Aurora A激酶研究进展

Aurora A激酶是进化上保守的有丝分裂丝/苏氨酸激酶Aurora激酶家族成员之一,在细胞内随细胞周期的变化呈动态分布,它广泛的参与了细胞周期不同阶段的各种事件,并在人类多种恶性肿瘤的发生发展过程中起到了至关重要的作用,因而很有可能成为一个极具前途的恶性肿瘤的分子治疗靶点。     

A phase I trial of CGS 16949A. A new aromatase inhibitor

CGS 16949A is a new, nonsteroidal competitive inhibitor of the aromatase enzyme. In this Phase I trial, 16 heavily pretreated postmenopausal patients with metastatic breast cancer were treated with escalating doses of CGS 16949A from 0.6 to 16 mg total daily oral dose. No hematologic, biochemical, or significant clinical toxicity was encountered. Endocrinologic and pharmacologic data were available from 12 of these patients. Maximum inhibition of estrogen biosynthesis was observed at a dose of 2 mg CGS 16949A daily. At this dose, the inhibition of estrogen biosynthesis was equivalent to 1000 mg aminoglutethimide (AG). The fall in plasma and urinary estrogens without a concomitant drop in androgens confirmed the specific blockade of aromatase activity. At doses of 4 to 16 mg daily, CGS 16949A appeared to inhibit the C21-hydroxylase enzyme as well. The t1/2 of CGS 16949A in the circulation was 10.5 hours. Of 16 evaluable patients there were two partial responses and seven patients with stable disease.     

A gist of gastrointestinal stromal tumors: A review

Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.     

Saikosaponin A inhibits influenza A virus replication and lung immunopathology

Fatal influenza outcomes result from a combination of rapid virus replication and collateral lung tissue damage caused by exaggerated pro-inflammatory host immune cell responses. There are few therapeutic agents that target both biological processes for the attenuation of influenza-induced lung pathology. We show that Saikosaponin A, a bioactive triterpene saponin with previouslyestablished anti-inflammatory effects, demonstrates both in vitro and in vivo anti-viral activity against influenza A virus infections. Saikosaponin A attenuated the replication of three different influenza A virus strains, including a highly pathogenic H5N1 strain, in human alveolar epithelial A549 cells. This anti-viral activity occurred through both downregulation of NF-κB signaling and caspase 3-dependent virus ribonucleoprotein nuclear export as demonstrated by NF-κB subunit p65 and influenza virus nucleoprotein nuclear translocation studies in influenza virus infected A549 cells. Critically, Saikosaponin A also attenuated viral replication, aberrant pro-inflammatory cytokine production and lung histopathology in the widely established H1N1 PR8 model of influenza A virus lethality in C57BL/6 mice. Flow cytometry studies of mouse bronchoalveolar lavage cells revealed that SSa exerted immunomodulatory effects through a selective attenuation of lung neutrophil and monocyte recruitment during the early peak of the innate immune response to PR8 infection. Altogether, our results indicate that Saikosaponin A possesses novel therapeutic potential for the treatment of pathological influenza virus infections.     

细节决定成败：神经外科的信条之一

成功的手术应该是由于正确的理由对正确的患者和疾病在正确的时间进行的正确的一系列围手术期处理和外科操作过程，每一个细节决定了手术的成败，患者的安全取决于许多方面：患者疾病的性质，医生的素质和技术，以及生活和工作的环境。因此其是一个系统工程。所以，完整的神经外科治疗过程是应包括术手术适应证和手术时机选择、术前计划、手术实施、围手术期的处理和后期康复等一整套的侦查、判断、决策的过程。     

A woman's heart

Adjuvant therapy in postmenopausal women with breast cancer may contribute to the expression of underlying cardiovascular disease or expose the heart to additional toxicities. Tamoxifen remains an important component of endocrine therapy for breast cancer, although major clinical trials of the aromatase inhibitors (AIs) anastrozole, letrozole, and exemestane suggest that these agents are more effective and better tolerated alternatives to tamoxifen. The AIs inhibit the conversion of androgens to estrogen in postmenopausal women; consequently, their mechanism of action differs from that of tamoxifen. Accordingly, although it has been observed that tamoxifen has some favorable effects on cardiovascular risk, such as reducing total cholesterol levels, because of its partial estrogen‐agonist properties, no such effects exist for the AIs. Some studies, particularly those that compare the AIs with tamoxifen, have suggested a less favorable impact of adjuvant AI therapy on cardiovascular risk. Comorbid conditions, including cardiovascular disease, emerge as competing causes of death as women with breast cancer continue to live longer, and the potential impact of adjuvant therapies on cardiovascular risk becomes an increasingly important consideration for clinicians. Cancer 2009. © 2009 American Cancer Society.     

A noticeable absence

Coronavirus disease 2019 (COVID-19) restrictions on visitation policies have created barriers for cancer caregivers and patients. Awareness of the critical role that cancer caregivers play should lead to better integration of the caregiver into clinical care and research after the pandemic ends.     

Expression of blood group A antigen during erythroid differentiation in A1 and A2 subjects

The expression of blood group A antigen on marrow and blood cells from A1 and A2 subjects was investigated by the binding of Helix pomatia and Dolichos biflorus lectins using immunofluorescence. These two lectins stained BFU-E-derived colonies from A subjects in the early days of culture before the expression of glycophorin. The erythroid origin of these cells was ascertained by the coexpression of two other very early erythroid markers. In bone marrow, the ultrastructural immunogold method revealed that the entire erythroid lineage including proerythroblasts was labeled by HPA, whereas no staining was observed on granulomonocytic cells including myeloblasts. Platelets from A subjects were HPA-labeled and so were platelets from an O subject preincubated in A plasma. Megakaryocytes obtained in CFU-MK-derived colonies were weakly and heterogeneously labeled by the HPA lectin. Cultures from A1 and A2 subjects were the reflection of the genetic differences only when investigations were performed on mature erythroblasts. In contrast, the great majority of immature erythroblasts both from A2 and A1 subjects were equally labeled by both lectins; during further erythroid maturation, binding of both lectins markedly diminished only on A2 erythroblasts. When marrow erythroblasts were investigated at electron microscopic level, heterogeneity of labeling among all stages of maturation was clearly observed in A2 subjects, with staining stronger on immature than on mature erythroblasts. Therefore, the genetic differences between A1 and A2 subjects are revealed during terminal erythroid differentiation.     

Serum amyloid A

BACKGROUND:

The authors investigated the expression of serum amyloid A (SAA) in endometrial endometrioid carcinoma and evaluated its potential as a serum biomarker.

METHODS:

SAA gene and protein expression levels were evaluated in endometrial endometrioid carcinoma and normal endometrial tissues, by real‐time polymerase chain reaction (PCR), immunohistochemistry (IHC), and flow cytometry. SAA concentration in 194 serum samples from 50 healthy women, 42 women with benign diseases, and 102 patients including 49 grade 1, 38 grade 2, and 15 grade 3 endometrial endometrioid carcinoma was also studied by a sensitive bead‐based immunoassay.

RESULTS:

SAA gene expression levels were significantly higher in endometrial endometrioid carcinoma when compared with normal endometrial tissues (mean copy number by real‐time PCR = 182 vs 1.9; P = .001). IHC revealed diffuse cytoplasmic SAA protein staining in poorly differentiated endometrial endometrioid carcinoma tissues. High intracellular levels of SAA were identified in primary endometrial endometrioid carcinoma cell lines evaluated by flow cytometry, and SAA was found to be actively secreted in vitro. SAA concentrations (μg/mL) had medians of 6.0 in normal healthy women and 6.0 in patients with benign disease (P = .92). In contrast, SAA values in the serum of endometrial endometrioid carcinoma patients had a median of 23.7, significantly higher than those of the healthy group (P = .001) and benign group (P = .001). Patients harboring G3 endometrial endometrioid carcinoma were found to have SAA concentrations significantly higher than those of G1/G2 patients.

CONCLUSIONS:

SAA is not only a liver‐secreted protein, but is also an endometrial endometrioid carcinoma cell product. SAA is expressed and actively secreted by G3 endometrial endometrioid carcinoma, and it is present in high concentration in the serum of endometrial endometrioid carcinoma patients. SAA may represent a novel biomarker for endometrial endometrioid carcinoma to monitor disease recurrence and response to therapy. Cancer 2010. © 2010 American Cancer Society.     

A giant tonsillolith

Tonsilloliths or calculi of the tonsil are calcifications that form in the crypts of the palatine tonsil or around it. Small concretions are asymptomatic while large calcifications produce symptoms such as odynophygia, dysphagia and referred otalgia. We describe a case of a 24 years old female who presented with a six month history of mild throat discomfort and was found to have a large (3.1 × 2.7 × 2.1 cm) calculus in her left tonsil for which a tonsillectomy was done. This is one of the largest reported cases in the world. The authors stress that symptoms of tonsillolith are unrelated to its size. The pertinent literature has been reviewed.     

Comparison of intracytoplasmic A particles and intracisternal A particles.

Intracytoplasmic A particles and intracisternal A particles are associated with mouse tumors of various types, and both can coexist in the cytoplasm of the same cell. The designation of both as A particles is based on the recognition that they share morphological similarities. A comparison of purified isolates of these two particles reveals that the structural protein profiles are different, but that there is some antigenic cross-reaction as demonstrated by immunodiffusion and complement fixation. This result does not appear to involve the major structural protein of intracisternal A particles, but may reflect the presence of common antigenic determinants located on minor proteins.