Prognostic Factors for the Development of Biochemical Recurrence after Radical Prostatectomy

Prostate cancer is one of the most common cancers in Western countries and is associated with a considerable risk of mortality. Biochemical recurrence following radical prostatectomy is a relatively common finding, affecting approximately 25% of cases. The aim of our paper was to identify factors that can predict the occurrence of biochemical recurrence, so the patient can be properly counselled pre- and postoperatively. Medline review of the literatures was done followed by a group discussion on the chosen publications and their valuable influence. Preoperative serum total PSA and clinical stage, together with prostatectomy Gleason grade, tumour volume, and perineural and vascular invasions, were the most important variables found to influence outcome

DNA ploidy and morphology of colon tumors in the adenoma - carcinoma sequence

Introduction. Chromosomal changes are widespread in the vast majority of colon carcinomas and aneuploidy is an established prognostic factor. However, this knowledge so far has no influence on tumor classification. We reported a morphology-based classification scheme, the core classification, that correlates with DNA ploidy. In particular, tripolar mitoses were identified as surrogate markers of a near triploid DNA content. In addition, a survey on chromosome numbers and survival rates in carcinomas suggested that triploidy as a particular state of aneuploidy may be correlated with a more aggressive tumor phenotype. We therefore aimed to analyse DNA ploidy in the colorectal adenoma–carcinoma sequence. Material and methods. The study collection consisted of 15 adenomas and 15 adenocarcinomas of 10 patients. Some of them showed a morphological transition between benign and malignant tumor components which were selectively analysed by DNA measurements. In addition, we assessed the morphological parameters of the core classification. Results. The main findings of the study may be summarized as follows. 1) DNA ploidy changes are already consistently detectable in colon adenomas. They are usually associated with hyperdiploidy. 2) Adenoma tissue adjacent to carcinomas, however, may carry a hypodiploid DNA content while the nearby carcinoma samples were hyperdiploid. Hypodiploidy may thus represent a transition state to near triploid carcinomas. 3) The size of tumor nuclei and mitoses usually reflects the ploidy level of colon tumors. Specifically, triploid mitoses may point to a near triploid DNA content. 4) Triploidy per se cannot be equated with tumor aggressiveness as it may already be found in adenocarcinoma in situ. 5) Tripolar and tetrapolar mitoses in invasive colon cancer, however, are potential indicators of an advanced chromosomal instability and seemed to be associated with advanced tumor stages. Conclusions. We present data that hypodiploidy may represent a transition state from adenoma to carcinoma in a subset of colorectal tumors and that near-triploidy may be associated with a more aggressive course of the disease. However, the interpretation of tripolar mitoses and triploidy is largely dependent on the cell type (benign vs. malignant) and tissue context (invasive vs. non-invasive cancer). Furthermore, its interpretation may be distinct for different tumor stages and histotypes. Aneuploidy and multipolar mitoses are frequent findings in cancer cells. Their relevance for tumor biology deserves further studies

Retroperitoneal lymph node dissection for residual masses after chemotherapy in nonseminomatous germ cell testicular tumor

<p>Abstract</p> <p>Background</p> <p>Retroperitoneal lymph node dissection has been advocated for the management of post-chemotherapy (PC-RPLND) residual masses of non-seminomatous germ cell tumors of the testis (NSGCT). There remains some debate as to the clinical benefit and associated morbidity. Our objective was to report our experience with PC-RPLND in NSGCT.</p> <p>Methods</p> <p>We have reviewed the clinical, pathologic and surgical parameters associated with PC-RPLND in a single institution. Between 1994 and 2008, three surgeons operated 73 patients with residual masses after cisplatin-based chemotherapy for a metastatic testicular cancer. Patients needed to have normal postchemotherapy serum tumor markers, no prior surgical attempts to resect retroperitoneal masses and resectable retroperitoneal tumor mass at surgery to be included in this analysis</p> <p>Results</p> <p>Mean age was 30.4 years old. Fifty-three percent had mixed germ cell tumors. The mean size of retroperitoneal metastasis was 6.3 and 4.0 cm, before and post-chemotherapy, respectively. In 56% of patients, the surgeon was able to perform a nerve sparing procedure. The overall complication rate was 27.4% and no patient died due to surgical complications. The pathologic review showed presence of fibrosis/necrosis, teratoma and viable tumor (non-teratoma) in 27 (37.0%), 30 (41.1%) and 16 (21.9%) patients, respectively. The subgroups presenting fibrosis and large tumors were more likely to have a surgical complication and had less nerve sparing procedures.</p> <p>Conclusion</p> <p>PC-RPLND is a relatively safe procedure. The presence of fibrosis and large residual masses are associated with surgical complications and non-nerve-sparing procedure.</p

Plasma Membrane Factor XIIIA Transglutaminase Activity Regulates Osteoblast Matrix Secretion and Deposition by Affecting Microtubule Dynamics

Transglutaminase activity, arising potentially from transglutaminase 2 (TG2) and Factor XIIIA (FXIIIA), has been linked to osteoblast differentiation where it is required for type I collagen and fibronectin matrix deposition. In this study we have used an irreversible TG-inhibitor to ‘block –and-track’ enzyme(s) targeted during osteoblast differentiation. We show that the irreversible TG-inhibitor is highly potent in inhibiting osteoblast differentiation and mineralization and reduces secretion of both fibronectin and type I collagen and their release from the cell surface. Tracking of the dansyl probe by Western blotting and immunofluorescence microscopy demonstrated that the inhibitor targets plasma membrane-associated FXIIIA. TG2 appears not to contribute to crosslinking activity on the osteoblast surface. Inhibition of FXIIIA with NC9 resulted in defective secretory vesicle delivery to the plasma membrane which was attributable to a disorganized microtubule network and decreased microtubule association with the plasma membrane. NC9 inhibition of FXIIIA resulted in destabilization of microtubules as assessed by cellular Glu-tubulin levels. Furthermore, NC9 blocked modification of Glu-tubulin into 150 kDa high-molecular weight Glu-tubulin form which was specifically localized to the plasma membrane. FXIIIA enzyme and its crosslinking activity were colocalized with plasma membrane-associated tubulin, and thus, it appears that FXIIIA crosslinking activity is directed towards stabilizing the interaction of microtubules with the plasma membrane. Our work provides the first mechanistic cues as to how transglutaminase activity could affect protein secretion and matrix deposition in osteoblasts and suggests a novel function for plasma membrane FXIIIA in microtubule dynamics

Antisense Phenotypes Reveal a Functional Expression of OsARF1, an Auxin Response Factor, in Transgenic Rice

OsARF1 is the first full-length member of auxin response factor (ARF) gene family to be cloned from monocot plant. Using quantitative RT-PCR this study found that, the transcript abundance of OsARF1 was significantly higher in embryonic tissues than in vegetative tissues. To investigate the effect of OsARF1 on the phenotype of rice, a cDNA fragment of OsARF1 was inserted in inverse orientation to the 35S promoter in vector pBin438 to produce an antisense (AS) construction. The AS-OsARF1 construct was transferred into rice (Oryza sativa L. japonica ) calli via Agrobacterium tumefaciens -mediated transformation. Molecular analysis of transgenic plants showed that the functional expression of OsARF1 was inhibited at mRNA level efficiently. The AS-OsARF1 plants showed extremely low growth, poor vigor, short curled leaves and tillered but were sterile. Therefore, the OsARF1 was shown to be essential for growth in vegetative organs and seed development

Serum Folate in Asthma: Does it Correlate to Severity? A Single Center Experience

Background: Bronchial asthma is the most common chronic childhood illness. It is characterized by airway inflammation and episodic airflow obstruction. Low serum folate has been inconsistently reported as a risk factor for bronchial asthma severity. Other studies reported an increased risk of asthma in children whose mothers received prenatal folic acid supplementation. Aim of the work: To compare serum folate level in asthmatic patients to non-asthmatic healthy controls, and to demonstrate whether folate level correlates to severity &/or frequency of asthma exacerbations and pulmonary function parameters. Methods: Forty-five asthmatic Egyptian children and an equal number of healthy controls were included. Serum folate level was measured in both groups and spirometry was performed for the asthmatic children. Results: Serum folate levels were significantly lower among patients (7.83ng/ml ± 2.47) versus controls (9.84ng/ml ± 3.47), (p value 0.002). Serum folate levels also had an inverse correlation with severity of asthma exacerbations (r = – 0.482), (p = 0.001) and their frequency (r = – 0.418), (p= 0.004). Serum folate levels inversely correlated as well with severity of asthma as a chronic illness (r = – 0.315), (p = 0.035). The cutoff point of serum folate level that was found to increase the severity of asthma exacerbations was calculated at ≤ 8.84ng/ml. Only 7 patients fell below the current normal reference range for serum folate. On the other hand, serum folate level did not significantly correlate with any of the pulmonary function test variables measured. Conclusions: Serum folate levels were lower in asthmatic children when compared to healthy controls, and it negatively correlated with asthma severity and exacerbations, but not to pulmonary function parameters. The cutoff serum folate level for increased severity of asthma exacerbations fell within the normal folate range for children. Further research is recommended to assess any possible beneficial effects for folate supplementation in asthma

An Unbiased Systems Genetics Approach to Mapping Genetic Loci Modulating Susceptibility to Severe Streptococcal Sepsis

Striking individual differences in severity of group A streptococcal (GAS) sepsis have been noted, even among patients infected with the same bacterial strain. We had provided evidence that HLA class II allelic variation contributes significantly to differences in systemic disease severity by modulating host responses to streptococcal superantigens. Inasmuch as the bacteria produce additional virulence factors that participate in the pathogenesis of this complex disease, we sought to identify additional gene networks modulating GAS sepsis. Accordingly, we applied a systems genetics approach using a panel of advanced recombinant inbred mice. By analyzing disease phenotypes in the context of mice genotypes we identified a highly significant quantitative trait locus (QTL) on Chromosome 2 between 22 and 34 Mb that strongly predicts disease severity, accounting for 25%–30% of variance. This QTL harbors several polymorphic genes known to regulate immune responses to bacterial infections. We evaluated candidate genes within this QTL using multiple parameters that included linkage, gene ontology, variation in gene expression, cocitation networks, and biological relevance, and identified interleukin1 alpha and prostaglandin E synthases pathways as key networks involved in modulating GAS sepsis severity. The association of GAS sepsis with multiple pathways underscores the complexity of traits modulating GAS sepsis and provides a powerful approach for analyzing interactive traits affecting outcomes of other infectious diseases

Molecular and pathological investigation of avian reovirus (ARV) in Egypt with the assessment of the genetic variability of field strains compared to vaccine strains

Avian orthoreovirus (ARV) is among the important viruses that cause drastic economic losses in the Egyptian poultry industry. Despite regular vaccination of breeder birds, a high prevalence of ARV infection in broilers has been noted in recent years. However, no reports have revealed the genetic and antigenic characteristics of Egyptian field ARV and vaccines used against it. Thus, this study was conducted to detect the molecular nature of emerging ARV strains in broiler chickens suffering from arthritis and tenosynovitis in comparison to vaccine strains. Synovial fluid samples (n = 400) were collected from 40 commercial broiler flocks in the Gharbia governorate, Egypt, and then pooled to obtain 40 samples, which were then used to screen ARV using reverse transcriptase polymerase chain reaction (RT-PCR) with the partial amplification of ARV sigma C gene. The obtained RT-PCR products were then sequenced, and their nucleotide and deduced amino acid sequences were analyzed together with other ARV field and vaccine strains from GenBank. RT-PCR successfully amplified the predicted 940 bp PCR products from all tested samples. The phylogenetic tree revealed that the analyzed ARV strains were clustered into six genotypic clusters and six protein clusters, with high antigenic diversity between the genotypic clusters. Surprisingly, our isolates were genetically different from vaccine strains, which aligned in genotypic cluster I/protein cluster I, while our strains were aligned in genotypic cluster V/protein cluster V. More importantly, our strains were highly divergent from vaccine strains used in Egypt, with 55.09–56.23% diversity. Sequence analysis using BioEdit software revealed high genetic and protein diversity between our isolates and vaccine strains (397/797 nucleotide substitutions and 148-149/265 amino acid substitutions). This high genetic diversity explains the vaccination failure and recurrent circulation of ARV in Egypt. The present data highlight the need to formulate a new effective vaccine from locally isolated ARV strains after a thorough screening of the molecular nature of circulating ARV in Egypt