What's new?

No protein is an island. Where one is askew, you'll often find others out of balance as well, and the group of interacting proteins and receptors known as the “endothelin axis” is no exception. These proteins are dysregulated in cancer development, and much study has focused on ET-1, which is increased in the disease cells. Less is known about ET-2 and ET-3, but the current paper reveals that these two proteins are shut down in rat and human colon cancer, and that boosting them may push back the disease by blocking ET-1.

What's new?

Resveratrol (RSV) is a plant polyphenol with promising anticancer features. In this study, the authors examined whether RSV could reduce proliferation of a Hodgkin-lymphoma (HL) cell line. They found that exposure to RSV led to an almost 20-fold increase in apoptosis and cell death, as well as reduced activity of sirtuin-1 (SIRT1). In addition to supporting a therapeutic role for RSV, data from this study suggest that SIRT1 may play a role in malignant transformation, and might have potential as a therapeutic target.

What's new?

Activation of the enzyme phospholipase Cγ1 (PLCγ1) is thought to contribute to cancer metastasis by enhancing cell motility. In breast cancer specifically, PLCγ1 may shorten disease-free survival, an association supported here by evidence that high expression of PLCγ1 and its activated nuclear forms is predictive of metastasis in early-stage breast cancer patients on adjuvant chemotherapy. The results suggest that activated PLCγ1 may be linked to chemotherapy resistance and could serve as a valuable prognostic marker and therapeutic target for breast cancer.

What's new?

Epidemiological and molecular studies have established intriguing links between the circadian rhythm and cancer. In this study, the authors monitored expression of key genes involved in the mammalian circadian clock in a mouse colon cancer model. They find disruptions of circadian homeostasis not only in colonic tumor cells, but also in surrounding colonic tissue as well as in other tissues, specifically in the liver. These results demonstrate a wide-spread loss of clock function and allow speculations into causal interactions between dysregulated clock-gene expression and colon tumor development.

What's new?

The EGFR transcript is overexpressed in 90 percent of head and neck squamous cell carcinomas (HNSCC); yet EGFR inhibitors have met with limited success in controlling the disease. New data reported here, however, reveal that knock-down of the docking protein GAB1 in HNSCC cells reduces EGFR signaling and sensitizes cells to the EGFR inhibitor gefitinib. The results indicate that GAB1 overexpression may be responsible for undermining the effectiveness of EGFR inhibitors in HNSCC.

What's new?

The proteins galectin and S100A9 both influence the progression of cervical cancer. Earlier investigation revealed that the two proteins make chemotherapy and radiation therapy more effective. In the current report, the authors showed that as cells progressed from normal to cancerous, they contained less galectin and S100A9. Furthermore, analysis of patient samples revealed that galectin, and to a lesser extent S100A9, improved 5-year survival rates.

What's new?

Polyposis-associated variations in the base excision repair gene MUTYH are distributed unevenly across different ethnicities, suggesting diverse mutation origins and founder effects. This haplotype analysis successfully documented the first MUTYH founder mutation—a splice variant known as c.933+3A>C, frequently detected in polyposis patients from northeastern Italy. Knowledge of the mutation's origins in this population could have important implications for genetic counseling and diagnosis.

What's new?

The types of immune cells within a tumor can play a crucial role in patient survival. In this study of ovarian cancer (OC), the authors examined the immune cells infiltrating tumor tissues of patients at various stages of the disease. They found that the pattern of cells shifted as the disease progressed, from an active anti-tumor immune response to one of immune suppression, with activated regulatory T cells (Tregs) becoming the most abundant cell type in advanced OC. The authors conclude that overcoming this suppressive microenvironment should play a role in new therapeutic protocols.

What's new?

This study indicates that hnRNP A1 is positively related to the metastatic potential of hepatocellular carcinoma (HCC) cells and that overexpression of hnRNP A1 promotes HCC cells invasion through the regulation of CD44v6 expression. Overexpression of hnRNP A1 predicts lower overall survivor and higher recurrence rates for HCC patients after curative resection. The expression levels of hnRNP A1 alone or in combination with CD44v6 in HCC patients are important because they may provide not only a predictor for HCC prognosis but also a therapeutic target for future studies.

What's new?

A disappointing proportion of patients with colon cancer who received adjuvant chemotherapy after radical surgery will nonetheless develop tumor recurrence. Patients' chances of relapse are currently being predicted using pathological staging, and additional markers are needed to help select high-risk patients. This study identified a new gene-expression signature that, along with tumor stage, provides a robust and easy-to-use and reliable mathematical algorithm to identify patients at higher risk of tumor relapse and shorter survival who may eventually benefit from a more aggressive therapeutic regimen and more intensive surveillance.

What's new?

Survivin and livin are anti-apoptotic genes that are expressed in many cancers but are undetectable in normal adult tissues. Here, a similar pattern of expression was observed in lung cancer patients versus patients with benign lung disease, using bronchial aspirates as a sample source for detection. The findings suggest that survivin and livin mRNA expression in bronchial aspirates could be used alongside findings from computerized tomography to facilitate the early diagnosis of lung cancer.

What's new?

This study shows the clinical relevance of a combination of five antigens as a blood-screening test for early breast cancer detection. The antigens were identified using a proteomic approach and validated in an independent cohort of 182 samples by ELISA. Since the effectiveness of mammographic screening declines in cohorts of patients with dense breast tissue and small lesions, testing for the status of this biomarker panel may help improve the detection of early-stage cancer in women.

What's new?

Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential conflicting effects of lactose, which may increase gonadotropin levels, and the beneficial anti-proliferative effects of calcium and vitamin D. We provide evidence of an overall inverse association with high intake of calcium, and identify novel inverse associations for calcium and vitamin D intake with specific histological subtypes of ovarian cancer.

What's new?

Few studies have asked whether adult height is associated with cancer risk. The authors analyzed data from a large prospective study of nearly 90,000 women, and found that greater height did indeed correlate with an increased risk of several types of cancer. The authors suggest that environmental factors associated with increased height, such as early diet or growth factor levels, may increase the risk of certain cancers later in life.

What's new?

The authors report that aspirin may reduce the risk of endometrial cancer by as much as half, particularly among obese women. Similar results were not observed for non-aspirin NSAIDs or paracetamol (acetaminophen). This may be because aspirin can influence cellular processes such as apoptosis and angiogenesis, which are crucial for the development and growth of malignancies.

What's new?

A new clinical practice guideline for gastric cancer introduced in 2009 in the Netherlands was examined for its impact on patterns of care. Analysis of data from a national cancer registry revealed that, while indicators for guideline adherence showed no major change, perioperative chemotherapy was used less often in the elderly and the proportion of patients that received adequate lymphadenectomy increased. The findings could have implications for the future development of gastric cancer care guidelines.

What's new?

Body mass index (BMI) has been associated with lung cancer risk, though no clear relationship has emerged in the scientific literature. In this meta-analysis, which emphasized control for confounding factors, obesity was associated with a decreased risk for lung cancer, particularly for smokers. Although the biological mechanism underlying this phenomenon is unclear, the results suggest that attention to nutrition and maintenance of body weight could lower lung cancer incidence among smokers.

What's new?

Most of the diagnostic and therapeutic modalities used for breast cancer more than 10 years ago remain in widespread use today. Understanding the extent to which access to those modalities can explain international differences in cancer survival therefore remains highly relevant. This is the largest population-based high-resolution study, with a common protocol, standard quality-control procedures and central analyses. The modelling approach to estimate net survival is a methodological strength.

What's new?

Sub-Saharan Africa is endemic for Kaposi's sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. The present study is the first to describe a molecular analysis of KSHV transmission to children in a longitudinal cohort of KSHV-positive children and their entire households in Zambia—a country endemic for KSHV and Kaposi's sarcoma. The results have important implications for the development of strategies to prevent KSHV transmission to young children and reduce Kaposi's sarcoma incidence in endemic areas.

What's new?

Despite known associations with breast cancer risk, whether high serum levels of insulin-like growth factor-1 (IGF-1) also iinfluences prognosis of the disease remains unclear. In this analysis of 600 breast cancer patients, increases in IGF-1 and the ratio of IGF-1 to its binding protein IGFBP-3 were associated with all-cause mortality. The relationship appeared to involve a threshold effect in which IGFBP-3 production eventually failed to keep pace with production of IGF-1, resulting in conditions favorable for tumor growth.

What's new?

In the search for effective chemotherapies, an ideal drug would not only stop tumors from growing, but would also inhibit angiogenesis. Plumbagin, a naphthaquinone derivative, may fit the bill. In this report, the authors studied the effects of plumbagin on various signaling pathways in ovarian cancer cells. They found that the drug inhibited proliferation regardless of the BRCA2 or oxygen status of the cells. Plumbagin also caused OVCAR-5 tumors in mice to regress, with a significant reduction of their vascular structure. Because plumbagin affects multiple pathways in cancer cells, it may offer a valuable addition to the chemotherapeutic arsenal.

What's new?

Tumor cells have increased glucose uptake and in addition accumulate other molecules such as amino acids and vitamins to higher levels than non-tumor cells. The authors hypothesized that this accumulation represents a tumor defense mechanism and tested the effect of a mixture of these substances called Active Mixture in murine and human xenograft tumor models. Active Mixture induced apoptosis of tumor cells both in vitro and in vivo and effectively diminished tumor growth in a variety of tumor models offering an interesting new perspective on tumor therapy.

What's new?

Japanese atomic-bomb survivors have been a critical source of information for insight into radiation-related thyroid cancer risk. In this analysis of survivor data from 1958 through 2005—one of the longest follow-up studies on thyroid cancer to date—radiation-associated thyroid cancer risk was found to persist for more than 50 years. The continued increase in risk, which was associated with long life and exposure to radiation in childhood or adolescence, could have important implications for clinical practice and public health measures.

What's new?

TP53 is mutated in approximately 30% of breast cancers, but this frequency fluctuates widely between tumor subclasses. The authors investigated p53 mutations in breast tumors from the luminal, basal, and molecular apocrine molecular subgroups. They found that subgroups differ not only in TP53 mutation frequency but also in mutation types and consequences. They detected a high prevalence of missense mutations in luminal tumors and truncating mutations in basal tumors. In apocrine molecular tumors, despite high prevalence of insertions/deletions, p53 truncation was not increased. The observations point to different mutational mechanisms, functional consequences, and/or selective pressures in different breast cancers subtypes.