyrosine kinase activity and potently suppresses the growth of HER2-overexpressing breast cancer cells and suggest that CDDO has a therapeutic potential in advanced breast cancer.

Animals↗

PubMed2005

Quality of life and sexual functioning in cervical cancer survivors.

PURPOSE: To compare quality of life and sexual functioning in cervical cancer survivors treated with either radical hysterectomy and lymph node dissection or radiotherapy. METHODS: Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free, and had either undergone surgery or radiotherapy, but not both. The two treatment groups were then compared using univariate analysis and multivariate linear regression with a control group of age- and race-matched women with no history of cancer. RESULTS: One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for analysis. When compared with surgery patients and controls using univariate analysis, radiation patients had significantly poorer scores on standardized questionnaires measuring health-related quality of life (physical and mental health), psychosocial distress and sexual functioning. The disparity in sexual function remained significant in a multivariate analysis. Univariate and multivariate analyses did not show significant differences between radical hysterectomy patients and controls on any of the outcome measures. CONCLUSION: Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did those treated with radical hysterectomy and lymph node dissection. In contrast, these data suggest that cervical cancer survivors treated with surgery alone can expect overall quality of life and sexual function not unlike that of peers without a history of cancer.

Adaptation, Psychological↗

PubMed2005

Role of detection method in predicting breast cancer survival: analysis of randomized screening trials.

BACKGROUND: Screening mammography detects breast cancers earlier than those detected symptomatically, and so mammographically detected breast cancers tend to have better prognoses. The so-called stage shift that results from screen detection is subject to lead-time and length biases, and so earlier detection may not translate into longer survival. We used data from three large breast cancer screening trials--Health Insurance Plan (HIP) of New York and two Canadian National Breast Cancer Screening Studies (CNBSS)--to investigate survival benefits of breast cancer screening beyond stage shift. We also address whether method of detection is an independent prognostic factor in breast cancer. METHODS: The HIP trial randomly assigned approximately 62,000 women to screening and control groups. The two CNBSS trial cohorts CNBSS-1 and CNBSS-2 included a total of 44,970 women in the screening group and 44,961 in the control group. After adjusting for stage and other tumor characteristics in a Cox proportional hazards model, survival distributions were compared by method of breast cancer detection with both univariate and multivariable analyses. All P values are two-sided. RESULTS: Breast cancers detected by screening mammography had a shift in stage distribution to earlier stages (for HIP, P < .001; for CNBSS-1, P = .03; and for CNBSS-2, P < .001). After adjusting for tumor size, lymph node status, and disease stage in a Cox proportional hazards model, method of detection was a statistically significant independent predictor of disease-specific survival. Patients with interval cancers had a 53% (95% confidence interval [CI] = 17% to 100%) greater hazard of death from breast cancer than patients with screen-detected cancers, and patients with cancer in the control groups had a 36% (95% CI = 10% to 68%) greater hazard of death than patients with screen-detected cancer. CONCLUSION: There was an apparent survival benefit beyond stage shift for patients with screen-detected breast cancers compared with patients with breast cancers detected otherwise. Method of detection appears to be an important prognostic factor, even after adjusting for known tumor characteristics. This finding suggests that clinical trialists should routinely collect information about method of detection.

Breast Neoplasms↗

PubMed2005

The cancer pain experience of Israeli adults 65 years and older: the influence of pain interference, symptom severity, and knowledge and attitudes on pain and pain control.

GOALS: Little is known about Israeli elders' cancer pain experience. The purpose of this study was to explore the cancer pain experience, including pain intensity, pain management index, pain interference, symptom severity, and knowledge and attitudes toward pain and pain control. PATIENTS AND METHODS: Descriptive cross-sectional methods were used to obtain data with four instruments. The patients were 39 Israelis 65 years and older who were receiving outpatient treatment for cancer in a major hospital center in Israel. RESULTS: Results showed that over half (56.7%) reported severe worst pain and had negative pain management indexes (56.4%). In addition, knowledge and attitudes toward pain and pain control were poor (54.55%). There were no significant relationships between pain intensity and other variables. However, pain interference demonstrated a significant positive relationship with symptom severity. Post hoc analysis revealed that Ashkenazi Jewish and more educated patients reported significantly less pain interference than Sephardic Jewish patients. CONCLUSION: Larger samples representative of the cultural differences in Israel are needed to more definitively identify elements of the cancer pain experience in Israeli elders that can be addressed to improve pain management.

Aged↗

PubMed2005

The cancer pain experience of Israeli and American patients 65 years and older.

With the aging of the world's population, cancer pain will become an increasingly important health issue. The purpose of this study was to describe the cancer pain experience of Americans (n = 60) and Israelis (n = 39) 65 years and older. Outpatients in teaching hospitals in the U.S. and in Israel completed study questionnaires. Thirty percent of the total variance of worst pain was explained by age, symptom severity, and cancer stage, and 40% of the total variance of pain interference was explained by whether they were American or Israeli, symptom severity, and sense of coherence. Israeli patients had significantly higher scores on worst pain and pain interference, and significantly lower pain management index (PMI) and knowledge and attitudes toward pain and pain control scores. Studies with larger samples and across different cultures are needed to confirm these findings in order to develop culturally appropriate interventions.

Adult↗

PubMed2005

The activity of taxanes compared with bleomycin, etoposide, and cisplatin in the treatment of sex cord-stromal ovarian tumors.

OBJECTIVE: We compared the efficacy and side effects of taxanes, with or without platinum, to bleomycin, etoposide, and cisplatin (BEP) in treating sex cord-stromal ovarian tumors. METHODS: We conducted a retrospective review of all patients with sex cord-stromal ovarian tumors seen at our institution from 1985 to 2002. Eligible patients were those who underwent pathologic confirmation, clinical evaluation, and treatment with a taxane or BEP for initial or recurrent disease. RESULTS: Of 222 patients identified, 21 received BEP for new (n = 11) or recurrent disease (n = 10); 44 received a taxane during 48 treatment episodes (four patients on two occasions each) for new (n = 11) or recurrent disease (n = 37). Newly diagnosed patients treated with BEP vs. taxanes had no significant difference in response rate (Fisher's exact test, P = 1), progression-free survival (PFS) (log-rank test, P = 0.213), or overall survival (log-rank test, P = 0.994). Among patients treated for recurrent measurable disease, the response rate was higher for BEP-treated (71%) than for taxane-treated patients (37%), but this was not statistically significant. In all patients treated for recurrent disease, there was no significant difference in failure to progress at chemotherapy completion between BEP- (70%) and taxane-treated patients (62%) or in median PFS (11.2 vs. 7.2 months). The presence of platinum in taxane-containing regimens correlated with response. Taxane-related side effects included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). BEP-related side effects included pulmonary fibrosis (n = 3) and neutropenia (n = 2). CONCLUSIONS: Taxanes demonstrated activity against sex cord-stromal tumors of the ovary and may be less toxic than BEP. Taxane and platinum combination chemotherapy warrants further investigation in this disease.

Adolescent↗

PubMed2005

Fas expression in lung metastasis from osteosarcoma patients.

The authors' animal studies have shown that the metastatic potential of osteosarcoma (OS) cells correlates inversely with Fas expression-that is, Fas-negative cells metastasize but Fas-positive cells do not. One reason for this in the context of OS lung metastases may be that Fas-positive cells are eliminated by engagement with the Fas ligand (FasL) constitutively expressed on the surface of pneumocytes, whereas Fas-negative tumor cells are not. The purpose of this study was to determine the status of Fas expression in OS lung metastases from patients. Specifically, archived paraffin-embedded specimens of lung metastases from 38 patients with OS were analyzed by immunohistochemistry. Lung nodules from 23 of the 38 patients (60%) were Fas negative, those from 12 patients (32%) were weakly positive, and that from only 1 patient (3%) was strongly positive. Findings in the samples from the remaining two patients (5%) could not be interpreted because of extensive necrosis. Most patients with the weakly positive tumors and the single patient with the strongly positive tumor received chemotherapy prior to lung resection. There was a significant correlation between Fas expression and the administration of preoperative salvage chemotherapy (P = 0.0013). These data indicate that loss of Fas may be one mechanism by which OS cells evade host resistance in the lung. Chemotherapy may induce regression by upregulating Fas.

Adolescent↗

PubMed2004

Delphi survey of nursing research priorities.

PURPOSE/OBJECTIVES: To identify oncology nurses priorities for topics and issues to be addressed by developing a clinical nursing research program at a large comprehensive cancer center. DESIGN: Delphi survey, completed in two rounds. SETTING: A large comprehensive cancer center in the southern United States. SAMPLE: All 1,500 RNs employed at the cancer center. Round I asked nurses to identify topics they believed needed to be studied, and 642 nurses responded. In round II, 567 nurses ranked these priorities. METHODS: Surveys were distributed to all nurses who work in a variety of settings at the cancer center. Open-ended responses from round I were content analyzed, round II rankings of importance were described, and factor analysis was performed. MAIN RESEARCH VARIABLES: 120 topics were identified from a content analysis of research areas described by nurses in the cancer center. FINDINGS: 120 research priorities were identified. Factor analysis revealed three factors: clinical care, nurses and skills, and administrative aspects. CONCLUSIONS: The top five research priorities identified at the cancer center were, in rank order, acute and chronic pain, infection rates and control, job satisfaction, nurse-patient ratios and staffing, and nurse retention. This study's survey included items similar to those on the recently conducted Oncology Nursing Society research priority survey. Pain and issues with infection were among the top five priorities in both surveys. IMPLICATIONS FOR NURSING: Conducting a survey to identify nurses perceptions of research was useful in involving nurses in the conduct of research, and the results were useful guides to beginning a coordinated program of nursing research.

Adult↗

PubMed2004

The activity of taxanes in the treatment of sex cord-stromal ovarian tumors.

PURPOSE: To determine the efficacy and side effects of taxanes, with or without platinum, for the treatment of sex cord-stromal tumors of the ovary. PATIENTS AND METHODS: We conducted a retrospective review of all patients seen from 1985 to 2002 at The University of Texas M.D. Anderson Cancer Center with ovarian sex cord-stromal tumors. Eligible patients underwent pathology confirmation and clinical evaluation at M.D. Anderson and received a taxane for initial or recurrent disease. RESULTS: Of 222 patients identified, 44 were eligible for analysis. For nine patients treated in the first-line adjuvant setting, median progression-free survival (PFS) was not reached at 51 months. Of two patients treated for measurable disease in the first-line setting, one had a complete response. Median PFS was 34.3 months; median overall survival (OS) was not reached. Median follow-up was 90.3 months (range, 39.4 to 140.5 months). Response rate for 30 patients treated with a taxane +/- platinum for recurrent, measurable disease was 42%. Median PFS was 19.6 months; median OS was not reached. Median follow-up was 100.7 months (range, 8.1 to 361.3 months). The presence of platinum correlated with response in the recurrent, measurable disease setting. The number of patients was insufficient to detect relative efficacy of paclitaxel and docetaxel. Adverse effects of paclitaxel included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). CONCLUSION: Taxanes seem to be active agents in the treatment of patients with sex cord-stromal tumors of the ovary. The combination of taxanes with platinum in the treatment of this disease deserves additional investigation.

Adolescent↗