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101.

Introduction

BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and platinum salts. HRD can be caused by BRCA mutations, and by other mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast cancers as these resemble BRCA1-mutated breast cancer closely and might also share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated, estrogen receptor (ER)-positive breast cancers have remained elusive. The current study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated breast cancers can identify breast cancer patients with TN as well as ER-positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing chemotherapy.

Methods

Array comparative genomic hybridization (aCGH) was used to classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1- and/or BRCA2-mutated breast cancers were defined as having a BRCA-likeCGH status, others as non-BCRA-likeCGH. Stage-III patients (n = 249) had participated in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide-thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide (FE90C) chemotherapy.

Results

Among patients with BRCA-likeCGH tumors (81/249, 32%), a significant benefit of HD-CTC compared to FE90C was observed regarding overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not seen for patients with non-BRCA-likeCGH tumors (adjusted hazard ratio 0.90, 95% CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-likeCGH tumors were ER-positive.

Conclusions

Distinct aCGH patterns differentiated between HER2-negative patients with a markedly improved outcome after adjuvant treatment with an intensified DNA-DSB-inducing regimen (BRCA-likeCGH patients) and those without benefit (non-BRCA-likeCGH patients).  相似文献   
102.
103.
目的 探讨孕妇妊娠晚期疲乏特征的潜在类别,比较不同类别孕妇在人口学特征及睡眠质量、心理韧性上的差异。方法 于2022年4—7月便利选取郑州市某三级甲等医院产科门诊就诊的251例孕妇为研究对象,采用一般资料调查表、疲劳自评量表、匹兹堡睡眠质量指数量表及心理韧性量表进行调查。结果 孕妇妊娠晚期疲乏特征可分为2个潜在类别,即高情境性-广泛疲乏型(29.08%)和积极情境性-疲乏低发型(70.92%);Logistic回归分析结果显示:孕周、不良妊娠史、睡眠质量及心理韧性是孕妇妊娠晚期疲乏特征的潜在类别的影响因素(P<0.05)。结论 孕妇妊娠晚期疲乏特征存在群体异质性,可分为2个潜在类别,妊娠周数较大、既往有不良妊娠史、睡眠质量差的孕妇妊娠晚期疲乏症状较重,应对该类别孕妇给予更多关注。  相似文献   
104.
新疆紫草颗粒剂与汤剂对药物流产效果影响的比较性研究   总被引:6,自引:1,他引:6  
目的:比较新疆紫草颗粒剂与紫草汤剂对米非司酮配伍米索前列醇药物流产效果的影响,及不良反应。方法:将648例妊娠38-45 d、要求终止妊娠的妇女,随机分成3组,各组在米非司酮配伍米索前列醇药物流产时分别加服紫草颗粒剂或安慰剂或紫草汤剂,对3组的流产效果、出血时间、月经恢复时间等及不良反应进行观察。结果:紫草颗粒剂组和汤剂组的完全流产率(97.74%、97.70%)、平均出血时间(12.0±4.1 d、12.7±3.8 d)均无显著性差异(P均>0.05),且均显著优于安慰剂组(91.90%、14.3±4.8 d)(P均<0.05)。3组药物流产后月经恢复时间均无显著性差异。但紫草汤剂服用时有明显异味。结论: 紫草颗粒剂祛除了紫草的异味,服用方便,对其提高药物流产疗效与紫草汤剂相同,有必要进一步探讨。  相似文献   
105.
目的研究宫颈癌组织中Raf激酶抑制蛋白(RKIP)和核因子xBp65(NF-κBp65)的表达,探讨二者表达之间的相关性及其与宫颈癌各临床病理因素之间的关系。方法用免疫组织化学方法检测69例宫颈癌组织、37例宫颈上皮内瘤变组织和18例正常宫颈组织的RKIP和NF-κBp65表达,并分析其与宫颈癌临床病理学特征的关系。结果宫颈癌组织中RKIP的表达低于宫颈上皮内瘤变及正常宫颈组织,而NF-κBp65的表达高于宫颈上皮内瘤变及正常宫颈组织,差异有统计学意义(Hc=45.124、38.107,Z=4.309~5.159,P〈O.01);RKIP和NF—κBp65在宫颈癌组织中的表达均与临床分期、有无淋巴结转移及肿瘤分化程度有关(χ^2=5.150~11.917,P〈0.05)。宫颈癌组织中RKIP与NF-κBp65的表达呈显著负相关(r=-0.464,P〈O.01)。结论RKIP表达的减少或缺失与宫颈癌的发生、发展密切相关,RKIP表达的减少或缺失可能通过上调NF—κBp65的表达促进宫颈癌的侵袭和转移。  相似文献   
106.
OBJECT: The goals of this study were to define the incidence of seizures in children with low-grade tumors, study seizure outcome after lesionectomy in these children, and identify risk factors for poor seizure outcome, METHODS: The authors performed a retrospective chart review of children who harbored low-grade brain tumors, experienced seizures, and were treated in a single institution, Statistical analyses included step-wise as well as single-variable binary logistic regression analyses.  相似文献   
107.

Introduction

To tailor local treatment in breast cancer patients there is a need for predicting ipsilateral recurrences after breast-conserving therapy. After adequate treatment (excision with free margins and radiotherapy), young age and incompletely excised extensive intraductal component are predictors for local recurrence, but many local recurrences can still not be predicted. Here we have used gene expression profiling by microarray analysis to identify gene expression profiles that can help to predict local recurrence in individual patients.

Methods

By using previously established gene expression profiles with proven value in predicting metastasis-free and overall survival (wound-response signature, 70-gene prognosis profile and hypoxia-induced profile) and training towards an optimal prediction of local recurrences in a training series, we establish a classifier for local recurrence after breast-conserving therapy.

Results

Validation of the different gene lists shows that the wound-response signature is able to separate patients with a high (29%) or low (5%) risk of a local recurrence at 10 years (sensitivity 87.5%, specificity 75%). In multivariable analysis the classifier is an independent predictor for local recurrence.

Conclusion

Our findings indicate that gene expression profiling can identify subgroups of patients at increased risk of developing a local recurrence after breast-conserving therapy.  相似文献   
108.
109.
There is evidence to suggest that histamine is a neurotransmitter in the CNS and functions in the regulation of arg-vasopressin (AVP) secretion. The posterior pituitary contains high levels of histamine and histamine N-methyltransferase (HNMT). Therefore, posterior pituitary histamine could also modulate the release of AVP. Paralleling the effect on AVP levels, the concentration of histamine in the rat posterior pituitary decreased from 18.8 +/- 2.7 ng/mg protein (x +/- SEM) to 12.9 +/- 1.9 ng/mg protein following 2 days of 2% (w/v) hypertonic saline administration and to 11.5 +/- 0.9 ng/mg protein with 7 days of treatment. Conversely, posterior pituitary HNMT activity was significantly elevated after hypertonic saline administration. Pituitary stalk transection did not reduce the concentration of histamine in the rat posterior pituitary although HNMT activity was reduced from 18.8 +/- 0.82 munits/gland to 9.22 +/- 1.56 munits/gland (x +/- SEM). These results indicate that histamine released from posterior pituitary mast cells could facilitate AVP release as part of the overall mechanism for osmotic stimulation of AVP secretion and support the concept that most posterior pituitary histamine is not neuronally derived from the brain. HNMT, on the other hand, may be contained in neurons disrupted by stalk section.  相似文献   
110.
In 1942, Dr. Seidlin of the Memorial Hospital in New York was faced with a 51-year- old patient who had undergone a thyroidectomy in 1923 [1]. At the time, the histologic diagnosis was a 'malignant adenoma' of the thyroid. In 1938 the patient returned with overt signs of thyroid hyperfunction (hyperthyroidism) and lower back pain. A metastasis was found in the lower spine, and surgically removed. Over the next years the patient remained hyperthyroid and developed more bone metastases. At the time of presentation to Dr. Seidlin, the patient was in an extremely poor condition: he was in severe pain, severely hyperthyroid, and severely underweight. At this time radioiodine therapy had just reached the clinical arena. In 1937 Hertz, Roberts and Evans investigated the rabbit's thyroid function using I-128 [2]. Later they pursued therapeutic goals for e.g. Graves' disease using I-130. They used dosages that we now know would have been merely diagnostic if it were not for a probable 10% I-131 contaminant [3]. Livingood and Seaborg identified I-131 as a separate isotope. In 1942 two groups independently reported on the successful treatment of hyperthyroidism with I-131 sodium iodide [4,5]. Radioiodine was so rare that it was recovered from the urine, purified and re-administered to the patient. The patient responded favourably to the radioiodine treatment, and he received several more courses of I-131. Geiger-counter examination of the patient revealed two previously unknown metastases, thereby indicating the diagnostic capabilities of radioiodine. The patient did very well on these courses: the hyperthyroidism subsided, the body-weight kg increased from 38 to 53 kilograms, and the pains diminished. This report of a potential cure for terminally ill patients fuelled the public imagination to a degree that it hit the political agenda. Effective on August 1, 1946, the Atomic Energy Act (AEA) made radioisotopes available for medical use in the USA. This date marks the beginning of 'atomic medicine', later named nuclear medicine.  相似文献   
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