Introduction: Epithelial ovarian cancer remains the gynecologic tumor with the highest rate of recurrence after initial optimal cytoreductive surgery followed by adjuvant chemotherapy. Unfortunately, with the development of recurrent ovarian cancer often comes the discovery of chemo-resistant disease. The absence of improvement in long term survival, notwithstanding the use of newer agents as is seen in other cancers, emphasizes the need for improved understanding of the processes that lead to chemo-resistant disease.
Areas Covered: This review will cover the following topics: 1. Molecular and cellular mechanisms in platinum and paclitaxel resistance 2. Other molecular mediators of chemo-resistance 3. Expression of stem cell markers in ovarian cancer and relationship to chemo-resistance 4. MicroRNA and long non-coding RNA expression in chemo-resistant ovarian cancer 5. Determination of chromosomal aberrations as markers of chemo-resistance 6. Molecular profiling in chemo-resistant disease.
A standard MEDLINE search was performed using the key words; ovarian cancer, chemo-resistant disease, molecular profiling, cancer stem cells and chemotherapy.
Expert Commentary: Over the next few years the challenge remains to precisely determine the mechanisms responsible for the onset and maintenance of chemo-resistance and to effectively target these mechanisms. 相似文献
The present studies investigated the expression of the two PDGF genes (c-sis/PDGF-2 and PDGF-1) and the PDGF-receptor b gene (PDGF-R) in 34 primary human astrocytomas. Northern blot analysis demonstrated the coexpression of the c-sis/PDGF-2 protooncogene and the PDGF-R gene in all astrocytomas examined. The majority of the tumors also expressed the PDGF-1 gene. There was no correlation between the expression of the two PDGF genes. Nonmalignant human brain tissue expressed the PDGF-R and PDGF-1 genes but not the c-sis/PDGF-2 protooncogene. In situ hybridization of astrocytoma tissue localized the expression of the c-sis and PDGF-R mRNA's in tumor cells. Capillary endothelial cells also expressed c-sis mRNA. In contrast, nonmalignant human brain tissue expressed only PDGF-R mRNA but not c-sis/PDGF-2 mRNA. The coexpression of a potent mitogenic growth factor protooncogene (c-sis) and its receptor gene in astrocytoma tumor cells suggests the presence of an autocrine mechanism that may contribute to the development and maintenance of astrocytomas. The expression of c-sis mRNA in tumor cells but not in nonmalignant brain cells may serve as an additional diagnostic criterion for the detection of astrocytomas in small tissue specimen using in situ hybridization for the detection of c-sis mRNA and/or immunostaining for the recognition of its protein product. 相似文献
Intact skin among many other functions provides a protective barrier between the body and its environment, which is critical in regulating transepidermal water loss (Wilkinson and Moor, 1982). The frequent application and removal of adhesives can damage skin by stripping away the outer epidermal layers. Older people, very young children and those with an underlying skin disorder may be particularly at risk (Gibelli et al, 1999; Lyons and Smith, 2003). Hydrocolloid adhesives, which hold moisture in the adhesive mass, are more skin friendly than the acrylic adhesives they now replace and have now become the material of choice for ostomy flanges and flange extenders (Smith et al, 2007). To understand stoma care nurses' awareness of the value of technologically advanced silicone and hydrocolloid products, the authors undertook a nationwide postal survey. The survey, commissioned by four companies in the United Kingdom, who make silicone and hydrocolloid products that can be used in stoma care, were keen to evaluate the awareness of these products to confirm their importance to the patient and why they should be appropriately categorized for reimbursement by the Department of Health. 相似文献
Fc fragments derived from human Ig were found to be capable of enhancing T cell-mediated, antigen-induced proliferative and mixed lymphocyte culture responses. Maximum enhancement occurred when suboptimal amounts of antigen or suboptimal numbers of stimulator cells were employed. Augmentation of the allogeneic mixed lymphocyte culture reaction requires an I-A and/or I-B subregion difference between effector and stimulator cell populations. Although a significant proliferative response was observed with K- or D- region differences, Fc fragments were unable to enhance the response. The T cell population acted upon by Fc fragments in the potentiation of these responses bears the Lyt-1(+)23(-) phenotype. 相似文献
OBJECTIVE: To investigate the numbers, clinical characteristics, resource use, and outcomes of admissions who met precise clinical and physiologic criteria for severe sepsis (as defined in the PROWESS trial) in the first 24 hrs in the intensive care unit. DESIGN: Observational cohort study, with retrospective analysis of prospectively collected data. SETTING: Ninety-one adult general intensive care units in England, Wales, and Northern Ireland between 1995 and 2000. PATIENTS: Patients were 56,673 adult admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We found that 27.1% of adult intensive care unit admissions met severe sepsis criteria in the first 24 hrs in the intensive care unit. Most were nonsurgical (67%), and the most common organ system dysfunctions were seen in the cardiovascular (88%) and respiratory (81%) systems. Modeling the data for England and Wales for 1997 suggested that 51 (95% confidence interval, 46-58) per 100,000 population per year were admitted to intensive care units and met severe sepsis criteria in the first 24 hrs.Of the intensive care unit admissions who met severe sepsis criteria in the first 24 hrs, 35% died before intensive care unit discharge and 47% died during their hospital stay. Hospital mortality rate ranged from 17% in the 16-19 age group to 64% in those >85 yrs. In England and Wales in 1997, an estimated 24 (95% confidence interval, 21-28) per 100,000 population per year died after intensive care unit admissions with severe sepsis in the first 24 hrs.For intensive care unit admissions who met severe sepsis criteria in the first 24 hrs, median intensive care unit length of stay was 3.56 days (interquartile range, 1.50-9.32) and median hospital length of stay was 18 days (interquartile range, 8-36 days). These admissions used 45% of the intensive care unit and 33% of the hospital bed days used by all intensive care unit admissions. CONCLUSIONS: Severe sepsis is common and presents a major challenge for clinicians, managers, and healthcare policymakers. Intensive care unit admissions meeting severe sepsis criteria have a high mortality rate and high resource use. 相似文献
BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) has been used in patients to increase the level of circulating hematopoietic progenitors. Although G-CSF has been administered to some healthy individuals, the kinetics of mobilization of peripheral blood stem cells (PBSCs), the optimum dose schedule and the incidence and nature of adverse reactions in normal individuals are not completely defined. STUDY DESIGN AND METHODS: Normal individuals (n = 102) who received G- CSF for 5 or 10 days at doses of 2, 5, 7.5, or 10 micrograms per kg per day were studied. The subjects were observed for symptoms and physical changes, and blood samples were obtained for a variety of laboratory tests. After 5 or 10 days of G-CSF treatment, PBSCs were collected by apheresis and analyzed. RESULTS: Overall, 89 percent of the individuals completed the 5-day treatment protocol and 88 percent completed the 10- day protocol without modification of the dose of G-CSF administered. Ninety percent of donors experienced some side effect of G-CSF. The most frequent effects noted were bone pain (83%), headache (39%), body aches (23%), fatigue (14%), and nausea and/or vomiting (12%). The dose of G-CSF administered directly affected the proportion of people with bone pain (p = 0.025) or body aches (p = 0.045) or who were feeling hot or having night sweats (p = 0.02) or taking analgesics (p = 0.01). With the 5-day dose schedule, several changes in serum chemistries occurred, including increases in alkaline phosphatase (p = 0.001), alanine aminotransferase (p = 0.0013), lactate dehydrogenase (p = 0.0001), and sodium (p = 0.0001). Decreases occurred in glucose (p = 0.045), potassium (p = 0.0004), bilirubin (p = 0.001), and blood urea nitrogen (p = 0.0017). In donors who received G-CSF for 5 days, the absolute neutrophil count was increased after one G-CSF dose, and it reached a maximum on Day 6, as did the number of CD34+ cells (64.6 +/? 55.9 × 10(6) cells/L). In those same donors, the platelet count after apheresis on Day 6 was 32 +/? 13 percent lower than pretreatment values (250 +/? 42 × 10(9) cells/L). In donors receiving G-CSF for 10 days, the neutrophil count reached a maximum on Day 8, but the number of CD34+ cells peaked on Day 6 (58.3 +/? 52.1 × 10(5) cells/L) and then declined. The platelet count decreased from pretreatment values by 28 +/? 12 percent prior to apheresis on Day 11. When individuals were treated for 5 days with G-CSF, the quantity of CD34+ cells collected was directly related to the G-CSF dose. When 5 micrograms per kg per day was given, 2.80 +/? 1.81 × 10(8) cells were collected, compared with collection of 4.67 +/? 3.11 × 10(8) cells when 10 micrograms per kg per day was given (p = 0.04). More important, PBSCs collected after 10 days of G-CSF administration (5 micrograms/kg/day) had significantly fewer CD34+ cells (0.82 +/? 0.37 × 10(8) cells, p = 0.01) than did PBSCs collected after 5 days of G-CSF (5 micrograms/kg/day). CONCLUSION: Most normal donors receiving G-CSF experience side effects, but these are mild to moderate in degree. Some alterations in blood chemistries occur, but none were clinically serious. Because of the symptoms associated with G-CSF, these individuals must be monitored closely. The treatment of normal donors with G-CSF for more than 5 days significantly decreased the number of circulating CD34+ cells and the quantity collected by apheresis. 相似文献