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CTRC-AACR San Antonio Breast Cancer Symposium, Dec. 5-9

CTRC-AACR San Antonio Breast Cancer Symposium, Dec. 5-9

The 40th Annual CTRC-AACR San Antonio Breast Cancer Symposium The annual meeting of the San Antonio Breast Cancer Symposium was held from Dec. 5 to 9 in San Antonio, Texas, and attracted more than 7,500 participants from around the world, including medical oncologists, radiation oncologists, researchers, and other health care professionals. The conference highlighted recent advances in the risk, diagnosis, treatment, and prevention of breast cancer, with presentations focusing on emerging treatments in hard-to-treat patient populations, including patients with metastatic breast cancer. In one study, Richard Gray, of the University of Oxford in the United Kingdom, and colleagues performed a meta-analysis of all trials that involved dose intensification of chemotherapy in breast cancer patients. The investigators found that giving exactly the same drug at the same doses but every two weeks rather than every three weeks reduced the risk of breast cancer recurrence and death by 15 and 13 percent, respectively. “In this analysis, the drugs were exactly the same and at the same dose — just the time frames were shorter. We also found similar results when looking at all other dose-intensification approaches, about a 15 percent lower risk of recurrence and death,” Gray said. “We were surprised by how strong and consistent the findings from our study were, and there were few additional side effects with dose-intense schedules compared with standard-schedule chemotherapy, so the benefits seem to outweigh the risks.” Press Release In the phase III EMBRACA study, Jennifer Litton, M.D., of the University of Texas MD Anderson Cancer Center in Houston, and colleagues evaluated the efficacy of the once-daily poly ADP-ribose polymerase (PARP) inhibitor, talazoparib, in...
Heavy metals in the volcanic environment and thyroid cancer.

Heavy metals in the volcanic environment and thyroid cancer.

Molecular and cellular endocrinology 2016 10 26457() 73-80 pii 10.1016/j.mce.2016.10.027 Abstract In the last two decades thyroid cancer incidence has increased worldwide more than any other cancer. Overdiagnosis of subclinical microcarcinomas has certainly contributed to this increase but many evidences indicate that a true increase, possibly due to environmental factors, has also occurred. Thyroid cancer incidence is markedly increased in volcanic areas. Thus, the volcanic environment is a good model to investigate the possible factors favoring thyroid cancer. In the volcanic area of Mt. Etna in Sicily, as well as in other volcanic areas, a non-anthropogenic pollution with heavy metals has been documented, a consequence of gas, ash and lava emission. Soil, water and atmosphere contamination, via the food chain, biocontaminate the residents as documented by high levels in the urines and the scalp hair compared to individuals living in adjacent non-volcanic areas. Trace amounts of metals are essential nutrients but, at higher concentrations, can be toxic for living cells. Metals can behave both as endocrine disruptors, perturbing the hormonal system, and as carcinogens, promoting malignant transformation. Similarly to other carcinogens, the transforming effect of heavy metals is higher in developing organisms as the fetus (contaminated via the mother) and individuals in early childhood. In the last decades environment metal pollution has greatly increased in industrialized countries. Although still within the "normal" limits for each single metal the hormesis effect (heavy metal activity at very low concentration because of biphasic, non linear cell response) and the possible potentiation effect resulting from the mixture of different metals acting synergistically can explain cell damage at very low concentrations. The effect of...
Carcinogenic risk and Bisphenol A exposure: A focus on molecular aspects in endoderm derived glands.

Carcinogenic risk and Bisphenol A exposure: A focus on molecular aspects in endoderm derived glands.

Molecular and cellular endocrinology 2017 01 19457() 20-34 pii 10.1016/j.mce.2017.01.027 Abstract Epidemiological and experimental evidence associates the exposure to Bisphenol A with the increase of cancer risk in several organs, including prostate. BPA targets different pathways involved in carcinogenicity including the Nuclear Receptors (i.e. estrogen and androgen receptors), stress regulated proteins and, finally, epigenetic changes. Here, we analyse BPA-dependent carcinogenesis in endoderm-derived glands, thyroid, liver, pancreas and prostate focusing on cell signalling, DNA damage repair pathways and epigenetic modifications. Mainly, we gather molecular data evidencing harmful effects at doses relevant for human risk (low-doses). Since few molecular data are available, above all for the pancreas, we analysed transcriptomic data generated in our laboratory to suggest possible mechanisms of BPA carcinogenicity in endoderm-derived glands, discussing the role of nuclear receptors and stress/NF-kB pathways. We evidence that an in vitro toxicogenomic approach might suggest mechanisms of toxicity applicable to cells having the same developmental origin. Although we cannot draw firm conclusions, published data summarized in this review suggest that exposure to BPA, primarily during the developmental stages, represents a risk for carcinogenesis of endoderm-derived...
CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma.

CXCR4/CXCR7/CXCL12 axis promotes an invasive phenotype in medullary thyroid carcinoma.

British journal of cancer 2017 11 07117(12) 1837-1845 doi 10.1038/bjc.2017.364 Abstract BACKGROUND Medullary thyroid carcinoma (MTC) is a rare and challenging endocrine malignancy. Once spread, the therapeutic options are limited and the outcome poor. For these patients, the identification of new druggable biological markers is of great importance. Here, we investigated the prognostic and biological role of the C-X-C chemokine receptors type 4 and 7 (CXCR4/7) in MTC. METHODS Eighty-six MTC and corresponding non-neoplastic thyroid specimens were immunohistochemically stained for CXCR4/7 using tissue microarray technology and expression levels correlated with clinicopathological variables. Medullary thyroid carcinoma cell line TT was treated with recombinant human SDF1α/CXCL12 (rh-SDF1α) and CXCR4 antagonists AMD3100 and WZ811. Changes in cell cycle activation, tumour cell invasiveness as well as changes in mRNA expression levels of genes associated with epithelial-mesenchymal transition (EMT) were investigated. RESULTS High CXCR4 expression was associated with large tumour size and metastatic disease. CXCR4 antagonists significantly reduced tumour cell invasiveness, while the treatment with rh-SDF1α stimulated invasive growth, caused cell cycle activation and induced EMT. CONCLUSIONS The CXCR4/CXCR7/CXCL12 axis plays an important role in MTC. We provide first evidence that the chemokine receptors might serve as potential therapeutic targets in patients with advanced MTC and offer new valuable insight into the underlying molecular machinery of metastatic...
Variations in the practice of molecular radiotherapy and implementation of dosimetry: results from a European survey.

Variations in the practice of molecular radiotherapy and implementation of dosimetry: results from a European survey.

EJNMMI physics 2017 12 044(1) 28 doi 10.1186/s40658-017-0193-4 Abstract BACKGROUND Currently, the implementation of dosimetry in molecular radiotherapy (MRT) is not well investigated, and in view of the Council Directive (2013/59/Euratom), there is a need to understand the current availability of dosimetry-based MRT in clinical practice and research studies. The aim of this study was to assess the current practice of MRT and dosimetry across European countries. METHODS An electronic questionnaire was distributed to European countries. This addressed 18 explicitly considered therapies, and for each therapy, a similar set of questions were included. Questions covered the number of patients and treatments during 2015, involvement of medical specialties and medical physicists, implementation of absorbed dose planning, post-therapy imaging and dosimetry, and the basis of therapy prescription. RESULTS Responses were obtained from 26 countries and 208 hospitals, administering in total 42,853 treatments. The most common therapies were 131I-NaI for benign thyroid diseases and thyroid ablation of adults. The involvement of a medical physicist (mean over all 18 therapies) was reported to be either minority or never by 32% of the responders. The percentage of responders that reported that dosimetry was included on an always/majority basis differed between the therapies and showed a median value of 36%. The highest percentages were obtained for 177Lu-PSMA therapy (100%), 90Y microspheres of glass (84%) and resin (82%), 131I-mIBG for neuroblastoma (59%), and 131I-NaI for benign thyroid diseases (54%). The majority of therapies were prescribed based on fixed-activity protocols. The highest number of absorbed-dose based prescriptions were reported for 90Y microsphere treatments in the liver (64% and 96% of responses for resin and glass, respectively), 131I-NaI...
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