Current medical treatment of estrogen receptor-positive breast cancer

Approximately 80% of breast cancers(BC) are estrogen receptor(ER)-positive and thus endocrine therapy(ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of(1) ovarian function suppression(OFS), usually obtained using gonadotropinreleasing hormone agonists(Gn RHa);(2) selective estrogen receptor modulators or down-regulators(SERMs or SERDs); and(3) aromatase inhibitors(AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs(i.e., tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs(i.e., fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type Ⅰ are permanent steroidal inhibitors of aromatase, while type Ⅱ are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs(i.e., anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors(palbociclib) and mammalian target of rapamycin(m TOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness.     

Expression of γ-H2AX and patient prognosis in breast cancer cohort

H2AX phosphorylation is a novel marker of DNA double-stranded breaks. In the present study, we assessed the γ-H2AX expression, its association with other clinicopathologic characteristics, and the prognosis in a cohort of 97 patients with breast cancer. Ninety-seven specimens of tumor tissue and 77 adjacent normal tissues from patients with breast cancer were examined. All patients underwent modified radical mastectomy or local tumor resection without lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry. Patients were followed after surgery for a mean duration of 70.1 ± 18.7 months (range, 6-93 months). The γ-H2AX staining was positive in 27 (27.8%) patients. The positive rates of H2AX were 26.0% and 2.6% in tumor tissue and adjacent normal tissues, respectively. γ-H2AX positive status was negatively associated with TNM staging, with 24 positive cases (32.4%) in TNM staging I-II, while no positive cases in TNM staging III-IV (P = 0.026). Sixteen patients (16.5%) died during the follow-up. No significant association between γ-H2AX expression and patient survival was detected. The unadjusted HR (hazard ratio) for γ-H2AX positive was 0.84 (95% CI: 0.27, 2.60). In TNM staging subgroup analysis, death only occurred in γ-H2AX negative patients. Our study is the first study to demonstrate that expression of γ-H2AX is associated with TNM staging. Due to the small sample and limited follow-up time, we did not observe a significant association between γ-H2AX and patient survival. γ-H2AX expression could be a potential biomarker for cancer diagnosis and prediction, and further studies are in need.     

Systematic analysis of the regulation of type three secreted effectors in <Emphasis Type="Italic">Salmonella enterica</Emphasis> serovar Typhimurium

Background  

The type III secretion system (TTSS) is an important virulence determinant of Gram-negative bacterial pathogens. It enables the injection of effector proteins into the cytosol of eukaryotic cells. These effectors ultimately manipulate the cellular functions of the infected organism. Salmonella enterica serovar Typhimurium encodes two virulence associated TTSSs encoded by the Salmonella Pathogenicity Islands (SPI) 1 and 2 that are required for the intestinal and systemic phases of the infection, respectively. However, recent studies suggest that the roles of these TTSSs are not restricted to these compartments. The regulation of TTSSs in Salmonella is very complex with several regulators operating to activate or to repress expression depending on the environmental conditions.     

Extraction of DNA from Phytophthora infestans Using QIAGEN Columns

High molecular weight DNA of Phytophthora infestans was extracted using a modification of the commercial QIAGEN column procedure. Both a 'maxi' and 'mini' procedure are described. The maxi procedure utilizes a QIAGEN-tip 500 column while the mini procedure utilizes a QIAGEN-tip 20 column. When fungal protoplasts were used as starting material from 9 g (fresh weight) of mycelium, nearly 500 μg of DNA in the size range of 20–200 kb was obtained and the product was successfully used in construction of a lambda genomic library. The modified QIAGBN method can replace the more timeconsuming, and expensive cesium chloride density gradient centrifugation for extraction of ultra-pure DNA from P. infestans .     

Relationships Among Group IV Phytophthora Species Inferred by Restriction Analysis of the ITS2 Region

The polymerase chain reaction (PCR) was used to amplify the ITS2 region of nuclear ribosomal DNA from six Phytophthora species which comprise taxonomic Group IV. Digestion of the ca. 600 bp PCR product with restriction enzymes Alu I, Dra I, Hha I, Hinf I, Msp I, and Taq I revealed variation which allowed relationships among the species to be assessed. P. infestans , P. mirabilis and P. phaseoli were indistinguishable from one another with all enzymes tested. With Alu I and Taq I. P. ilicis , P. colocasiae . and P. hibernalis each showed unique banding patterns different from the common banding pattern shared by P. infestans . P. mirabilis . and P. hibernalis . Dra I allowed differentiation of P. ilicis and P. colocasiae from P. infestans , P. mirabilis , P. phaseoli , and P. hibernalis . all of which shared a common banding pattern. Hha I allowed differentiation of P. colocasiae and P. hibernalis from P. infestans, P. mirabilis, P. phaseoli , and P. ilicis . Hinf I allowed differentiation of P. ilicis and P. hibernalis , (each of which showed a unique banding pattern) from P. infestans, P. mirabilis, P. phaseoli , and P. colocasiae . Msp I allowed differentiation of P. hibernalis from the other five species. Species groupings determined by restriction analysis of ITS2 were consistent with those based on morphological criteria. These results show that restriction analysis of PCR-amplified TS2 regions can be useful as an adjunct to morphological criteria in Phytophthora species identification.     

AChemS: the beginning. Association for Chemoreception Sciences

This paper unfolds the events, the people and the times that led up to the founding of AChemS and fashioned its character during its early formative years. It describes the path over which AChemS came, going from the original assertions and denials for the need of such an organization to its later inception and nascent development. This narration highlights such topics as the debate over the need for AChemS, the role of National Science Foundation in the founding of AChemS, the derivation of the Association's name, the choice of Sarasota and the Hyatt House as the meeting site, the generation of the programs for the early annual meetings, the adoption of the bylaws, the process of incorporation and tax deferment, and the birth of the Givaudan Lectureship. Most emphatically highlighted, however, is the enthusiasm, commitment and hard work that the members of the chemosensory research community displayed in bringing AChemS to fruition.