{"title":"Second-line chemotherapy with tauromustine in metastatic breast cancer in postmenopausal women: a phase II study.","authors":"P Ernst, I Balslev, H T Mouridsen","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14772976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Open-label phase II trial of recombinant beta interferon (IFN-beta (ser)) in patients with colorectal cancer.","authors":"P L Triozzi, P Kenney, D Young, J J Rinehart","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14436104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Azacitidine is a pyrimidine ring analog of cytidine that is incorporated into RNA causing alteration in RNA synthesis and processing and resulting in inhibition of protein synthesis. Azacitidine as the deoxynucleotide is also incorporated into DNA inhibiting its synthesis and blocking cytosine methylation by noncompetitive inhibition of DNA methyltransferase. The resulting hypomethylation of DNA is thought to induce gene activation and expression and cell differentiation. This may be an underlying factor in azacitidine's antileukemic activity and also contributes to its carcinogenic and tumor-promoting properties in experimental models.
{"title":"Biochemistry of azacitidine: a review.","authors":"A B Glover, B Leyland-Jones","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Azacitidine is a pyrimidine ring analog of cytidine that is incorporated into RNA causing alteration in RNA synthesis and processing and resulting in inhibition of protein synthesis. Azacitidine as the deoxynucleotide is also incorporated into DNA inhibiting its synthesis and blocking cytosine methylation by noncompetitive inhibition of DNA methyltransferase. The resulting hypomethylation of DNA is thought to induce gene activation and expression and cell differentiation. This may be an underlying factor in azacitidine's antileukemic activity and also contributes to its carcinogenic and tumor-promoting properties in experimental models.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13590045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A limited sampling model was developed for vinblastine to estimate the total area under the concentration time curve (AUC) using only two timepoints. Detailed pharmacokinetic analysis (16 timepoints) was performed in 30 patients treated with a small bolus dose (3 mg/m2) of vinblastine. A model for the total AUC was developed by multiple linear regression, using the first 15 patients as the training data set: AUC = 38.0 C10 + 73.8 C36 - 12.9, where C10 and C36 represent the serum vinblastine concentration at 10 hours and 36 hours, respectively (r = 0.99, P less than 0.0001). The model was validated on the other 15 patients, the test data set (r = 0.94, P less than 0.0001), with a mean predictive error of 13%. Limited sampling models may facilitate large-scale pharmacodynamic studies of new anticancer drugs, in order to relate the estimated AUC to toxicity and/or response without the need for detailed pharmacokinetic analysis.
建立了长春碱的有限采样模型,仅用两个时间点估计浓度时间曲线下的总面积(AUC)。对30例小剂量(3mg /m2)长春花碱治疗的患者进行了详细的药代动力学分析(16个时间点)。以前15例患者为训练数据集,通过多元线性回归建立总AUC模型:AUC = 38.0 C10 + 73.8 C36 - 12.9,其中C10和C36分别代表10小时和36小时的血清长春碱浓度(r = 0.99, P < 0.0001)。在另外15例患者的试验数据集上验证该模型(r = 0.94, P < 0.0001),平均预测误差为13%。有限的抽样模型可以促进新的抗癌药物的大规模药效学研究,以便在不需要详细的药代动力学分析的情况下将估计的AUC与毒性和/或反应联系起来。
{"title":"Limited sampling model for vinblastine pharmacokinetics.","authors":"M J Ratain, N J Vogelzang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A limited sampling model was developed for vinblastine to estimate the total area under the concentration time curve (AUC) using only two timepoints. Detailed pharmacokinetic analysis (16 timepoints) was performed in 30 patients treated with a small bolus dose (3 mg/m2) of vinblastine. A model for the total AUC was developed by multiple linear regression, using the first 15 patients as the training data set: AUC = 38.0 C10 + 73.8 C36 - 12.9, where C10 and C36 represent the serum vinblastine concentration at 10 hours and 36 hours, respectively (r = 0.99, P less than 0.0001). The model was validated on the other 15 patients, the test data set (r = 0.94, P less than 0.0001), with a mean predictive error of 13%. Limited sampling models may facilitate large-scale pharmacodynamic studies of new anticancer drugs, in order to relate the estimated AUC to toxicity and/or response without the need for detailed pharmacokinetic analysis.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14772268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K Wilson, W Shelley, A Belch, L Brandes, D Bergsagel, P Klimo, D White, A Willan
Intravenous or oral cyclophosphamide, 150-250 mg/m2 (500 mg maximum), once per week with alternate-day oral prednisone, 100 mg, was given to 57 myeloma patients resistant to melphalan and prednisone (MP). Seven responses in 28 primary MP-resistant patients and ten responses in 29 secondary MP-resistant patients were observed. Previous response to MP was not a significant factor in predicting response to weekly cyclophosphamide and alternate-day prednisone. The results suggest that the regimen of weekly cyclophosphamide and alternate-day prednisone may be as effective as more aggressive regimens in the treatment of patients with myeloma who have failed MP therapy. However, a randomized trial would be required to determine the relative contributions of cyclophosphamide and prednisone to the effectiveness of this regimen.
{"title":"Weekly cyclophosphamide and alternate-day prednisone: an effective secondary therapy in multiple myeloma.","authors":"K Wilson, W Shelley, A Belch, L Brandes, D Bergsagel, P Klimo, D White, A Willan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Intravenous or oral cyclophosphamide, 150-250 mg/m2 (500 mg maximum), once per week with alternate-day oral prednisone, 100 mg, was given to 57 myeloma patients resistant to melphalan and prednisone (MP). Seven responses in 28 primary MP-resistant patients and ten responses in 29 secondary MP-resistant patients were observed. Previous response to MP was not a significant factor in predicting response to weekly cyclophosphamide and alternate-day prednisone. The results suggest that the regimen of weekly cyclophosphamide and alternate-day prednisone may be as effective as more aggressive regimens in the treatment of patients with myeloma who have failed MP therapy. However, a randomized trial would be required to determine the relative contributions of cyclophosphamide and prednisone to the effectiveness of this regimen.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14772974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M R Posner, J F Belliveau, A B Weitberg, K Sabbath, M C Wiemann, F J Cummings, P Calabresi
Twenty-one evaluable patients with metastatic colorectal carcinoma were treated with a combination of continuous-infusion cisplatin (25 mg/m2/day X 3 days) and bolus 5-fluorouracil (400 mg/m2/day X 3 days). Toxicity was minimal. Seven patients (33%) responded. All responses were observed among the 16 previously untreated patients (44%) and lasted a median of 30 weeks. The results indicate the need for phase III trials of this treatment.
{"title":"Continuous-infusion cisplatin and bolus 5-fluorouracil in colorectal carcinoma.","authors":"M R Posner, J F Belliveau, A B Weitberg, K Sabbath, M C Wiemann, F J Cummings, P Calabresi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Twenty-one evaluable patients with metastatic colorectal carcinoma were treated with a combination of continuous-infusion cisplatin (25 mg/m2/day X 3 days) and bolus 5-fluorouracil (400 mg/m2/day X 3 days). Toxicity was minimal. Seven patients (33%) responded. All responses were observed among the 16 previously untreated patients (44%) and lasted a median of 30 weeks. The results indicate the need for phase III trials of this treatment.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14436103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F A Shepherd, W K Evans, R MacCormick, R Feld, J C Yau
For two chemotherapy regimens to be truly non-cross-resistant, each should be active as first-line therapy and also as second-line therapy. The effectiveness of both cyclophosphamide, doxorubicin, and vincristine (CAV) and etoposide and cisplatin (VPP) in previously untreated patients with small cell lung cancer has been well-documented. Also, VPP has caused tumor regression in up to 50% of patients when used as second-line therapy after CAV. The effectiveness of CAV after progression or relapse after VPP has not been documented. We identified 29 patients who received CAV after their tumors failed to respond or relapsed after VPP or etoposide and carboplatin (VPC). There were 21 male and eight female patients (median age, 57 years; range, 30-79). Thirteen patients were treated following failure to respond to VPP or VPC and 16 at the time of relapse. Eight patients had limited disease and 21 had extensive disease. Metastatic sites included liver (11 patients), bone (ten), lymph nodes (seven), bone marrow (three), brain (four), and contralateral lung (one). There were three complete responses (durations of 16, 22, and 26 weeks) and five partial responses (duration, 8+ to 36 weeks). Three patients had stable disease and 18 patients had disease progression while receiving treatment. The median survival of the entire group was 15 weeks. Responding patients had a median survival of 34 weeks (range, 8+ to 72+) and stable and nonresponding patients had a survival of only 9 weeks (range, 2-38). A granulocyte count nadir less than 500 X 10(9)/L was seen after 7.9% of evaluable treatment cycles and a platelet count nadir less than 50,000 X 10(9)/L occurred after only 5.3% of cycles. Five patients required transfusion for anemia, and two patients required dose reduction of vincristine for peripheral neuropathy. This study demonstrates that CAV has limited activity following failure to respond to VPP.
对于两种真正无交叉耐药的化疗方案,每一种都应该作为一线治疗和二线治疗有效。环磷酰胺、阿霉素和长春新碱(CAV)以及依托泊苷和顺铂(VPP)治疗先前未经治疗的小细胞肺癌患者的有效性已经得到了充分的证明。此外,当VPP作为CAV后的二线治疗时,高达50%的患者肿瘤消退。在VPP进展或复发后CAV的有效性尚未得到证实。我们确定了29例在VPP或依托泊苷加卡铂(VPC)治疗后肿瘤无效或复发后接受CAV治疗的患者。男性21例,女性8例(中位年龄57岁;范围内,30 - 79)。13名患者在VPP或VPC治疗无效后接受治疗,16名患者在复发时接受治疗。局限性病变8例,广泛性病变21例。转移部位包括肝(11例)、骨(10例)、淋巴结(7例)、骨髓(3例)、脑(4例)和对侧肺(1例)。有3个完全缓解(持续时间为16、22和26周)和5个部分缓解(持续时间为8+至36周)。3例病情稳定,18例在治疗过程中病情进展。整个组的中位生存期为15周。应答患者的中位生存期为34周(范围8+至72+),而稳定和无应答患者的生存期仅为9周(范围2-38)。在7.9%的可评估治疗周期后,粒细胞计数最低低于500 X 10(9)/L,血小板计数最低低于50,000 X 10(9)/L仅在5.3%的周期后发生。5例患者因贫血需要输血,2例患者因周围神经病变需要减少长春新碱的剂量。本研究表明,CAV在对VPP无效后活性有限。
{"title":"Cyclophosphamide, doxorubicin, and vincristine in etoposide- and cisplatin-resistant small cell lung cancer.","authors":"F A Shepherd, W K Evans, R MacCormick, R Feld, J C Yau","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>For two chemotherapy regimens to be truly non-cross-resistant, each should be active as first-line therapy and also as second-line therapy. The effectiveness of both cyclophosphamide, doxorubicin, and vincristine (CAV) and etoposide and cisplatin (VPP) in previously untreated patients with small cell lung cancer has been well-documented. Also, VPP has caused tumor regression in up to 50% of patients when used as second-line therapy after CAV. The effectiveness of CAV after progression or relapse after VPP has not been documented. We identified 29 patients who received CAV after their tumors failed to respond or relapsed after VPP or etoposide and carboplatin (VPC). There were 21 male and eight female patients (median age, 57 years; range, 30-79). Thirteen patients were treated following failure to respond to VPP or VPC and 16 at the time of relapse. Eight patients had limited disease and 21 had extensive disease. Metastatic sites included liver (11 patients), bone (ten), lymph nodes (seven), bone marrow (three), brain (four), and contralateral lung (one). There were three complete responses (durations of 16, 22, and 26 weeks) and five partial responses (duration, 8+ to 36 weeks). Three patients had stable disease and 18 patients had disease progression while receiving treatment. The median survival of the entire group was 15 weeks. Responding patients had a median survival of 34 weeks (range, 8+ to 72+) and stable and nonresponding patients had a survival of only 9 weeks (range, 2-38). A granulocyte count nadir less than 500 X 10(9)/L was seen after 7.9% of evaluable treatment cycles and a platelet count nadir less than 50,000 X 10(9)/L occurred after only 5.3% of cycles. Five patients required transfusion for anemia, and two patients required dose reduction of vincristine for peripheral neuropathy. This study demonstrates that CAV has limited activity following failure to respond to VPP.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13959048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The hypothesis that more selective antitumor activity may be achieved by cytotoxic agents which selectively bind to estrogen receptors (ER) in human cancer cells was tested. We have synthesized three nitrosourea derivatives of estradiol or hexestrol, and compared the ER binding affinity and cytotoxic activity of these compounds against ER-positive and -negative breast cancer cell lines in vitro. Specific binding to ER in the cytosol of MCF-7 human breast cancer cells was demonstrated in these conjugates: 17 alpha-CNU greater than 17 beta-CNU greater than HEX-CNU greater than lomustine (CCNU). The order of cytotoxicity of these derivatives against human breast cancer cells appeared to correlate with their binding affinity to ER. All three estrogen nitrosourea conjugates were more cytotoxic than CCNU, a clinically useful antitumor nitrosourea which does not bind to ER. The contribution of the estrogen moiety to the cytotoxicity of 17 alpha-CNU was demonstrated by the greater activity of the conjugate than that of a combination of estrogen and CCNU. However, cytotoxicity of these compounds against the receptor-positive MCF-7 and receptor-negative Evsa-T human breast cancer cell lines was similar. The latter finding suggested that cytotoxicity of these conjugates may not be mediated through ER. The difference in stability of these nitrosourea conjugates in aqueous buffer may partly explain their differences in cytotoxicity.
{"title":"Estrogen receptor-binding affinity and cytotoxic activity of three new estrogen-nitrosourea conjugates in human breast cancer cell lines in vitro.","authors":"H Y Lam, P K Ng, G J Goldenberg, C M Wong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The hypothesis that more selective antitumor activity may be achieved by cytotoxic agents which selectively bind to estrogen receptors (ER) in human cancer cells was tested. We have synthesized three nitrosourea derivatives of estradiol or hexestrol, and compared the ER binding affinity and cytotoxic activity of these compounds against ER-positive and -negative breast cancer cell lines in vitro. Specific binding to ER in the cytosol of MCF-7 human breast cancer cells was demonstrated in these conjugates: 17 alpha-CNU greater than 17 beta-CNU greater than HEX-CNU greater than lomustine (CCNU). The order of cytotoxicity of these derivatives against human breast cancer cells appeared to correlate with their binding affinity to ER. All three estrogen nitrosourea conjugates were more cytotoxic than CCNU, a clinically useful antitumor nitrosourea which does not bind to ER. The contribution of the estrogen moiety to the cytotoxicity of 17 alpha-CNU was demonstrated by the greater activity of the conjugate than that of a combination of estrogen and CCNU. However, cytotoxicity of these compounds against the receptor-positive MCF-7 and receptor-negative Evsa-T human breast cancer cell lines was similar. The latter finding suggested that cytotoxicity of these conjugates may not be mediated through ER. The difference in stability of these nitrosourea conjugates in aqueous buffer may partly explain their differences in cytotoxicity.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14772264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y O Tan, C Hendrickson, K McWhirter, M Kohler, J F Hannigan, R W Carlson
{"title":"Phase II evaluation of oral medroxyprogesterone acetate in advanced breast cancer: a Northern California Oncology Group Study.","authors":"Y O Tan, C Hendrickson, K McWhirter, M Kohler, J F Hannigan, R W Carlson","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14093873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R S Gelman, D C Tormey, R Betensky, E G Mansour, H C Falkson, G Falkson, R H Creech, D G Haller
This study of 2382 breast, 182 rectal, 817 colon, and 351 lung cancer patients treated with combination chemotherapy on eight phase III Eastern Cooperative Oncology Group protocols indicates that 69% would receive a higher dose of at least one drug if surface area were calculated from actual weight rather than from the minimum of actual and ideal weight. Forty-eight percent of the patients would have at least a 10% increase in drug dose based on actual weight. Only on the premenopausal adjuvant breast cancer protocol and among women on the rectal adjuvant study do the differences in dose based on actual rather than ideal weight increase significantly with age. On the postmenopausal adjuvant breast study and on the lung cancer study, the differences in dose decrease significantly with age. For all age decades and both sexes within each protocol, the mean differences between dose based on actual and dose based on ideal weights were on the same order as the rounding factors for the 11 drugs studied. From the literature on the effect of doses of common chemotherapies on leukopenia, it appears that the percent of hematologic toxicity would not be raised to unacceptable levels by using actual weight to set doses.
{"title":"Actual versus ideal weight in the calculation of surface area: effects on dose of 11 chemotherapy agents.","authors":"R S Gelman, D C Tormey, R Betensky, E G Mansour, H C Falkson, G Falkson, R H Creech, D G Haller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study of 2382 breast, 182 rectal, 817 colon, and 351 lung cancer patients treated with combination chemotherapy on eight phase III Eastern Cooperative Oncology Group protocols indicates that 69% would receive a higher dose of at least one drug if surface area were calculated from actual weight rather than from the minimum of actual and ideal weight. Forty-eight percent of the patients would have at least a 10% increase in drug dose based on actual weight. Only on the premenopausal adjuvant breast cancer protocol and among women on the rectal adjuvant study do the differences in dose based on actual rather than ideal weight increase significantly with age. On the postmenopausal adjuvant breast study and on the lung cancer study, the differences in dose decrease significantly with age. For all age decades and both sexes within each protocol, the mean differences between dose based on actual and dose based on ideal weights were on the same order as the rounding factors for the 11 drugs studied. From the literature on the effect of doses of common chemotherapies on leukopenia, it appears that the percent of hematologic toxicity would not be raised to unacceptable levels by using actual weight to set doses.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14772265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}