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Background: Somatic embryogenesis offers a reliable method for cucumber (Cucumis sativus L.) regeneration and genetic enhancement against Fusarium wilt. This study aimed to establish a tailored somatic embryogenesis system for Egyptian cultivars, fostering genetic improvements and Fusarium wilt-resistance lines., Results: Employing the Optimal Arbitrary Design (OAD) approach, we optimized the induction medium, initiating prolific embryogenic calli (53.3 %) at 1 mg/L 2,4-D. The cotyledonary leaf (CL) was the preferred explant, showing 60 % embryogenic callus development. Bieth Alpha exhibited higher responsiveness, generating ∼ 18 somatic embryos per explant compared to Prince's ∼ 10. Somatic embryogenesis system validation used quantitative RT-PCR, showing Cucumis sativus splicing factor 3B subunit (CUS1) and an embryogenesis marker gene expression exclusively within embryogenic calli and mainly during embryogenesis initiation. Evaluating fungal toxin filtrate concentrations for selecting embryogenic calli, the S2 selection (25 % filtrate, four subculture cycles) was chosen for somatic embryo development. To gauge the ramifications of selection at the genetic stratum, an in-depth analysis was executed. A cluster analysis grounded in ISSR banding patterns revealed a distinct separation between in vivo-cultivated plants of the two cultivars and regenerated plants devoid of pathogen filtrate treatment or those regenerated post-filtrate treatment. This segregation distinctly underscores the discernible genetic impact of the selection process., Conclusions: The highest embryogenic capacity (53.3%) was achieved in this study by optimizing the induction stage, which demonstrated the optimal concentrations of BA and 2,4-D for induced proembryonic masses. Moreover, consistent gene expression throughout both stages of embryogenesis suggests that our system unequivocally follows the somatic embryogenesis pathway., (Copyright © 2024. Published by Elsevier Inc.)

Background: Soybean mosaic virus (SMV) is a devastating disease that threatens soybean plants worldwide. The different soybean genotypes displayed different responses to SMV strains. This study aimed to investigate the response of different selected soybean cultivars to SMV infection in Egypt based on their specific genetic makeup., Result: The symptoms of SMV infection and the viral concentration were evaluated in eight soybean cultivars (Giza 21, Giza 22, Giza 35, Giza 82, Giza 111, Crawford, H4L4, and PI416937) using ELISA assay. The results indicated that Giza 21 and Giza 35 were moderately tolerant to SMV infection, while Giza 82 was the least tolerant cultivar. Giza 22, Giza 111, and PI416937 were less tolerant; however, H4L4 and Crawford were identified as the most tolerant cultivars against SMV infection. The chi-square analysis showed a significant association between the different selected cultivars and their response against SMV infection. The PCR test showed the presence of RSV1 (3gG2), RSV1 (5gG3), and RSV3 loci, and the absence of the RSV4 locus gene. The expression analysis of the selected defense genes (EDS1, PAD4, EDR1, ERF1, and JAR) showed variations in the fold changes between infected and non-infected soybean cultivars, suggesting that these genes might play a crucial role in this pathosystem. Additionally, there was a strong positive association between the expression levels of EDR1 and ERF1., Conclusion: The study found the presence of RSV1 (3gG2), RSV1 (5gG3), and RSV3 loci in selected soybean cultivars, but not RSV4. The analysis of gene expression indicated that certain defense genes may play a vital role in the pathosystem. This research is the first of its kind in Egypt to genotype soybean cultivars regarding different RSV loci. The findings could be beneficial for further research on understanding the molecular mechanisms involved in SMV infection and its management., (© 2023. Academy of Scientific Research and Technology.)

Taking into consideration, the challenges faced by the environment and agro-ecosystem make increased for suggestions more reliable methods to help increase food security and deal with difficult environmental problems. Environmental factors play a critical role in the growth, development, and productivity of crop plants. Unfavorable changes in these factors, such as abiotic stresses, can result in plant growth deficiencies, yield reductions, long-lasting damage, and even death of the plants. In reflection of this, cyanobacteria are now considered important microorganisms that can improve the fertility of soils and the productivity of crop plants due to their different features like photosynthesis, great biomass yield, ability to fix the atmospheric N 2, capability to grow on non-arable lands, and varied water sources. Furthermore, numerous cyanobacteria consist of biologically active substances like pigments, amino acids, polysaccharides, phytohormones, and vitamins that support plant growth enhancement. Many studies have exposed the probable role of these compounds in the alleviation of abiotic stress in crop plants and have concluded with evidence of physiological, biochemical, and molecular mechanisms that confirm that cyanobacteria can decrease the stress and induce plant growth. This review discussed the promising effects of cyanobacteria and their possible mode of action to control the growth and development of crop plants as an effective method to overcome different stresses., Competing Interests: Competing InterestsThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2023.)

Background: A useful technique for growing large amounts of plant material is in vitro propagation of important medicinal plants. The present investigation deals with the enhancement of secondary metabolite production via elicitation using gamma (γ)-radiation and phenylalanine (Phe) precursor feeding in callus cultures of Silybum marianum L., Results: Seeds were exposed to two doses of γ-radiation (25 and 50 Gy) and the calli derived from stem explants  obtained from seedlings of these radiated seeds were treated with different concentrations of Phe. The biosynthesis of phenols and flavonoids was evaluated. It was found that callus cultures derived from explants of the seeds exposed to 25 Gy γ-radiation and treated with 4 mg/l Phe accumulated the maximum phenolic content (34.27±0.02 mg/g d.wt.), while the highest flavonoid content (9.56±0.12 mg/g d.wt.) was found in callus cultures derived from explants of seeds radiated with 25 Gy γ-radiation and subjected to 1 mg/l Phe. Similarly, HPLC quantification revealed that the production of flavonoids was highly accumulated (1343.06 μg/mg d.wt.) in callus cultures from explants of seeds  exposed to 25 Gy γ-radiation and grown at 1 mg/l Phe compared to the other treatments. In addition, a total of 11 important flavonoids have been determined in all callus cultures, except for acacetin-7-O-rutinoside, which was not found in the callus culture of the control., Conclusions: These findings suggest that γ-radiation combined with Phe can improve the metabolism of S. marianum L. and could be used to produce such valuable metabolites on a commercial scale., (© 2022. The Author(s).)

Background: Numerous pesticides and herbicides used in excess cause oxidative stress in plants. These chemicals protect plants from weeds and pests, but they also have very negative side effects, making them common abiotic stressors. One of the most significant nutritional crops in the world is the wheat plant. Conditions of herbicide stress have a negative impact on the plant's phonological phases and metabolic pathways. Plants primarily make an effort to adjust to the environment and develop oxidative homeostasis, which supports stress tolerance., Methods: When controlling broadleaf weeds that emerge after cereal crop plants have been planted, bromoxynil is frequently used as a selective-contact herbicide. This study looked at the effects of the cyanobacteria Arthrospira platensis and Nostoc muscorum aqueous extracts, tryptophan, and bromoxynil (Bh) alone or in combination on wheat plant growth parameters. Both tryptophan and cyanobacterial extract were used as chemical and natural safeners against Bh application. The antioxidant activity and transcriptome studies using qRT-PCR were assayed after 24, 48, 72, 96 h, and 15 days from Bh application in the vegetation stage of wheat plants (55 days old)., Results: In comparison with plants treated with Bh, wheat plants treated with cyanobacteria and tryptophan showed improvements in all growth parameters. Following application of Bh, wheat plants showed reduced glutathione content, as well as reduced antioxidant enzyme activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-s-transferase. The combination of different treatments and Bh caused alleviation of the harmful effect induced by Bh on the measured parameters. Additionally, the expression of glutathione synthase and glutathione peroxidase, in addition to those of three genes ( Zeta , Tau , and Lambda ) of the GST gene family, was significantly upregulated when using Bh alone or in combination with different treatments, particularly after 24 h of treatment., Conclusion: The current study suggests using cyanobacterial extracts, particularly the A. platensis extract, for the development of an antioxidant defense system against herbicide toxicity, which would improve the metabolic response of developed wheat plants.

Objective: It has been proved that bystander cardiopulmonary resuscitation (CPR) saves lives and it is important to rise the willingness of the general population to help cardiac arrest victims. The primary objective of the present study is to assess the levels of the knowledge and attitude toward CPR among the young population who underwent the largest CPR training session in an official attempt to enter the Guinness Book of Records., Methods: Through a cross-sectional design, the study had 2,528 subjects, who met the inclusion and exclusion criteria during the largest CPR training session at the King Abdul-Aziz Sports City Stadium, Makkah city, Saudi Arabia., Results: Descriptive statistics showed that two-thirds (72%) of the subjects were in the age category of less than 20 years. At least 50% of the subjects had a Bachelor's degree. Overall, the findings of this study suggested a good level of knowledge and attitude against CPR and this is might be attributed to certain factors which are mainly the high level of education, age, and gender factors ( P value < 0.05)., Conclusion: Our findings support the need for proper and high-quality training for each member in the community about CPR as well as using social media and online training to highlight the importance of CPR among the young population., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Root survival to flooding-induced hypoxic stress is dependent upon maintaining the functionality of the root apical meristem quiescent center (QC), a process that is governed by the basipetal flow of auxin leading to the formation of an auxin maximum, which is needed for the establishment of a highly oxidized environment specifying the QC niche. Perturbations in auxin flow and distribution along the root profile occurring during hypoxia can shift the redox state of the QC towards a more reduced environment, leading to the activation of the QC, degradation of the meristem, and root abortion. The maize phytoglobin gene ZmPgb1.1 is involved in minimizing these damaging effects during hypoxia in processes that result in sustaining the PIN-mediated auxin maximum and an oxidized environment in the QC. The oxidized environment is accomplished by maintaining the activity of redox enzymes oxidizing ascorbate and glutathione. These events, compromised in QCs suppressing ZmPgb1.1, ensure the functionality of the QC and root meristems under conditions of low oxygen, resulting in stable root performance., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Background: Salmonella is considered to be the second largest source of infection in food-borne diseases. It is also considered one of the most important dangers particularly in the meat and dairy industry. Therefore, the main objective of our study was to determine the relationship between thermotolerance of a Salmonella serotype and the expression of DnaK and HtrA genes., Results: In this study, expression of the two genes DnaK and HtrA was compared under four different temperatures 37 °C, 42 °C, 50 °C, and 55 °C in two serotypes of Salmonella enterica subsp. enterica. One of them was isolated from tahini product and identified as Salmonella enterica subsp. enterica serovar choleraesuis. This identified serotype was found to be more thermotolerant than the second serotype (Salmonella enterica subsp. enterica serovar typhimurium (ATCC 13311)), which was used as reference. This conclusion was based on D and Z values, which were used to compare thermoresistance ability of the two serotypes under four different temperatures 60 °C, 65 °C, 70 °C, and 75 °C. In addition, the results of qRT-PCR showed that after 43 °C (induction temperature), the relative expression (fold change) of DnaK and HtrA genes increased up to 5 and 47, respectively, comparing to their expression at 37 °C., Conclusions: Thermotolerance of the identified S. choleraesuis serotype showed significantly high expression levels of DnaK and HtrA genes.

In order to investigate the salt tolerance mechanism in Egyptian lentils, five cultivars were grown under different salinity levels. The results indicated that Giza 9 is salt-tolerant, while Giza 4 is a salt-sensitive lentil cultivar, as Giza 9 showed the highest germination percentage and relative water content, the lowest decline in root and shoot length, and the highest proline content. Relative gene expression of ADH , CYS3 , APX , SOD , and GR was significantly upregulated in Giza 9 roots after 24 h of high salt treatment (250 mM), while CAT transcripts level was non-significantly reduced (0.5-fold) relative to control. However, in Giza 4, only CAT gene was significantly upregulated in both root (2.3-fold) and shoot (8.5-fold) tissues. Investigation of ascorbate-glutathione enzymatic activities revealed significantly higher ascorbate peroxidase and glutathione reductase activities in Giza 9 roots compared to its shoots. Moreover, endogenous reduced glutathione (GSH) content as well as reduced ascorbate content were significantly high in the roots of Giza 9 compared to Giza 4. These results strongly indicate the involvement of ascorbate-glutathione cycle in the tolerance mechanism of Giza 9. Furthermore, exogenous application of 350 μM of GSH assisted Giza 4 seedlings to tolerate salinity stress. As far as we know, this is the first work reporting the involvement of ascorbate-glutathione cycle in salt tolerance of lentil.

Background: Malignant pleural mesothelioma is an aggressive cancer with highly vascularised tumours. It has poor prognosis and few treatment options after failure of first-line chemotherapy. NGR-hTNF is a vascular-targeting drug that increases penetration of intratumoral chemotherapy and T-cell infiltration by modifying the tumour microenvironment. In this trial, we aimed to investigate the efficacy and safety of NGR-hTNF in patients with malignant pleural mesothelioma who had progressed during or after a first-line treatment., Methods: NGR015 was a randomised, double-blind, placebo-controlled phase 3 trial done in 41 centres in 12 countries. Eligible participants had malignant pleural mesothelioma of any histological subtype (epithelial, sarcomatoid, or mixed), were aged 18 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2 and radiologically documented progressive disease after one pemetrexed-based chemotherapy regimen. Participants were randomly assigned to receive weekly NGR-hTNF 0·8 μg/m 2 intravenously plus best investigator choice (n=200), or placebo plus best investigator choice (n=200). Best investigator choice was decided before random assignment and could be single-agent gemcitabine (1000-1250 mg/m 2 intravenously), vinorelbine (25 mg/m 2 intravenously or 60 mg/m 2 orally), doxorubicin (60-75 mg/m 2 intravenously), or best supportive care only. Patients were randomised (1:1) with a block size of four after stratification for performance status and best investigator choice. The primary study endpoint was overall survival in the intention-to-treat population. The trial is closed to new participants and is registered with ClinicalTrials.gov (NCT01098266)., Findings: Between April 12, 2010 and Jan 21, 2013, we enrolled 400 eligible participants. 381 (95%) of 400 patients were selected to receive chemotherapy before all participants were randomly assigned to receive NGF-hTNF plus best investigator choice (n=200) or placebo plus best investigator choice (n=200). At the cutoff date (April 29, 2014), the median follow-up was 18·7 months (IQR 15·1-24·4), and overall survival did not differ between the two treatment groups (median 8·5 months [95% CI 7·2-9·9] in the NGR-hTNF group vs 8·0 months [6·6-8·9] in the placebo group; hazard ratio 0·94, 95% CI 0·75-1·18; p=0·58). Grade 3 or worse study-emergent adverse events occurred in 136 (70%) of patients receiving NGR-hTNF versus 118 (61%) of patients receiving placebo, with the most common being neutropenia (35 [18%] of 193 patients vs 36 [19%] of 193 patients), pain (11 [6%] vs 16 [8%]), dyspnoea (nine [5%] vs seven [4%]), and chills (nine [5%] vs none). 50 (26%) patients in the NGR-hTNF group had a serious adverse event, compared with 47 (24%) in the placebo group. Treatment-related serious adverse events occurred in 17 (9%) patients in the NGR-hTNF group and 20 patients (10%) in the placebo group. There were 12 deaths in the NGR-hTNF group and 13 deaths in the placebo group, but none were treatment related., Interpretation: The study did not meet its primary endpoint. The hypothesis-generating findings from the subgroup analyses deserve a confirmatory randomised trial because patients who rapidly progress after first-line treatment have a poor prognosis., Funding: MolMed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Metronomic chemotherapy (MC) has shown efficacy in patients with metastatic breast cancer (MBC). We therefore tested the efficacy and toxicity of MC in pretreated MBC., Patients and Methods: This prospective phase II study included 50 patients with heavily pretreated MBC who received MC in the form of continuous oral cyclophosphamide 50 mg/day and oral methotrexate 2.5 mg twice per day on days 1 and 2 every week. The primary end point was progression-free survival (PFS), whereas the secondary end points were response rate, overall survival (OS), and safety., Results: Forty-eight patients were assessed. One patient achieved complete response and 10 patients had partial response, whereas 19 patients had stable disease. The median PFS was 5 months, whereas the median OS was 7 months. Patients with negative progesterone receptors, Eastern Cooperative Oncology Group performance status (PS) 1, achieving response, and those who developed leucopenia, neutropenia, and anemia had significant prolonged PFS, whereas patients with early stage at presentation, receiving < 5 previous treatment lines, achieving response, and experiencing anemia with MC had significant superior OS. In multivariate analysis, achieving response, PS 1, a longer time interval from initial diagnosis until starting MC, and anemia were independent prognostic factors for longer PFS. Initial stage at presentation, number of previous treatment lines, and response were independent prognostic factors for OS., Conclusions: MC is an attractive treatment approach that is effective and less toxic. There are certain groups of patients who seem to benefit more, especially those who experienced toxicity with treatment. Larger trials are warranted to assess this approach early in the course of the disease and with other more active agents., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gamma radiation is a very effective tool for inducing genetic variation in characters of many plants. Black seeds of M2 mutant were obtained after exposure of an Egyptian cowpea cultivar (Kaha 1) to a low dose of gamma rays. Segregation of seed coat color, weight of 100 seeds and seed eye pattern of the black seeds of this mutant line were further examined in this study. Four colors were observed for seed coat in the M3 plants ranging from cream to reddish brown and three eye patterns were distinguished from each other. SDS-PAGE of the seed storage proteins showed 18 protein bands; five of these bands disappeared in the seeds of M3 plants compared to M2 and M0 controls while other 5 protein bands were specifically observed in seeds of M3 plants. PCR analysis using twelve ISSR primers showed 47 polymorphic and 8 unique amplicons. The eight unique amplicons were characteristic of the cream coat color and brown wide eye pattern (M03-G10) while the polymorphic bands were shared by 6 coat-color groups. A PCR fragment of 850 bp was amplified, using primer HB-12, in M3-G04 which showed high-100 seed weight. These results demonstrated the mutagenic effects of gamma rays on seed coat color, weight of 100 seeds and eye pattern of cowpea M3 mutant plants.

Background: Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival., Methods: This double-blind, randomised, placebo-controlled trial was done in 90 international centres. Patients with measurable advanced malignant pleural mesothelioma and disease progression after one or two previous systemic regimens were eligible. After stratification for Karnofsky performance status, histology, and number of previous chemotherapy regimens, patients were randomly assigned (1:1) by use of an interactive voice response system with a block size of four to either treatment with vorinostat or placebo. Patients received oral vorinostat 300 mg (or matching placebo) twice daily on days 1, 2, 3, 8, 9, 10, 15, 16, and 17 of a 21-day cycle. The primary endpoints were overall survival and safety and tolerability of vorinostat. The primary efficacy comparison was done in the intention-to-treat population, and safety and tolerability was assessed in the treated population. This trial is registered with ClinicalTrials.gov, number NCT00128102., Findings: From July 12, 2005, to Feb 14, 2011, 661 patients were enrolled and randomly assigned to receive either vorinostat (n=329) or placebo (n=332) and included in the intention-to-treat analysis. Median overall survival for vorinostat was 30·7 weeks (95% CI 26·7-36·1) versus 27·1 weeks (23·1-31·9) for placebo (hazard ratio 0·98, 95% CI 0·83-1·17, p=0·86). The most common grade 3 or worse adverse events for patients treated with vorinostat were fatigue or malaise (51 [16%] patients in the vorinostat group vs 25 [8%] in the placebo group]) and dyspnoea (35 [11%] vs 45 [14%])., Interpretation: In this randomised trial, vorinostat given as a second-line or third-line therapy did not improve overall survival and cannot be recommended as a therapy for patients with advanced malignant pleural mesothelioma., Funding: Merck & Co., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC), overall survival (OS) as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed., Methods and Findings: We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs) or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an "all-comer" design). Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs) (0.99 vs. 1.04), the former exhibited greater progression-free survival-hazard ratios (PFS-HR) (mean, 0.40 vs. 1.01; P<0.01). A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%). The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01). An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%., Conclusion: The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of ∼0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial.

Background: This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of malignant pleural mesothelioma (MPM) with validation of progression free survival rate at 18 weeks (PFSR-18)(1) as primary end-point., Methods: Chemotherapy-naïve patients with histologically proven MPM and performance status (PS) 0/1, were treated with cisplatin 75 mg/m(2) on day 1 and bortezomib 1.3mg/m(2) on days 1, 4, 8, 11 every 3 weeks. The primary end-point validation utilised the landmark method., Results: Between 2007 and 2010 82 patients were entered. PFSR-18 was 53% (80% confidence intervals, CIs, 42-64%). The overall survival (OS) was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The median PFS was 5.1months (95% CI 3.3-6.5) and the response rate was 28.4% (95% CI 18.9-39.5%). The most frequent grade 3-4 toxicities were hyponatremia (46%), hypokalaemia (17%), fatigue (12.2%), thrombocytopenia (11%), neutropenia (9.7%) and neurotoxicity (motor, sensory, other: 1.2%, 8.5%, 2.4%). There were two toxic deaths (32 and 74days) due to acute pneumonitis and cardiac arrest. End-point validation showed that patients with no progression/progression at 18 weeks had median OS of 16.9/11.9 months, respectively. Hazard ratio was 0.46 (CI 0.32-0.67), logrank test and C-index were 0.007 and 0.60., Conclusion: The 50% PFSR-18 for CB was contained within the 80% CI for (42-64%). Therefore the null hypothesis could not be rejected. Accordingly this combination does not warrant further investigation. PFSR-18 was confirmed as a strong predictor of survival., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive disease with a generally poor prognosis. Since escape from cell cycle checkpoint control is common in several solid tumors, the present study was performed to evaluate the role of some cell cycle regulatory genes in the development and progression of MPM., Patients and Methods: Aberrant expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP), p53, mdm2 and Rb was assessed in 55 MPM cases from Egypt using immunohistochemistry and PCR techniques. Results were correlated with clinico-pathological prognostic factors, overall and disease free survival (OS&DFS)., Results: Altered expression of p14(ARF), p16(INK4A), p21(waf), p27(KIP1), Rb, p53 and mdm2 proteins was detected in 50.9%, 54.5%, 53.3%, 61.8%, 53.3%, 58.2%, and 50.8% of cases, respectively. SV40 infection significantly correlated with p14(ARF), 16(INK4A), p27(kip1) and Rb aberrations (p=0.014, p=0.02, p=0.01, p=-0.01). Asbestos exposure significantly correlated with p53, p21(waf) and mdm2 aberrations (p=0.001, p=0.03, p=0.02). On multivariate analysis PS ≥ 2, p27(KIP1) and Rb aberrations were independent prognostic factors for OS (p=0.016, p=0.011, p=0.003) whereas on tumor recurrence, p27(KIP1) and Rb aberrations were independent prognostic factors for DFS (p=0.002, p=0.03, p=0.01)., Conclusions: MPM is a complex disease characterized by multiple genetic aberrations; some of them involve cell cycle regulatory genes. p14(ARF), p16(INK4A), Rb and p27(KIP1) seem to be involved in SV40-associated MPM whereas mdm2, p53 and p21(WAF) are related to asbestos exposure. In addition to recurrence and PS, only p27(KIP1)and Rb could be used as molecular prognostic markers in MPM., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Superior sulcus tumors are a complex subset of tumors accounting for less than 5% of lung tumors., Methods: Twenty-three patients admitted between 2001 and 2007 were included in the study,. Computed tomography scan of the chest was considered the primary diagnostic and staging investigation for all patients. Radiation therapy was given preoperatively to 20 patients, neoadjuvant chemotherapy was given to 13 patients., Results: There were 22 men and one woman in the study. The mean age was 53 years. Lobectomy was performed in 20 patients and wedge resection was done for three patients. Three to five ribs were resected in all patients. Extended resections were performed in eight patients. Positive mediastinal lymph nodes were found six patients. The staging was: Stage IIB (11 patients); Stage IIIA (four patients), Stage IIIB (six patients) and Stage IV (two patients). Negative resection margin was achieved in 18 patients. Postoperative complications developed in nine patients, there was one operation related mortality. Tumor recurrence developed in 16 patients. The mean survival time was 2.8 years and the overall 5-years survival was 26%., Conclusion: Multimodality treatment gives satisfactory results with low morbidity and mortality rates and acceptable survival., (© Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.)

A lung cancer committee from the Middle East and North Africa (MENA) region was established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Non-Small Cell Lung Cancer to create a platform for standard care in the region. The committee comprised different experts in thoracic oncology from the region, including the disciplines of medical and clinical oncology, radiation oncology, thoracic surgery, pulmonary medicine, radiology, and pathology. The committee reviewed version 2 of the 2009 NCCN Guidelines on Non-Small Cell Lung Cancer and identified recommendations requiring modification for the region using published evidence and relevant experience. These suggested modifications were discussed among the group and with a United States-based NCCN expert for approval. The recommended modifications, with justification and references, were categorized based on the NCCN Guidelines flow. This article describes these recommended modifications. The process of adapting the first NCCN-based guidelines in the region is a step toward helping to improve lung cancer care in the region and encouraging networking and collaboration.

Background: Post pneumonectomy bronchopleural fistula represents the most serious complication in thoracic surgery. Delayed fistula following tri modality treatment for mesothelioma is a serious problem regarding diagnosis and treatment. Surgical repair of the bronchial stump through a lateral thoracotomy is a dangerous attempt due to mediastinal fibrothorax and the risk of pulmonary artery stump damage., Patients and Methods: Between 2002 and 2007, 85 extra pleural pneumonectomies for mesothelioma were performed. Only 58 patients completed the assigned tri modality treatment, five of them developed delayed bronchial stump dehiscence. The interval between primary surgery and stump dehiscence ranged from 6 months to 2 years., Results: There were 4 right and one left sided fistulae. We had 4 males and one female, the mean age was 41 years. Bronchial stump was stapled in 3 patients and hand sewn closure was used in the remaining 2. By bronchoscopy, no stump recurrence was observed, but all patients with stapled bronchus had longer remaining stump. Empyema was present in all patients. All complicated patients received 2 field post operative radiotherapy with mediastinal dose of 40-45 Grays. The initial treatment consisted of tube thoracostomy followed by exploration through the previous thoracotomy incision with thorough curettage and wash of the infected space and removal of any exposed infected mesh. Bronchial stump was identified and re sutured. Re enforcement of the bronchial stump was done. Three patients required mechanical ventilation and 2 of them died. Surgery was successful in the remaining 3 patients., Conclusion: Delayed bronchial stump dehiscence is liable to develop especially for right sided lesions. Prophylactic augmentation of right sided stumps with vascularised muscle flap, shielding of pathology proven negative stumps during radiotherapy and improvement of radiation techniques may improve the dose distribution., Key Words: Delayed - Bronchial - Stump - Fistula - Tri modality - Mesothelioma.

Background: The incidence and pattern of nodal metastases in mesothelioma are not well understood. This study was conducted to evaluate the prevalence and pattern of nodal metastasis in mesothelioma patients., Methods: The study included 53 patients with mesothelioma. The first 37 patients (group I) underwent combined modality treatment without preoperative mediastinoscopy. The second group included 16 patients (group II) with pretreatment mediastinoscopy., Results: A total of 18 patients had positive lymph nodes, 12 in group I and 6 in group II; of the latter, 4 had positive mediastinoscopy and 2 had positive nodes on final pathology. Postoperatively, a mean of 14 nodes were dissected (range, 5 to 34). In the post-pleuropneumonectomy group, 6 of 14 patients had positive hilar node metastases in addition to positive mediastinal lymph nodes. One patient had positive hilar nodes only. Of the 49 patients operated on, only 7 had no lung invasion by pathologic evaluation, and none had positive hilar nodes. The mechanism of spread of the disease to hilar nodes may be through lung invasion and not due to direct spread from the pleura. This observation raises the possibility that mediastinal nodes should be considered the primary station in patients with mesothelioma, whereas hilar node metastasis necessitated lung invasion first., Conclusions: The pattern of nodal metastases may be different from that of lung cancer, and multicenter studies are needed to evaluate this observation.

Background: Gemcitabine is an active agent in the treatment of bladder cancer. The enzyme deoxycytidine kinase catalyzes the phosphorylation of gemcitabine into the active gemcitabine triphosphate. After an infusion during 30 minutes, this enzyme will be saturated, therefore, accumulation of higher intracellular concentrations of the active gemcitabine triphosphate could be achieved by prolonging the infusion time of gemcitabine., Patients and Methods: Based on previously published Phase I trials, the efficacy and safety of a combination of cisplatin and gemcitabine given as prolonged infusion were tried in a Phase II study of 57 untreated patients with stage III/IV bladder cancer, which is the most common malignant tumor among Egyptian males. Patients received gemcitabine (250 mg/m(2) during 6-hour infusion) on days 1 and 8, and cisplatin (70 mg/m(2)) on day 2 every 21-day cycle., Results: The 41 males and 16 females had a median age of 55 years (range 37-77). A total of 37 patients had transitional cell, 15 had squamous cell, 2 had adenocarcinoma, and 3 had undifferentiated cell carcinoma. The median number of cycles given to these 57 patients was 4 (range 1-6). Of 54 evaluable patients, 5 (9.4%) had complete remission, and 27 (50%) partial remission, for an overall response rate of 59.4%. These results are comparable to those of a previous Phase II study of the same combination but with gemcitabine given in the standard dose and schedule. Responses were observed at all disease sites. Both hematologic and nonhematologic toxicity were treatable and not severe., Conclusions: Prolonged infusion of gemcitabine and cisplatin is an effective treatment for advanced bilharzial-related bladder cancer. Toxicity, especially myelosuppression, is surprisingly mild. This combination deserves to be tried in other different disease categories.

Asbestos has been recognized in Egypt since a long time as ancient Egyptians were using it in mummification. Mesothelioma in Egypt is mainly attributed to environmental origin with a high incidence of women and young adults affected. The incidence of mesothelioma is rising in Egypt. Epidemiological data for 635 malignant mesothelioma (MM) patients over 4 years in the third Millennium were collected from the National Cancer Institute (NCI), Cairo University and Abbassia Chest hospital. This number is more than four times the number diagnosed in the previous 11 years at NCI. A clinicopathological study was done for 100 malignant pleural mesothelioma (MPM) patients and showed that asbestos exposure and SV40 positivity were evident in 67% and 60% of cases, respectively. The median survival was 14.3 months and the 1 and 2 year survival rates were 60% and 27%, respectively. Evaluation of p53 and pRb immunohistochemically showed that pRb alteration was related to poor survival. Other biological prognostic factors such as EGFR, HER-2, glutathione S transferase (GST) and MDR were evaluated in 50 cases. Overexpression of EGFR was correlated with lack of clinical benefit and poor survival. GST potentiated the effect of EGFR on survival. The use of EGFR inhibitors may have a role in the treatment of MM. Asbestos in Cairo is a silent killer and measures toward eliminating it entirely or at least strictly controlling human contact with this dangerous carcinogen have to be taken in order to combat the coming epidemic of mesothelioma in Egypt.

Early bolting in sugar beet (Beta vulgaris L.) is controlled by the dominant gene B. From an incomplete physical map around the B gene, 18 bacterial artificial chromosomes (BACs) were selected for marker development. Three BACs were shotgun-sequenced, and 61 open reading frames (ORFs) were identified. Together with 104 BAC ends from 54 BACs, a total number of 55,464 nucleotides were sequenced. Of these, 37 BAC ends and 12 ORFs were selected for marker development. Thirty-one percent of the sequences were found to be single copy and 24%, low copy. From these sequences, 15 markers from ten different BACs were developed. Ten polymorphisms were determined by simple agarose gel electrophoresis of either restricted or non-restricted PCR products. Another five markers were determined by tetra-primer amplification refractory mutation system-PCR. In order to select candidate BACs for cloning the gene, genetic linkage between seven markers and the bolting gene was calculated using 1,617 plants from an F2 population segregating for early bolting. The recombination values ranged between 0.0033 and 0.0201. In addition, a set of 41 wild and cultivated Beta accessions differing in their early bolting character was genotyped with seven markers. A common haplotype encompassing two marker loci and the b allele was found in all sugar beet varieties, indicating complete linkage disequilibrium between these loci. This suggests that the bolting gene is located in close vicinity to these markers, and the corresponding BACs can be used for cloning the gene.

Aim of the Work: The aim of the present study is to document the antitumor activity of the combination of gemcitabine and cisplatin for the treatment of advanced NSCLC, asses the nature and severity of the side effects and elicit the impact of the combination chemotherapy on progression free survival and overall survival., Patients and Methods: From August 1997 to August 2001, we conducted a phase II study of gemcitabine and cisplatin in 60 chemonaive patients (21 stage IIIB and 39 stage IV). For the first 34 cases, gemcitabine was given at a dose of 1,000 mg/m2 IV on days 1, 8 and 15 with cisplatin 100 mg/m2 on day 15, every 28 days. In the following 26 patients, the regimen was modified to gemcitabine 1,250 mg/m2 days 1 and 8 and cisplatin 80 mg/m2 day 1, every 21 days., Results: Patients included 53 males and 7 females [median age, 52 years (range, 28-69)]. Twenty-nine had adenocarcinoma, 18 large-cell carcinoma and 13 squamous-cell carcinoma. Thirty-one patients had a performance status (PS) of 2 and 22 presented with weight loss. All patients were evaluable for response. Three patients achieved a complete response (CR) and 22 had partial response (PR), giving an overall response of 41.7%, with a median duration of 10 months (range, 4-46 months). The time to progression (TTP) was 8 months (range, 2-46 months), with a median overall survival of 9 months (range, 2-46 months). The one-year survival rate was 30.3% for the entire study population, 44% for responders, and statistically improved in patients with a PS of I and those with no weight loss. A total of 255 cycles were administered (median, four cycles/patient). Myelosuppression was significant (but manageable) with grade 3/4 neutropenia in 32.6% of cases, anemia in 18.6% and thrombocytopenia in 20.4%. Nonhematologic toxicity was limited to grade 3/4 nausea and vomiting in 28.8% of cases and impaired liver enzymes in 13.6%., Conclusion: Inspite of the relatively poor prognostic characteristics in the study population, gemcitabine and cisplatin, was an effective combination with tolerable, manageable toxicity in advanced NSCLC.

In sugar beet (Beta vulgaris L.), early bolting is caused by a single dominant gene, designated B. Twenty AFLP markers selected from a 7.8-cM segment of the B region on chromosome 2 were used to screen a YAC library, and a first-generation physical map including the B gene, made up of 11 YACs, was established. Because the genome coverage of the YAC library was low, a BAC library was constructed in the vector pBeloBAC11. This library consists of 57,600 clones with an average insert size of 116 kb, corresponding to 8.8 genome equivalents. Screening of the BAC library with chloroplast and mitochondrial DNA probes indicated that less than 0.1% of the clones contained organelle-derived DNA. To fill the gaps in the physical map around the B gene, the BAC library was screened with four AFLP markers and 10 YAC-derived probes. In total, 54 different BACs were identified. Overlaps between BACs were detected by using BAC termini amplified by PCR as probes, and by RFLP fingerprinting. In this way, a minimal tiling path of the central 4.6-cM region was constructed, which consists of 14 BACs. The B locus was localized to a 360-kb contig, a size which makes positional cloning of the gene feasible.