背景与目的:华蟾素目前广泛应用于肿瘤的治疗中,由于在80年代上市,未进行临床Ⅰ期研究,无法确定其最大耐受剂量。因此本文旨在观察华蟾素治疗肝细胞癌、肺癌和胰腺癌的最大耐受剂量和不良反应,同时评价治疗疗效。方法:Ⅲ、Ⅳ期肝细胞癌...背景与目的:华蟾素目前广泛应用于肿瘤的治疗中,由于在80年代上市,未进行临床Ⅰ期研究,无法确定其最大耐受剂量。因此本文旨在观察华蟾素治疗肝细胞癌、肺癌和胰腺癌的最大耐受剂量和不良反应,同时评价治疗疗效。方法:Ⅲ、Ⅳ期肝细胞癌、非小细胞肺癌和胰腺癌接受华蟾素治疗,采用静脉滴注,连续14 d,21 d为一疗程。如果没有出现剂量限制性毒性,治疗将持续2个疗程。剂量递增的方案为:10、20、40、60、90和120 m l/(m2.d)。结果:入组15例患者(每个剂量组为3例)中,11例为肝癌,2例胰腺癌和2例肺癌。第五剂量组结束时没有发现剂量限制性毒性(DLT)。其中14例患者可评价疗效,6例(42.9%)为SD,8例(57.1%)为PD。在第一剂量组中,1例肝癌患者肿瘤缩小20%并维持11个月。结论:本研究最高剂量达到常规剂量的8倍,尚未出现剂量限制性毒性。部分患者获得了肿瘤缩小或稳定的疗效。展开更多
AIM:To examine whether acupuncture can prevent prolonged postoperative ileus(PPOI)after intraperitoneal surgery for colon cancer. METHODS:Ninety patients were recruited from the Fudan University Cancer Hospital,Shangh...AIM:To examine whether acupuncture can prevent prolonged postoperative ileus(PPOI)after intraperitoneal surgery for colon cancer. METHODS:Ninety patients were recruited from the Fudan University Cancer Hospital,Shanghai,China. After surgery,patients were randomized to receive acupuncture(once daily,starting on postoperative day 1, for up to six consecutive days)or usual care.PPOI was defined as an inability to pass flatus or have a bowel movement by 96 h after surgery.The main outcomes were time to first flatus,time to first bowel movement, and electrogastroenterography.Secondary outcomes were quality of life(QOL)measures,including pain, nausea,insomnia,abdominal distension/fullness,and sense of well-being. RESULTS:No significant differences in PPOI on day 4 (P=0.71)or QOL measures were found between the groups.There were also no group differences when the data were analyzed by examining those whose PPOI had resolved by day 5(P=0.69)or day 6(P= 0.88).No adverse events related to acupuncture were reported. CONCLUSION:Acupuncture did not prevent PPOI andwas not useful for treating PPOI once it had developed in this population.展开更多
Objectives： To evaluate the effects of the Chinese medicine （CM） five-element music on quality of life for senior and non-senior advanced cancer patients. Methods： With a randomized controlled trial, 170 advanced ...Objectives： To evaluate the effects of the Chinese medicine （CM） five-element music on quality of life for senior and non-senior advanced cancer patients. Methods： With a randomized controlled trial, 170 advanced cancer patients were randomly assigned to three groups： the CM five-element music group （68 patients）, the Western music therapy group （68 cases）, and the no music therapy group （34 cases）. All patients of 70 years old or older were considered seniors and the remaining patients younger than 70 years were considered non- seniors. Patients in the CM five-element music group listened to CM five-element music, the patients in the Western music group listened to Western music, and the patients in the no music group did not listen to music. A course of treatment was 3 weeks, with 30 rain each day, 5 days a week. The Hospice Quality of Life Index- Revised （HQOLI-R） and Karnofsky performance score （KPS） were measured in the three groups before and after treatment. The symptom diary score was measured in the three groups every 3 days, 7 times in total. Results： CM five-element music group showed a significant difference of HQOLI-R, KPS and symptom diary score with other groups （all P〈0.01）. There were significant differences of HQOLI-R, symptom diary score, and KPS after treatment in CM five-element music group and other groups in the non-senior subgroup （P〈0.05）. Additionally, there were significant differences in HQOLI-R and KPS after treatment among the three groups in the senior subgroup （P〈0.05）. Conclusions： CM five-element music therapy could improve the quality of life and KPS for senior and non senior advanced cancer patients, and it could improve subjective symptoms for non-senior advanced cancer patients.展开更多
1996年，美国全国多发性硬化协会（US National Multiple Sclerosis Society, NMSS）的临床试验建议委员会（Advisory Committee on Clinical Trials in Multiple Sclerosis）根据对多发性硬化（multiple sclerosis，MS）专家的调查问...1996年，美国全国多发性硬化协会（US National Multiple Sclerosis Society, NMSS）的临床试验建议委员会（Advisory Committee on Clinical Trials in Multiple Sclerosis）根据对多发性硬化（multiple sclerosis，MS）专家的调查问卷确立了MS基于病程的临床分型，旨在明确自然史和人口学研究的亚组定义、促进临床试验受试者的均质化纳入以及在医生和MS患者之间的明确交流，确定了复发缓解型（RRMS）、继发进展型（SPMS）、原发进展型（PPMS）和进展复发型（PRMS）四种类型，并给出了良性和恶性MS的定义。展开更多
Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- b...Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- binds RANKL with high affinity and specificity and inhibits RANKL action. Methods: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of- 1.8 to - 4.0 at the lumbar spine or- 1.8 to- 3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open- label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Results: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C- telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. Conclusions: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis.展开更多
Ovarian cancer is a lethal gynecologic malignancy with greater than 70% of women presenting with advanced stage disease. Despite new treatments, long term outcomes have not significantly changed in the past 30 years w...Ovarian cancer is a lethal gynecologic malignancy with greater than 70% of women presenting with advanced stage disease. Despite new treatments, long term outcomes have not significantly changed in the past 30 years with the five-year overall survival remaining between 20% and 40% for stage Ⅲ and Ⅳ disease. In contrast patients with stage Ⅰ disease have a greater than 90% five-year overall survival. Detection of ovarian cancer at an early stage would likely have significant impact on mortality rate. Screening biomarkers discovered at the bench have not translated to success in clinical trials. Existing screening modalities have not demonstrated survival benefit in completed prospective trials. Advances in high throughput screening are making it possible to evaluate the development of ovarian cancer in ways never before imagined. Data in the form of human "-omes" including the proteome, genome, metabolome, and transcriptome are now available in various packaged forms. With the correct pooling of resources including prospective collection of patient specimens, integration of high throughput screening, and use of molecular heterogeneity in biomarker discovery, we are poised to make progress in ovarian cancer screening. This review will summarize current biomarkers, imaging, and multimodality screening strategies in the context of emerging technologies.展开更多
Rat protein DE is an androgen-dependent cysteine-rich secretory protein （CRISP） synthesized by proximal epididymal regions. DE, also known as CRISP-1, is localized on the equatorial segment of acrosome-reacted sperm...Rat protein DE is an androgen-dependent cysteine-rich secretory protein （CRISP） synthesized by proximal epididymal regions. DE, also known as CRISP-1, is localized on the equatorial segment of acrosome-reacted spermatozoa and participates in gamete fusion through binding to egg complementary sites. Immunization of rats with DE inhibits fertility and sperm fusion ability, suggesting that DE represents a good epididymal contraceptive target. Recombinant DE fragments and synthetic peptides revealed that DE binds to the egg via a 12-amino acid region of an evolutionarily conserved motif, Signature 2 （S2）. The ability of other CRISP to bind to the rat egg was correlated with their S2 amino acid sequences. Although testicular protein Tpx- 1 （CRISP-2） was capable of binding to rodent eggs, human epididymal AEG-related protein （ARP） and helothermine （from lizard saliva） were not. The S2 region presented only two substitutions in Tpx-1 and four in ARP and helothermine, compared with the DE S2, suggesting that this amino acid sequence was relevant for egg interaction. Studies with Tpx- 1 and anti-Tpx- 1 revealed the participation of this protein in gamete fusion through binding to complementary sites in the egg. In competition studies, DE reduced binding of Tpx- 1 dose-dependently, indicating that both CRISP share the egg complementary sites. That anti-DE and anti-Tpx-1 inhibit sperm-egg fusion while recognizing only the corresponding proteins, suggests functional cooperation between these homologous CRISP to ensure fertilization success. These results increase our understanding of the molecular mechanisms of gamete fusion and contribute to the development of new and safer fertility regulating methods. （Asian J Androl 2007 July; 9： 528-532）展开更多
AIM: To assess the safety and efficacy of trans-arterial chemo-embolization (TACE) in very elderly patients. METHODS: A prospective cohort study, from 2001 to 2010, compared clinical outcomes following TACE between pa...AIM: To assess the safety and efficacy of trans-arterial chemo-embolization (TACE) in very elderly patients. METHODS: A prospective cohort study, from 2001 to 2010, compared clinical outcomes following TACE between patients ≥ 75 years old and younger patients (aged between 65 and 75 years and younger than 65 years) with hepatocellular carcinoma (HCC), diagnosed according to the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases criteria. The decision that patients were not candidates for curative therapy was made by a multidisciplinary HCC team. Data collected included demographics, co-morbidities, liver disease etiology, liver disease severity and the number of procedures. The primary outcome was mortality; secondary outcomes included post-embolization syndrome (nausea, fever, abdominal right upper quadrant pain, increase in liver enzymes with no evidence of sepsis and with a clinical course limited to 3-4 d post procedure) and 30-d complications. Additionally, changes in liver enzyme measurements were assessed [alanine and aspartate aminotransferase (ALT and AST), gamma-glutamyl transpeptidase and alkaline phosphatase] in the week following TACE. Analysis employed both univariate and multivariate methods (Cox regression models). RESULTS: Of 102 patients who underwent TACE as sole treatment, 10 patients (9.8%) were > 80 years old at diagnosis; 13 (12.7%) were between 75 and 80 years, 45 (44.1%) were between 65 and 75 years and 34 (33.3%) were younger than 65 years. Survival analysis demonstrated similar survival patterns between the elderly patients and younger patients. Age was also not associated with the adverse event rate. Survival rates at 1, 2 and 3 years from diagnosis were 74%, 37% and 31% among patients < 65 years; 83%, 66% and 48% among patients aged 65 to 75 years; and 86%, 41% and 23% among patients ≥ 75 years. There were no differences between the age groups in the pre-procedural care, including preventive treatment for contrast nephropat展开更多
文摘背景与目的:华蟾素目前广泛应用于肿瘤的治疗中,由于在80年代上市,未进行临床Ⅰ期研究,无法确定其最大耐受剂量。因此本文旨在观察华蟾素治疗肝细胞癌、肺癌和胰腺癌的最大耐受剂量和不良反应,同时评价治疗疗效。方法:Ⅲ、Ⅳ期肝细胞癌、非小细胞肺癌和胰腺癌接受华蟾素治疗,采用静脉滴注,连续14 d,21 d为一疗程。如果没有出现剂量限制性毒性,治疗将持续2个疗程。剂量递增的方案为:10、20、40、60、90和120 m l/(m2.d)。结果:入组15例患者(每个剂量组为3例)中,11例为肝癌,2例胰腺癌和2例肺癌。第五剂量组结束时没有发现剂量限制性毒性(DLT)。其中14例患者可评价疗效,6例(42.9%)为SD,8例(57.1%)为PD。在第一剂量组中,1例肝癌患者肿瘤缩小20%并维持11个月。结论:本研究最高剂量达到常规剂量的8倍,尚未出现剂量限制性毒性。部分患者获得了肿瘤缩小或稳定的疗效。
基金Supported by US National Cancer Institute (NCI) grants CA108084 and CA12153031
文摘AIM:To examine whether acupuncture can prevent prolonged postoperative ileus(PPOI)after intraperitoneal surgery for colon cancer. METHODS:Ninety patients were recruited from the Fudan University Cancer Hospital,Shanghai,China. After surgery,patients were randomized to receive acupuncture(once daily,starting on postoperative day 1, for up to six consecutive days)or usual care.PPOI was defined as an inability to pass flatus or have a bowel movement by 96 h after surgery.The main outcomes were time to first flatus,time to first bowel movement, and electrogastroenterography.Secondary outcomes were quality of life(QOL)measures,including pain, nausea,insomnia,abdominal distension/fullness,and sense of well-being. RESULTS:No significant differences in PPOI on day 4 (P=0.71)or QOL measures were found between the groups.There were also no group differences when the data were analyzed by examining those whose PPOI had resolved by day 5(P=0.69)or day 6(P= 0.88).No adverse events related to acupuncture were reported. CONCLUSION:Acupuncture did not prevent PPOI andwas not useful for treating PPOI once it had developed in this population.
基金Supported by the project of Chinese Geriatric Oncology Society of the"Eleventh five-year"Plan of Ministry of Civil Affairs(No.2008-47-2-45)
文摘Objectives： To evaluate the effects of the Chinese medicine （CM） five-element music on quality of life for senior and non-senior advanced cancer patients. Methods： With a randomized controlled trial, 170 advanced cancer patients were randomly assigned to three groups： the CM five-element music group （68 patients）, the Western music therapy group （68 cases）, and the no music therapy group （34 cases）. All patients of 70 years old or older were considered seniors and the remaining patients younger than 70 years were considered non- seniors. Patients in the CM five-element music group listened to CM five-element music, the patients in the Western music group listened to Western music, and the patients in the no music group did not listen to music. A course of treatment was 3 weeks, with 30 rain each day, 5 days a week. The Hospice Quality of Life Index- Revised （HQOLI-R） and Karnofsky performance score （KPS） were measured in the three groups before and after treatment. The symptom diary score was measured in the three groups every 3 days, 7 times in total. Results： CM five-element music group showed a significant difference of HQOLI-R, KPS and symptom diary score with other groups （all P〈0.01）. There were significant differences of HQOLI-R, symptom diary score, and KPS after treatment in CM five-element music group and other groups in the non-senior subgroup （P〈0.05）. Additionally, there were significant differences in HQOLI-R and KPS after treatment among the three groups in the senior subgroup （P〈0.05）. Conclusions： CM five-element music therapy could improve the quality of life and KPS for senior and non senior advanced cancer patients, and it could improve subjective symptoms for non-senior advanced cancer patients.
文摘1996年，美国全国多发性硬化协会（US National Multiple Sclerosis Society, NMSS）的临床试验建议委员会（Advisory Committee on Clinical Trials in Multiple Sclerosis）根据对多发性硬化（multiple sclerosis，MS）专家的调查问卷确立了MS基于病程的临床分型，旨在明确自然史和人口学研究的亚组定义、促进临床试验受试者的均质化纳入以及在医生和MS患者之间的明确交流，确定了复发缓解型（RRMS）、继发进展型（SPMS）、原发进展型（PPMS）和进展复发型（PRMS）四种类型，并给出了良性和恶性MS的定义。
文摘Background: Receptor activator of nuclear factor- κ B ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162)- binds RANKL with high affinity and specificity and inhibits RANKL action. Methods: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of- 1.8 to - 4.0 at the lumbar spine or- 1.8 to- 3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open- label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Results: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C- telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. Conclusions: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis.
文摘Ovarian cancer is a lethal gynecologic malignancy with greater than 70% of women presenting with advanced stage disease. Despite new treatments, long term outcomes have not significantly changed in the past 30 years with the five-year overall survival remaining between 20% and 40% for stage Ⅲ and Ⅳ disease. In contrast patients with stage Ⅰ disease have a greater than 90% five-year overall survival. Detection of ovarian cancer at an early stage would likely have significant impact on mortality rate. Screening biomarkers discovered at the bench have not translated to success in clinical trials. Existing screening modalities have not demonstrated survival benefit in completed prospective trials. Advances in high throughput screening are making it possible to evaluate the development of ovarian cancer in ways never before imagined. Data in the form of human "-omes" including the proteome, genome, metabolome, and transcriptome are now available in various packaged forms. With the correct pooling of resources including prospective collection of patient specimens, integration of high throughput screening, and use of molecular heterogeneity in biomarker discovery, we are poised to make progress in ovarian cancer screening. This review will summarize current biomarkers, imaging, and multimodality screening strategies in the context of emerging technologies.
文摘Rat protein DE is an androgen-dependent cysteine-rich secretory protein （CRISP） synthesized by proximal epididymal regions. DE, also known as CRISP-1, is localized on the equatorial segment of acrosome-reacted spermatozoa and participates in gamete fusion through binding to egg complementary sites. Immunization of rats with DE inhibits fertility and sperm fusion ability, suggesting that DE represents a good epididymal contraceptive target. Recombinant DE fragments and synthetic peptides revealed that DE binds to the egg via a 12-amino acid region of an evolutionarily conserved motif, Signature 2 （S2）. The ability of other CRISP to bind to the rat egg was correlated with their S2 amino acid sequences. Although testicular protein Tpx- 1 （CRISP-2） was capable of binding to rodent eggs, human epididymal AEG-related protein （ARP） and helothermine （from lizard saliva） were not. The S2 region presented only two substitutions in Tpx-1 and four in ARP and helothermine, compared with the DE S2, suggesting that this amino acid sequence was relevant for egg interaction. Studies with Tpx- 1 and anti-Tpx- 1 revealed the participation of this protein in gamete fusion through binding to complementary sites in the egg. In competition studies, DE reduced binding of Tpx- 1 dose-dependently, indicating that both CRISP share the egg complementary sites. That anti-DE and anti-Tpx-1 inhibit sperm-egg fusion while recognizing only the corresponding proteins, suggests functional cooperation between these homologous CRISP to ensure fertilization success. These results increase our understanding of the molecular mechanisms of gamete fusion and contribute to the development of new and safer fertility regulating methods. （Asian J Androl 2007 July; 9： 528-532）
基金Supported by The UJIA-UK Eli Gold Trust and the Hadassah Salzberg and Puerto-Rico endowments (partially)
文摘AIM: To assess the safety and efficacy of trans-arterial chemo-embolization (TACE) in very elderly patients. METHODS: A prospective cohort study, from 2001 to 2010, compared clinical outcomes following TACE between patients ≥ 75 years old and younger patients (aged between 65 and 75 years and younger than 65 years) with hepatocellular carcinoma (HCC), diagnosed according to the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases criteria. The decision that patients were not candidates for curative therapy was made by a multidisciplinary HCC team. Data collected included demographics, co-morbidities, liver disease etiology, liver disease severity and the number of procedures. The primary outcome was mortality; secondary outcomes included post-embolization syndrome (nausea, fever, abdominal right upper quadrant pain, increase in liver enzymes with no evidence of sepsis and with a clinical course limited to 3-4 d post procedure) and 30-d complications. Additionally, changes in liver enzyme measurements were assessed [alanine and aspartate aminotransferase (ALT and AST), gamma-glutamyl transpeptidase and alkaline phosphatase] in the week following TACE. Analysis employed both univariate and multivariate methods (Cox regression models). RESULTS: Of 102 patients who underwent TACE as sole treatment, 10 patients (9.8%) were > 80 years old at diagnosis; 13 (12.7%) were between 75 and 80 years, 45 (44.1%) were between 65 and 75 years and 34 (33.3%) were younger than 65 years. Survival analysis demonstrated similar survival patterns between the elderly patients and younger patients. Age was also not associated with the adverse event rate. Survival rates at 1, 2 and 3 years from diagnosis were 74%, 37% and 31% among patients < 65 years; 83%, 66% and 48% among patients aged 65 to 75 years; and 86%, 41% and 23% among patients ≥ 75 years. There were no differences between the age groups in the pre-procedural care, including preventive treatment for contrast nephropat
