What's new?

Only palliative therapies are presently available for advanced, metastatic prostate cancer. Growth hormone-releasing hormone (GHRH) is produced in prostate tumors where it acts through receptors different from those in the pituitary. The present study sheds more light on the inhibitory action of GHRH antagonists on the growth of PC3 human androgen-independent human prostate cancers. GHRH antagonists were also shown to reduce the expression of angiogenic and metastatic factors. Consequently, GHRH antagonists could be considered for the development of new therapies for advanced androgen-independent or castration-resistant prostate cancer.

What's new?

While the enzyme inhibitor FK866 is known to have anti-tumor activity against various human cancer cells, researchers haven't fully understood how or why it works. The authors found that FK866 is able to induce apoptosis in leukemic cells by indirectly activating the tumor-suppressor protein p53. FK866 might, therefore, be useful in combination with existing chemotherapies in the treatment of p53-positive leukemias, and possibly also in drug-resistant leukemias that overexpress p53 inhibitors such as the sirtuin SIRT1.

What's new?

Szczyrba and colleagues previously identified several microRNAs that are dysregulated in prostate cancer cells. They now pinpoint the target mRNAs for some of them. They show that expression of Zinc Finger protein 217 (ZNF217), a known proto-oncogene in breast or colon carcinoma, is regulated by miR-24. Because miR-24 is downregulated in prostate cancer cells, ZNF217 levels are increased, providing a novel link between ZNF217 and prostate cancer.

What's new?

While the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has been implicated in cancer, its biological relevance in malignant disease has remained unclear. Here, MIF was discovered to serve as a novel independent predictor of clinical outcome in patients with surgically resected pancreatic tumors. Furthermore, MIF enhanced the aggressiveness of pancreatic tumors by inducing epithelial to mesenchymal transition (EMT) and caused resistance to the chemotherapeutic drug gemcitabine. The findings indicate that MIF may be a candidate therapeutic target for this lethal malignancy.

What's new?

Rhabdomyosarcoma (RMS) is a soft tissue cancer that primarily affects children and adolescents. RMS cells overproduce specificity protein transcription factors Sp1, Sp3, and Sp4. The NSAID tolfenamic acid (TA) downregulates Sp in other cancers. The authors tested TA on RMS cells, both in cell culture and in mice, and showed that it effects a drop in Sp gene expression and slows the growth of the cancer cells. TA, which is less toxic than the treatments currently used for RMS, could thus provide a better treatment for the disease.

What's new?

Although gene fusion events involving the transcriptional regulator ERG occur in the majority of prostate cancers, they remain uncharacterized molecularly. Here, in a cohort of 640 prostate cancer patients, protein levels of SLC45A3, an ERG fusion partner, were discovered to be down-regulated, while ERG gene rearrangements were correlated with ERG protein overexpression. These molecular features may be characteristic of a subclass of ERG-rearranged prostate cancers and could be relevant for assessing disease prognosis.

What's new?

Platelet-derived growth factor (PDGF) signaling pathways are crucial for the migration of metastasis-promoting mesenchymal stem cells (MSCs) to the tumor microenvironment in human colon cancer. In this study employing orthotopic transplantation of human MSCs and colon cancer cells in mice, inhibition of PDGF signaling with the drug imatinib was found to influence interactions between bone marrow-derived MSCs and tumor cells, suggesting that stroma-directed imatinib therapy could be effective against colon cancer progression.

What's new?

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, for which the clinically and pathologically relevant immunohistochemical features have been characterized. By comparison, the genetic alterations underlying the disease remain unclear. In this study, a distinct profile of oncogenic mutations in the RAS/RAF and PI3K/AKT pathways in EMPD tumors was elucidated. Tumors harboring PIK3CA and AKT1 mutations were found to frequently correlate with severe disease phenotype. The data provide novel insight into the genetic mechanisms of EMPD and identify potential therapeutic targets.

What's new?

REST is known as a transcriptional silencer with tumor suppressive functions in non-neuronal cells. However, recent findings point towards a tumor-promoting function of REST. The authors identify a molecular mechanism how REST promotes non-neuronal cancers by regulating levels of the Telomeric Repeat Binding Factor 2 (TRF2). These results provide novel insight into the versatile function of REST in non-neuronal cancers and link the factor with the DNA damage response via TRF2.

What's new?

Elevated lactate production is associated with poor survival and immune escape in malignant glioma. In this study, the nonsteroidal anti-inflammatory drug diclofenac was found to decrease lactate production in murine glioma cells and to inhibit the expression of the lactate-encoding gene lactate dehydrogenase-A (LDH-A) in vitro. While diclofenac exerts a direct inhibitory effect on T-cells, preventing its co-administration with active immunotherapies, it may be an attractive agent for counteracting local immune suppression in malignant glioma.

What's new?

Molecular markers for predicting oral cancer development in premalignant oral leukoplakia are urgently needed. The current study is the first to demonstrate that the expression of cancer stem cell markers ALDH1 and CD133 correlate with a high risk of malignant transformation in a large series of patients with premalignant oral leukoplakia who received a long-term follow-up. The findings suggest that the two molecular markers may serve as predictors to identify oral premalignant lesions with a high risk of oral cancer development.

What's new?

This is the largest study to date to confirm the prognostic value of the preoperative polypeptide-specific antigen (TPS) level as a serum tumor marker in breast cancer. The study also demonstrated for the first time that preoperative TPS is a significant prognostic marker for survival, especially in luminal A subtype patients. The preoperative TPS level may thus be combined with an established prognostic factor for clinical use to better predict patient outcomes, improve ineffective treatments, and facilitate the individualization of therapy for breast cancer patients.

What's new?

Assessing the prognosis of human papillomavirus (HPV)-associated oropharyngeal cancer has been limited by the inability of existing assays to distinguish between the molecular signatures of different HPV types. Here, 13 high-risk HPV types were profiled successfully using an algorithm-based real-time RT-PCR method. In addition, the expression signature of the cyclin-dependent kinase inhibitor p16 was found to specifically reflect HPV transcriptional activity, indicating that p16 could be used as a surrogate marker for HPV activity in oropharyngeal cancer.

What's new?

Melatonin has been proposed as a key mediator of chronodisruption, a disturbance that may underlie the probable carcinogenic effects of shift-work in humans. In this prospective study, sleep duration and pre-diagnostic melatonin levels were investigated in association with breast cancer risk in an Asian population. Risk was not significantly related to sleep duration or melatonin levels derived from randomly timed spot urine sample suggesting that randomly timed, spot urine is not appropriate as a surrogate marker of melatonin profile in humans, despite earlier evidence supporting this possibility.

What's new?

This research describes the association of genetic variation in interleukin genes with risk for colon or rectal cancer, as well as with survival from these diseases. Few of these associations were modified by lifestyle factors such as obesity, smoking, or NSAID/aspirin use, although several associations were modified by current estrogen use. As a whole, the data suggest that interleukins play a role in both risk and survival for colon and rectal cancers, and set the stage for future studies of specific mechanisms involved.

What's new?

In Chile, cervical cancer mortality is four times that in developed countries. The authors evaluated screening procedures in Chile, to find out whether prevention could be improved by incorporating HPV typing as well as Pap testing. Currently, the cervical cancer prevention program in Chile relies upon Pap testing, but the effectiveness of the test depends on the skill and training of the providers. The authors tested 8000 women using both Pap and HPV testing, and they report that HPV testing showed much higher sensitivity than Pap testing, suggesting that HPV testing be incorporated into public health screening procedures.

What's new?

Data on lifelong occupational history collected as part of a population-based study conducted in France was used to investigate the role of night work in breast cancer. The results indicate that night work increases breast cancer risk, particularly in women who worked night shifts before their first full-term pregnancy. The findings suggest that incompletely differentiated cells of the mammary gland before a woman's first childbirth may be particularly susceptible to the potentially carcinogenic effects of circadian disruption.

What's new?

The study estimates the association between the vaccination status of teenage girls against the human papillomavirus and the participation of their mothers in cervical cancer screening using nationwide registries. The authors also quantify the projected impact of the positive association between girls' HPV vaccination and their own screening later in life on the future incidence of cervical cancer. Finally, they identify groups at risk for non-participation in cancer prevention with the view to assist the design of future interventions. There is concern that the same women who did not receive the vaccine against the human papillomavirus as teenagers will also not participate in cervical cancer screening as adults. The authors show that participation is indeed selective, but that the two cervical cancer prevention programs are nonetheless set to complement each other, ensuring the cost-effectiveness of HPV vaccination.

What's new?

Cancer of unknown primary site (CUP) has a high rate of mortality. If the primary site of these metastases could be identified more often, patients could receive more effective treatment. The data in this study support the hypothesis that metastases to the lymph nodes in CUP often originate in the organs that drain into those lymph nodes. The authors also found that lung cancer was frequently the cause of death in CUP, and they stress the importance of thoroughly investigating the lung as a primary source of CUP.

What's new?

Long and short cytosine-adenine (CA) repeat polymorphisms in the estrogen receptor-beta gene (ESR2) have been associated with increased colon cancer risk in postmenopausal women of different ages and ethnicities. In the present study, long ESR2 CA repeats were found to increase risk in postmenopausal Japanese women under age 75. Low BMI and high isoflavone intake augmented risk, indicating that aging as well as estrogen modification may influence ESR2 CA repeat polymorphism colon cancer pathogenesis.

What's new?

Low-grade squamous intraepithelial lesion (LSIL) is a common cytologic finding in cervical screening, with only 10–20% of LSIS patients showing significant histologic abnormalities and many of these cytologic changes regressing spontaneously without precancer. To date, however, no markers or molecular tests have adequately enhanced the positive predictive value of LSIL for clinically relevant cervical precancer. The authors showed that testing for high-risk human papillomavirus (HPV) DNA in women with LSIL is effective in identifying high-grade cervical lesions, thereby avoiding unnecessary referrals to colposcopy and potential over-treatment of non-progressive lesions, especially for women over 40.

What's new?

Harnessing the ability of dendritic cells to activate immune processes and promote tolerance of antigens is of particular interest in the area of tumor immunotherapy and vaccine development. Here, a novel dendritic cell-based antitumour vaccine was generated by silencing the immunosuppressive tryptophan-degrading enzyme indoleamine-2, 3-dioxygenase (IDO). IDO silencing slowed tumor progression and limited the generation of T regulatory cells in a murine breast cancer model. The findings suggest that immunosuppressive gene silencing could be used to enhance the efficacy of dendritic cell-based vaccines.

What's new?

The BH3 mimetic ABT-263 has been evaluated in clinical trials for the treatment of small cell lung cancer (SCLC) but has demonstrated little success as a single agent. The problem may be that ABT-263 alone is ineffective. When the drug was used in combination with an immunotoxin in a resistant SCLC cell line, the cells were effectively killed. Acting together, the two agents showed remarkable cytotoxic synergy. The data suggest that both immunotoxins and ABT-263 should be considered for combination treatment.