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he taxonomy of FicusL., 1753 species is confusing because of the intense morphological variability and the ambiguity of the taxa. This study handled 36 macro-morphological characteristics to clarify the taxonomic identity of the taxa. The study revealed that Ficusis represented in the Egyptian gardens with forty-one taxa; 33 species, 4 subspecies and 4 varieties, and classified into five subgenera: FicusCorner, 1960; TeregaRaf., 1838; SycomorusRaf.,1838; Synoecia(Miq.) Miq.,1867, and SpherosukeRaf.,1838; out of them seven were misidentified. Amongst, four newFicustaxa were recently introduced to Egypt namely: F. linguasubsp. linguaWarb. ex De Wild. & T. Durand, 1901; F. pumilaL., 1753; F. rumphiiBlume, 1825, and F. surForssk., 1775. The application of the multivariate analyses in plant systematics namely the two-way clustering analysis and the principal component analysis revealed that the qualitative characters as the presence or absence of lateral peduncular or ostiolar bracts and the leaf margin delimit the differentiation of subgenera within genus Ficus. Whereas the qualitative characters of the leaf as leaf arrangement, lamina shape, length, ratio of length to width, base, apex, number of lateral veins, stipules and figs either pedunculate or sessile, shape, and width are significantly separating the species within the different sections. Seven different identification keys of the studied taxa based on the examined characters are provided. In addition, a diagrammatic key for all the studied taxa is given.

Abstract The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Abstract Purpose The primary aim of NSABP FB-7 was to determine the pathologic complete response (pCR) rate in locally advanced HER2-positive (HER2+) breast cancer patients treated with neoadjuvant trastuzumab or neratinib or the combination and weekly paclitaxel followed by standard doxorubicin plus cyclophosphamide. The secondary aims include biomarker analyses. Experimental design pCR was tested for association with treatment, gene expression, and a single nucleotide polymorphism (SNP) in the Fc fragment of the IgG receptor IIIa-158V/F (FCGR3A). Pre-treatment biopsies and residual tumors were also compared to identify molecular changes. Results The numerical pCR rate in the trastuzumab plus neratinib arm (50% [95%CI 34–66%]) was greater than that for single-targeted therapies with trastuzumab (38% [95%CI 24–54]) or neratinib (33% [95%CI 20–50]) in the overall cohort but was not statistically significant. Hormone receptor-negative (HR−) tumors had a higher pCR rate than HR+ tumors in all three treatment arms, with the highest pCR rate in the combination arm. Diarrhea was the most frequent adverse event and occurred in virtually all patients who received neratinib-based therapy. Grade 3 diarrhea was reported in 31% of patients; there were no grade 4 events. Our 8-gene signature, previously validated for trastuzumab benefit in two different clinical trials in the adjuvant setting, was correlated with pCR across all arms of NSABP FB-7. Specifically, patients predicted to receive no trastuzumab benefit had a significantly lower pCR rate than did patients predicted to receive the most benefit (P = 0.03). FCGR genotyping showed that patients who were homozygous for the Fc low-binding phenylalanine (F) allele for FCGR3A-158V/F were less likely to achieve pCR. Conclusions Combining trastuzumab plus neratinib with paclitaxel increased the absolute pCR rate in the overall cohort and in HR− patients. The 8-gene signature, which is validated for predicting trastuzumab benefit in the adjuvant setting, was associated with pCR in the neoadjuvant setting, but remains to be validated as a predictive marker in a larger neoadjuvant clinical trial. HR status, and the FCGR3A-158V/F genotype, also warrant further investigation to identify HER2+ patients who may benefit from additional anti-HER2 therapies beyond trastuzumab. All of these markers will require further validation in the neoadjuvant setting. Trials registration ClinicalTrials.gov, NCT01008150. Retrospectively registered on October 5, 2010.

For the first time, an updated checklist of Acacia, Senegalia and Vachellia species in Egypt is provided, focusing on the exotic species. Taking into consideration the retypification of genus Acacia ratified at the Melbourne International Botanical Congress (IBC, 2011), a process of reclassification has taken place worldwide in recent years. The review of Acacia and its segregates in Egypt became necessary in light of the available information cited in classical works during the last century. In Egypt, various taxa formerly placed in Acacia s.l., have been transferred to Acacia s.s., Acaciella, Senegalia, Parasenegalia and Vachellia. The present study is a contribution towards clarifying the nomenclatural status of all recorded species of Acacia and its segregate genera. This study recorded 144 taxa (125 species and 19 infraspecific taxa). Only 14 taxa (four species and 10 infraspecific taxa) are indigenous to Egypt (included now under Senegalia and Vachellia). The other 130 taxa had been introduced to Egypt during the last century. Out of the 130 taxa, 79 taxa have been recorded in literature. The focus of this study is the remaining 51 exotic taxa that have been traced as living species in Egyptian gardens or as herbarium specimens in Egyptian herbaria. The studied exotic taxa are accommodated under Acacia s.s. (24 taxa), Senegalia (14 taxa) and Vachellia (13 taxa). Identification keys for the studied genera, generic groups and species have been provided using different taxonomic criteria. For each taxon, the validated name with the first citation followed by relevant Egyptian citations, typification, synonyms, distinctive features, origin, ecology (when available), utilisation and selected specimens are provided. The study revealed the presence of 22 newly recorded taxa in Egypt. Additionally, a list of excluded, unvalidated and unresolved names is given.

Egypt is characterized by its hyper-arid desert environment with high temperature, scanty rainfall, high evapotranspiration rate, and patchy scattered precipitation-dependent vegetation. Located in this peculiar ecosystem, the northeastern part of the eastern desert occupies vast areas where this study was conducted. Despite some protection in this area, destruction of plant cover, soil erosion, and degradation of natural habitat are still occurring. Among the complex array of anthropogenic disturbances that directly affect species diversity, over-grazing, road construction, over-collection of plants, salinization, over-cutting, military activities, urbanization, and industrialization were encountered. The aim of this study was to assess the effect on long-lasting anthropopressure on the current floristic and ecological status of the unprotected area in comparison to the protected one. Two areas were chosen for detailed studies: protected (Wadi Degla; WD) and unprotected (Cairo-Suez road, SR). Fourteen soil variables were used to assess the soil–vegetation relationships in the two areas. An assessment of seven human activities (over-grazing, over-collection, introduced species, land degradation, urbanization, solid wastes, and military activities) was carried out at four levels of disturbance intensities. A floristic presence/absence data set of 25 plots × 56 species, including 14 plots for SR and 11 plots for WD, was employed in the analyses. The application of multivariate analysis techniques such as cluster analysis (for classification), indicator species analysis (ISA) and the multi-response permutation procedure (MRPP), canonical correspondence analysis (CCA), and redundancy analysis (RDA) for ordination were performed in the data analysis. Generally, a total of 85 plant species belonging to 68 genera and 30 families was recorded. Asteraceae, Chenopodiaceae, Fabaceae, Zygophyllaceae, Poaceae, Brassicaceae, and Geraniaceae were the largest families, constituting more than 50% of the total flora. Chamaephytes, therophytes, hemicryptophytes, and phanerophytes prevail in the life form spectrum. Chorological analysis showed that the Saharo-Arabian element, whether pure or combined with other chorotypes, dominated the current flora, whereas the Mediterranean chorotype was very poorly represented. Application of cluster analysis yielded eight vegetation groups: I–IV for the Cairo-Suez road, and V–VIII for Wadi Degla. This study indicated the disappearance of several plant communities that were previously of common occurrence such as Retama raetam, Anabasis articulata, Ephedra alata, Artemisia monosperma, Zygophyllum decumbens, Lasiurus hirsutus, and Panicum turgidum. Partial CCA (pCCA) for the unprotected area revealed that most of the variance (45.7%) was attributed to the anthropogenic variables more than soil factors (14.5%). Like what was revealed in other unprotected areas, a clear relationship between anthropogenic pressure and habitat fragmentation was observed. Long-term, intensive human activities caused vegetation degradation, species loss, and a decline in plant richness. Hence, the highest species richness value was recorded in the protected area. Over-grazing, land degradation, and military activities were not correlated with the diversity indices, whereas over-collection of plant species, urbanization, and solid wastes were significantly negatively correlated with both α-diversity and the Shannon–Wiener index. Suitable protection measures should be taken to reduce the anthropogenic pressures in this ecosystem as well as some conservation programs and management plans should be implemented to save biodiversity.

Four simple and sensitive spectrophotometric methods were developed for the determination of the sulfhydryl containing drug mesna (MSN). Methods I and II rely on nucleophilic aromatic substitution reactions using two UV tagging reagents namely: 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) for method I and 2,4-dinitrofluorobenzene (DNFB) for method II. Both reactions took place in alkaline buffered medium and the obtained yellowish products were measured at 414 and 332 nm for methods I and II, respectively. Methods III and IV are indirect spectrophotometric methods based on the suppressive effect of MSN on the absorption of two ternary complex systems which are composed of 1,10-phenanthroline, silver and eosin for method III and 1,10-phenanthroline, silver and bromopyrogallol red for method IV. The decrease in absorbance of the ternary complexes was measured at 547 and 635 nm for methods III and IV, respectively. All the experimental parameters affecting these reactions were carefully studied and optimized. The methods were validated as per the ICH guidelines. The methods were applicable in the linearity ranges 4–18 μg/mL for method I, 4–16 μg/mL for method II, 0.25–2.25 μg/mL for method III and 0.25–1.75 μg/mL for method IV. The proposed methods were successfully applied for the analysis of MSN in its commercial ampoules and no interference was encountered from the present excipients as indicated by the satisfactory percentage recoveries. The results obtained were in a good agreement with those obtained from a previously published method of the investigated drug.

After the publication of this work [1] the authors have reported that in Table 3 The letter “T” in columns 5 and 7 should not be there.

Molecular subtypes of colorectal tumors are associated with prognosis and prediction for treatment benefit from chemotherapy. The purpose of this study was two-fold: 1) to determine the association of colorectal (CRC) molecular subtypes with response to targeted therapies in pre-clinical models and 2) to identify treatments for CRC stem-like subtype because these tumors are associated with a very poor patient prognosis. Eleven CRC cell lines were classified into molecular subtypes and tested for their response to pan-ERBB, MEK, and ERK inhibitors as single agents and in combination. All six inflammatory or TA cell lines were exquisitely sensitive to the combination of MEK and neratinib whereas all five stem-like cell lines were resistant. Growth inhibition in sensitive cell lines was greater with the combination than with either drug alone even in cell lines with KRAS mutations. The combination inhibited pERK in inflammatory cell lines but not in four out of five stem-like cell lines. MEK162 plus neratinib were synergistic in cell culture and xenograft models in inflammatory cell lines. The ERK inhibitor, SCH772984, down-regulated pERK, decreased cell viability, and was synergistic with neratinib in both inflammatory and stem-like subtypes. These results suggest that inhibition of pERK is a critical node in decreasing cell viability of stem-like CRC tumors. Our results also suggest that CRC molecular subtypes may yield predictive information and may help to identify patients who may respond to targeted inhibitors.

A new, reliable, sensitive and stability-indicating gradient HPLC method was introduced for the simultaneous determination of two anti-hepatotoxic polyphenolic drugs (Silymarin and Curcumin). The method was adapted to analyze both drugs in their dosage forms (tablets and capsules) with no interference from common excipients. The photo diode array detector was used as a tool for peak identification and purity confirmation especially that both drugs have several reported peaks. In order to assess the stability-indicating power of the assay procedure, SIL and CUR were subjected to different forced degradation studies: acidic, alkaline and neutral hydrolysis, photo-degradation, oxidative degradation and dry heat. The developed method could efficiently separate the parent drug peak from the degradation products peaks. The method was validated according to the ICH guidelines with respect to linearity, detection and quantitation limits, accuracy, precision, specificity, and robustness. Finally, the results of the proposed method for determination of SIL were statistically compared to the official BP method and no significant difference was found between them.

A validated, simple and sensitive stability-indicating HPLC method was introduced for the analysis of Pentoxifylline in the presence of its pharmacopeial related substances, Caffeine anhydrous and Theophylline anhydrous, in the presence of its forced degradation products. This was achieved using a gradient DAD–HPLC method in order to achieve a good separation between the related substance peaks, complying with the pharmacopeial requirement, and an adequate retention time for the Pentoxifylline peak. The method was validated according to the ICH guidelines and different HPLC parameters were optimized for the determination of Pentoxifylline in its dosage form (sustained release tablets). Furthermore, the study of forced degradation of Pentoxifylline was done under various conditions including; hydrolysis (acid, alkaline and neutral), oxidation, dry heat and photo-decomposition. The proposed method could separate Pentoxifylline peak from those of the different forced degradation product peaks and the purity of the Pentoxifylline peak was confirmed using the photo-diode array detector.

Essential thrombocythemia is one of the myeloproliferative neoplasms with a plethora of thrombohemorrhagic complications. Hydroxyurea has been proven to be an effective treatment for this condition. However, it is not without side effects. We herein report 3 patients with essential thrombocythemia treated with hydroxyurea who developed refractory leg ulcers, and we outline their successful management. We also review the literature to shed light on the mechanism of this toxicity. Awareness of this important treatment complication is important to avoid the pitfall of futile invasive interventions.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.