Archive for » Januar, 2014 «

Donnerstag, Januar 30th, 2014 | Author:

A group of researchers from Mexico’s General Hospital, Health Secretariat, Medicine Faculty and the Institute of Cellular Physiology of the National Autonomous University of Mexico (UNAM) identified a therapeutic target for cervix cancer: gene CDKN3.

Donnerstag, Januar 30th, 2014 | Author:

Of all cancers, lung cancer is the biggest killer in both men and women. According to the American Lung Association, it causes more deaths than colon, breast and prostate cancer combined. Diagnosing the disease can involve a number of tests, but scientists have discovered that specific compounds in exhaled breath may be used to diagnose the disease in its early stages.

Category: lung cancer  | Leave a Comment
Donnerstag, Januar 30th, 2014 | Author:

Medivation Inc. and Astellas Pharma Inc. have announced final results on the primary and secondary efficacy endpoints from the Phase 3 PREVAIL trial of enzalutamide in patients with chemotherapy-naïve metastatic prostate cancer who have failed androgen deprivation therapy and have few or no symptoms.

Donnerstag, Januar 30th, 2014 | Author:

In recent years, mutations in two metabolic enzymes, isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2), have been identified in approximately 20 percent of all acute myeloid leukemias (AML). As a result, mutant IDH proteins have been proposed as attractive drug targets for this common form of adult leukemia.

Category: lymphoma  | Leave a Comment
Donnerstag, Januar 30th, 2014 | Author:

IntroductionThe Runt-related transcription factor Runx2 is critical for skeletal development but is also aberrantly expressed in breast cancers, and promotes cell growth and invasion. A de-regulated serine/threonine kinase Akt signaling pathway is implicated in mammary carcinogenesis and cell survival; however the mechanisms underlying Runx2 role in survival of invasive breast cancer cells are still unclear.
Methods:
The phenotypic analysis of Runx2 function in cell survival was performed by gene silencing and flow cytometric analysis in highly invasive MDA-MB-231 and SUM-159-PT mammary epithelial cell lines. The expression analysis of Runx2 and pAkt (serine 473) proteins in metastatic breast cancer specimens was performed by immunohistochemistry. The mRNA and protein levels of kinases and phosphatases functional in Akt signaling were determined by real-time PCR and western blotting, while DNA-protein interaction was studied by chromatin immunoprecipitation assays.
Results:
The high Runx2 levels in invasive mammary epithelial cell lines promoted cell survival in Akt phosphorylation (pAkt-serine 473) dependent manner. The analysis of kinases and phosphatases associated with pAkt regulation revealed that Runx2 promotes pAkt levels via mammalian target of rapamycin complex-2 (mTORC2). The recruitment of Runx2 on mTOR promoter coupled with Runx2-dependent expression of mTORC2 component Rictor defined Runx2 function in pAkt-mediated survival of invasive breast cancer cells.
Conclusions:
Our results identified a novel mechanism of Runx2 regulatory crosstalk in Akt signaling that could have important consequences in targeting invasive breast cancer-associated cell survival.

Donnerstag, Januar 30th, 2014 | Author:

Paracrine signaling mechanisms play a critical role in both normal mammary gland development and breast cancer. Dissection of these mechanisms using genetically engineered mouse models has provided significant insight into our understanding of the mechanisms that guide intratumoral heterogeneity. In the following perspective, we briefly review some of the emerging concepts in this field and emphasize why elucidation of these pathways will be important for future progress in devising new and improved combinatorial therapeutic approaches for breast and other solid cancers.

Donnerstag, Januar 30th, 2014 | Author:

IntroductionAlthough aromatase inhibitors (AIs; for example, letrozole) are highly effective in treating estrogen receptor positive (ER+) breast cancer, a significant percentage of patients either do not respond to AIs or become resistant to them. Previous studies suggest that acquired resistance to AIs involves a switch from dependence on ER signaling to dependence on growth factor-mediated pathways, such as human epidermal growth factor receptor-2 (HER2). However, the role of HER2, and the identity of other relevant factors that may be used as biomarkers or therapeutic targets remain unknown. This study investigated the potential role of transcription factor hypoxia inducible factor 1 (HIF-1) in acquired AI resistance, and its regulation by HER2.
Methods:
In vitro studies using AI (letrozole or exemestane)-resistant and AI-sensitive cells were conducted to investigate the regulation and role of HIF-1 in AI resistance. Western blot and RT-PCR analyses were conducted to compare protein and mRNA expression, respectively, of ERalpha, HER2, and HIF-1alpha (inducible HIF-1 subunit) in AI-resistant versus AI-sensitive cells. Similar expression analyses were also done, along with chromatin immunoprecipitation (ChIP), to identify previously known HIF-1 target genes, such as breast cancer resistance protein (BCRP), that may also play a role in AI resistance. Letrozole-resistant cells were treated with inhibitors to HER2, kinase pathways, and ERalpha to elucidate the regulation of HIF-1 and BCRP. Lastly, cells were treated with inhibitors or inducers of HIF-1alpha to determine its importance.
Results:
Basal HIF-1alpha protein and BCRP mRNA and protein are higher in AI-resistant and HER2-transfected cells than in AI-sensitive, HER2- parental cells under nonhypoxic conditions. HIF-1alpha expression in AI-resistant cells is likely regulated by HER2 activated-phosphatidylinositide-3-kinase/Akt-protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway, as its expression was inhibited by HER2 inhibitors and kinase pathway inhibitors. Inhibition or upregulation of HIF-1alpha affects breast cancer cell expression of BCRP; AI responsiveness; and expression of cancer stem cell characteristics, partially through BCRP.
Conclusions:
One of the mechanisms of AI resistance may be through regulation of nonhypoxic HIF-1 target genes, such as BCRP, implicated in chemoresistance. Thus, HIF-1 should be explored further for its potential as a biomarker of and therapeutic target.

Donnerstag, Januar 30th, 2014 | Author:

An early stage study shows melatonin – a hormone that regulates the body’s sleep and awake cycles – may have the potential to help slow the growth of certain breast cancer tumors, according to researchers from Henry Ford Hospital in Detroit and Foundation for Research Support of the State of São Paulo.

Donnerstag, Januar 30th, 2014 | Author:

A new study, published in the American Association for Cancer Research’s journal Cancer Prevention Research, challenges the current recommendations for management of a type of breast tissue abnormality.

Donnerstag, Januar 30th, 2014 | Author:

A new US study finds that yoga can benefit breast cancer survivors by reducing fatigue and inflammation. While yoga has many components, the researchers believe breathing and meditation probably had the biggest impact.