What's new?

The present study aimed to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analysis of the low-abundance transcriptome. Aberrant cancer-specific intracellular pathways such as the wnt/hedgehog and the PI3K and genes like CTBP1 were identified. Most of the differentially expressed low-abundance transcripts were not detected when the whole transcriptome was analyzed. CTBP1 was further identified as a novel target for sensitization of gastric cancer cells to chemotherapeutic drugs that have shown limited effectiveness in the clinics. The study of the low-abundance transcriptome might help to improve response to mainstay treatments and develop novel therapies.

What's new?

In the quest to bring the body's own immune defenses to bear against cancer, researchers have investigated the receptor TLR9, a toll-like receptor that initiates a cascade of immune responses. Although activating TLR9 provided a boost to chemotherapy in animal models, further trials showed no benefit over chemotherapy alone. The current study compared lung cancer in mice with and without TLR9 inactivation. The authors found that expressing TLR9 promoted angiogenesis and cancer progression, and reduced survival. Perhaps understanding how TLR9 boosts angiogenesis can help refine its development as an anti-cancer agent.

What's new?

Hepatocellular carcinoma (HCC) is a deadly disease, with a small percentage of patients qualifying for liver resection or transplantation, the only potentially curative treatments. Improvements in treatment and prevention, however, may be possible through a better understanding of how cirrhosis predisposes individuals to HCC. This study implicates platelet derived growth factor-C (PDGF-C) as a possible driver of stromal changes that lead to epithelial neoplasia in the liver. In transgenic mice, hepatic PDGF-C expression altered the liver microenvironment, promoting carcinogenesis. The transgenic PDGF-C pre-clinical HCC model may be useful for testing novel therapies that target the hepatic tumor microenvironment.

What's new?

This study aimed to investigate whether a previously-developed ex vivo lung cancer 4D model—which forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern—is a better mimic of the natural history of lung cancer growth in patients. The authors found that the 4D model leads to change in gene expression in the human lung cancer A549 cell line that correlates with poor survival in patients. Since patients with larger tumors have a worse rate of survival, the 4D model may be a good mimic of natural progression of tumor growth.

What's new

Commonly absent in hepatocellular carcinoma is the liver protein glycine N-methyltransferase (GNMT), a proposed tumor suppressor. While GNMT and its role in preventing tumor formation have been studied extensively, this study reveals a hitherto unknown mechanism by which the protein may participate in tumor suppression. In knockout mice and engineered cell lines, GNMT deletion led to DNA damage in conditions of folate depletion. Furthermore, its overexpression not only improved cellular methylation kinetics but also enhanced DNA synthesis and repair, in both in vitro and in vivo model systems.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent disease for which survival has not improved over the last decades. Here, the authors found that miR-134 was highly expressed in HNSCC tumor tissues. High miR-134 expression was associated with nodal metastasis and mortality in patients and acted as an independent predictor of poor survival. Mouse studies confirmed the role of miR-134 expression in tumorigenesis and cervical lymph node metastasis. miR-134 was found to target the WWOX tumor suppressor in HNSCC cells, suggesting that anti-miR-134 or WWOX induction strategies could serve as a potential intervention against HNSCC genesis or metastasis.

What's new?

The bacteria H. pylori is known to cause gastric cancer, but genetic changes can also contribute, particularly in high-risk populations. Identifying these genetic changes in patients could help clinicians make more accurate prognosis of gastric cancer. These authors looked at variation in genes of the Fas signaling pathway, searching for a connection with GC in a high-risk Chinese population. They found that changes in ten specific genes contributed to GC risk in the population, suggesting further work to investigate the functions of those genes.

What's new?

When two phenotypically distinct, yet genetically related lymphomas occur in one patient (composite lymphomas), this represents a unique opportunity to study the multistep transformation process in the pathogenesis of B cell lymphomas. Here, the authors present a case consisting of a Hodgkin and a mantle cell lymphoma. The two lymphomas were clonally related and carried the genetic translocation with the cyclin D1 gene translocated into the IGH locus, a characteristic for a mantle cell lymphoma. They further showed an identical TP53 function-impairing mutation, and later independently acquired a TP53 heterozygous deletion (convergent evolution). The authors see this close genetic relationship as evidence for subclonal evolution of a Hodgkin lymphoma from a mantle cell lymphoma.

What's new?

Although the DNA of Merkel cell polyomavirus (MCV) is regularly found in most Merkel cell carcinoma tumors, it is also common in healthy skin. The presence of MCV-specific antibodies is higher among Merkel cell carcinoma patients, but the prospective value of this finding has not been formally established. Here, the authors demonstrate that the risk of future Merkel cell carcinoma is increased among subjects with high levels of MCV antibodies, especially in females, thus supporting the model that MCV is etiologically linked to Merkel cell carcinoma.

What's new?

Here the authors describe the complex role of the oxygen sensor PHD2 in tumor-associated immune cells in a conditional PHD2-deficient mouse line. They demonstrate that the observed reduced tumor volume is a consequence of opposing changes including the drastic down-regulation of numerous pro- as well as anti-tumoral genes and an imbalance between enhanced cell death and greater proliferation of tumor cells. They confined this complex phenotype to the crosstalk of PHD2-deficient myeloid cells and T-lymphocytes. The findings reveal a multifaceted role for PHD2 in hematopoietic lineages during tumor development and might have important implications for the development of tumor therapies.

What's new?

Cancer immunotherapy often fails because of the immunosuppressive environment of the tumor and the lack of infiltration with antigen-specific T cells. This study demonstrates that low-dose tumor irradiation combined with a cancer vaccine can change the intratumoral immune balance in favor of antitumor immune activation. Therapeutic immununization of mice with a Semliki Forest virus-based vector expressing human papilloma virus E6/E7 oncoproteins resulted in an 85-fold increase in the ratio of antitumoral CD8+ T cells to immune suppressive myeloid-derived suppressor cells at the tumor site. This raises the hope that a combination regimen might be a promising strategy to enhance the success of therapeutic tumor vaccination.

What's new?

Galectin-1 is a glycan-binding protein that plays a major role in the aggressiveness of glioblastomas (GBMs), via a number of different mechanisms. In different types of tumors, galectin-1 has been demonstrated to contribute to tumor-mediated immune evasion. Whether glioma-derived galectin-1 also contributes to glioma-mediated immune evasion is unknown, however. In this study, the authors found that glioma-derived galectin-1 plays an important role in the regulation of myeloid cell accumulation within the tumor microenvironment. They also found that silencing of galectin-1 could improve glioma-bearing mice survival. Intratumoral silencing of galectin-1 may therefore offer a promising adjuvant treatment modality for patients with high-grade glioma.

What's new?

Serres et al. have established a model of brain metastasis in the rat that enables serial in vivo MRI studies. They demonstrate differential signal changes across structural and vascular MRI modalities that are associated with either micrometastatic or advanced metastatic growth. The authors also demonstrate the sensitivity of fMRI to early metastatic growth. They propose, therefore, that the use of multimodal MRI may yield greater insight into the stage and progression of brain metastases than single modality MRI.

What's new?

Women with low-grade cervical intraepithelial neoplasia 1 (CIN1) detected by positive Pap smear but accompanied by negative colposcopic biopsy present unique challenges for follow-up, especially since CIN1 is known to often regress. The situation could be helped in part through the use of a biomarker for CIN1 progression, such as p16 overexpression. This study shows that p16 has low prognostic sensitivity for patients with CIN2+ (CIN2 or worse) but is associated with elevated risk for these advanced conditions. The data suggest that p16 overexpression may be useful in evaluating the intensity of follow-up needed after a negative colposcopy.

What's new?

Missed detection of metastases in sentinel lymph node biopsy for node-negative breast cancer, which is notoriously difficult to diagnose, may lead to additional surgeries. So, to improve detection rates, the authors of this study developed a technique known as the semi-dry dot-blot (SDB) method, which employs anti-pancytokeratin antibody to identify cancer cells in lymph node tissue. Clinical results reported here show that the SBD method is accurate at least 98 percent of the time for several malignancies. In nodenegative breast cancer, accuracy was a remarkable 96.6 percent. The short time required for the test could help speed diagnosis.

What's new?

Breast cancer awareness programs can bring great benefits for women and the communities they live in. But just how cost-effective these programs are in low-and-middle-income countries, where breast cancer is an increasing public health concern and where outreach can be challenging, has been unclear. Fortunately, the message from this study, which centered on the Ashanti region of Ghana, is that breast cancer awareness programs are paying big dividends for women's knowledge, attitudes, and practice. Women who attended programs not only enjoyed higher knowledge scores than their non-participant counterparts, but also were more likely to perform breast self-examinations.

What's new?

The past decade has seen the rapid development of detection techniques for disseminated tumor cells (DTCs) in solid tumors. While DTCs detection in the bone marrow of breast cancer patients is associated with poor outcome, data on hematogenous tumor cell dissemination in cervical cancer are scarce. This is the largest study on the detection of DTCs in the bone marrow of patients with primary cervical carcinoma. The results show that dissemination into bone marrow is a common phenomenon in cervical cancer and correlates with higher tumor load, but lacks prognostic relevance. Alternative methods may be needed to establish prognostic potential.

What's new?

Do anti-epileptic medications increase the risk of cancer? The question has been debated for decades with no clear answer. In this study, the authors used a large Danish registry to tease out the contribution of medication use versus epilepsy alone to cancer rates. Their findings indicate that anti-epileptic medications may not be as strongly carcinogenic as has been feared, and suggest that some aspect of epilepsy itself—or perhaps an etiologic factor common to both epilepsy and cancer—is responsible for the previously observed association between these medications and increased cancer risk.

What's new?

About 3-5 percent of colorectal cancer cases are associated with a highly penetrant dominant inherited syndrome. However, established guidelines for the surveillance of Familial Colorectal Cancer (FCC), in which the Polyposis syndromes and Lynch syndrome have been excluded, are lacking. This study suggests that FCC and late-onset FCC (LOFCC) patients should be managed with five-yearly colonoscopies between ages 30 and 40, with more intensive surveillance in individuals who develop multiple or high-risk adenomas. Little evidence was found to support intensive screening before age 30.

What's new?

Although the H.pylori bacteria is the primary cause of gastric cancer, in some cases the Epstein-Barr virus also appears to be involved. In this study, the authors compared smoking and alcohol use between patients with EBV-positive and EBV-negative gastric cancers. No association was found with alcohol use, but smokers were more likely to have EBV-positive cancer.

What's new?

Endometrial thickness is related to obesity and menopausal hormone use, factors associated with a higher incidence of breast and endometrial carcinomas. Given these associations, the authors of this study investigated whether endometrial thickness was independently associated with incident breast or endometrial carcinoma risk. In a cohort of 1,272 women, an endometrial thickness greater than five millimeters was associated with a two-fold increase in risk for breast carcinoma and a five-fold increase in risk for endometrial carcinoma.

What's new?

Non-small cell lung cancer is often associated with co-existing chronic obstructive pulmonary disease. Smoking is a common risk factor for both diseases independently, but here the authors studied how smoking affects the risk to develop the combined disease. They show that ex-smokers and smokers have an ∼5–10-fold higher risk to develop the combined disease as compared to developing cancer alone. Smoking dosage was the most important risk factor for the combined disease, especially in women and among patients with a squamous cell carcinoma subtype, pointing to gender- and cancer subtype specific influences on the combined disease.

What's new?

The impact of alcohol consumption or smoking on prostate-cancer risk has been unclear. Using a large, prospective study, the authors investigated the association between these activities and prostate cancer according to stage at diagnosis. They found that alcohol was associated with advanced disease. Both alcohol and smoking were also associated with advanced prostate cancers that were detected by subjective symptoms. These results suggest that abstinence from alcohol and prohibition of smoking might play an important role in the prevention of advanced prostate cancer.

What's new?

The battle against cancer is physically and mentally taxing for many patients and can lead to declines in quality of life. Here, health-related quality of life (HRQOL) data indicates that patients with locally recurrent rectal cancer (LRRC) score worse on Future Perspective and Physical, Social, and Sexual Function measures than healthy individuals and patients with non-advanced disease or locally advanced rectal cancer. Fewer than 50 percent of men and 35 percent of women with the disease were sexually active following operative clinical courses, and only a small number reported the use of aids to improve sexual function.

What's new?

The tyrosine kinase inhibitor imatinib has become the standard therapy for Chronic Myeloid Leukemia (CML). However, imatinib is not curative since most patients who discontinue therapy relapse, indicating that leukemia initiating cells are resistant. Here the authors demonstrated that arsenic and interferon alpha (IFN) inhibited the clonogenic activity of human primary CML cells. In a murine CML model, arsenic/IFN sharply diminished transplantation of CML cells, pointing to exhaustion of CML initiating cells. These studies plea for clinical exploration of this combination, knowing that IFN and arsenic have both previously shown clinical activity in CML, alone or in combination with imatinib.

What's new?

A considerable percentage of rectal cancers are resistant to preoperative chemoradiotherapy, which exposes patients to the potential side effects of both irradiation and chemotherapy without clear benefits. In this study, IL-6-stimulated expression levels of phosphorylated STAT3 were remarkably higher in chemoradiotherapy-resistant colorectal cancer cell lines. RNAi- and small molecule-mediated STAT3 inhibition sensitized to chemoradiotherapy in vitro in a dose-dependent manner, which led to a profound chemoradiotherapy-sensitization in a subcutaneous xenograft model. These results highlight a potential role of STAT3 in treatment resistance, and provide first proof of concept that STAT3 represents a promising novel molecular target for sensitizing resistant rectal cancers to chemoradiotherapy.

What's new?

Nearly 70 percent of women develop uterine leiomyomas, or fibroids, by age 50. While benign, these tumors are associated with a high incidence of conditions that adversely affect the pelvis and reproductive system. Despite their prevalence and morbidity, however, little is known about the mechanisms behind uterine leiomyoma formation. Whole exome sequencing of MED12 mutation-negative and mutation-positive uterine leiomyomas performed in this study reveals that these tumors do not carry recurrent mutations in genes other than MED12. The findings suggest that MED12 mutations alone may be sufficient for tumor development and shed light on benign tumorigenesis.