The Zika epidemic could be over in three years – but by then up to 93.4 million people may have been infected, including 1.65 million women of childbearing age, and tens of thousands of babies could be affected. But even if the epidemic fizzles out, this could be a temporary relief: a decade lat...
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Using novel computational and biochemical approaches, scientists have accurately designed and built from scratch 10 large protein icosahedra -- polyhedra with 20 faces -- similar to viral capsids that carry viral DNA. The designed structures are made of two different engineered proteins, present...
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Transmission of Zika virus (ZIKV) was first detected in Colombia in September 2015. As of April 2016, Colombia had reported over 65,000 cases of Zika virus disease (ZVD). We analysed daily surveillance data of ZVD cases reported to the health authorities of San Andres and Girardot, Colombia, bet...
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This June Disney released the anticipated Pixar Animation Studios sequel Finding Dory to earn the largest animated film opening receipts in North America ever. The popularity of the original Finding Nemo in 2003 led to reportedly increased demand for clownfish like Nemo for pets; some conce...
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The outcomes and recurrence patterns for patients with combined clinical stage II and III breast cancer treated with local but not regional radiotherapy after neoadjuvant chemotherapy (NAC) and surgery are poorly documented.
We performed a retrospective review of a prospectively collected database comprised of breast cancer patients who received NAC at our institution. 172 patients met the specified criteria of receiving NAC, surgery inclusive of axillary nodal dissection and post-operative local (but not regional) radiotherapy.
One hundred eleven patients (64.5 %) were of combined clinical stage II and 61 (35.5 %) stage III at diagnosis. 103 patients (59.9 %) were clinically node positive with 101 cN1. On post-NAC pathology 29 (16.9 %) patients had a complete response, 30 (17.6 %) were combined yp stage I, 104 (60.5 %) yp stage II and 9 (5.2 %) yp stage III. 77 (44.8 %) were node positive on post-NAC pathology, all ypN1. 52.3 % were treated with breast conservation. At a median follow up of 67 months, 56 patients experienced breast cancer recurrence and 47 had died with breast cancer the dominant cause. Actuarial 5 and 10 year estimated freedom from locoregional recurrence (FFLRR), freedom from distant metastases (FFDM), disease free (DFS) and overall survival (OS) were 90 and 83.5, 74.5 and 64, 69.5 and 56, 79.5 and 65 % respectively. The most common pattern of failure was distant alone (without local or regional failure). Regional failure as the only site of first failure occurred in just three patients but was a component of first failure in a further twelve. Predictive factors on multivariate analysis for FFLRR were clinical stage II and estrogen receptor positivity. Prognostic factors were ypN0 stage and estrogen receptor positive status.
Local radiotherapy alone may be reasonable for selected patients. Isolated distant recurrence is the dominant mode of failure for breast cancer patients who have received local radiotherapy without regional coverage following NAC.
Acquired and inherent radioresistance of tumor cells is related to tumor relapse and poor prognosis – not only in head and neck squamous cell carcinoma (HNSCC). The underlying molecular mechanisms are largely unknown. Therefore, systemic in-depth analyses are needed to identify key regulators of radioresistance. In the present study, subclones of the CAL-33 HNSCC cell line with different radiosensitivity were analyzed to identify signaling pathways related to the different phenotypes.
Subclones with altered radiosensitivity were generated by fractionated irradiation of the parental CAL-33 cells. Differences in radiosensitivity were confirmed in colony formation assays. Selected subclones were characterized at the genomic and transcriptomic level by SKY, array CGH, and mRNA-microarray analyses. Time-course gene expression analyses upon irradiation using a natural cubic spline regression model identified temporally differentially expressed genes. Moreover, early and late responding genes were identified. Gene association networks were reconstructed using partial correlation. The Reactome pathway database was employed to conduct pathway enrichment analyses.
The characterization of two subclones with enhanced radiation resistance (RP) and enhanced radiosensitivity (SP) revealed distinct genomic and transcriptomic changes compared to the parental cells. Differentially expressed genes after irradiation shared by both subclones pointed to important pathways of the early and late radiation response, including senescence, apoptosis, DNA repair, Wnt, PI3K/AKT, and Rho GTPase signaling. The analysis of the most important nodes of the gene association networks revealed pathways specific to the radiation response in different phenotypes of radiosensitivity. Exemplarily, for the RP subclone the senescence-associated secretory phenotype (SASP) together with GPCR ligand binding were considered as crucial. Also, the expression of endogenous retrovirus ERV3-1in response to irradiation has been observed, and the related gene association networks have been identified.
Our study presents comprehensive gene expression data of CAL-33 subclones with different radiation sensitivity. The resulting networks and pathways associated with the resistant phenotype are of special interest and include the SASP. The radiation-associated expression of ERV3-1 also appears highly attractive for further studies of the molecular mechanisms underlying acquired radioresistance. The identified pathways may represent key players of radioresistance, which could serve as potential targets for molecularly designed, therapeutical intervention.
