Growth of breast cancer recurrences assessed by consecutive MRI

<p>Abstract</p> <p>Background</p> <p>Women with a personal history of breast cancer have a high risk of developing an ipsi- or contralateral recurrence. We aimed to compare the growth rate of primary breast cancer and recurrences in women who had undergone prior breast magnetic resonance imaging (MRI).</p> <p>Methods</p> <p>Three hundred and sixty-two women were diagnosed with breast cancer and had undergone breast MRI at the time of diagnosis in our institution (2005 - 2009). Among them, 37 had at least one prior breast MRI with the lesion being visible but not diagnosed as cancer. A linear regression of tumour volume measured on MRI scans and time data was performed using a generalized logistic model to calculate growth rates. The primary objective was to compare the tumour growth rate of patients with either primary breast cancer (no history of breast cancer) or ipsi- or contralateral recurrences of breast cancer.</p> <p>Results</p> <p>Twenty women had no history of breast cancer and 17 patients were diagnosed as recurrences (7 and 10 were ipsi- and contralateral, respectively). The tumour growth rate was higher in contralateral recurrences than in ipsilateral recurrences (growth rate [10^-3days^-1] 3.56 vs 1.38, p < .001) or primary cancer (3.56 vs 2.09, p = 0.01). Differences in tumour growth were not significant for other patient-, tumour- or treatment-related characteristics.</p> <p>Conclusions</p> <p>These findings suggest that contralateral breast cancer presents accelerated growth compared to ipsilateral recurrences or primary breast events.</p

Intricate macrophage-colorectal cancer cell communication in response to radiation

Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively. Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar fractionated scheme to that used during cancer patients' treatment (2 Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co-culture with macrophages increased the mRNA expression of metabolism- and survival-related genes more in SW1463 than in RKO. The presence of macrophages also upregulated glucose transporter 1 expression in irradiated SW1463, but not in RKO cells. In addition, the influence of cancer cells on the expression of pro- and anti-inflammatory macrophage markers, upon radiation exposure, was also evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti-inflammatory CCL18. However, RKO cells induce an increase of macrophage pro-inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data demonstrated that macrophages and cancer cells mutually influence their response to radiation. Notably, conditioned medium from irradiated co-cultures increased non-irradiated RKO cell migration and invasion and did not impact on angiogenesis in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of primary human macrophage-cancer cell co-cultures revealed an intricate cell communication in response to ionizing radiation, which should be considered when developing therapies adjuvant to radiotherapy

Epithelial cancers in the post-genomic era: should we reconsider our lifestyle?

The age-related epithelial cancers of the breast, colorectum and prostate are the most prevalent and are increasing in our aging populations. Epithelial cells turnover rapidly and mutations naturally accumulate throughout life. Most epithelial cancers arise from this normal mutation rate. All elderly individuals will harbour many cells with the requisite mutations and most will develop occult neoplastic lesions. Although essential for initiation, these mutations are not sufficient for the progression of cancer to a life-threatening disease. This progression appears to be dependent on context: the tissue ecosystem within individuals and lifestyle exposures across populations of individuals. Together, this implies that the seeds may be plentiful but they only germinate in the right soil. The incidence of these cancers is much lower in Eastern countries but is increasing with Westernisation and increases more acutely in migrants to the West. A Western lifestyle is strongly associated with perturbed metabolism, as evidenced by the epidemics of obesity and diabetes: this may also provide the setting enabling the progression of epithelial cancers. Epidemiology has indicated that metabolic biomarkers are prospectively associated with cancer incidence and prognosis. Furthermore, within cancer research, there has been a rediscovery that a switch in cell metabolism is critical for cancer progression but this is set within the metabolic status of the host. The seed may only germinate if the soil is fertile. This perspective brings together the different avenues of investigation implicating the role that metabolism may play within the context of post-genomic concepts of cancer

A prospective study of long-term dysphagia following total laryngectomy

A prospective study of long-term dysphagia following total laryngectomy. Objective: To evaluate the degree of dysphagia in patients before and after total laryngectomy using the Performance Status Scale for Head and Neck Cancer Patients (PSS) and to determine the effects of post-operative radiation therapy, neck dissection, and pharyngoesophageal spasm on PSS scores. Methods: We performed a controlled, prospective study at a tertiary referral university hospital. Twenty consecutive patients undergoing laryngectomy were included. Patients were followed for at least two years post-operative, without evidence of local, regional, or distant disease. Only patients with squamous cell carcinoma limited to the endolarynx requiring total laryngectomy with or without elective neck dissection for surgical management of cancer and with no pre-operative treatment were included. Dysphagia was evaluated by PSS prior to surgery and again two years post-operatively with an emphasis on eating in public and normalcy of diet domains. Video fluoroscopic evaluation of swallowing was performed one year after treatment. Results: The relative number of patients with low mean scores in PSS (i.e. usually swallow paste of fluid food in presence of some selected persons or alone; 50) increased after total laryngectomy (p = 0.04). Patients with lower scores reported more frequent spasm of the pharyngoesophageal segment (p = 0.005). Mean scores of both domains decreased after surgery (p<0.05). Conclusion: Eating in public and normalcy of diet scores decreased in 50% of patients after total laryngectomy.7210310

Doe Program—Developing a Scientific Basis for Responses to Low-Dose Exposures: Impact on Dose-Response Relationships

The DOE Low Dose Radiation Research Program focuses on biological mechanisms involved in response to low doses of both low and high-LET radiation (<0.1Gy). This research program represents a merging of new technologies with cutting edge biological techniques associated with genomics. This merger enables observation of radiation-induced cellular and molecular changes previously undetectable. These low-dose responses define mechanisms of interaction of radiation with living systems, and characterize the shape of dose-response. The research from this program suggests radiation paradigms regarding the involvement of radiation in the carcinogenic process. New biological phe-nomena observed at low doses include initial radiation-induced DNA damage and repair, changes in gene expression, adaptive responses and bystander effects. However, information from this cellular-molecular level cannot be directly extrapolated to risks in human populations. Links must be carefully developed between dose-response relationships at the cell and tissue levels and risk to human populations. The challenge and the ultimate goal of the Program is to determine if basic scientific data can be combined with more traditional epidemiological methods to improve the estimation of radiation risk from low level radiation exposures