Preventing Breast Cancer Through Identification and Pharmacologic Management of High-Risk Patients

Breast cancer remains the most common cancer in women in the United States. For certain women at high risk for breast cancer, endocrine therapy (ET) can greatly decrease the risk. Tools such as the Breast Cancer Risk Assessment Tool (or Gail Model) and the International Breast Cancer Intervention Study risk calculator are available to help identify women at increased risk for breast cancer. Physician awareness of family history, reproductive and lifestyle factors, dense breast tissue, and history of benign proliferative breast disease are important when identifying high-risk women. The updated US Preventive Services Task Force and American Society of Clinical Oncology guidelines encourage primary care providers to identify at-risk women and offer risk-reducing medications. Among the various ETs, which include tamoxifen, raloxifene, anastrozole, and exemestane, tamoxifen is the only one available for premenopausal women aged 35 years and older. A shared decision-making process should be used to increase the usage of ET and must be individualized. This individualized approach must account for each woman’s medical history and weigh the benefits and risks of ET in combination with the personal values of the patient.     

Synthesis and in-vitro antimicrobial activity of secondary and tertiary amines containing 2-chloro-6-methylquinoline moiety

A number of secondary and tertiary amines bearing 2-chloro-6-methylquinoline were synthesized by nucleophilic substitution reaction of 3-(chloromethyl)-2-chloro-6-methylquinoline with substituted aromatic primary and secondary amines in presence of catalytic amount of triethylamine (TEA) and K(2)CO(3). All the compounds were characterized by combined use of IR, (1)H-NMR, (13)C-NMR, mass spectral data, and microanalyses. The newly synthesized quinolinyl amines were screened in vitro for their antifungal activity against Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369, Penicillium citrinum NCIM 768 and for antibacterial activity strains viz. Escherichia coli NCTC 10418, Staphylococcus aureus NCTC 65710, and Pseudomonas aeruginosa NCTC 10662 by agar diffusion technique. Results of the preliminary screening revealed that some of the compounds mainly those with electron withdrawing groups in the phenyl ring showed promising antifungal activity.     

Joongpoongtang 05 (JP05) confers neuroprotection via anti-apoptotic activities in Neuro-2a cells during oxygen-glucose deprivation and reperfusion

To evaluate the anti-apoptotic effects of Joongpoongtang 05 (JP05), a mixture of plant extracts, on a Neuro-2a (N2a) cell model of oxygen and glucose deprivation (OGD)/reperfusion (OGDR), a neuroblastoma cell injury model was induced by OGDR. This model allowed us to investigate cerebral ischemic changes and the protective effects of JP05. JP05 treatment significantly enhanced cell viability and reduced the levels of lactate dehydrogenase, nitric oxide, reactive oxygen species and the oxidants/antioxidants balance in neuronal cells as compared to the untreated OGDR group. Here, JP05 reduced OGDR-induced expressions of heme oxygenase-1 and nitric oxide synthase, which may contribute to the neuroprotection. JP05 also partially reversed the effects of OGDR on NF-κB and activated Akt production. Our findings suggest that JP05 confers neuroprotective effects via anti-apoptotic property against OGDR-induced free radical injury in N2a cells.     

Evaluation of the use of digital images for a national prostate core external quality assurance scheme

Harnden P, Coleman D, Moss S, Kodikara S, Griffin N R & Melia J

(2011) Histopathology 59 , 703–709 Evaluation of the use of digital images for a national prostate core external quality assurance scheme Aims: To evaluate the use of virtual images as an alternative to glass slides to expand the number of participants in the External Quality Assurance Scheme for prostatic biopsies. Methods and results: Benign and neoplastic cases, previously circulated as glass slides, were selected to include cases that had demonstrated a high level of agreement (n = 10) and a lesser degree of agreement (n = 10). Whole slide virtual images were circulated to 68 pathologists; 51 responses were returned. The levels of agreement for the primary diagnosis and for Gleason grading of cancers were analysed using kappa statistics. Responses for glass slides versus images were compared for the 24 pathologists for whom data were available. Levels of agreement for diagnostic categories using virtual slides were moderate to substantial, comparable to those found using glass slides. The level of agreement for Gleason grades 8–10 was substantial, but for lower grades was fair or moderate, poorer than for the glass slide circulation. Conclusions: Circulation of virtual images of biopsy material is a suitable alternative to glass slide‐based schemes for the evaluation of diagnostic consistency. The majority of participants agreed that the ability to evaluate limited diagnostic material outweighed the disadvantages of a virtual system.     

CALLA negative precursor B lymphoblastic leukemia with MLL gene translocation and an unusual FISH signal pattern

Rearrangements of the mixed lineage leukemia (MLL) gene at 11q23 commonly occur in infants with CALLA negative B lymphoblastic leukemia (B-ALL). Most often, these are detected by conventional karyotyping; however, fluorescent in-situ hybridization (FISH) with the help of a dual-color break-apart probe is used to identify cryptic translocations. When there is an MLL gene translocation, the usual FISH signal pattern is 1 red-1 green-1 yellow fusion signal pattern. We present a case of an infant with CALLA negative precursor B-ALL with a characteristic translocation t(4;11) (q21;q23), however, with an unusual MLL FISH signal pattern.     

Relationship between 6-mercaptopurine dose and 6-thioguanine nucleotide levels in patients with inflammatory bowel disease

BACKGROUND: 6-Thioguanine nucleotides (6-TGN) are active metabolites of azathioprine (AZA) and 6-mercaptopurine (6MP). Higher remission rates have been observed in patients with higher 6-TGN levels. However, many physicians prescribe AZA/6MP using milligrams per kilogram (mg/kg) dosing regimens without measuring 6-TGN levels. The aim of this study was to examine the association between 6MP dose and 6-TGN levels. METHODS: We conducted a cross-sectional study of patients treated for inflammatory bowel disease (IBD) with AZA or 6MP, whose 6-TGN levels were measured. Patients with low or intermediate thiopurine methyl transferase (TPMT) activity were excluded. AZA dose was converted to 6MP equivalents. The relationship between dose and 6-TGN levels was assessed with the Spearman correlation coefficient. We used logistic regression to assess the relationship between dose and 6-TGN levels of >230 pmol/8 x 10(8). RESULTS: In this study, 155 patients met our inclusion criteria (median dose, 1.01 +/- 0.40; range, 0.61-1.41 mg/kg). There was a weak correlation between 6-TGN levels and the absolute dose (rho = 0.18, P = 0.04) and the dose in mg/kg (rho = 0.19, P = 0.03). The correlation between mg/kg dosage and 6-TGN levels was slightly stronger in those using concomitant 5-aminosalicylate (5-ASA) medications (rho = 0.24, P = 0.02). Compared with <1.0 mg/kg per day, doses of > or =1.5 mg/kg per day were strongly associated with 6-TGN levels of >230 pmol/8 x 10(8) RBC (adjusted odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.1-11.8). However, only 37% of patients receiving > or =1.0 mg/kg per day had 6-TGN levels of >230 pmol/8 x 10(8) RBC. CONCLUSIONS: 6MP dose is weakly associated with 6-TGN levels. The use of standard mg/kg dosing regimens will result in low 6-TGN levels in most patients.