Genetic and metabolic predictors of chemosensitivity in oligodendroglial neoplasms

The −1p/−19q genotype predicts chemosensitivity in oligodendroglial neoplasms, but some with intact 1p/19q also respond and not all with 1p/19q loss derive durable benefit from chemotherapy. We have evaluated the predictive and prognostic significance of pretherapy 201Tl and 18F-FDG SPECT and genotype in 38 primary and 10 recurrent oligodendroglial neoplasms following PCV chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII and was associated with response (Fisher-Exact: P=0.000) and prolonged progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank: P=0.0048). Response was unrelated to metabolism, with tumours with high or low metabolism showing response. Increased 18F-FDG or 201Tl uptake predicted shorter progression-free survival (PFS) in the series (log-rank: 201Tl P=0.0097, 18F-FDG P=0.0170) and in cases with or without the −1p/−19q genotype. Elevated metabolism was associated with shorter OS in cases with intact 1p/19q (log-rank: 18F-FDG P=0.0077; 201Tl P=0.0004) and shorter PFS in responders (log-rank: 18F-FDG P=0.005; 201Tl P=0.0132). 201Tl uptake and 1p/19q loss were independent predictors of survival in multivariate analysis. In this initial study, 201Tl and 18F-FDG uptake did not predict response to PCV, but may be associated with poor survival following therapy irrespective of genotype. This may be clinically useful warranting further study

Dose dense 1 week on/1 week off temozolomide in recurrent glioma: a retrospective study

Alternative temozolomide regimens have been proposed to overcome O6-methylguanine-DNA methyltransferase mediated resistance. We investigated the efficacy and tolerability of 1 week on/1 week off temozolomide (ddTMZ) regimen in a cohort of patients treated with ddTMZ between 2005 and 2011 for the progression of a glioblastoma during or after chemo-radiation with temozolomide or a recurrence of another type of glioma after radiotherapy and at least one line of chemotherapy. Patients received ddTMZ at 100–150 mg/m2/d (days 1–7 and 15–21 in cycles of 28-days). All patients had a contrast enhancing lesion on MRI and the response was assessed by MRI using the RANO criteria; complete and partial responses were considered objective responses. Fifty-three patients were included. The median number of cycles of ddTMZ was 4 (range 1–12). Eight patients discontinued chemotherapy because of toxicity. Two of 24 patients with a progressive glioblastoma had an objective response; progression free survival at 6 months (PFS-6) in glioblastoma was 29%. Three of the 16 patients with a recurrent WHO grade 2 or 3 astrocytoma or oligodendroglioma or oligo-astrocytoma without combined 1p and 19q loss had an objective response and PFS-6 in these patients was 38%. Four out of the 12 evaluable patients with a recurrent WHO grade 2 or 3 oligodendroglioma or oligo-astrocytoma with combined 1p and 19q loss had an objective response; PFS-6 in these patients was 62%. This study indicates that ddTMZ is safe and effective in recurrent glioma, despite previous temozolomide and/or nitrosourea chemotherapy. Our data do not suggest superior efficacy of this schedule as compared to the standard day 1–5 every 4 weeks schedule

Analysis of EGFR, HER2, and TOP2A gene status and chromosomal polysomy in gastric adenocarcinoma from Chinese patients

<p>Abstract</p> <p>Background</p> <p>The EGFR and HER2 genes are located on chromosomes 7 and 17, respectively. They are therapeutic targets in some tumors. The TOP2A gene, which is located near HER2 on chromosome 17, is the target of many chemotherapeutic agents, and co-amplification of HER2 and TOP2A has been described in several tumor types. Herein, we investigated the gene status of EGFR, HER2, and TOP2A in Chinese gastric carcinoma patients. We determined the rate of polysomy for chromosomes 7 and 17, and we attempted to clarify the relationship between EGFR, HER2, and TOP2A gene copy number and increased expression of their encoded proteins. Furthermore, we tried to address the relationship between alterations in EGFR, HER2, and TOP2A and chromosome polysomy.</p> <p>Methods</p> <p>One hundred cases of formalin fixed and paraffin embedded tumor tissues from Chinese gastric carcinoma patients were investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) methods.</p> <p>Results</p> <p>Forty-two percent of the cases showed EGFR overexpression; 16% showed EGFR FISH positive; 6% showed HER2 overexpression; and 11% showed HER2 gene amplification, including all six HER2 overexpression cases. TOP2A nuclear staining (nuclear index, NI) was determined in all 100 tumors: NI values ranged from 0.5 – 90%. Three percent of the tumors showed TOP2A gene amplification, which were all accompanied by HER2 gene amplification. Nineteen percent of the tumors showed chromosome 7 polysomy, and 16% showed chromosome 17 polysomy. Chromosome 7 polysomy correlated significantly with EGFR FISH-positivity, but was not associated with EGFR overexpression. HER2 overexpression associated significantly with HER2 gene amplification. TOP2A gene amplification was significantly associated with HER2 gene amplification. No relationship was found between alterations in the <it>EGFR</it>, <it>HER2</it>, and <it>TOP2A </it>genes and clinicopathologic variables of gastric carcinoma.</p> <p>Conclusion</p> <p>The data from our study suggest that chromosome 7 polysomy may be responsible for increased EGFR gene copy number in gastric carcinomas, and that HER2 gene amplification may be the major reason for HER2 protein overexpression. A combined investigation of the gene status of EGFR, HER2, and TOP2A should facilitate the identification of a target therapeutic regimen for gastric carcinoma patients.</p

Co-Deletion of Chromosome 1p/19q and IDH1/2 Mutation in Glioma Subsets of Brain Tumors in Chinese Patients

OBJECTIVE: To characterize co-deletion of chromosome 1p/19q and IDH1/2 mutation in Chinese brain tumor patients and to assess their associations with clinical features. METHODS: In a series of 528 patients with gliomas, pathological and radiological materials were reviewed. Pathological constituents of tumor subsets, incidences of 1p/19q co-deletion and IDH1/2 mutation in gliomas by regions and sides in the brain were analyzed. RESULTS: Overall, 1p and 19q was detected in 339 patients by FISH method while the sequence of IDH1/2 was determined in 280 patients. Gliomas of frontal, temporal and insular origin had significantly different pathological constituents of tumor subsets (P<0.001). Gliomas of frontal origin had significantly higher incidence of 1p/19q co-deletion (50.4%) and IDH1/2 mutation (73.5%) than those of non-frontal origin (27.0% and 48.5%, respectively) (P<0.001), while gliomas of temporal origin had significantly lower incidence of 1p/19q co-deletion (23.9%) and IDH1/2 mutation (41.7%) than those of non-temporal origin (39.9% and 63.2%, respectively) (P = 0.013 and P = 0.003, respectively). Subgroup analysis confirmed these findings in oligoastrocytic and oligodendroglial tumors, respectively. Although the difference of 1p/19q co-deletion was not statistically significant in temporal oligodendroglial tumors, the trend was marginally significant (P = 0.082). However, gliomas from different sides of the brain did not show significant different pathological constituents, incidences of 1p/19q co-deletion or IDH1/2 mutation. CONCLUSION: Preferential distribution of pathological subsets, 1p/19q co-deletion and IDH1/2 mutation were confirmed in some brain regions in Chinese glioma patients, implying their distinctive tumor genesis and predictive value for prognosis

Improved Siderotic Nodule Detection in Cirrhosis with Susceptibility-Weighted Magnetic Resonance Imaging: A Prospective Study

BACKGROUND: Hepatic cirrhosis is a common pathway of progressive liver destruction from multiple causes. Iron uptake can occur within the hepatic parenchyma or within the various nodules that form in a cirrhotic liver, termed siderotic nodules. Siderotic nodule formation has been shown to correlate with inflammatory activity, and while the relationship between siderotic nodule formation and malignancy remains unclear, iron distribution within hepatic nodules has known implications for the detection of hepatocellular carcinoma. We aimed to evaluate the role of abdominal susceptibility-weighted imaging in the detection of siderotic nodules in cirrhotic patients. METHODOLOGY/PRINCIPAL FINDINGS: Forty-six (46) cirrhotic patients with at least one siderotic nodule detected on previous imaging underwent both computed tomography and magnetic resonance imaging (T1-, T2-, T2*-, and susceptibility-weighted imaging) at 3.0 Tesla. Imaging data was independently analyzed by two radiologists. Siderotic nodule count was determined for each modality and imaging sequence. For each magnetic resonance imaging technique, siderotic nodule conspicuity was assessed on a 3 point scale (1 = weak, 2 = moderate, 3 = strong). More nodules were detected by susceptibility weighted imaging (n = 2935) than any other technique, and significantly more than by T2* weighted imaging (n = 1696, p<0.0001). Lesion conspicuity was also highest with susceptibility-weighted imaging, with all nodules found to be moderate (n = 6) or strong (n = 40); a statistically significant difference (p<0.001). CONCLUSIONS: Susceptibility-weighted imaging had the greatest lesion conspicuity and detected the highest number of siderotic nodules suggesting it is the most sensitive imaging technique to detect siderotic nodules in cirrhotic patients

I Undervalue You but I Need You: The Dissociation of Attitude and Memory Toward In-Group Members

In the present study, the in-group bias or in-group derogation among mainland Chinese was investigated through a rating task and a recognition test. In two experiments,participants from two universities with similar ranks rated novel faces or names and then had a recognition test. Half of the faces or names were labeled as participants' own university and the other half were labeled as their counterpart. Results showed that, for either faces or names, rating scores for out-group members were consistently higher than those for in-group members, whereas the recognition accuracy showed just the opposite. These results indicated that the attitude and memory for group-relevant information might be dissociated among Mainland Chinese

Comparative transcriptome sequencing of germline and somatic tissues of the Ascaris suum gonad

<p>Abstract</p> <p>Background</p> <p><it>Ascaris suum </it>(large roundworm of pigs) is a parasitic nematode that causes substantial losses to the meat industry. This nematode is suitable for biochemical studies because, unlike <it>C. elegans</it>, homogeneous tissue samples can be obtained by dissection. It has large sperm, produced in great numbers that permit biochemical studies of sperm motility. Widespread study of <it>A. suum </it>would be facilitated by more comprehensive genome resources and, to this end, we have produced a gonad transcriptome of <it>A. suum</it>.</p> <p>Results</p> <p>Two 454 pyrosequencing runs generated 572,982 and 588,651 reads for germline (TES) and somatic (VAS) tissues of the <it>A. suum </it>gonad, respectively. 86% of the high-quality (HQ) reads were assembled into 9,955 contigs and 69,791 HQ reads remained as singletons. 2.4 million bp of unique sequences were obtained with a coverage that reached 16.1-fold. 4,877 contigs and 14,339 singletons were annotated according to the <it>C. elegans </it>protein and the Kyoto Encyclopedia of Genes and Genomes (KEGG) protein databases. Comparison of TES and VAS transcriptomes demonstrated that genes participating in DNA replication, RNA transcription and ubiquitin-proteasome pathways are expressed at significantly higher levels in TES tissues than in VAS tissues. Comparison of the <it>A. suum </it>TES transcriptome with the <it>C. elegans </it>microarray dataset identified 165 <it>A. suum </it>germline-enriched genes (83% are spermatogenesis-enriched). Many of these genes encode serine/threonine kinases and phosphatases (KPs) as well as tyrosine KPs. Immunoblot analysis further suggested a critical role of phosphorylation in both testis development and spermatogenesis. A total of 2,681 <it>A. suum </it>genes were identified to have associated RNAi phenotypes in <it>C. elegans</it>, the majority of which display embryonic lethality, slow growth, larval arrest or sterility.</p> <p>Conclusions</p> <p>Using deep sequencing technology, this study has produced a gonad transcriptome of <it>A. suum</it>. By comparison with <it>C. elegans </it>datasets, we identified sets of genes associated with spermatogenesis and gonad development in <it>A. suum</it>. The newly identified genes encoding KPs may help determine signaling pathways that operate during spermatogenesis. A large portion of <it>A. suum </it>gonadal genes have related RNAi phenotypes in <it>C. elegans </it>and, thus, might be RNAi targets for parasite control.</p