Purpose
We describe the clinico-pathologic and mammographic characteristics of inflammatory breast cancer (IBC) and non-IBC cases enrolled in a case–control study. Because IBC is a clinico-pathologic ...entity with rapid appearance of erythema and other signs, its diagnosis is based on clinical observation and thus, by necessity, subjective. Therefore, we evaluate our cases by photographic review by outside expert clinicians and by degree of adherence to the two most recent definitions of IBC: the international expert panel consensus statement and American Joint Committee on Cancer (AJCC) 8th edition (we used the slightly less restrictive 7th edition definition for our study).
Methods
We enrolled 267 IBC and 274 age- and geographically matched non-IBC cases at 6 sites in Egypt, Tunisia, and Morocco in a case–control study of IBC conducted between 2009 and 2015. We collected clinico-pathologic and mammographic data and standardized medical photographs of the breast.
Results
We identified many differences between IBC and non-IBC cases: 54.5% versus 68.8% were estrogen receptor-positive, 39.9% versus 14.8% human epidermal growth factor receptor 2-positive, 91% versus 4% exhibited erythema, 63% versus 97% had a mass, and 57% versus 10% had mammographic evidence of skin thickening. Seventy-six percent of IBC cases adhered to the expert panel consensus statement and 36% to the AJCC definition; 86 percent were confirmed as IBC by either photographic review or adherence to the consensus statement.
Conclusions
We successfully identified distinct groups of IBC and non-IBC cases. The reliability of IBC diagnosis would benefit from expert review of standardized medical photographs and associated clinical information.
The outcome of colorectal cancer varies depending on ethnic origin. Egyptian colorectal carcinoma is surprisingly young-age disease with high proportion of rectal and advanced stage cancers.
We ...characterized 69 sporadic Egyptian colorectal cancers for promoter methylation at 24 tumor suppressor genes, microsatellite instability, and expression of mismatch repair, p53, and β-catenin proteins. Data were compared with 80 Western colorectal carcinoma of sporadic and familial origin from Finland.
Egyptian colorectal carcinomas showed significantly higher methylation of the microsatellite stable (MSS) tumors as reflected by the average number of methylated genes per case (P = 0.00002) and tumor suppressor gene methylator phenotype (TSGMP), defined here as methylation of ≥ 5 genes, (P = 0.0001) compared with the sporadic Western cancers. The TSGMP was associated with advanced stage in the Egyptian cancers (P = 0.0016). Four genes were differentially methylated between Egyptian and Western cases, of which the association of CDKN2B/p15 methylation with Egyptian origin was outstanding (P = 4.83 E-10). Egyptian carcinoma also showed significantly lower frequency of nuclear β-catenin localization than the sporadic Western cancers (P = 0.00006) but similar to that of the familial Western subset designated as familial colorectal cancer type X.
We show novel pathway in colon carcinogenesis marked by high methylation of MSS cancers, remarkable CDKN2B/p15 methylation, and low frequency of Wnt signaling activation.
Our findings highlight the possible effect of environmental exposures in carcinogenesis through DNA methylation and should have applications in prevention, molecular diagnosis, prognosis, and treatment.
Primary enteric-type adenocarcinoma of the urinary bladder is relatively uncommon. We present our experience with 109 pure, non-urachal cases—the largest series to date. This work was undertaken with ...the aim of describing the immunohistochemical features of adenocarcinoma of the urinary bladder associated with schistosomiasis, illustrating their histologic and immunohistochemical similarities to colorectal carcinomas. Partial or total cystectomy specimens from a cohort of Egyptian and American patients with the diagnosis of primary adenocarcinoma of the urinary bladder (109 cases) were reviewed. Paraffin sections of each tumour were stained using the labelled streptavidin–biotin method using antibodies cytokeratin 20, cytokeratin 7, CDX2, MLH1, and villin. Clinical follow-up was available for at least 36 months. An enteric (colonic) morphology was seen in most tumours; some with signet ring cells or mucinous elements. Five tumours were composed predominantly of signet ring cells and two demonstrated a pure mucinous morphology. In cases where adjacent normal mucosa was present, 23% showed either colonic metaplasia or intestinal-type cystitis glandularis. Furthermore, 24% of enteric-type adenocarcinomas had associated villous or tubulovillous adenomas with or without dysplasia. Cytokeratin 20 was expressed by 90%, cytokeratin 7 by 17%, CDX2 by 100% and villin and MLH1 by 76% and 48% of tumours respectively. The majority of tumours presented with an advanced stage and followed an aggressive clinical course.
In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.
Improvement of current results of therapy for large cell non-Hodgkin lymphoma patients can be achieved by optimization of initial treatment or application of risk-adapted therapy. The international ...prognostic index ( IPI), introduced to identify high-risk patients, was recently criticized because it was based on clinical risk factors only, ignoring important tumor molecular risk factors and it fails to identify a sector of high-risk patients, who ultimately relapse.
The aim of this study is to evaluate the value of two tumor biomarkers:MIB-1 and p53 as potential risk factors in diffuse large cell lymphoma. MIB-1 measures tumor cell proliferation, whereas p53 is related to tumor progression and response to chemotherapy.
The study was done on 69 adult patients with diffuse large cell NHL ( 58 B-phenotype and 11 T-phenotype). Clinical risk assessment was determined by the IPI and patients with a score of 3 or more were considered high-risk. Expression of MIB-1 and p53 was determined by immunohistochemistry and nuclear staining was quantitated by image analysis. Immunoexpression was considered high for MIB-1 nuclear count 50% and p53 counts 20%. Evaluation included both response to chemotherapy ( mostly CHOP), as well as 2- year overall survival analysis.
The IPI was the only clinical variable which had a significant impact on survival. Overexpression of both MIB-1 and p53 was associated with poor response to treatment, as well as unfavorable survival. Combined risk factor analysis revealed that only MIB-1 was an independent variable. MIB-1 could also identify some high-risk patients previously categorized in the IPI lowrisk group.
MIB-1 is an independent biologic risk factor for large cell NHL. In order to optimize risk assessment of these patients, it is recommended to construct a new prognostic index by adding MIB-1 overexpression to the other clinical factors of standard IPI. This may allow better identification of high-risk patients and help to guide planning of effective initial treatment. Key Words:NHL - MIB-1 - p53 - CHOP - Risk factors.
Abstract Background: Melatonin is a peptide neurohormone naturally synthesized in the brain by the pineal gland. The basic function of melatonin is related to the causation and regulation of the ...sleep–wake cycle (circadian cycle). Cadmium (Cd) is a hazardous heavy metal and its toxic effects induce extensive tissue damage. The present study was undertaken to elucidate the efficiency of exogenous melatonin in attenuating Cd-induced oxidative stress. Methods: The experimental rats were allotted into four groups ( n = 20), designated as untreated control, melatonin accessed, Cd exposed, and Cd exposed with access. Results: The hematological and biochemical parameters (serum and tissues) of Cd-exposed rats were significantly altered. Cd-exposed rats that received melatonin demonstrated increased erythrocytic indices; showed significantly increased levels of total proteins, catalase, total thiols, and glutathione; and exhibited decreased levels of blood Cd, urea, creatinine, bilirubin, malondialdehyde, and hydrogen peroxide. Conclusions: It was concluded that melatonin has an efficient antioxidant activity in attenuating oxidative stress induced by Cd.
We previously described striking molecular features including high frequency of membranous β-catenin in subsets of familial colon cancers with as yet unknown predisposition. We hypothesized that such ...tumors might carry mutations in Wnt/β-catenin target genes. Fibroblast growth factor 9 (FGF9) was an attractive target, as it maps to a common area of loss of heterozygosity (LOH) in colorectal carcinomas on 13q12.11. Here, we report, for the first time, the occurrence of FGF9 mutations in human cancers. We found a total of six distinct FGF9 mutations including one frameshift, four missense, and one nonsense, in 10 (six colorectal and four endometrial) out of 203 tumors and cell lines. The frameshift mutation was detected in five different tumors. Mapping of these mutations onto the crystal structure of FGF9 predicted that they should all lead to loss of function albeit through variable mechanisms. The p.R173K mutation should diminish ligand affinity for heparin/heparan sulfate, the p.V192M, p.D203G, and p.L188YfsX18 (FGF9Δ²⁰⁵⁻²⁰⁸) mutations should negatively impact ligand's interaction with receptor, while p.G84E and p.E142X (FGF9Δ¹⁴²⁻²⁰⁸) mutations should interfere with ligand folding. Consistent with these structural predictions, the p.V192M, p.D203G, and p.L188YfsX18 (FGF9Δ²⁰⁵⁻²⁰⁸) mutations impaired the ability of ligand to activate mitogen-activated protein kinase (MAPK) cascade in cultured cells expressing FGF receptors. LOH was observed in seven out of nine FGF9 mutant tumors, supporting the predicted loss of function. Interestingly, eight out of 10 (80%) of the FGF9 mutant tumors showed normal membranous β-catenin expression and the absence of mutation in the β-catenin gene (CTNNB1). These data suggest that FGF9 plays a role in colorectal and endometrial carcinogenesis. Hum Mutat 29(3), 390-397, 2008.
Introduction. It is believed that children with mild to borderline intellectual functioning are not successful in processing the information received from peers and other people in their surroundings ...during social interactions, which leads to challenging and aggressive behavior. The purpose of this study was to investigate the effect of social information processing (SIP) model intervention on reducing challenging behavior among children with mild to borderline intellectual functioning. Method. For the purpose of this study, a two-way repeated measures ANOVA, with pre-post – and follow up test in two groups were employed. A total of 40 children in the age of 5–10 participated. Participants were 33 boys and 7 girls with a mean age of 8.32 (SD=3.14) and a mean IQ of 75.64 (SD=7.34). Results. Findings from this study revealed the effectiveness of social information processing (SIP) model intervention on reducing challenging behavior among children with mild to bor-derline intellectual functioning. Discussion and Conclusion. In conclusion, results from this study suggested that children with mild to borderline intellectual functioning utilized the Social Information Processing (SIP) Model and their challenging behaviors and prosocial behaviors (challenging behavior) could be reduced. Application and implications, limitations, future research were included.
Introduction: It is believed that children with mild to borderline intellectual functioning are not successful in processing the information received from peers and other people in their surroundings ...during social interactions, which leads to challenging and aggressive behavior. The purpose of this study was to investigate the effect of social information processing (SIP) model intervention on reducing challenging behavior among children with mild to borderline intellectual functioning. Method: For the purpose of this study, a two-way repeated measures ANOVA, with pre-post -- and follow up test in two groups were employed. A total of 40 children in the age of 5-10 participated. Participants were 33 boys and 7 girls with a mean age of 8.32 (SD=3.14) and a mean IQ of 75.64 (SD=7.34). Results: Findings from this study revealed the effectiveness of social information processing (SIP) model intervention on reducing challenging behavior among children with mild to borderline intellectual functioning. Discussion and Conclusion: In conclusion, results from this study suggested that children with mild to borderline intellectual functioning utilized the Social Information Processing (SIP) Model and their challenging behaviors and prosocial behaviors (challenging behavior) could be reduced. Application and implications, limitations, future research were included.
Introduction: Inability to self-regulate learning is likely to be an indication of internet/mobile phone use. When students have low self-regulation, this may negatively predict problematic ...smartphone use. Additionally, problematic smartphone use could be a predictor of academic procrastination. The aim of this study was to investigate the mediating role of self-regulated learning in the relationship between academic procrastination and problematic smartphone use among third year-middle school learning disabled students. Method: For the purpose of this study, quantitative survey research was employed. The independent variable is AP, PSU is the dependent variable and SRL is the moderating variable. 228 students from the four schools were selected. They were all in third year. They aged 14-15 years. Results: Self-regulated learning correlates negatively with academic procrastination, and smartphone addiction. On the other hand, self-regulated learning was found to be positively correlated with Problematic Smartphone Use. This study found that academic procrastination predicted negatively self-regulated learning. SLR predicted AP. Discussion and Conclusion: The results of this study raised our awareness of the mediating role of self-regulated learning in the relationship between academic procrastination and problematic smartphone use among third year-middle school learning disabled student.
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