What's new?

Cucurbitacins are plant compounds that have been reported to have anti-cancer and anti-inflammatory activities. In this study, the authors tested the effect of combining cucurbitacin B (CuB) with standard chemotherapy agents against breast cancer cells. They found that CuB acted synergistically with those agents, to inhibit proliferation and increase apoptosis of breast-cancer cells in vitro. The combined therapy also markedly inhibited the growth of breast-tumor xenografts in mice, without increasing toxicity. Cucurbitacin B may thus provide a promising adjunct therapy for breast cancer treatment.

What's new?

Polycyclic aromatic hydrocarbons (PAHs) likely play a role in esophageal squamous cell carcinoma (ESCC) through the formation of DNA adducts. Variation in adduct formation among people with similar exposures is however not well understood. Here the authors show that female non-smokers in a population at high risk of ESCC had exceptionally high DNA adducts, with large inter-individual variations best explained by a combination of PAH phase I metabolizing genes and nucleotide excision repair (NER) capacity. This study shows the importance of studying a large set of combined polymorphisms and NER phenotyping together, and sheds light on PAH-related carcinogenesis in non-smokers.

What's new?

Smoking is a major risk factor for oropharyngeal cancer, but its impact on prognosis remains unclear. Likewise, there is uncertainty about whether smoking exposure impacts survival specifically for tonsillar cancers caused by human papillomavirus (HPV). While smoking was found to predict overall survival in this follow-up study of more than 400 patients with squamous cell carcinoma of the tonsil, interactions between HPV and smoking were statistically insignificant. Furthermore, the effect of smoking status on locoregional control and disease-specific survival outcome was of limited statistical importance.

What's new?

Chemokines are major regulators of cell motility previously implicated in cancer metastasis. Here, the authors link the C-C chemokine receptor 4 (CCR4) and its ligand CCL22 to lymph node metastasis of head and neck cancer cells by analyzing samples from patients and a mouse model. They find that the metastasis of cancer cells expressing CCR4 on their surface was promoted via the CCR4/CCL22 interaction in an autocrine and paracrine manner involving M2-like macrophages. These findings point to the CCR4/CCL22 axis as a potential new target for diagnostic and therapeutic development in head and neck cancer patients with lymph node metastases, a condition with otherwise poor prognosis.

What's new?

Malignant rhabdoid tumors (MRTs) are rare, extremely aggressive cancers occurring in young children primarily through inactivation of the SNF5 (INI1, SMARCB1) tumor suppressor gene. This study characterizes the first MRT cell lines derived from genetically engineered mouse models as well as the effects of genetic background on in vivo MRT development. These cell lines will provide critical new reagents for dissecting the mechanisms that drive the epigenetic instability found in these unique tumors as well as serve as biological models for testing novel drugs for the treatment of this aggressive disease.

What's new?

Resistance to platinum chemotherapy negatively impacts patient outcomes in ovarian cancer, and proficient DNA repair is an important mechanism underlying such resistance. With XRCC1 being a key player in DNA repair, here the authors set to investigate its expression in ovarian cancer. They show for the first time that XRCC1 expression is associated with adverse clinicopathological features in ovarian cancer and also predicts platinum resistance and poor survival outcomes. Using preclinical models, the authors also demonstrate that XRCC1 deficiency results in sensitivity to cisplatin and provide mechanistic confirmation that XRCC1 is a promising predictive biomarker in ovarian cancer.

What's new?

Hypoxia is one hallmark of many solid tumors. Prolyl-4-hydroxylase domain (PHD) enzymes contribute to initiating the cellular response to reduced oxygen availability, but their role in tumor development remains incompletely understood. Here the authors show that the cellular oxygen sensor PHD2 affects TGF-β1 processing in breast carcinoma cells. The data thus demonstrate that two tumor growth relevant pathways—namely, oxygen sensing regulated by PHD2 and tumor cell progression regulated by TGF-β1—are connected at the molecular level. The impact of this connection was further demonstrated in a SCID mouse tumor model and biopsies of 294 breast carcinoma patients.

What's new?

Short telomere length in human leukocytes has been associated with increased risk for certain types of cancer. Here, in a study of Chinese patients, susceptibility to esophageal squamous cell carcinoma (ESCC) in particular was linked to single nucleotide polymorphisms (SNPs) that alter leukocyte telomere length. Stratified analyses showed that associations between ESCC risk and risk alleles in SNPs rs621559 and rs398652 are more pronounced in males. The results highlight the significance of telomere polymorphism in cancer risk.

What's new?

Medullary thyroid carcinoma (MTC) is a rare thyroid tumor of parafollicular cells. In its familial form, it is caused by mutations in the RET proto-oncogene but the cause of sporadic forms is less clear. The authors examined the association of a common RET polymorphism (G691S) with MTC in a meta-analysis of published association studies and 93 still unreported MTC patients. G691S is the only non-synonymous variant in the RET gene accounting for enhanced RET signaling transduction. They report that the variant allele increases the risk for MTC in a recessive manner, which is more evident among females. This supports the notion that this common RET variant plays a critical role in overall MTC predisposition and that, likely, it also modifies the age at onset and gender effect on the disease risk.

What's new?

The development of chemotherapeutic resistance is thought to be driven largely by the dysregulation of apoptotic pathways, which promotes the survival of tumor cells. As a result, the selection of effective treatments for patients is facilitated by knowledge of the molecular factors that mediate resistance. That knowledge base is expanded here, by the discovery that elevated expression of the heat shock protein crystallin αB (CRYAB) may impair TRAIL- and cisplatin-induced apoptosis in ovarian tumors. The findings indicate that CRYAB could serve not only to identify patients with the highest probability of responding to certain treatments but also as a prognostic biomarker for ovarian cancer.

What's new?

Phase III clinical trials of human papilloma virus (HPV) vaccination have shown ≥95% efficacy against HPV16/18-associated cervical intraepithelial neoplasia (CIN) grade 2/3. Long-term surveillance is, however, needed to determine the overall vaccine efficacy against the most stringent cervical neoplasia end-points: CIN3 and invasive cervical carcinoma. This proof-of-principle study shows that passive cancer registry-based follow-up of HPV-vaccinated, placebo-vaccinated, and unvaccinated reference cohorts for long-term HPV vaccine efficacy is feasible. The preliminary observations are reassuring and suggest that results of vaccine efficacy against cervical cancer will be available within the next 5 to 10 years.

What's new?

A promising avenue of cancer research involves the use of molecules that increase the innate immune response against tumor cells. One such immunostimulatory molecule is Myd88. Paradoxically, however, Myd88 also appears to play a role in suppressing this immune response, via cells called “myeloid derived suppressor cells” (MDSCs). In this study, the authors examined Myd88′s role in MDSC activation, and found that a peptide that inhibits Myd88′s function in MDSCs can slow tumor growth. These results suggest a new strategy for increasing immunity against established tumors.

What's new?

Over the last decade liquid-based cytology (LBC) has replaced conventional cytology (CC) for cervical cancer screening in some countries. However, the debate on the superiority of LBC over CC is still ongoing. Here the authors carried out the first large randomized controlled trial in a non-organized cervical cancer screening system to compare LBC, alone and in combination with computer-assisted imaging technology, to CC in the detection of histologically confirmed cervical intraepithelial neoplasia. They found that in an opportunistic screening system LBC had a significantly higher relative sensitivity compared to conventional cytology. Addition of computer assistance to LBC did not further improve sensitivity.

What's new?

The polymerase chain reaction (PCR) enables the detection of DNA mutations in large pools of wild-type sequences. However, while PCR-based methods have advanced significantly, they remain relatively insensitive to minority alleles and low-level mutations. One such mutation is the drug resistance-associated T790M mutation in the epidermal growth factor receptor in non-small cell lung cancer, which was successfully detected in this study by coupling PCR with the thermostable restriction endonuclease BstU1. The sensitivity and one-step reaction of real-time digestion-PCR suggests that it may be more practical than direct PCR sequencing for the screening of minority somatic mutations in clinical samples.

What's new?

Widespread screening for prostate cancer means that early-stage cancers are frequently identified and treated regardless of aggressiveness. A good detection technique that can distinguish between aggressive and non-aggressive disease could prevent the unnecessary treatment of indolent disease, which can be simply monitored. Small non-coding RNAs, called miRNAs, have been used to differentiate cancers, but no single miRNA has been proven as a prostate cancer biomarker. In this report, the authors tested a set of four different miRNAs as a diagnostic and prognostic tool for prostate cancer. They found that their miRNA index successfully predicted diagnosis, even better than PSA, making it a promising avenue for larger studies.

What's new

This study is the first to identify poor documentation of family history and low referrals of endometrial cancer patients with possible Lynch syndrome to genetic services. Our study highlights the need for closer liaison between oncologists and geneticists to improve management of patients with hereditary endometrial cancer, and demonstrates that a family history questionnaire developed and tested in a research setting can be used in specialist clinics to improve identification of at-risk patients.

What's new?

The prognostic and diagnostic value of microRNA (miRNA) expression aberrations in lung cancer has been studied intensely in recent years. However, due to the application of different technological platforms and small sample size, the miRNA expression profiling efforts have led to inconsistent results. Using a meta-analysis of more than 1100 lung cancer and non-cancerous samples from 20 original studies, here the authors have identified a meta-signature of seven up- and eight down-regulated miRNAs. Their analysis highlights the challenges related with the development of miRNA-based tests and emphasizes the need for rigorous evaluation of the results before proceeding to clinical trials.

What's new?

According to the incessant ovulation hypothesis, later menarcheal age might decrease risk of ovarian cancer by decreasing the number of ovulations that occur in a woman's lifetime. However, the results of epidemiologic studies that have explored a possible association between menarcheal age and ovarian cancer have been inconsistent. Here, in a meta-analysis of 27 cohort and case-control studies, menarcheal age was found to be inversely associated with ovarian cancer risk. The authors suggest that larger studies should be performed in order to stratify results by cancer grade and histotype.

What's new?

Esophageal cancer is the fifth leading cause of cancer-related deaths in men and the eighth leading cause in women worldwide. This study examined the potential of using microRNA and inflammatory gene expression patterns as prognostic classifiers for esophageal squamous cell carcinoma (ESCC). The data showed that microRNA and inflammatory gene expression patterns are associated with prognosis in ESCC, suggesting that they could be developed, alone or in combination, as prognostic classifiers to guide therapeutic decisions. If these microRNAs or inflammatory genes are mechanistically involved in ESCC cancer progression, development of therapies based on these genes may also be appropriate.

What's new?

Cancer registries have provided population-based, comparative cancer-survival statistics since the 1950′s, and have identified significant differences across Europe. An important question has been: what factors are responsible for these differences? This study, called EUROCHIP-3, found that only 15% of all population-based cancer registries actually collect the three most important indicators for determining inequality in cancer care and survival in Europe. The authors recommend that extra resources be made available to improve this very efficient tool for comparing cancer burden and the effects of national cancer plans.

What's new?

Many factors can affect susceptibility to breast cancer, including menopausal status and diet. This study investigated the association between breast cancer and an adapted version of the “Mediterranean diet,” excluding alcohol. They found that the diet reduced the risk of breast cancer by 6% overall, and by 7% in postmenopausal women. For tumors lacking the estrogen or progesterone receptors, however, the diet reduced risk by 20% in postmenopausal women. This study also confirmed a previously observed lack of association between Mediterranean diet and breast cancer in premenopausal women.

What's new?

Bone morphogenic proteins (BMPs) appear to play a critical role in the progression and metastasis of breast cancer, but little is known about the relationship between BMP gene variants and disease risk. In this analysis of breast cancers among non-Hispanic white, Hispanic, and Native American women, single nucleotide polymorphisms (SNPs) in BMP genes were found to be associated with menopausal status and tumor estrogen receptor and progesterone receptor status. In addition, BMP genes were more commonly associated with breast cancer in women of Native American ancestry. The findings highlight the significance of BMP genetic variation as well as human genetic ancestry in breast cancer.

What's new?

Although vitamin D has been hypothesized to reduce cancer risk, epidemiologic evidence for prostate cancer is inconsistent. The authors previously observed in a prospective cohort study that prostate cancer risk was increased when circulating vitamin D was high. Here, they find that this association is substantially stronger when vitamin D binding protein (DBP) concentrations are also elevated. The data suggest that DBP, the primary vitamin D transporter, modulates the impact of vitamin D status on prostate cancer.

What's new?

Finding a molecular marker could help stratify patients into groups based on the likely severity of their disease. This paper evaluated the prevalence and prognostic significance of the cell membrane protein EPCAM. Some studies have associated loss of EPCAM with negative tumor characteristics and lower survival, but other studies have failed to support that. This study analyzed tumor microarray data from over 1000 different renal cell carcinoma samples. The authors found a significant correlation between the presence of EPCAM and favorable tumor features as well as increased overall survival.

What's new?

Therapeutic ultrasound may promote drug uptake in tumors through induced oscillation of injected microbubbles, which enhances microvessel permeability. However, sufficient stimulation with low-intensity ultrasound of injected circulating microbubbles, such as those used as diagnostic contrast agents, can also trigger profound antivascular effects in tumors, including reduced blood flow. In this study, antivascular effects induced using ultrasound with microbubbles in combination with an antiangiogenic therapy, metronomic cyclophosphamide, was associated with tumor growth inhibition and prolonged survival in mice. This novel approach, distinct from drug uptake promotion strategies, is amenable to implementation on clinical therapeutic ultrasound systems.

What's new?

Small molecule tyrosine kinase inhibitors (TKIs) directed against the VEGF receptor have been approved for use in cancer therapy. In several small trials, however, adverse venous thromboembolism events (VTEs) have been associated with the drugs. This meta-analysis of the incidence of VTEs across 14 studies found no significant increase in VTE risk with the use of VEGFR-TKIs. Rather, VTE risk in cancer patients was determined to be driven predominantly by tumor type, host factors, and concomitant usage of anticancer agents. The results could prove valuable for clinicians who use VEGFR-TKIs to treat patients with solid cancers.

What's new?

The causes of childhood brain tumors are largely unknown, but because they generally appear before age 5, prenatal factors seem likely to play a role. In this study, the authors collected data on the occupations of parents of children with and without brain tumors. Parental exposure to diesel exhaust, they found, increased likelihood of childhood brain tumors. Both maternal and paternal exposure increased the tumor risk, while exposure to other types of engine exhausts had no effect.