Publications by authors named "Mohamed L Salem"

53 Publications

WITHDRAWN: Reduced fitness of the mosquito Culex pipiens (Diptera: Culicidae) after feeding on a blood meal with hepatitis C virus.

J Invertebr Pathol 2021 Jan 28:107522. Epub 2021 Jan 28.

Department of Zoology, Faculty of Science, Tanta University, Tanta 31527, Egypt.

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http://dx.doi.org/10.1016/j.jip.2020.107522DOI Listing
January 2021

Immunosuppressive role of Benzo[a]pyrene in induction of lung cancer in mice.

Chem Biol Interact 2021 Jan 24;333:109330. Epub 2020 Nov 24.

Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Aim: Benzo[a]pyrene [BP] is one of the major carcinogenic precursors of cigarette smoke that primary affects the lung at its first proximity. The goal of the current research was to elucidate new mechanisms underlying the tumorigenic impact of oral BP in the lung of mice, with focus on immunosuppressive effects and cancer stemming properties.

Methods: Female albino mice (n = 44) were divided into 2 groups: normal control and BP group. BP was administered orally to mice (50 mg/kg body weight), twice a week for four weeks in succession. At the end of experiment (22 weeks), gene expression were measured for transforming growth factor-β (TGF-β), cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death ligand 1(PD-L1), forkhead box protein P3 (FOXP3) and interleukin 12 (IL-12) and CD83, CD8 and CD166 cell percentage were measured in lung tissue.

Results: The results indicated the tumorigenic role of BP in the lung which was evidenced by histopathological examination. BP group also showed immunosuppressive role which evidenced by increased expression of lung TGF-β, CTLA-4, PD-L1, FOXP3 genes and decreased expression of lung IL-12 gene compared with normal control group. BP group also showed decreased CD83 cells, CD8 cells and increased number of CD166 cells.

Conclusion: Our findings indicated that BP has immunosuppressive role in lung cancer besides increasing the percentage of cancer stem like cells.
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http://dx.doi.org/10.1016/j.cbi.2020.109330DOI Listing
January 2021

Ramadan intermittent fasting and immunity: An important topic in the era of COVID-19.

Ann Thorac Med 2020 Jul-Sep;15(3):125-133. Epub 2020 Jun 18.

Department of Medicine, College of Medicine, University Sleep Disorders Center, King Saud University, Reyad, Saudi Arabia.

WITH the growing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-related coronavirus (SARS-CoV-2) infection, a parallel growing interest arose concerning potential preventive and adjunct therapies, dietary and lifestyle modifications, and remedies that may boost the immunity against SARS-CoV-2 infection. Furthermore, as Ramadan intermittent religious fasting that is practiced by about one and a half billion Muslims throughout the globe is coincide this year with COVID-19 pandemic, a growing debate rose concerning the expected impact of fasting during Ramadan month and the associated dietary and lifestyle behaviors on the body's immunity against the pandemic infection. Published literature was searched to find out how intermittent fasting (IF) and its model of Ramadan affect the various aspects related to the body's immunity against microbial infections. IF was found to impact immunity by changing different related elements, including oxidative stress and inflammation, metabolism, body weight, and body composition. Dietary and lifestyle modifications during Ramadan month and their impact on immunity, such as water intake and hydration status, sleep duration and timing, caloric intake and mealtime, and social and spirtual activities, were addressed. Further research is warranted to figure out how IF during ramadan affects immunity against SARS-CoV-2 infection.
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http://dx.doi.org/10.4103/atm.ATM_151_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423203PMC
June 2020

Treatment options for autoimmune bullous dermatoses other than systemic steroids: A systematic review and network meta-analysis.

Dermatol Ther 2020 11 7;33(6):e13861. Epub 2020 Jul 7.

Immunology and Biotechnology Division, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.

Autoimmune blistering diseases can eventually cause life-threatening complications if left untreated. Although there is no cure for these bullous diseases; their therapy is based on suppressing the immune system to cease the de novo formation of the generated antibodies. The current study aimed to assess the safety and efficacy of using standing alone alternative therapies beyond systemic steroids for management of autoimmune bullous diseases. We searched six literature databases for both randomized and quasi-randomized clinical trials that assessed the efficacy of drugs other than systemic steroids in autoimmune bullous diseases. Outcomes were calculated as odds ratios with 95% confidence-interval. We used the R software to perform conventional and network meta-analyses with a frequentist approach. The network ranking order for 629 bullous pemphigoid patients, from the best to the worst was, clobetasol propionate cream (40 mg; (P-score = .87), clobetasol propionate cream (10-30 mg; P-score = .77), nicotinamide plus tetracycline (P-score = .56), steroids (P-score = .29) and doxycycline (P-score = .01). Limitations of this study are the small sample of the included studies except for blister trial and lack of randomization in most trials. To conclude, Combined doxycycline and nicotinamides are safer and more effective option for extensive bullous pemphigoid patients than the usual use of systemic steroids. For limited disease, topical corticosteroid (40 mg/d) use provides a safer and better response modality than the other proposed treatments.
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http://dx.doi.org/10.1111/dth.13861DOI Listing
November 2020

Anti-neoplastic and immunomodulatory potency of co-treatment based on bovine lactoferrin and/or muramyl dipeptide in tumor-bearing mice.

Toxicol Res (Camb) 2020 Apr 24;9(2):137-147. Epub 2020 Apr 24.

Zoology Department, Faculty of Science, Menoufia University, Shibin El Kom 32511, Egypt.

The current study investigates anti-neoplastic and immunomodulatory activities of co-treatment based on bovine lactoferrin (bLF) and/or muramyl dipeptide (MDP) with or without cisplatin (Cis) in tumor-bearing mice. In the present study, bLF (100 mg/kg; orally) and MDP (0.5 mg/kg; subcutaneously) was administered alone or together. MDP or bLF was co-treated with Cis (1 mg/kg; intraperitoneally) in mice-bearing Ehrlich solid carcinoma. Tumor size, tumor mass proliferation, apoptosis using immunohistochemistry, the alteration in spleen cell proliferation, phenotype using flow cytometry and white blood cells total and differential counts were detected. Treatment with Cis or (bLF and MDP) significantly reduced tumor size, upregulated the pro-apoptotic p53 expression and downregulated the anti-apoptotic Bcl-2 and proliferative marker PCNA expression compared to non-treated tumor-bearing animals. Moreover, co-treatment of MDP and Cis significantly potentiated the reduction of the tumor size, downregulated the Bcl-2 and PCNA expression and upregulated the p53 expression compared to Cis-treated animals. While bLF and Cis co-treatment positively controlled PCNA and p53 expression compared to tumor-bearing animals, it significantly potentiated the reduction of the tumor size and downregulated the Bcl-2 expression compared to Cis-treated animals. Co-treatment of (bLF and MDP), (bLF and Cis) or (MDP and Cis) increased the spleen cell proliferation and altered the immunological profile of the CD3CD4, CD3CD8, CD3CD4CD69, CD3CD8CD69 and CD11bLy6G cells to achieve better immune response against tumor. In conclusion, co-treatments based on bLF and/or MDP are promising therapies against cancer, through their potency to control proliferation, enhance apoptosis and improve the immune status against tumor cells.
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http://dx.doi.org/10.1093/toxres/tfaa012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233322PMC
April 2020

Correlations between MHLC scores and Indicators of Immune Response in Egyptian Women with Breast Cancer.

Gulf J Oncolog 2020 Jan;1(32):7-11

Oncology Department, Faculty of Medicine, Tanta University, Egypt.

Background: Recent studies indicate the immune dysfunction in cancer patients in comparison with healthy individuals. The quality and quantity of this dysfunction are not equal in all patients even with similar cancer type.

Aim: This study aims to correlate health locus of control (HLC) beliefs with CD4+ helper T (Thelper) cells, T regulatory (Treg) cells, NK cells, IL-1ß and TNF-a in breast cancer patients.

Patients And Methods: The study included 30 early diagnostic breast cancer patients who responded to Form C of the MHLC questionnaire that assessed internal (IHLC), chance (CHLC), doctor (DHLC) and other person's (OHLC) control of the patient's health status. Peripheral blood samples were collected to analyze the numbers and phenotype of Thelper cells, Treg cells and NK cells by flow cytometry and to measure gene expression of IL-1ß and TNF-a with real time PCR.

Results: A significant positive correlation was found between IHLC with Thelper cells and NK cells. However, a significant inverse correlation was found between DHLC with NK, Thelper and Treg cells.

Conclusion: There is strong probability that the quality of immunity in cancer patients is related to their MHLC beliefs. Further research is recommended for studying whether MHLC beliefs of patients with other types of cancer can improve their immune responses and how beliefs control immune system.
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January 2020

The Toll-Like Receptor 3 Agonist Polyriboinosinic Polyribocytidylic Acid Increases the Numbers of NK Cells with Distinct Phenotype in the Liver of B6 Mice.

J Immunol Res 2020 5;2020:2489407. Epub 2020 Mar 5.

Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, Saudi Arabia.

One of the activating factors of the cells of the innate immune system is the agonists of toll-like receptors (TLRs). Our earlier publications detailed how poly(I:C), a TLR3 agonist, elevates the NK cell population and the associated antigen-specific CD8 T cell responses. This study involved a single treatment of the B6 mice with poly(I:C) intraperitoneally. To perform a detailed phenotypic analysis, mononuclear cells were prepared from each of the liver, peripheral blood, and spleen. These cells were then examined for their NK cell population by flow cytometric analysis following cell staining with indicated antibodies. The findings of the study showed that the NK cell population of the liver with an NK1.1CD11bCD11c B220Ly6G phenotype was elevated following the treatment with poly(I:C). In the absence of CD11b molecule (CR3 mice), poly(I:C) can still increase the remained numbers of NK cells with NK1.1CD11b and NK1.1Ly6G phenotypes in the liver while their numbers in the blood decrease. After the treatment with anti-AGM1 Ab, which induced depletion of NK1.1CD11b cells and partial depletion of CD3NK1.1 and NK1.1CD11b cell populations, poly(I:C) normalized the partial decreases in the numbers of NK cells concomitant with increased numbers of NK1.1CD11b cell population in both liver and blood. Regarding mice with a TLR3 phenotype, their injection with poly(I:C) resulted in the partial elevation in the NK cell population as compared to wild-type B6 mice. To summarise, the TLR3 agonist poly(I:C) results in the elevation of a subset of liver NK cells expressing the two myeloid markers CD11c and CD11b. The effect of poly(I:C) on NK cells is partially dependent on TLR3 and independent of the presence of CD11b.
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http://dx.doi.org/10.1155/2020/2489407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077049PMC
September 2020

A new strategy for enhancing antitumor immune response using dendritic cells loaded with chemo-resistant cancer stem-like cells in experimental mice model.

Mol Immunol 2019 07 30;111:106-117. Epub 2019 Apr 30.

Biochemistry Department, Faculty of Pharmacy, Tanta University, Egypt. Electronic address:

Background And Aim: Cancer stem cells (CSCs) are rare cell population present in the tumor bulk that are thought to be the reason for treatment failure following chemotherapy in terms of their intrinsic chemo-resistance. Our study aimed to develop an effective therapeutic strategy to target chemo-resistant cancer stem - like cells population in solid Ehrlich carcinoma (SEC) mice model using dendritic cells (DCs) loaded with enriched tumor cells lysate bearing CSC-like phenotype as a vaccine.

Materials And Methods: Ehrlich carcinoma cell line was exposed to different concentrations of cisplatin, doxorubicin, or paclitaxel. Drug treatment that resulted in drug surviving cells with the highest expression of CSCs markers (CD44/CD24) was selected to obtain enriched cell cultures with resistant CSCs population. Dendritic cells were isolated from mice bone marrow, pulsed with enriched CSC lysate, analyzed and identified (CD11c, CD83 and CD86). SEC-bearing mice were treated with loaded or unloaded DCs either as single treatment or in combination with repeated low doses of cisplatin. IFN- γ serum level and p53gene expression in tumor tissues were determined by ELISA and real-time PCR, respectively.

Results And Conclusion: The results revealed that vaccination with CSC loaded DCs significantly reduced tumor size, prolonged survival rate, increased IFN-γ serum levels, and upregulated p53gene expression in SEC bearing mice. These findings were more evident and significant in the group co-treated with CSC-DC and cisplatin rather than other treated groups. This study opens the field for combining CSC-targeted immunotherapy with repeated low doses chemotherapy as an effective strategy to improve anticancer immune responses.
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http://dx.doi.org/10.1016/j.molimm.2019.04.001DOI Listing
July 2019

Cyclophosphamide eradicates murine immunogenic tumor coding for a non-self-antigen and induces antitumor immunity.

Int J Immunopathol Pharmacol 2018 Jan-Dec;32:2058738418796591

5 Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.

Although the majority of cancers respond to chemotherapy, most cancer types relapse, at least in part, due to the poor immunogenicity of most tumor. We have reported before that treatment of tumor bearing mice with a combination of the anti-cancer chemotherapy cyclophosphamide (CTX) and immunotherapy can result in complete tumor regression using T-cell receptor (TCR) transgenic CD8 T cells specific to antigens. This study aimed to determine whether chemotherapy can cure immunogenic tumor which expresses non-self-tumor antigen and result in antitumor immunity. Either EL4 cell line, a poorly immunogenic thymoma, or EG7, a clone of EL4 cells transfected with ovalbumin (OVA), as a non-self-antigen were inoculated subcutaneously into wild type or splenectomized C57BL/6 mice and then treated once with intraperitoneal (i.p.) injection of 4 mg CTX/mouse. In certain experiments, the mice were rechallenged with the same tumor type 1-2 months after the primary challenge. Treatment of EL4 bearing mice with CTX induced transient antitumor effect followed by tumor progression. Interestingly, however, treatment of EG7-bearing mice with CTX resulted in regression of early and advanced tumors. EG7 tumor-free mice rejected the second and the third challenges with EG7 cells, but not with challenge EL4 cells. These antitumor effects did not require spleen, since splenectomized mice showed similar antitumor effects of CTX on EG7 cells. Taken together, these data indicate that expression of non-self-antigen by poorly immunogenic tumor might be a reliable means to increase its immunogenicity and its response to chemotherapy.
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http://dx.doi.org/10.1177/2058738418796591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168726PMC
December 2018

A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell-dendritic cell-based vaccine.

Oncol Lett 2018 Jul 4;16(1):529-535. Epub 2018 May 4.

Medical Biochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11976, Egypt.

Dendritic cells (DCs) have been used in a number of clinical trials for cancer immunotherapy; however, they have achieved limited success in solid tumors. Consequently the aim of the present study was to identify a novel potential immunotherapeutic target for breast cancer patients through optimization of a viable DC-based vaccine. Immature DCs were primed by viable MCF-7 breast cancer cells and the activity and maturation of DCs were assessed through measuring CD83, CD86 and major histocompatibility complex (MHC)-II expression, in addition to different T cell subpopulations, namely CD4 T cells, CD8 T cells, and CD4CD25 forkhead box protein 3 (Foxp3) regulatory T cells (Tregs), by flow cytometric analysis. Foxp3 level was also measured by enzyme-linked immunosorbent assay (ELISA) in addition to reverse-transcription quantitative polymerase chain reaction. The levels of interleukin-12 (IL-12) and interferon-γ (IFN-γ) were determined by ELISA. Finally, the cytotoxicity of cytotoxic T lymphocytes (CTLs) was evaluated through measuring lactate dehydrogenase (LDH) release by ELISA. The results demonstrated that CD83, CD86 and MHC-II DCs were significantly elevated (P<0.001) following priming with breast cancer cells. In addition, there was increased activation of CD4 and CD8 T-cells, with a significant decrease of CD4CD25Foxp3 Tregs (P<0.001). Furthermore, a significant downregulation of FOXP3 gene expression (P<0.001) was identified, and a significant decrease in the level of its protein following activation (P<0.001) was demonstrated by ELISA. Additionally, significant increases in the secretion of IL-12 and IFN-γ (P=0.001) were observed. LDH release was significantly increased (P<0.001), indicating a marked cytotoxicity of CTLs against cancer cells. Therefore viable breast cancer cell-DC-based vaccines could expose an innovative avenue for a novel breast cancer immunotherapy.
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http://dx.doi.org/10.3892/ol.2018.8631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006460PMC
July 2018

Loading of doxorubicin and thymoquinone with F2 gel nanofibers improves the antitumor activity and ameliorates doxorubicin-associated nephrotoxicity.

Life Sci 2018 Aug 6;207:461-470. Epub 2018 Jun 6.

Biochemistry Department, Faculty of Pharmacy, Menoufia University, Egypt.

Aims: This study aimed to elucidate the benefits of nanoformulation of doxorubicin (DOX) and thymoquinone (TQ) loaded with nanofibers of poly-N-acetyl glucosamine (pGlcNAc), which is known as F2 gel, over their conventional free forms. Moreover, evaluate the role of TQ in improving chemotherapeutic effect and ameliorating nephrotoxicity of DOX.

Main Methods: The drugs were loaded into F2 gel followed by measurement of physicochemical characterization. Next, MCF-7 and HEPG2 cells were treated with the prepared formulations and assessed for apoptosis alongside with cellular proliferation. Furthermore, we experimentally induced Heps liver carcinoma in mice and at the end of the treatment, mice were sacrificed and serum samples were used to assess nephrotoxicity markers; blood urea nitrogen (BUN) and creatinine. Additionally, renal tissue was used for determination of oxidative markers and antioxidant enzymes; whereas, tumor tissue was utilized to measure nuclear factor kappa B (NF-κB) and caspase 3.

Key Findings: Nanoformulation showed dramatic increase in apoptosis, caspase 3, and antioxidant enzymes; in contrast to, dramatic fall in cell viability, tumor volume, oxidative and nephrotoxicity markers, and NF-κB compared to corresponding free therapies. Combined therapy was superior in conserving the measured parameters compared to other treated groups.

Significance: F2 gel loaded with DOX and TQ revealed enhanced antitumor activity with minimal toxicity. Moreover, using TQ as an adjuvant with DOX could augment its cytotoxicity and ameliorate nephrotoxicity.
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http://dx.doi.org/10.1016/j.lfs.2018.06.008DOI Listing
August 2018

Fibroblast growth factor 2 decreases bleomycin-induced pulmonary fibrosis and inhibits fibroblast collagen production and myofibroblast differentiation.

J Pathol 2018 09 5;246(1):54-66. Epub 2018 Jul 5.

University of Chicago, Department of Medicine, Section of Pulmonary and Critical Care Medicine, Chicago, IL, USA.

Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin-induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double-transgenic (DTG) mice with doxycycline-inducible overexpression of human FGF2 (SPC-rtTA;TRE-hFGF2) or single-transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild-type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline-induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 overexpression was induced at day 0 or day 7 after bleomycin. FGF2 overexpression did not alter epithelial gene expression, bronchoalveolar lavage cellularity or total protein. In vitro studies using primary mouse and human lung fibroblasts showed that FGF2 strongly inhibited baseline and TGFβ1-induced expression of alpha smooth muscle actin (αSMA), collagen, and connective tissue growth factor. While FGF2 did not suppress phosphorylation of Smad2 or Smad-dependent gene expression, FGF2 inhibited TGFβ1-induced stress fiber formation and serum response factor-dependent gene expression. FGF2 inhibition of stress fiber formation and αSMA requires FGF receptor 1 (FGFR1) and downstream MEK/ERK, but not AKT signaling. In summary, overexpression of FGF2 protects against bleomycin-induced pulmonary fibrosis in vivo and reverses TGFβ1-induced collagen and αSMA expression and stress fiber formation in lung fibroblasts in vitro, without affecting either inflammation or epithelial gene expression. Our results suggest that in the lung, FGF2 is antifibrotic in part through decreased collagen expression and fibroblast to myofibroblast differentiation. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175645PMC
September 2018

Enhanced Lymphodepletion Is Insufficient to Replace Exogenous IL2 or IL15 Therapy in Augmenting the Efficacy of Adoptively Transferred Effector CD8 T Cells.

Cancer Res 2018 06 10;78(11):3067-3074. Epub 2018 Apr 10.

Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.

Effector CD8 T cells conditioned with IL12 during activation mediate enhanced antitumor efficacy after adoptive transfer into lymphodepleted hosts; this is due in part to improved IL7 responsiveness. Therefore, we hypothesized that increasing the intensity or type of lymphodepletion would deplete more IL7-consuming host cells and improve the persistence and antitumor activity of IL12-conditioned CD8 T cells. Using cyclophosphamide, fludarabine, and total body irradiation (TBI, 6 Gy) either individually or in combination, we found that combined lymphodepletion best enhanced T-cell engraftment in mice. This improvement was strongly related to the extent of leukopenia, as posttransfer levels of donor T cells inversely correlated to host cell counts after lymphodepletion. Despite the improvement in engraftment seen with combination lymphodepletion, dual-agent lymphodepletion did not augment the antitumor efficacy of donor T cells compared with TBI alone. Similarly, IL7 supplementation after TBI and transfer of tumor-reactive T cells failed to improve persistence or antitumor immunity. However, IL15 or IL2 supplementation greatly augmented the persistence and antitumor efficacy of donor tumor-reactive T cells. Our results indicate that the amount of host IL7 induced after single agent lymphodepletion is sufficient to potentiate the expansion and antitumor activity of donor T cells, and that the efficacy of future regimens may be improved by providing posttransfer support with IL2 or IL15. The relationship between lymphodepletion and cytokine support plays a critical role in determining donor T-cell engraftment and antitumor efficacy. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-2153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108084PMC
June 2018

Hb Moscva [β24(B6)Gly→Asp (GGT>GAT), HBB: c.74G>A]: An Unstable Hemoglobin Newly Detected as a De Novo Mutation in a Mauritanian Patient.

Hemoglobin 2018 Jan 22;42(1):7-10. Epub 2018 Mar 22.

c Laboratory of Cell and Molecular Hematology , Pasteur Institute of Tunis, University of Tunis El Manar , Tunis , Tunisia.

Unstable hemoglobins (Hbs) are a group of Hb disorders that could be the origin of chronic hemolytic anemia. Most of these disorders are caused by point mutations taking place in the globin genes and affecting the stability of the Hb molecule. They are inherited as autosomal dominant diseases and described worldwide. Herein we report a new observation of an unstable variant in the Mauritanian population. The patient was a young girl of Mauritanian origin. She presented with chronic hemolytic anemia with an unknown etiology after being referred to several medical centers. Laboratory investigations based on routine analyses, capillary electrophoresis (CE), cation exchange high performance liquid chromatography (HPLC) and DNA sequencing revealed an abnormal unstable Hb known as Hb Moscva [β24(B6)Gly→Asp (GGT>GAT), HBB: c.74G>A] that occurred as a de novo mutation newly detected in an African girl of Mauritanian origin.
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http://dx.doi.org/10.1080/03630269.2018.1428620DOI Listing
January 2018

Ethnicity influences breast cancer stem cells' drug resistance.

Breast J 2018 07 2;24(4):701-703. Epub 2018 Mar 2.

Breast Biology Group, Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, UK.

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http://dx.doi.org/10.1111/tbj.13021DOI Listing
July 2018

Enhanced anticancer effect and reduced toxicity of doxorubicin in combination with thymoquinone released from poly-N-acetyl glucosamine nanomatrix in mice bearing solid Ehrlish carcinoma.

Eur J Pharm Sci 2017 Nov 7;109:525-532. Epub 2017 Sep 7.

Biochemistry Department, Faculty of Pharmacy, Menoufia University, Egypt. Electronic address:

The incidence of breast cancer remarkably increases all over the world. Therefore, there is a great demand to introduce new approaches into cancer treatment field. The current study was designated to evaluate the role of doxorubicin (DOX) and/or thymoquinone (TQ) nanomatrix in potentiating the cytotoxicity of either drug, and to investigate the ability of TQ to reduce cardiotoxicity of DOX in solid Ehrlich carcinoma (SEC)-bearing mice. DOX and TQ were loaded into F2 gel, which is a fully-acetylated poly-N-acetyl glucosamine nanofiber. SEC was induced in female albino mice as a model for experimentally induced breast cancer. Mice were randomly divided into eight groups (n=10): normal control, tumor control, F2 gel, free DOX, DOX+F2 gel, free TQ, TQ+F2 gel, and DOX+TQ+F2 gel. On day 28th from tumor inoculation, mice were sacrificed and blood samples were collected for measurement of the cardiac markers; lactate dehydrogenase (LDH) and creatine kinase (CK-MB). In addition, cardiac tissue was utilized for determination of lipid peroxide, and tumor tissue was used for measurement of anti-apoptotic protein Bcl-2 as well as gene expression of the tumor suppressor gene P53. DOX and/or TQ showed a significant reduction in tumor volume, cardiac markers, tumor Bcl-2, and P53 upregulation compared to free conventional therapies. Co-treatment with DOX+TQ+F2 gel was superior to all other groups in exerting beneficial effects. Use of TQ as an adjuvant therapy with DOX could improve its cytotoxic effects and limit its cardiac toxicity. Furthermore, loading of DOX and/or TQ into F2 gel showed a remarkable anti-cancer activity.
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http://dx.doi.org/10.1016/j.ejps.2017.09.012DOI Listing
November 2017

Synergistic combination of murine bone marrow-derived dendritic cells loaded ex vivo with whole tumor lysate and systemic chemotherapy mediates antitumor immune responses in vivo.

Biomed Pharmacother 2017 Sep 23;93:286-295. Epub 2017 Jun 23.

Zoology Department, Faculty of Science, Tanta University, El-Giesh St., Gharbia province, Tanta 31527, Egypt.

In order to get mature dendritic cells (DC) that is a crucial prerequisite for success in tumor immunotherapy protocols. Herein, we assumed that administration of murine bone marrow (BM)-derived DC (BM-DC), loaded ex vivo with whole Ehrlich ascites carcinoma (EAC) lysate, in the context of systemic chemotherapy cyclophosphamide (CTX) to induce antitumor immune responses, may be a good strategy to improve the presentation of tumor-specific antigens to the immune system. In the first series of experiments, BM cells generated either from BM of naïve mice or from BM of EAC-bearing mice were cultured in the presence of GM-CSF and IL-4 for 6days. At day 7, cells were loaded for 48h with one of the following maturation agents: EAC lysate (1mg/ml), poly-inosinic: polycytidylic acid [poly(I:C)] (25μg/ml) or mRNA encoding human telomerase reverse transcriptase (hTERT-mRNA) (2μg/ml). In the second series of experiments, EAC-bearing mice were intraperitoneally (i.p.) injected with CTX followed by i.p. vaccination with DC, loaded ex vivo with EAC lysate. DC yield and the phenotypic expression of maturity-related surface markers of DC (i.e. CD11b and CD11c) in both series of experiments were investigated. As a result, a significant decrease in the number of DC generated from poly(I:C)-supplemented BM culture from EAC-bearing mice has been detected. Loading of BM cells with poly(I:C), EAC lysate or hTERT-mRNA could induce the expression of CD11b and CD11c. Additionally, vaccination of EAC-bearing mice with DC loaded ex vivo with EAC lysate following CTX treatment, resulted in increases in the percentage of multiple populations of CD11bCD11c in BM, spleen and peripheral blood (PB). To conclude, further researches to clarify the mechanism involved in DC maturation are crucial not only to comprehend DC biology but also to optimize DC immunotherapy protocols.
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http://dx.doi.org/10.1016/j.biopha.2017.06.046DOI Listing
September 2017

Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer.

J Hematol Oncol 2017 04 7;10(1):82. Epub 2017 Apr 7.

Department of Surgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC, 29425, USA.

Background: Dendritic cells (DCs) enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, in conjunction with toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC).

Methods: We generated autologous DCs from the peripheral blood of HLA-A2 patients with PC. DCs were pulsed with three distinct A2-restricted peptides: 1) human telomerase reverse transcriptase (hTERT, TERT572Y), 2) carcinoembryonic antigen (CEA; Cap1-6D), and 3) survivin (SRV.A2). Patients received four intradermal injections of 1 × 10 peptide-pulsed DC vaccines every 2 weeks (Day 0, 14, 28, and 42). Concurrently, patients received intramuscular administration of Poly-ICLC at 30 μg/Kg on vaccination days (i.e., day 0, 14, 28, and 42), as well as on days 3, 17, 21, 31, 37, and 45. Our key objective was to assess safety and feasibility. The effect of DC vaccination on immune response was measured at each DC injection time point by enumerating the phenotype and function of patient T cells.

Results: Twelve patients underwent apheresis: nine patients with metastatic disease, and three patients with locally advanced unresectable disease. Vaccines were successfully manufactured from all individuals. We found that this treatment was well-tolerated, with the most common symptoms being fatigue and/or self-limiting flu-like symptoms. Among the eight patients who underwent imaging on day 56, four patients experienced stable disease while four patients had disease progression. The median overall survival was 7.7 months. One patient survived for 28 months post leukapheresis. MHC class I -tetramer analysis before and after vaccination revealed effective generation of antigen-specific T cells in three patients with stable disease.

Conclusion: Vaccination with peptide-pulsed DCs in combination with poly-ICLC is safe and induces a measurable tumor specific T cell population in patients with advanced PC.

Trial Registration: NCT01410968 ; Name of registry: clinicaltrials.gov; Date of registration: 08/04/2011).
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http://dx.doi.org/10.1186/s13045-017-0459-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384142PMC
April 2017

In vitro and in vivo antitumor effects of the Egyptian scorpion Androctonus amoreuxi venom in an Ehrlich ascites tumor model.

Springerplus 2016 10;5:570. Epub 2016 May 10.

Zoology Department, Faculty of Science, Suez Canal University, Ismailia, 41522 Egypt.

Scorpion venom is a highly complex mixture of about 100-700 different components, where peptides are the major constituents with various biological and pharmacological properties including anticancer activities. In this study, anticancer efficacy of the venom of the Egyptian scorpion Androctonus amoreuxi has been evaluated. In vitro, the human breast cancer MCF-7 cell line was treated with the venom and the IC50 was estimated. In vivo studies, Ehrlich ascites carcinoma (EAC) cells were inoculated into CD-1 mice intraperitoneally to form liquid tumor or subcutaneously to form solid tumor and then treated with intraperitoneal injection with venom (0.22 mg/kg) every other day. The total tumor cells in the ascitic fluid and the size of the solid tumor were assessed after 14 and 30 days, respectively. In addition, the mean survival time (MST), body weight, tumor volume, PCV, viability of tumor cells, CBC, AST, ALP, creatinine, oxidative stress biomarkers (GSH, MDA, PCC), tumor marker Ki67, growth factor VEGF and caspase-3 were measured in normal control, EAC control and venom-treated groups (n = 6). Treatment with venom induced anti-tumor effects against liquid and in solid tumors as indicated by a significant (P < 0.05) reduction in tumor volume/size, count of viable EAC cells, expression of Ki67 and VEGF as well as by remarkable increases in MST and caspase-3 expression as compared to non-treated group. Interestingly, the venom restored the altered hematological and biochemical parameters of tumor-bearing animals and significantly increased their life span. These data indicate to (1) the cytotoxic potential effects of A. amoreuxi on tumor cells via anti-proliferative, apoptotic and anti-angiogenic activities; (2) opening a new avenue for further studies on the anti-cancer effects of this agent.
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http://dx.doi.org/10.1186/s40064-016-2269-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864766PMC
June 2016

Acute inflammation induces immunomodulatory effects on myeloid cells associated with anti-tumor responses in a tumor mouse model.

J Adv Res 2016 Mar 19;7(2):243-53. Epub 2015 Jun 19.

Physiology Unit, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.

Given the self nature of cancer, anti-tumor immune response is weak. As such, acute inflammation induced by microbial products can induce signals that result in initiation of an inflammatory cascade that helps activation of immune cells. We aimed to compare the nature and magnitude of acute inflammation induced by toll-like receptor ligands (TLRLs) on the tumor growth and the associated inflammatory immune responses. To induce acute inflammation in tumor-bearing host, CD1 mice were inoculated with intraperitoneal (i.p.) injection of Ehrlich ascites carcinoma (EAC) (5 × 10(5) cells/mouse), and then treated with i.p. injection on day 1, day 7 or days 1 + 7 with: (1) polyinosinic:polycytidylic (poly(I:C)) (TLR3L); (2) Poly-ICLC (clinical grade of TLR3L); (3) Bacillus Calmette Guerin (BCG) (coding for TLR9L); (4) Complete Freund's adjuvant (CFA) (coding for TLR9L); and (5) Incomplete Freund's Adjuvant (IFA). Treatment with poly(I:C), Poly-ICLC, BCG, CFA, or IFA induced anti-tumor activities as measured by 79.1%, 75.94%, 73.94%, 71.88% and 47.75% decreases, respectively in the total number of tumor cells collected 7 days after tumor challenge. Among the tested TLRLs, both poly(I:C) (TLR3L) and BCG (contain TLR9L) showed the highest anti-tumor effects as reflected by the decrease in the number of EAc cells. These effects were associated with a 2-fold increase in the numbers of inflammatory cells expressing the myeloid markers CD11b(+)Ly6G(+), CD11b(+)Ly6G(-), and CD11b(+)Ly6G(-). We concluded that Provision of the proper inflammatory signal with optimally defined magnitude and duration during tumor growth can induce inflammatory immune cells with potent anti-tumor responses without vaccination.
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http://dx.doi.org/10.1016/j.jare.2015.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767798PMC
March 2016

Bone marrow mononuclear cells enhance anti-inflammatory effects of pravastatin against isoproterenol-induced myocardial infarction in rats.

J Immunotoxicol 2016 05 25;13(3):393-402. Epub 2015 Nov 25.

a Pharmacology and Toxicology Department, Faculty of Pharmacy , Tanta University , Tanta , Egypt ;

The current study investigated the combinatorial effect of pravastatin (PRAV) and bone marrow mononuclear cells (BM-MNC) on acute myocardial infarction (AMI) induced experimentally in rats. After induction of MI, rats were given oral PRAV (20 mg/kg/day) for 28 days or a bolus intravenous injection (via lateral vein) of a total of 14 × 10(6) autologous BM-MNC or a combination of both. Serum brain natriuretic peptide (BNP) and histologic changes in cardiac tissues were assessed. Cardiac contents of lipid peroxides, superoxide dismutase (SOD) and inflammatory biomarkers including tumor necrosis factor (TNF)-α and interleukin (IL)-1β as well as vascular endothelial growth factor (VEGF) and nitric oxide (NO) were also measured. Combined PRAV and BM-MNC treatment significantly suppressed serum BNP. Cardiac cell apoptosis and inflammatory cell infiltration in heart tissue decreased significantly in both the PRAV and the PRAV + BM-MNC groups. Cardiac lipid peroxides along with TNFα and IL-1β levels were significantly reduced in both the PRAV and PRAV + BM-MNC hosts with an increase in SOD levels. However, the combined treatment increased cardiac NO levels and did not modify cardiac VEGF levels. The current results indicated that administration of BM-MNC improved the therapeutic efficacy of PRAV treatment by improving the morphology of infarcted hearts as well as decreasing inflammation in a host, but did not do so by inducing therapeutic angiogenesis.
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http://dx.doi.org/10.3109/1547691X.2015.1111959DOI Listing
May 2016

Programmed death-1/programmed death-L1 signaling pathway and its blockade in hepatitis C virus immunotherapy.

World J Hepatol 2015 Oct;7(23):2449-58

Mohamed L Salem, Center of Excellence in Cancer Research, Tanta University, Tanta 31527, Egypt.

Chronic hepatitis C virus (HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HCV are key features of chronic HCV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HCV. Cytotoxic CD8(+) T lymphocytes (CTLs) play a critical role in the control of HCV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1 (PD-1) receptor and its ligand PD-L1 function in a T cell co-inhibitory pathway, which either blocks the function of CTLs or the differentiation of CD8(+) T cells. During chronic HCV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HCV-specific CD8(+) T cells. As such, blockade of the PD-1/PD-L1 pathway in these CD8(+) T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HCV immunity. Understanding how chronic HCV infection induces upregulation of PD-1 on HCV specific T cells and how the PD-1/PD-L1 interaction develops HCV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HCV infections, which will significantly improve HCV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HCV therapy.
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http://dx.doi.org/10.4254/wjh.v7.i23.2449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4606200PMC
October 2015

Interleukin-12 enhances the function and anti-tumor activity in murine and human CD8(+) T cells.

Cancer Immunol Immunother 2015 May 13;64(5):539-49. Epub 2015 Feb 13.

Department of Surgery, Medical University of South Carolina, 86 Jonathan Lucas Street, HO506, Charleston, SC, 29425, USA,

Mouse CD8(+) T cells conditioned with interleukin (IL)-12 ex vivo mediate the potent regression of established melanoma when transferred into lymphodepleted mice. However, the quantitative and qualitative changes induced by IL-12 in the responding mouse CD8(+) T cells have not been well defined. Moreover, the mechanisms by which IL-12-conditioning impacts human CD8(+) T cells, and how such cells might be expanded prior to infusion into patients is not known. We found that ex vivo IL-12-conditioning of mouse CD8(+) T cells led to a tenfold-100-fold increase in persistence and anti-tumor efficacy upon adoptive transfer into lymphodepleted mice. The enhancing effect of IL-12 was associated with maintenance of functional avidity. Importantly, in the context of ongoing ACT clinical trials, human CD8(+) T cells genetically modified with a tyrosinase-specific T cell receptor (TCR) exhibited significantly enhanced functional activity when conditioned with IL-12 as indicated by heightened granzyme B expression and elevated peptide-specific CD107a degranulation. This effect was sustainable despite the 20 days of in vitro cellular expansion required to expand cells over 1,000-fold allowing adequate cell numbers for administration to cancer patients. Overall, these findings support the efficacy and feasibility of ex vivo IL-12-conditioning of TCR-modified human CD8(+) T cells for adoptive transfer and cancer therapy.
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http://dx.doi.org/10.1007/s00262-015-1655-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804872PMC
May 2015

Immunobiology and signaling pathways of cancer stem cells: implication for cancer therapy.

Cytotechnology 2015 Oct 17;67(5):749-59. Epub 2014 Dec 17.

Immunology and Biotechnology Division, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt,

Cancer stem cells (CSCs) need to survive cancer treatments with a specific end goal to provide new, more differentiated, metastatic-prone cancerous cells. This happens through diverse signals delivered within the tumor microenvironment where ample evidence indicates that altered developmental signaling pathways play an essential role in maintaining CSCs and accordingly the survival and the progression of the tumor itself. This review summarizes findings on the immunobiological properties of CSCs as compared with cancerous non-stem cells involving the expression of immunological molecules, cytokines and tumor antigens as well as the roles of the Notch, Wnt and Hedgehog pathways in the brain, breast and colon CSCs. We concluded that if CSCs are the main driving force behind tumor support and growth then understanding the molecular mechanisms and the immunological properties directing these cells for immune tolerance is of great clinical significance. Such knowledge will contribute to designing better targeted therapies that could prevent tumor recurrence and accordingly significantly improve cancer treatments and patient survival.
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http://dx.doi.org/10.1007/s10616-014-9830-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545436PMC
October 2015

Autologous transplantation of CD34(+) bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia.

Cytotechnology 2016 Aug 16;68(4):771-81. Epub 2014 Dec 16.

Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Center of Excellence in Cancer Research, Tanta University, Tanta, Egypt.

Patients with a decrease in limb perfusion with a potential threat to limb viability manifested by ischemic rest pain, ischemic ulcers, and/or gangrene are considered to have critical limb ischemia (CLI). Because of this generally poor outcome, there is a strong need for attempting any procedure to save the affected limb. The aim of this work is to evaluate the possibility to use stem cell therapy as a treatment option for patients with chronic critical lower limb ischemia with no distal run off. This study includes 20 patients with chronic critical lower limb ischemia with no distal run off who are unsuitable for vascular or endovascular option. These patients underwent stem cell therapy (SCT) by autologous transplantation of bone marrow derived mononuclear cells. 55 % of patients treated with SCT showed improvement of the rest pain after the first month, 60 % continued improvement of the rest pain after 6 months, 75 % after 1 year and 80 % after 2 years and continued without any deterioration till the third year. Limb salvage rate after STC was 80 % after the first year till the end of the second and third years. SCT can result in angiogenesis in patients with no-option CLI, providing a foundation for the application of this therapy to leg ischemia.
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http://dx.doi.org/10.1007/s10616-014-9828-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960127PMC
August 2016

The use of dendritic cells for peptide-based vaccination in cancer immunotherapy.

Authors:
Mohamed L Salem

Methods Mol Biol 2014 ;1139:479-503

Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.

Effective antitumor immunity requires the generation and persistence of functional tumor-specific T-cell responses. Among the critical factors that often control these responses is how the antigen is delivered and presented to T cells. The use of peptide-based vaccination has been found to be a promising means to induce antitumor T-cell responses but with limited effects even if the peptide is co-delivered with a potent adjuvant. This limited response could be due to cancer-induced dysfunction in dendritic cells (DC), which play a central role in shaping the quantity and quality of antitumor immunity. Therefore, DC-based peptide delivery of tumor antigen is becoming a potential approach in cancer immunotherapy. In this approach, autologous DC are generated from their precursors in bone marrow or peripheral blood mononuclear cells, loaded with tumor antigen(s) and then infused back to the tumor-bearing host in about 7 days. This DC-based vaccination can act as an antigen delivery vehicle as well as a potent adjuvant, resulting in measurable antitumor immunity in several cancer settings in preclinical and clinical studies. This chapter focuses on DC-based vaccination and how this approach can be more efficacious in cancer immunotherapy.Effective antitumor immunity requires the generation and persistence of functional tumor-specific T-cell responses. Among the critical factors that often control these responses is how the antigen is delivered and presented to T cells. The use of peptide-based vaccination has been found to be a promising means to induce antitumor T-cell responses but with limited effects even if the peptide is co-delivered with a potent adjuvant. This limited response could be due to cancer-induced dysfunction in dendritic cells (DC), which play a central role in shaping the quantity and quality of antitumor immunity. Therefore, DC-based peptide delivery of tumor antigen is becoming a potential approach in cancer immunotherapy. In this approach, autologous DC are generated from their precursors in bone marrow or peripheral blood mononuclear cells, loaded with tumor antigen(s) and then infused back to the tumor-bearing host in about 7 days. This DC-based vaccination can act as an antigen delivery vehicle as well as a potent adjuvant, resulting in measurable antitumor immunity in several cancer settings in preclinical and clinical studies. This chapter focuses on DC-based vaccination and how this approach can be more efficacious in cancer immunotherapy.
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http://dx.doi.org/10.1007/978-1-4939-0345-0_37DOI Listing
November 2014

G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b+Gr-1+ myeloid cells without compromising CD8+ T cell immune responses.

J Hematol Oncol 2013 Oct 1;6:75. Epub 2013 Oct 1.

Background: Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo.

Methods: We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice.

Results: We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b+Gr-1+ myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8+ T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation.

Conclusions: Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF.
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http://dx.doi.org/10.1186/1756-8722-6-75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850648PMC
October 2013

Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: role of CD62L.

Immunol Res 2013 Dec;57(1-3):23-33

Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA,

CD62L governs the circulation of CD8(+) T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8(+) T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8(+) T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8(+) cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L(-/-) CD8(+) T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L(-/-) CD8(+) T cells were functionally indistinguishable from CD62L(+/+) CD8(+) T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor-specific CD8(+) T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT(-/-) animals), CD8(+) T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals. These results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8(+) T cells.
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http://dx.doi.org/10.1007/s12026-013-8456-1DOI Listing
December 2013

Immunomodulatory effects of IL-12 released from poly-N-acetyl glucosamine gel matrix during schistosomiasis infection.

Cytotechnology 2014 Aug 26;66(4):667-75. Epub 2013 Jul 26.

Immunology and Biotechnology Division, Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt,

We have reported recently that Interleukin-12 (IL-12) released from poly-N-acetyl glucosamine gel matrix (F2 gel/IL-12) is more effective than free IL-12 to enhance vaccination of mice with Schistosoma soluble worm antigen preparation. The aim of this study is to evaluate the effect of F2 gel/IL-12 on the inflammatory responses in mice undergoing schistosomiasis infection in absence of vaccination. To achieve this, mice undergoing Schistosoma mansoni infection or cured from this infection, after treatment with praziquantil (PZQ), were treated with subcutaneous injection of IL-12 for 3 consecutive days or once with F2 gel loaded with IL-12 (F2 gel/IL-12). The treatment was started on day 35 days after infection. For infection, mice were infected with 100 cercariae of S. mansoni using tail immersion method. We found that treatment with F2 gel/IL-12 induced significant decreases in the egg burden with a moderate reduction in the size of granuloma and decrease in the cellular granulomatous reaction in the lung as compared to infected mice treated with IL-12. These effects of F2 gel/IL-12 were more pronounced in infected mice previously treated with the anti-schistosomal drug PZQ. The total numbers of white blood cells in all treated mice showed similar profile. Treatment with IL-12 or F2 gel/IL-12, however, showed significant reduction in the number of mononuclear cells when compared with non-treated infected mice. In conclusion, this study showed the ability of IL-12 released from F2 gel to lower the inflammatory response to Schistosoma infection even in absence of vaccination.
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http://dx.doi.org/10.1007/s10616-013-9620-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082772PMC
August 2014

Hb S [β6(A3)Glu→Val, GAG>GTG] and β-globin gene cluster haplotype distribution in Mauritania.

Hemoglobin 2012 24;36(4):311-5. Epub 2012 May 24.

Départment de Biologie, Faculté des Sciences et Techniques, Nouakchott, Mauritanie.

Of 1050 Mauritanian blood donors screened from the two main racial groups, i.e., the Moors and Black Africans, 60 were found to carry Hb S [β6(A3)Glu→Val, GAG>GTG], giving a global frequency of 5.71%. The prevalence observed in the Black African Mauritanians (10.69%) is almost five times that found in the Moor group (2.25%). Four of the five main β(S) haplotypes were detected in this study: Senegal (77.8%), Benin (8.8%), Arab-Indian (5.5%) and Bantu (4.4%). These data showed that Hb S is a serious public health problem in Mauritania. They also confirm the ethnic heterogeneity of the Mauritanian population.
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http://dx.doi.org/10.3109/03630269.2012.688782DOI Listing
October 2012
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