What's new?

The purpose of this study was to explore the mechanisms of angiogenic microenvironment formation using EGFRvIII-positive glioblastoma as a model. EGFRvIII is regarded as a poor prognosis marker in gliomas because of its potential to confer enhanced tumorigenicity. Here, the authors confirm that EGFRvIII promotes a more malignant microenvironment in mice, as demonstrated by greater expression of the pro-angiogenic and tumorigenic factor VEGF. C/EBPβ-mediated regulation of IL-6 is indispensable for maintenance of this angiogenic microenvironment. In contrast, the drug genistein inhibits the development of tumor angiogenesis through a mechanism involving CHOP-mediated inhibition of C/EBPβ and the subsequent down-regulation of IL-6.

What's new?

What happens on a cellular level when androgen receptor is blocked in prostate cancer? Cutting off androgen to the tumor alleviates the disease for a while, but eventually androgen receptor levels bounce back and the cancer resurges. How? In this paper, the authors searched for genes that helped the cancer survive despite the lack of androgen. They zeroed in on one gene, HSPBAP1, that correlates with poor survival. Without HSPBAP1, prostate cancer cells could no longer express androgen-receptor target genes. This protein interacts with androgen receptor in the nucleus and appears to maintain AR-signaling in the absence of androgen.

What's new?

Some skin cancers such as squamous cell carcinomas occur more often in immune compromised individuals, pointing to an infectious agent as cause. In an unbiased approach the authors used next-generation sequencing to examine 91 non-melanoma skin cancer lesions. Most skin lesions contained Human Papilloma Virus (HPV). The authors cloned and sequenced a new type, HPV type 197, present in 34 of the 91 skin lesions. HPV197 has only 75% similarity with the most closely related known HPV (HPV178), suggesting a possible new agent involved in the carcinogenesis of non-melanoma skin lesions.

What's new?

Over the last decade, metformin, an anti-diabetic drug, has gained significant attention as an anti-cancer drug because of its association with a dramatically decreased risk of some cancers. The underlying mechanisms of action, however, remain largely unknown. Here, using a mouse hepatocellular carcinoma (HCC) model, the authors found an important and previously unidentified effect of metformin with the inhibition of HCC growth through an indirect path mediated by IL-22. The findings also provide evidence for immune-modulatory effects of metformin in HCC. Taken together, these data broaden our current understanding of the mechanisms of action of metformin in liver cancer treatment.

What's new?

Since recurrent glioblastoma multiforme (GBM) is often resistant to radiotherapy and chemotherapy, immunotherapy has been proposed as an alternative. Unfortunately, both GBM tumors and standard therapies can induce immune suppression. In this study, the authors asked whether these therapies might also actually enhance the ability of GBM cells to modulate the immune response. They found that treated glioma cells are indeed more immunosuppressive than untreated cells, and form tumors at a faster rate in vivo. This may be a critical finding for the timing of immunotherapy with conventional treatment.

What's new?

Carcinoembryonic antigen (CEA) is found in the serum of patients with various cancers and is correlated with an increased risk of cancer recurrence and metastasis. To shed light on the influence of CEA on T cells, here the authors investigate the co-inhibitory role of CEA during human T cell stimulation by TCR engagement. They show that CEA-overexpressing tumor cells or multimeric CEA significantly inhibit T cell activation, proliferation, and cytokine production. Collectively, the data suggest that multimeric CEA, such as cell-associated CEA, can hinder T cell stimulation upon TCR engagement, which may contribute to an immune escape mechanism for tumors.

What's new?

The differentiation antigen NY-BR-1 appears as a suitable target antigen for T cell based immunotherapy approaches against breast cancer. Although antibody titers as well as CD8⁺ T cell responses specific for NY-BR-1 have been described in breast cancer patients, information about NY-BR-1-specific CD4⁺ T cell responses is still lacking. This article presents the first NY-BR-1-specific HLA-DRB1*0301– and HLA-DRB1*04-restricted T cell epitopes and provides evidence for their clinical relevance. The paper furthermore demonstrates the suitability of murine HLA-restricted CD4⁺ T cell lines for the screening of CD4⁺ T cell epitopes processed in human target cells.

What's new?

While platinum-based chemotherapy currently represents the standard of care for non-small cell lung cancer (NSCLC), patients show rapid onset of resistance. Here, the authors demonstrate a possible involvement of ATF2--a transcription factor involved in stress and DNA damage--in NSCLC platinum-resistance, thus identifying a putative target for the restoration of platinum sensitivity. They further show that celastrol--a plant extract used in traditional Chinese medicine as an anti-inflammatory agent--was able to reduce ATF2 activity and restore cisplatin efficacy in resistant cell lines through the functional inhibition of ATF2/cJUN.

What's new?

The detection of cell-free RNA (cf-RNA) in biological fluids raises possibilities for the development of new diagnostic assays for cancer. Such an assay may be applicable particularly for clear cell renal cell carcinoma (ccRCC). In this study, the urinary cf-RNA integrity index in ccRCC patients was found to be significantly reduced compared to control subjects. However, small-sized cf-RNA fragments, including small fragments (98 bp) of VEGF mRNA, were present at increased levels in the urine of cancer patients. Additional investigation is needed to confirm the findings and to define the clinical utility of cf-RNA detection for ccRCC.

What's new?

Tumor exosomes—membrane vesicles of endocytic origin abundantly secreted by tumor cells and readily detected in body fluids—have recently emerged as a potential, non-invasive diagnostic tool. This study shows that the serum of pancreatic cancer (PaCa) patients contains detectable amounts of PaCa stem cell marker-expressing exosomes. Furthermore, the miRNA profile of serum exosomes in PaCa patients differs significantly from that of healthy donors and patients with non-malignant disease. A blinded screening study of PaCa patients' serum exosomes revealed a combined evaluation of a panel of PaCa-associated miRNA and stem cell biomarkers to provide a highly sensitive, minimally-invasive diagnostic tool.

What's new?

Reported geographical and racial differences in childhood cancer incidence contribute to hypotheses regarding the possible risk factors for the disease. Analysis of data from the National Cancer Registry of South Africa uncovered marked differences in childhood cancer incidence within South African populations, with significantly higher rates in Whites compared to Blacks. Compared to data from Germany (representing childhood cancer incidence in Western countries) lower rates were even found in South African Whites, with the greatest differences being noted for the Black population. Under-diagnosis and under-reporting may drive in part the observed patterns. These findings are highly informative for future policy making and improving access to health care services in South Africa.

What's new?

How much does behavior really affect cancer risk? These authors set out to measure just that. First, they created a Healthy Lifestyle Index, which quantified five modifiable behaviors, such as smoking and physical activity. Then, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), they assigned each participant a score between 0 and 4 on each of the behaviors. It turned out that with each point added to a person's Healthy Lifestyle Index score, breast cancer risk fell by 3%, suggesting that public programs to help women maintain these behaviors could be worthwhile for cancer prevention.

What's new?

Population-based cancer registries allow researchers to evaluate current quality and recent trends in cancer care. In this study, the authors assembled a comprehensive overview of relative cancer survival in Germany from 2007 to 2010. They also compared survival rates in Germany with those in the United States, and among various age groups. They found that relative survival has improved recently for most cancers, with multiple myeloma, non-Hodgkin lymphoma, prostate cancer and colorectal cancer showing the greatest improvement.

What's new?

MC1R has important pigmentary biological functions, and inherited variations in the gene are well-known markers of melanoma risk. But whether those variants are also associated with disease survival is unknown. Here, germline variation at MC1R was associated with improved melanoma-specific survival in carriers who lacked a consensus MC1R allele. By contrast, the ASIP TG/TG diplotype, which also is known to be associated with melanoma risk, was linked to a 5-fold increase in hazard of death from melanoma. The findings indicate a complex but influential role for pigmentary genetic loci in melanoma outcomes.

What's new?

This is the first study to examine whether glucose control as measured with HbA1c level and chronic liver diseases are associated with hepatocellular carcinoma (HCC) in Chinese type-2 diabetic patients. A positive association was found between HbA1c level and HCC risk, with a level of HbA1c ≥ 9% being a predictor of HCC risk. Furthermore, the level of HbA1c ≥ 9% and chronic liver diseases were significantly jointly associated with HCC risk. HCC incidence is rapidly increasing worldwide, and lifestyle or treatment interventions to maintain a satisfactory control over glycemia and chronic liver diseases may reduce the burden of HCC.

What's new?

There is emerging interest in understanding the role of progesterone receptors (PRs)—of which two isoforms have been described, PRA and PRB—in breast cancer. This study investigates the proliferative effect of antiprogestins depending on the relative expression of PRA and PRB. The results provide mechanistic evidence that the responsiveness of breast cancer to antiprogestin treatment is determined by the ratio of expression of PRA and PRB isoforms. Antiprogestins selectively inhibit PRA-overexpressing tumors by increasing the SMRT/AIB1 balance at the CCND1 and MYC promoters. The results may pave the way for a personalized use of antiprogestins in breast cancer treatment.

What's new?

The nuclear bile acid receptor FXR has been shown to exert tumor-protective functions in the liver and intestine. This study provides evidence that the liver-derived plasma protein and tumor suppressor histidine-rich glycoprotein (HRG) is a novel and most likely direct transcriptional target gene of FXR. Plasma HRG levels in healthy male volunteers increased 1.6-fold after daily administration of 0.5 mg/kg of the non-steroidal FXR agonist PX20606 for seven days, raising the possibility that potent FXR agonists might be beneficial in serious health conditions with reduced HRG such as hepatocellular carcinoma but also other solid cancers, liver failure, sepsis, and preeclampsia.

What's new?

The unique irradiation geometry of synchrotron microbeam radiation therapy (MRT) allows for the delivery of very high doses of radiation to brain tumors, with limited damage to the surrounding normal tissue. Interestingly, MRT induces a wide spectrum of transcriptomic changes in tumor and normal tissue in the brain. Here, significant transcriptomic modulation was detected for 316 genes in intracranial tumor tissue following MRT. Among those genes, 30 were specific to brain tumors, remaining undetected in normal tissue before and after MRT. Mechanisms associated with changes in those transcripts may augment or limit the effectiveness of MRT.

What's new?

One strategy to thwart lung cancer is inhibiting the epidermal growth factor receptor, EGFR. As always, though, some cancer cells develop resistance to this treatment with the help of a mutation, T790M, in the EGFR kinase domain. In this paper, the authors describe a new way to overcome that acquired resistance. Combining next-generation EGFR inhibitors with SAHA, a histone deacetylase inhibitor, boosted cancer cell death by both apoptosis and autophagy; furthermore, the combined treatment slowed tumor growth in xenograft model better than EGFR inhibitors alone.

What's new?

Ultrasound is commonly used to assess “early” responses to neoadjuvant chemotherapy, which is given before primary treatment of breast cancer to shrink the tumor. However, its remains unclear whether ultrasound can accurately predict the absence of all residual invasive cancer in the breast tissue (pathological complete response). The authors performed an extensive study using Response Evaluation Criteria in Solid Tumors and World Health Organization criteria for response. Accuracy was higher than previously reported, indicating that the role of ultrasound is currently underestimated in response assessment guidelines.