Insulin priming effect on estradiol-induced breast cancer metabolism and growth

Diabetes is a risk factor for breast cancer development and is associated with poor prognosis for breast cancer patients. However, the molecular and biochemical mechanisms underlying the association between diabetes and breast cancer have not been fully elucidated. Here, we investigated estradiol response in MCF-7 breast cancer cells with or without chronic exposure to insulin. We found that insulin priming is necessary and specific for estradiol-induced cancer cell growth, and induces anaplerotic shunting of glucose into macromolecule biosynthesis in the estradiol treated cells. Treatment with ERK or Akt specific inhibitors, U0126 or {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, respectively, suppressed estradiol-induced growth. Interestingly, molecular analysis revealed that estradiol treatment markedly increases expression of cyclin A and B, and decreases p21 and p27 in the insulin-primed cells. In addition, estradiol treatment activated metabolic genes in pentose phosphate (PPP) and serine biosynthesis pathways in the insulin-primed cells while insulin priming decreased metabolic gene expression associated with glucose catabolism in the breast cancer cells. Finally, we found that anti-diabetic drug metformin and AMPK ligand AICAR, but not thiazolidinediones (TZDs), specifically suppress the estradiol-induced cellular growth in the insulin-primed cells. These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.     

肠毒素大肠杆菌攻毒小鼠模型的建立以及疫苗候选株保护效果的评价

目的:建立肠毒素大肠杆菌攻毒小鼠模型以及应用模型对疫苗候选株免疫效果进行评价．方法:通过鼻饲半数致死量(LD50)肠毒素大肠杆菌E44813,E44815和E11881A观察小鼠肺病理学变化、肺部细菌清除情况变化,建立肠毒素大肠杆菌鼻饲小鼠模型;应用鼻饲小鼠模型观察疫苗候选株FE1,FE3,FE6保护效果．结果:鼻饲LD50剂量肠毒素大肠杆菌小鼠的病理特征是肺组织存在大量的淋巴细胞、巨噬细胞、中性粒细胞和浆细胞,为多病灶支气管肺炎,肺部细菌清除缓慢,至第7天仍能检测到105数量级的细菌．应用疫苗候选株免疫后进行攻毒,小鼠没有发病和死亡,病理特征主要是淋巴细胞少量增多,肺部细菌清除迅速,至第7天已检测不到细菌,与对照有显著性差异(0 CFU／g vs 6．2×105,5．4×105,2．3×105 CFU／g,P<0．05)．结论:肠毒素大肠杆菌鼻饲小鼠模型能够为疫苗筛选和评价提供了有效途径,同时也证实了疫苗候选株FE1,FE3,FE6具有良好的免疫保护效果．     

An in vitro limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse

We have developed a limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse using a miniturized stroma- dependent bone marrow culture assay in vitro. The cells were overlaid on irradiated stromal layers in microtiter wells in a range of concentrations, and frequencies of cobblestone area-forming cells (CAFC) were calculated by employing Poisson statistics. The production of secondary granulocyte/macrophage colony-forming units (CFU-G/M) in the adherent layer of individual wells was correlated with the presence of such cobblestone areas. CAFC frequencies were determined in bone marrow cell suspensions that were either enriched for marrow repopulating ability (MRA) in vivo, while depleted for spleen colony- forming units (CFU-S), or vice versa. The separation of bone marrow cells (BMC) was either based on centrifugal elutriation, or monoclonal antibody-mediated magnetic depletion of cells carrying cell surface differentiation antigens, and subsequent sorting on the basis of light scatter and rhodamine-123 retention as a measure of mitochondrial activity. In addition, 5-fluorouracil-resistant BMC were studied. Our investigations show that a time-dependent cobblestone area formation exists that reflects the turnover time and primitiveness of CAFC. The frequency of precursors forming cobblestone areas on day 28 after overlay is proposed to be a measure for MRA, whereas the day-7 CAFC frequency closely corresponds with day-12 CFU-S numbers in the suspensions tested.     

A rare case of voluminous brain abscess due to Actinomyces meyeri and Aggregatibacter aphrophilus: is there any evidence for a prolonged antibiotic oral relay?

We present the case of a patient with a voluminous cerebral abscess caused by Aggregatibacter aphrophilus and Actinomyces meyeri occurring a week post dental scaling. Both these bacteria are rarely involved in brain abscesses, and so far, cases of cerebral actinomyces have mostly been treated surgically and with intravenous (IV) antibiotics for 3–4 months, then put on oral antibiotic therapy with penicillin or amoxicillin for a further 3–12 months. Our patient underwent drainage through craniotomy and was subsequently put on intravenous ceftriaxone for 3 months accompanied by brain imaging control at the end of this period which showed complete regression of the abscess. Following parenteral treatment, no oral antibiotics were given since pharmacokinetic properties do not allow to attain high tissue concentration in the brain. This treatment gave excellent results.     

SAPHO syndrome masquerading as metastatic bone disease

A 46‐year‐old woman who had had a right mastectomy for breast carcinoma a month before underwent bone scintigraphy. The examination revealed multiple pelvic, vertebral and sternal hot spots suggestive of bone metastases. Standard X‐rays and CT confirmed the presence of bony lesions but they were not typical of bone metastases. As the radiographic appearance was reminiscent of SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis), bone biopsies were performed. Histology showed fibrosis and hyperostosis but no tumour cells. On further questioning, the patient revealed she had had palmar pustulosis and sacroiliitis some years earlier. The purpose of the case report is to show that accurate diagnosis of SAPHO syndrome requires careful clinical and radiological examinations.     

Idiopathic osteosclerosis mimicry of a tooth: case report

This report presents two cases of idiopathic osteosclerosis involving the maxilla and mandible which were identified as a buccally impacted canine and a retained root, respectively, on clinical and plain radiographical examinations. Both patients were females who presented with hypodontia. Radiographic evaluation revealed solitary well-defined radiopaque masses with thickened cortical border. Both patients were undergoing orthodontic treatment and one was planned for a surgical traction of unerupted tooth prior to cone-beam CT assessment. In this report, we reviewed the clinical findings and explained the radiographic appearance of idiopathic osteosclerosis through plain radiographs and cone-beam CT to facilitate its identification among general dentists and oral and maxillofacial radiologists.     

The prognostic significance of facial lymphoedema in HIV-seropositive subjects with Kaposi sarcoma

Background

Kaposi Sarcoma (KS) is a multifocal angioproliferative neoplasm characterized by inflammation, oedema, neoangiogenesis and spindle cell proliferation. The pathogenesis of human immunodeficiency virus (HIV)-associated KS (HIV-KS) is multifactorial. HHV-8 is an essential factor but not in itself sufficient to cause HIV-KS, the development of which is influenced by HIV, by increased production of cytokines and by growth factors. Whether HIV-KS is a true malignancy or a reactive hyperplastic inflammatory condition is debatable.

Results and Conclusion

Oedema of the face, legs and hands is a prominent feature of HIV-KS and is probably caused by lymphoedema related to the HIV-KS lesions. The cases of two HIV-seropositive subjects with KS-associated facial lymphoedema are reported. Extensive oral HIV-KS in association with facial oedema in the absence of anti-retroviral treatment appears to be an indication of a poor prognosis.