Presence of Human Herpes Virus 6 (HHV6) in pediatric lymphomas: impact on clinical course and association with cytomegalovirus infection

<p>Abstract</p> <p>Background</p> <p>Activation of herpes virus 6 (HHV6) has seen in Hodgkin's and non-Hodgkin's Lymphoma (HL&NHL) as a result of lymphoma associated immunosuppression. Multiple studies have suggested an association between both HHV6 and cytomegalovirus CMV for development of CMV disease affecting the pathogenesis of lymphoma. Therefore, this study investigated the frequency of HHV6, its impact on clinical manifestations of lymphoma and its possible association with risk for development of CMV infection in pediatric lymphoma patients.</p> <p>Methods</p> <p>Presence of HHV6 DNA and CMV DNA was investigated by PCR assay in both WBC's and plasma samples from 50 patients diagnosed with HL or NHL. CMV antibody titer was also determined in sera obtained from each patient. Twenty apparently healthy siblings were used as a control group.</p> <p>Results</p> <p>In a study group of 50 patients diagnosed with HL or NHL, 23/50 (46%) were found to be positive for herpes virus DNA (HHV6 or CMV) in WBC's or plasma by PCR assay and this was significantly higher than its presence in the pediatric control group 2/20 (10%) (p = 0.005). Ten out of these 23 (43%) were found to have active CMV infection. Fifty six percent of patients with CMV infection were found among NHL cases with B- subtype. The presence of both herpes viruses DNA was significantly associated with more frequent episodes of febrile neutropenia (median 3 episodes), absolute neutrophil count (< 0.8), lymphocytes (< 0.5), and low hemoglobin level (< 9.1), (p < 0.05).</p> <p>Conclusion</p> <p>The presence of HHV6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection which may result in a severe outcome among pediatric lymphoma patients.</p

Does HOXA9 Gene Expression in Egyptian Chronic Myelogenous Leukemia Patients Affect Disease Progression? A Retrospective Cohort Study

OBJECTIVE: Chronic myelogenous leukemia (CML) is a clonal stem cell disease and is consistently associated with the BCR-ABL fusion gene. The chronic phase of the disease tends to pass into an accelerated phase and eventually leads to acute leukemia if left untreated. Oncoproteins necessary for leukemic transformation are both fundamentally and clinically relevant to identify as they might be new molecular targets for the development of specific anti-leukemic drugs. This study is an initial step to define the proportion of HOXA9 gene expression in some Egyptians with chronic-phase CML at diagnosis and to evaluate its relation with BCR-ABL expression and its clinical significance. METHODS: Sixty-two newly diagnosed CML patients (56 in chronic phase, 1 in accelerated phase, and 5 in blastic crises) were enrolled in the study. HOXA9 and BCR-ABL gene expressions were detected by one-step RT-PCR. ABL was chosen as a control gene to calculate HOXA9/ABL and BCR-ABL/ABL ratios from densitometric values of PCR product intensities. RESULTS: HOXA9 expression was encountered in 25/56 (44.6%) of newly diagnosed CML patients in the chronic phase. The median expression was 0.31 (range: 0.08-1.37) in relation to the ABL gene, with a higher frequency of expression in CML patients presenting with splenomegaly (p<0.001), high Sokal score (p<0.001), and BCR-ABL expression from the first round (p=0.004). No association could be detected with other clinical parameters, overall survival, or disease-free survival. CONCLUSION: HOXA9 expression is closely related to poor prognostic factors, but we could not demonstrate its relationship to patient survival

Prognostic value of IDH1 mutations identified with PCR-RFLP assay in acute myeloid leukemia patients

Background: Somatic mutations in isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors. Recently theses mutations were demonstrated in acute myeloid leukemia (AML). So far, assessment of these mutations relied on the DNA sequencing technique. Aim of the work: The aim of this study was to detect somatic mutations in IDH1 gene using mismatched primers suitable for endonuclease based detection, without the need for DNA sequencing, and to estimate its prognostic value, on patients with de novo AML. Methods: Residual DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de novo AML was used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was adapted to IDH1gene, codon 132 mutations screening. Results: The frequency of IDH1 mutations was 13%. In the non-acute promyelocytic leukemia group (non-APL), IDH1 mutations were significantly associated with FLT3-ITD negative patients (p = 0.03). Patients with IDH1 mutations did not achieve complete remission (CR). There was a trend for shorter overall survival (OS) in patients with IDH1 mutation compared to those with wild type (p = 0.08). Conclusion: IDH1 mutations are recurring genetic alterations in AML and they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP method allows for a fast, inexpensive, and sensitive method for the detection of IDH1 mutations in AML

Bacteremia due to ESKAPE pathogens: An emerging problem in cancer patients

Background and aim: In recent years, a few of the antibiotic-resistant bacteria, known as ESKAPE pathogens, have been found responsible for serious infections. We investigated the risk factors, and impact of ESKAPE pathogens on course of blood stream infections (BSIs) in cancer patients in comparison to coagulase negative Staphylococci (CoNS). Patients and methods: The data of patients with ESKAPE positive blood cultures at National Cancer Institute, Cairo University were analyzed. Identification and antimicrobial susceptibility of isolates were done using Microscan Walk Away 96. Results: In a 6 month period, ESKAPE pathogens were isolated from non-duplicate blood cultures in 81 episodes of 72 cases of pediatric cancer patients, while CoNS were isolated from 135 blood cultures of 116 patients. The ESKAPE pathogens isolated were Enterobacter spp., methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci in 12%, 23%, 37%, 10%, 9%, and 9% of episodes, respectively. Health-care acquired infections constituted 75% of ESKAPE infections. Duration of episodes and overall mortality were significantly higher in ESKAPE BSIs when compared to CoNS (14.5 ± 7.6 versus 09.9 ± 6.9), and (26% versus 4%); respectively, p value <0.001. Conclusions: ESKAPE pathogens were significantly associated with higher rates of morbidity and mortality indicating the need for improving the means of prevention of these types of infections within health care premises. Microbiology laboratories have a role in defining more dangerous infections and rapid diagnostics are required in the era of resistance

First-line paclitaxel and cisplatin used sequentially or in combination in metastatic breast cancer: A phase II randomized study

Introduction: Breast cancer (BC) is the commonest cancer among females worldwide. Some patients present initially at advanced stages and more than 50% of them will develop metastasis (MBC) at some point. Compared to single agents, combination chemotherapy produces higher response rates (RR), longer progression-free survival (PFS) than single agents. This is associated with remarkably higher toxicities. At the same time, overall survival (OS) is comparable. This study aimed to compare safety and efficacy of combination and sequential chemotherapy. Patients and Methods: Forty-six MBC patients were randomized to receive 6 cycles of the combination of paclitaxel (175 mg/m2) and cisplatin (70 mg/m2) (combination PC) or paclitaxel for 3 cycles followed by cisplatin for 3 cycles (sequential PC). Endpoints were RR, PFS, OS and safety. Results: Both combination and sequential PC produced similar RR (52% in both arms) and disease control rates (78.3% vs. 73.9%, p = .652). Responses were faster in the combination arm. Median PFS was 8.2 months in the combination compared to 5.0 months in the sequential arm (p = .064). The median OS was 16.5 and 18.8 months in the combination and sequential arms, respectively (p = .866). The combination was more toxic than sequential PC. Grade 3 toxicities were higher with combination PC than to sequential PC (48% vs. 4.3%; p < .001). Conclusion: Sequential agent chemotherapy may provide similar response rate and overall survival to combination chemotherapy with much lower toxicities. The former can be considered the standard practice in most instances

Impact of different biochemical markers in serum of patients with benign and malignant liver diseases

The only hope for effective treatment of liver cancer lies in early detection or screening for populations who are at high risk for developing liver cancer. This study was designed to study the levels of a collection of biochemical markers in the sera of patients suffering from hepatocellular carcinoma (HCC) and its predisposing diseases. The ultimate aim is to investigate their diagnostic impact in the early detection of HCC and discriminate from benign liver diseases. The study was carried out on 217 individuals divided into the following groups: Group 1: Normal controls, Group 2: Schistosomal patients (Schist), Group 3: Hepatitis B patients (HBV), Group 4: Hepatitis C patients (HCV), Group 5: Cirrhotic patients (Cirr), and Group 6: Hepatocellular carcinoma patients (HCC). The last group was further subdivided into the following subgroups: a – HCC alone; b – HCC on top of schistosomiasis; c – HCC on top of HBV; d – Hepato-cellular carcinoma on top of HCV; e – HCC on top of cirrhosis. Their sera were subjected to a quantitative determination of the tumour necrosis factor-alpha (TNF-α), epidermal growth factor and its receptor (EGF and EGFR), glutathione-S-transferase alpha (GST-α), iron, ferritin, transferrin, alpha-1-antitrypsin (α1AT) and alpha-fetoprotein (αFP). The results of this study indicate that it is advisable to determine a panel of markers composed of αFP, TNF-α and GST-α to confirm diagnosis of HCC and distinguish it from other benign liver diseases

Prevalence of MMTV-Like env Sequences and Its Association with BRCA1/2 Genes Mutations Among Egyptian Breast Cancer Patients

BackgroundMouse mammary tumor virus (MMTV) is thought to have a role in human breast cancer (BC) pathogenesis. BRCA1 and 2 genes mutations are well-established risk factors for BC. The purpose of this study was to evaluate the presence of MMTV in familial and non-familial Egyptian breast cancer patients. We also aimed to establish a correlation between BRCAs genes mutations and MMTV infection in those patients.Patients and methodsThe study was included 80 BC patients and 10 healthy women were included as a control group. We used PCR to amplify a 250-bp MMTV-like env sequence. We also used PCR followed by direct sequencing to identify the genetic variation of exons 2, 13, 19 of BRCA1 gene and exon 9 and region f of exon 11 of BRCA2 gene. High resolution melting (HRM) analysis was used to screen the selected exons of BRCA1/2 genes in order to detect different variants.ResultsMMTV DNA-like env sequences were detected in 70%, 76% of familial and non-familial BC patients, respectively, and it was not detected in any of the control subjects. The presence of viral sequences was associated with larger tumor size in the sporadic patients. Seventy BC patients showed variations in BRCA1/2 genes according to HRM analysis and sequencing analysis showed two different sequences of polymorphism among 22 familial and non-familial BC patients.ConclusionMMTV DNA was present among BC patients and it was associated with increased tumor growth. This indicates a potential role for MMTV in BC patients with and without deleterious mutation in BRCA1/2 genes

Prognostic significance of plasma osteopontin level in breast cancer patients

Many studies have demonstrated that osteopontin (OPN) contributes functionally to aggressive behaviour in many tumours including breast cancer