Stereotactic core biopsy was performed on 200 women for 206 mammographically suspicious non-palpable lesions detected over a period of 2 years as part of the Australian national programme for early detection of breast cancer. This study aimed to assess the reliability of stereotactic core biopsy in this context and to develop a protocol for the evaluation of stereotactic core biopsy in mammographically detected non-palpable breast lesions. Fifty-one of 52 malignant lesions found by stereotactic core biopsy were confirmed by excision biopsy (one women declined excision). Nine (4.5%) women had atypical ductal hyperplasia on stereotactic core biopsy; at excision, six were low grade carcinomas (in situ or invasive carcinomas), one was a 3 mm focus of grade 3 invasive duct carcinoma, one was atypical ductal hyperplasia, and one patient refused excision biopsy. In 29 (14.5%) women the histology of the stereotactic core biopsy was considered not to correlate with the radiological abnormality, and excision biopsy was advised: in four of these women carcinomas were found. One hundred and ten (55%) women had 116 benign lesions on stereotactic core biopsy: on follow-up, one of these patients has been found to have a carcinoma. Core biopsy number and sequence were analysed demonstrating that no particular biopsy was more diagnostic than any other, and that the diagnostic yield of three cores was statistically equal to that of five cores. The procedure was well-tolerated and there were few complications. Thus, stereotactic core biopsy is an accurate and safe method for diagnosis of mammographically detected non-palpable breast lesions, and we believe it is the diagnostic technique of choice in breast cancer screening programmes. However, a stereotactic core biopsy diagnosis of atypical ductal hyperplasia requires excision biopsy since a diagnosis of low grade intraduct carcinoma cannot be excluded. Furthermore, if tissue obtained by stereotactic core biopsy does not correlate with the mammographic abnormality, excision biopsy should be performed.

Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread. These disseminated hybrids outnumber conventionally defined circulating tumor cells (CTCs) in cancer patients. It is unknown if CHCs represent a generalized cancer mechanism for cell dissemination, or if this population is relevant to the metastatic cascade. Herein, we detect CHCs in the peripheral blood of patients with cancer in myriad disease sites encompassing epithelial and non-epithelial malignancies. Further, we demonstrate that in vivo-derived hybrid cells harbor tumor-initiating capacity in murine cancer models and that CHCs from human breast cancer patients express stem cell antigens, features consistent with the potential to seed and grow at metastatic sites. Finally, we reveal heterogeneity of CHC phenotypes reflect key tumor features, including oncogenic mutations and functional protein expression. Importantly, this novel population of disseminated neoplastic cells opens a new area in cancer biology and renewed opportunity for battling metastatic disease.

Recent studies showed that enteric helminth infection improved symptoms in patients with inflammatory bowel disease as well as in experimental models of colitis. The aim of this study was to determine the mechanism of the protective effect of helminth infection on colitis-induced changes in immune and epithelial cell function. BALB/c mice received an oral infection of Heligmosomoides polygyrus third-stage larvae, were given intrarectal saline or trinitrobenzene sulfonic acid (TNBS) on day 10 postinfection, and were studied 4 days later. Separate groups of mice received intrarectal saline or TNBS on day 10 and were studied on day 14. Muscle-free colonic mucosae were mounted in Ussing chambers to measure mucosal permeability and secretion.

Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aβ plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced Aβ levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed.

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