What's new?

Persistent infection with Helicobacter pylori contributes to gastric diseases including chronic gastritis and gastric cancer. Although COX-2 and STAT3 are known to contribute to the initiation and progression of H. pylori-associated gastric inflammation and tumorigenesis, the crosstalk between COX-2 and STAT3 in H. pylori pathogenesis has yet not been identified. Here, the authors report that H. pylori rapidly triggers STAT3 signaling and induces STAT3-dependent COX-2 expression. COX-2 in turn regulates IL-6/STAT3 signaling. Thus, a positive feedback loop between STAT3 and COX-2 is at play in the basal condition and H. pylori infectious condition, and may also contribute to gastric tumorigenesis.

What's new?

Solid tumors inevitably develop oxygen-starved microenvironments, to which tumor cells become uniquely adapted. In some types of tumors, adaptation appears to be facilitated in part by oncogenic KRAS, whose expression is induced in hypoxic environments. In this study, KRAS was found to cooperate with hypoxia to potently induce the angiogenic factor adrenomedullin (ADM) in colon cancer cells. ADM was found to mediate colon cancer invasion in vitro, while its knockdown in vivo led to tumor suppression. The findings highlight the importance of the tumor microenvironment in the context of therapeutic target discovery.

What's new?

Partition-defective 3 (PAR-3) protein is implicated in the development and maintenance of cell polarity, the loss of which is associated with cell transformation in tumor development. The present study, based on experiments in clear cell renal cell carcinoma (ccRCC) cell lines, reveals that the PAR-3-encoding gene, PARD3, is amplified in R-180 cells, which are derived from an aggressive ccRCC. PARD3 amplification was associated with elevated PAR-3 expression and abnormal cytoskeletal organization, which was restored upon PARD3 knockdown. The results suggest that PAR-3 may help regulate cytoskeletal organization and thereby maintain cell polarity.

What's new?

Cervical cancer is caused by persistent infection with high-risk human papilloma virus types but how persistently infected tumor cells manipulate immune cells in their microenvironment remains an urgent open question. This study demonstrates that cervical cancer cells promote the recruitment of monocytes and actively reprogram their function during differentiation and maturation to dendritic cells. Impaired functions of reprogramed dendritic cells include downregulation of CCR7 expression, a chemokine receptor involved in lymph node homing, as well as upregulation of matrix metalloproteinase 9 expression, both caused by secretion of the cytokine IL-6 from cervical cancer cells. These findings point to IL-6 as a promising new target for adjuvant therapy in patients with cervical carcinoma.

What's new?

Karyotypic alteration is a driving force of cancer evolution, but its effects on the transcriptome are not well understood. In the present study, the pattern of genome alteration and expression dynamics during somatic evolution was interrogated using an immortalization model. The model revealed that major karyotypic alterations, such as structural or numerical changes, result in significant deviations in gene expression, suggesting that karyotype changes influence gene expression. The data further indicates that karyotype and transcriptome pathways are in constant flux during somatic cellular evolution and that this flux is essential for cancer formation.

What's new?

RAD51D mutations have recently been identified in breast (BC) and ovarian (OC) cancer families. Although RAD51D mutations are associated with hereditary OC, such an association is less clear in BC. This study determined the prevalence of germline RAD51D mutations in Spanish BC/OC families testing negative for BRCA1/BRCA2 mutations. RAD51D mutations were found in almost 1% (4/491) of BC/OC families. These families had only one OC case, with some carriers presenting BC, suggesting that RAD51D testing should be offered to all BC/OC families. The existence of an increased risk of BC should be considered when setting the follow-up and prevention measures.

What's new?

Familial thyroid cancer is highly heritable and far more aggressive than the sporadic variety, but so far, no gene has been fingered as the culprit. In this paper, the authors tested several common SNPs that had been linked to sporadic thyroid cancer, and traced the way they travel in families that inherit the disease. One region, near the gene FOXE1, did associate with the disease, but no causal variants have yet been identified.

What's new?

Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16^INK4A is often used as a surrogate marker for HPV infection, although there is still controversy with respect to its reliability. The aim of this study was to determine if p16^INK4A overexpression can accurately predict both high-risk and low-risk-HPV presence in (pre)malignant and benign head and neck lesions. This results show that p16^INK4A overexpression is a reliable surrogate indicator for high-risk-HPV16 in oropharyngeal squamous cell carcinomas (OPSCC) and tonsillar dysplasias, but not for low-risk-HPV6/11-positive benign and premalignant tonsillar and laryngeal lesions.

What's new?

The bacteria H. pylori is the strongest known risk factor for gastric cancer, but only a small percentage of those infected ever develop cancer. To help predict who those will be, researchers have identified several markers that associate with gastric cancer. This study sought to expand on earlier data associating the presence of antibodies to these markers with the risk of developing gastric lesions and cancer in a high-risk population. Patients with antibodies for either CagA and GroEL were more likely to have gastric lesions progress to cancer, as were people who had antibodies for more than three markers. These tests could be useful in assessing risk among those with H. pylori infections.

What's new?

Some colorectal cancers exhibit an inflammatory response called the Crohn's-like lymphoid reaction (CLR), in which lymphoid aggregates form around tumors. It's not clear yet, however, what these aggregates reveal about cancer prognosis. In this study, the authors report a new method for quantifying the density of the CLR; they then compared the CLR with the prevalence of different immune cell types in the tumor area. The number of mature DC cells correlated closely with the density of the lymphoid aggregates, suggesting that the CLR plays a role in adaptive tumor immunity. High CLR density correlated with low tumor stage, but also correlated with better survival regardless of stage.

What's new?

The most common variant of cutaneous T-cell lymphoma is mycosis fungoides (MF). In MF, expression of the FoxP3 transcription factor decreases. This paper looked at the relationship between FoxP3 and another transcription factor, HIF-1 α, and their influence on MF. In skin lesions from patients with the disease, the authors found excess HIF-1 α compared with controls. They also observed that HIF-1 α levels rise, and FoxP3 levels fall, as the disease progresses. When they blocked HIF-1 α, more FoxP3+ cells arose, suggesting that overexpression of HIF-1 α does reduce FoxP3 levels and perhaps promote disease progression.

What's new?

Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action for the anti-EGFR drug cetuximab. Oncogenic mutations in KRAS confer resistance to cetuximab treatment in colorectal cancer (CRC); however, it has been unclear whether these mutations impair cetuximab-mediated ADCC. In this study, the authors found that they do, and also identified an alternative, perforin-independent mechanism by which this occurs.

What's new?

It is well known that a tumors' microenvironment can impair the anti-tumor immune response. The culprits are usually assumed to be various suppressor cells and cytokines. In this study, however, the authors found that seemingly innocuous, naïve T cells may also play a significant role—simply by accumulating and possibly out-competing activated effector cells within the tumor. A better understanding of the signals produced by the tumor microenvironment may allow researchers to alter this T-cell pool, thus enhancing the immune response.

What's new?

While liquid based cytology (LBC) and automation assisted reading of cytological samples have been widely implemented in cervical screening, little is known about how cytological abnormality proportions change by age as a consequence of new technology implementation. This population-based study evaluated age-dependent changes after routine implementation of LBC, being one of the first studies analyzing the cervical cytology outcomes of different brands. The impact of LBC implementation varied considerably with age, with LBC tending to widen the age-specific differences in the proportions of abnormal samples. Imaging assisted reading, however, appeared to increase the proportions of abnormal cytology across age groups.

What's new?

Serum antibodies against tumour-associated antigens (TAAs) have shown promise as biomarkers for early cancer detection. In this study, the authors asked whether autoantibodies to specific glycopeptides correlated with colorectal cancer (CRC). They found that an assay for autoantibodies to aberrant glycosylated MUC1 predicted CRC with 95% specificity—but with low sensitivity. However, when the assay combined MUC1 with p53, the sensitivity increased to 32%. These finding suggest that a combination of antibody signatures may eventually enable a biomarker panel for the early detection of CRC.

What's new?

The identification of biomolecules associated with hepatocellular carcinoma (HCC) could greatly improve screening for early disease detection. Ubiquitous mitochondrial creatine kinase (uMtCK) could be a promising marker in this context, though its relevance in HCC is unclear, as it may be associated with mitochondrial stability rather than carcinogenesis. Here, in transgenic mice susceptible to the loss of liver mitochondrial integrity, uMtCK was found to be elevated in HCC tissue but not in non-tumorous liver tissue. Increased uMtCK was further linked to reduced expression of ASB9 and elevated risk for HCC-related death.

What's new?

The inverse association of glioma with seroreactivity to varicella virus (VZV) suggests that VZV serological response may help protect against brain tumors. In the present study, the serological response to VZV was deconstructed through assessment of antibodies to specific VZV proteins in glioma cases and controls. The data reveals distinct associations for individual proteins and a strong interaction with allergy pathology, in which VZV seroreactivity in highly allergic individuals was associated with a reduced occurrence of glioma. The findings warrant further research into viral etiologies and the role of immune mechanisms in glioma.

What's new?

Risk-reducing surgery involving a combination of hysterectomy and bilateral salpingo-oophorectomy (BSO) is recommended for women who are BRCA-positive. However, it remains unclear whether the combined approach is beneficial for women actually diagnosed with breast cancer. Here, analysis of data on 21,067 women diagnosed with primary breast cancer in Queensland, Australia, between 1997 and 2008 shows that risk-reducing surgery cut mortality in half for premenopausal patients. Prophylactic surgery, however, did not appear to benefit postmenopausal patients. The findings challenge the idea that non-invasive endocrine treatment is as effective as prophylactic surgery for premenopausal women with breast cancer.

What's new?

Women who don't have routine screening face a significantly increased risk of developing cervical cancer compared to those who do. Would these women be more likely to participate in screening if they could simply mail in a test from home? In this study, the authors found that the answer was yes: Offering a human papillomavirus (HPV) self-test for to non-attendees in a well-run cervical-cancer screening program increased participation, and will likely lead to no additional cost to the health-care sector.

What's new

Some HPVs contribute to cervical cancer, but other types, called genus beta HPVs, commonly infect the skin and are associated with squamous cell carcinoma. In this study, the authors investigated the association between genus-beta HPV DNA found in plucked eyebrow hairs and the presence of SCC, as well as the presence of genus-beta HPV DNA in the tumor tissue. They found that the viruses were found in eyebrow hairs more often in those with cancer than those without, suggesting that the virus plays a role in cancer development, and could make a good therapeutic target.

What's new?

Cytoreductive nephrectomy has been shown to confer a survival advantage in randomized trials of patients with metastatic renal cell carcinoma (RCC) receiving immunotherapy. It is unknown, however, whether it still affords patients a survival benefit above that provided by newer systemic therapies. This study reports that, despite a lower proportion of patients now receiving cytoreductive nephrectomy, it remains associated with improved survival in multivariable and propensity-score matched cohorts, conferring a greater apparent benefit in the targeted therapy era. Prospective randomized trials are needed to confirm the benefit of cytoreductive nephrectomy among patients with metastatic RCC treated with novel targeted therapies.

What's new?

While radiation exposure from the 1986 Chernobyl accident led to dramatic increases in thyroid cancer among people living within the vicinity of the reactor, health consequences for populations outside the former Soviet Union remain unclear. Here, the effect of Chernobyl fallout over a period of nearly 20 years in Finland was investigated using individual-level residential and cancer data. Only a single malignancy, colon cancer in women, was found to be associated with radiation exposure from the accident. The findings support current thinking that the possible impact on cancer incidence at the population level is likely to remain small.

What's new?

The quadrivalent human papillomavirus (HPV) vaccine is the current standard for most immunization programs. However, a nonavalent HPV vaccine will soon be available. While this newer vaccine may be effective in preventing cervical and other cancers, will it also be cost-effective? In this study, the authors found that the nonavalent vaccine will likely be the most cost-effective of the two alternatives, assuming that its efficacy against HPV-types 16/18 is comparable to that of the quadrivalent vaccine.