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1.
The association of MTHFR and CBS variants with the doubling time and responsiveness to several chemodrugs was analyzed in 26 human cancer xenografts. The tumors homozygous for the absence of insertion (NN) for the CBS 844ins68bp were more chemosensitive than those with insertion (NI) to TS-1 (P=0.0048), suggesting a potential effect of this variant on fluoropyrimidine efficacy. Furthermore, the doubling time of tumors with a variant C allele (AC or CC) in MTHFR-A1298C was significantly longer than that of tumors with a normal allele (AA) (P=0.0008). Twenty-nine cellular proliferation-related genes were associated with MTHFR-A1298C genotyping and with the doubling time. 相似文献
2.
为了选择有效抗癌药提供临床使用以提高化疗疗效 ,用MTT分析 ,对 32例头颈肿瘤术后切下的标本进行体外细胞培养 ,再用 5 -Fu ,VCR ,MTX ,BLM ,DDP ,ADM ,PYM和CTX进行药敏试验 .结果 :对 5 -Fu敏感 2 7例 ,占 84 4% ,VCR敏感 7例 ,占 2 1 9% ;MTX敏感 2 0例 ,占 6 2 5 % ;BLM敏感 2 6例 ,占 81 3% ;DDP敏感 2 6例 ,占 81 3% ;ADM敏感 13例 ,占 40 6 % ;PYM敏感 2 1例 ,占 6 5 6 % ;CTX敏感 1例 ,占 3 1% .32例患者化疗效果满意 ,未出现明显的副作用 ,均存活 3a以上 ,术后常规检查及复查未见复发或转移 .结果表明 :MTT法用于肿瘤细胞药敏试验是一种准确、快速、简便、经济 ,不需放射性同位素 ,结果重复性好的方法 ,值得推广应用 . 相似文献
3.
目的筛选非小细胞肺癌药敏试验的条件。方法取25例非小细胞肺癌患者的瘤细胞,用四甲基偶氮唑盐(MTT)法观察9种化疗药物,在不同浓度、不同时间对瘤细胞的敏感性。结果9种化疗药物对瘤细胞的敏感性,有随着药物浓度的增加、作用时间的延长而增高的趋势,但每个药物都有各自的特点。结论非小细胞肺癌细胞MTT法药敏试验的浓度应为临床用药量的计算值,药物作用时间应以48h为宜。 相似文献
4.
目的 探讨ATP生物荧光肿瘤药敏检测技术 (ATP TCA )在乳腺癌化疗中的临床意义及应用价值。方法 选用 10种常用乳腺癌化疗药物 ,应用ATP TCA对 40例乳腺癌改良根治术标本、淋巴结活检和胸腔积液标本进行药敏检测 ,评估肿瘤细胞对化疗药物的敏感性。结果 ATP TCA对乳腺癌标本的可评价率为 90 .0 % ,化疗药物对乳腺癌的杀伤作用具有较强的个体差异性 ,10种化疗药物的敏感性分别为 :氟尿嘧啶 ( 5 Fu) 3 3 .3 %、顺铂 (DDP) 3 7.5 %、环磷酰胺 (CTX ) 2 9.2 %、足叶已甙 (VP 16)16.7%、丝裂霉素 (MMC) 2 2 .0 %、表阿霉素 (EPI) 41.7%、诺维本 (NVB) 45 .8%、阿霉素 (ADM ) 41.7%、泰素 (PTX) 5 4.2 %、羟基喜树碱 (HCPT) 2 5 .0 %。初步研究表明ATP TCA体外检测结果与实际临床疗效具有良好的相关性。结论 ATP TCA是准确的、可靠的肿瘤药敏检测技术 ,其检测结果与临床实际疗效具有良好相关性 ,可用于指导乳腺癌术后化疗 相似文献
5.
Absence of p53 Overexpression and Favorable Response to Cisplatin-based Neoadjuvant Chemotherapy in Urothelial Carcinomas 总被引:3,自引:0,他引:3
Yoshiyuki Kakehi Enver Özdemir Tomonori Habuchi Hirohiko Yamabe Takayuki Hashimura Yoshitaka Katsura Osamu Yoshida 《Cancer science》1998,89(2):214-220
It has been controversial whether cancer cells harboring loss or inactivation of the tumor suppressor p53 are resistant or sensitive to DNA-damaging agents including cisplatin and doxorubicin. Overexpression of mdm2 oncoprotein, a negative regulator of p53, is assumed to be an alternative to p53 dysfunction. Archival urothelial carcinoma specimens obtained from 60 patients prior to cisplatin-based chemotherapy were immunohistochemically studied for overexpression of p53 and mdm2. Thirty-two patients (group I) were treated with chemotherapy in the neoadjuvant setting, while 28 patients (group II) underwent chemotherapy for distant metastases or inoperable locoregional tumors. In group I, the responsiveness was correlated with staining status of p53 ( P =0.0225) and the combination of p53 and mdm2 ( P =0.0497). Negative staining of p53 and negative for both p53 and mdm2 could have predicted favorable response to chemotherapy in 16 of 18 (88.9%) and in 12 of 13 (92.3%) tumors, respectively. On the other hand, p53-positive and p53 and/or mdm2-positive staining could have predicted poor response only in 7 of 14 (50.0%) and 8 of 19 (42.1%) tumors, respectively. Disease-specific survival of the p53-negative group was significantly superior to that of the p53-positive group ( P =0.0086). Difference in survival did not become more significant when overexpression of mdm2 was taken into consideration ( P =0.0456). In contrast, in group II, there was no correlation of responsiveness to chemotherapy or survival with p53- or p53/mdm2-staining status. The patients with urothelial carcinomas negative for overexpression of p53 will benefit from neoadjuvant chemotherapy. From clinical viewpoint, however, p53 status alone or the combination of p53 and mdm2 status is not enough to identify those patients who will not benefit from the treatment. 相似文献
6.
Association of Loss of Heterozygosity at the p53 Locus with Chemoresistance in Osteosarcomas 总被引:4,自引:0,他引:4
Akiteru Goto Hiroaki Kanda Yuichi Ishikawa Seiichi Matsumoto Noriyoshi Kawaguchi Rikuo Machinami Yo Kato Tomoyuki Kitagawa 《Cancer science》1998,89(5):539-547
Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite insensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 ( p 53) and 13q14 ( Rb ) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p 53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p 53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss ( P <0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p 53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas. 相似文献
7.
Lajos Pusztai Savitri Krishnamurti Jorge Perez Cardona Nour Sneige Francisco J. Esteva Marina Volchenok Patricia Breitenfelder Shu-Wan Kau Shin Takayama Stanislaw Krajewski John C. Reed Robert C. Bast Jr. Gabriel N. Hortobagyi 《Cancer investigation》2005,22(2):248-256
It has been suggested that expression of anti-apoptotic proteins such as Bcl-2 or BAG-1 may confer cellular resistance to chemotherapy. A corollary of this hypothesis is that expression of these proteins may predict clinical response to treatment and that Bcl-2- or BAG-1-positive cells may selectively be enriched in postchemotherapy tissue specimens. The goal of this exploratory pilot study was to assess these two predictions by using immunohistochemistry in 29 paired pre- and postchemotherapy breast tissue specimens obtained from patients who underwent preoperative doxorubicin-based chemotherapy. All breast cancers expressed BAG-1 protein, and, in individual tumors, 40-100% of neoplastic cells stained positive for this protein. Homogenous cytoplasmic staining was typically observed, though neoplastic cells also showed nuclear staining in many specimens. We found no correlation between prechemotherapy expression of BAG-1 and subsequent pathological response to cytotoxic therapy. Paired pre- and posttreatment specimens showed similar levels of BAG-1 expression when residual tumor could be assessed. Bcl-2 was expressed in 55% of cancers and was localized to the cytoplasm. Absence of Bcl-2 expression in prechemotherapy specimens was associated with more frequent complete pathological response (58% vs. 20%; p = 0.04). However, similar to BAG-1, no difference between pre- and posttherapy expression of Bcl-2 was observed in neoplastic cells in paired tissue specimens. These observations suggest that BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues. However, it does not appear to determine response to doxorubicin-based chemotherapy. In contrast, lack of Bcl-2 expression was associated with a higher probability of complete pathological response to doxorubicin-based chemotherapy. 相似文献
8.
目的研究恶性肿瘤患者外周血细胞对化疗药物的敏感性,为临床筛选化疗方案、实行肿瘤个体化疗提供依据。方法应用MTT法体外测定160例癌患者外周血(淋巴细胞及粒细胞)标本对临床常用化疗药物的敏感性。结果①5种癌患者外周血淋巴细胞和粒细胞对同一化疗药物敏感率呈正相关性,且均有统计学意义(P〈0.05)。②胃癌、非小细胞肺癌(NSCLC)和卵巢癌患者的外周血淋巴细胞及粒细胞对试验化疗药物敏感性差异有统计学意义(P〈0.05),而肝癌、淋巴瘤(NHL)检测结果差异未有统计学意义(P〉0.05)。③HCPT在非小细胞肺癌和TAX、Vm-26在卵巢癌患者的外周血药敏试验中,粒细胞较淋巴细胞对化疗药物抑制率高,差异有统计学意义(P〈0.05)。结论肿瘤患者外周血细胞体外药敏试验对临床肿瘤化疗用药有一定预见性,有助于临床医师筛选有效化疗药物,制定合理化疗方案,为个体化疗用药提供了重要的参考依据。 相似文献
9.
目的 通过分析围产期孕妇生殖道B族链球菌(GBS)的感染和耐药性及不良妊娠结局,为临床医师制定有效的预防和治疗措施提供依据.方法 2013年1月至2015年2月,对795例围产期孕妇生殖道分泌物进行GBS培养鉴定与药敏试验,并观察临床症状及不良妊娠结局,对结果进行统计学分析.结果 795例孕妇中共检出GBS携带者256例,带菌率为32.2%.<30岁组(28.9%)与≥30岁组(42.3%)的带菌率差异具有统计学意义(x2=19.095,P<0.01).GBS阳性者与GBS阴性者的临床症状发生率(18.8% vs 8.0%)差异具有统计学意义(x 2=39.514,P< 0.01).10种抗菌药物(万古霉素、利奈唑胺、青霉素、氨苄西林、头孢曲松、呋喃妥因、左氧氟沙星、克林霉素、红霉素及四环素)耐药率分别为:0%、0%、0.6%、3.1%、6.6%、9.6%、21.9%、23.8%、29.9%及58.1%.D-抑菌圈试验阳性率为23.9%.GBS阳性组与GBS阴性组比较,胎膜早破、早产、宫内感染及新生儿感染发生率的差异均有统计学意义(P<0.01).结论 该区围产期孕妇GBS带菌率较高,且高龄者易于感染;围产期孕妇感染GBS可增加不良妊娠结局的发生,应据药敏试验结果选择敏感性抗生素予以临床干预. 相似文献
10.
《Archivos de bronconeumología》2020,56(9):578-585
Background and ObjectiveVentilatory inefficiency (high V′E/V′CO2) and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis. Low resting PaCO2 suggests increased chemosensitivity or an altered PaCO2 set-point. We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO2 set-point, exercise capacity, hemodynamics and V′E/V′CO2.MethodsPulmonary arterial hypertension (n = 34), chronic thromboembolic pulmonary hypertension (CTEPH, n = 19) and pulmonary veno-occlusive disease (PVOD, n = 6) patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing. Patients were grouped according to resting PaCO2: hypocapnic (PaCO2 ≤34 mmHg) or normocapnic (PaCO2 35–45 mmHg). The PaCO2 set-point was estimated by the maximal value of end-tidal PCO2 (maximal PETCO2) between the anaerobic threshold and respiratory compensation point.ResultsThe hypocapnic group (n = 39) had lower resting cardiac index (3.1 ±0.8 vs. 3.7 ±0.7 L/min/m2, p < 0.01), lower peak V′O2 (15.8 ± 3.5 vs. 20.7 ± 4.3 mL/kg/min, p < 0.01), and higher V′E/V′CO2 slope (60.6 ± 17.6 vs. 38.2 ± 8.0, p < 0.01). At peak exercise, hypocapic patients had lower PaO2, higher VD/VT and higher P(a-ET)CO2. Maximal PETCO2 (r = 0.59) and VD/VT (r = −0.59) were more related to cardiac index than PaO2 or PaCO2 at rest or peak exercise. Maximal PETCO2 was the strongest correlate of V′E/V′CO2 slope (r = −0.86), peak V′O2 (r = 0.64) and peak work rate (r = 0.49).ConclusionsResting hypocapnia is associated with worse cardiac function, more ventilatory inefficiency and reduced exercise capacity. This could be explained by elevated chemosensitivity and lower PaCO2 set-point. Maximal PETCO2 may be a useful non-invasive marker of PaCO2 setpoint and disease severity even with submaximal effort. 相似文献