, "Sorafenib- Taurine Combination Model for Hepatocellular Carcinoma Cells: Immunological Aspects", Asian Pacific Journal of Cancer Prevention,, vol. 20, issue 10, pp. 3007 -- 3013, 2019.
Hamid, F. A. F., M. K. Singer, M. N. El-Rouby, M. M. Said, R. H. Tabashy, and M. E. El-Houseini, "HepG2 Attenuation Induced by RNase A Modulates Gene Profiling and Immunophenotypic Characterization of Some Immune Cells Operating in Cancer Vaccine", Journal of Cancer Research Updates, vol. 7, issue 1, pp. 27-34, 2018.
FF, A. H., S. M. K, E. - R. MN, S. MM, T. RH, and E. - H. ME, "A Novel Potential Strategy for Enhancing Antigen Presentation of Human Hepatocellular Carcinoma Cells Propagated ex-vivo Using a Ribonuclease Enzyme System", SAJ Cancer Sci, vol. 5, issue 1, pp. 102-109, 2018.
Abdellateif, M. S., S. M. Shaarawy, E. Z. Kandeel, A. H. El-Habashy, M. L. Salem, and M. E. El-Houseini, "A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell-dendritic cell-based vaccine.", Oncology letters, vol. 16, issue 1, pp. 529-535, 2018 Jul. Abstract

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.

AlSadek, D. M. M., H. A. Badr, T. A. Al-Shafie, S. M. El-Bahr, M. E. El-Houseini, L. B. Djansugurova, C. - Z. Li, and H. Ahmed, "Cancer cell death induced by nanomagnetolectin.", European journal of cell biology, vol. 96, issue 6, pp. 600-611, 2017 Sep. Abstract

Magnetic nanoparticles represent a new paradigm for molecular targeting therapy in cancer. However, the transformative targeting potential of magnetic nanoparticles has been stymied by a key obstacle-safe delivery to specified target cells in vivo. As cancer cells grow under nutrient deprivation and hypoxic conditions and decorate cell surface with excessive sialoglycans, sialic acid binding lectins might be suitable for targeting cancer cells in vivo. Here we explore the potential of magnetic nanoparticles functionalized with wheat germ lectin (WGA) conjugate, so-called nanomagnetolectin, as apoptotic targetable agents for prostate cancer. In the presence of magnetic field (magnetofection) for 15min, 2.46nM nanomagnetolectin significantly promoted apoptosis (∼12-fold, p value <0.01) of prostate cancer cells (LNCaP, PC-3, DU-145) compared to normal prostate epithelial cells (PrEC, PNT2, PZ-HPV-7), when supplemented with 10mM sialic acid under nutrient deprived condition. Nanomagnetolectin targets cell-surface glycosylation, particularly sialic acid as nanomagnetolectin induced apoptosis of cancer cells largely diminished (only 2 to 2.5-fold) compared to normal cells. The efficacy of magnetofected nanomagnetolectin was demonstrated in orthotopically xenografted (DU-145) mice, where tumor was not only completely arrested, but also reduced significantly (p value <0.001). This was further corroborated in subcutaneous xenograft model, where nanomagnetolectin in the presence of magnetic field and photothermal heating at ∼42°C induced apoptosis of tumor by ∼4-fold compared to tumor section heated at ∼42°C, but without magnetic field. Taken all together, the study demonstrates, for the first time, the utility of nanomagnetolectin as a potential cancer therapeutic.

Abdel Wahab, A. H. A., H. I. Abo-Zeid, M. I. El-Husseini, M. Ismail, and A. M. El-Khor, "Role of loss of heterozygosity on chromosomes 8 and 9 in the development and progression of cancer bladder.", Journal of the Egyptian National Cancer Institute, vol. 17, issue 4, pp. 260-9, 2005 Dec. Abstract

BACKGROUND: Loss of heterozygosity (LOH) in tumor samples is believed to be a marker for the absence of a functional tumor suppressor gene. Non-random chromosome deletion and LOH at specific chromosomal regions are identified in a number of common human cancers including carcinoma of the bladder, which is considered the most predominant cancer in Egypt due to the prevalence of schistosomiasis.

PURPOSE: The main objective of the present study is to clarify the role of chromosomes 8 and 9 in the establishment and/or progression of schistosomiasis-related bladder cancer through detection of LOH of 8 microsatellite markers on both chromosomes. It also aims to compare the LOH pattern of the tested markers between schistosomiasis- associated and non schistosomiasis-associated bladder cancer.

MATERIAL AND METHODS: To achieve this purpose, DNA was extracted from the tumor specimens and the corresponding peripheral blood samples of 42 primary bladder cancer patients (schistosomal and non schistosomal). Twenty nine of these were diagnosed as squamous cell type (SCC), 11 were transitional (TCC), and 2 were adenocarcinoma (with different stages and grades). LOH at chromosomes 8 and 9 was evaluated for 8 highly polymorphic microsatellite markers distributed at different regions of both chromosomes using the dinucleotide repeat-PCR technique.

RESULTS: The overall percentage of LOH in chromosome 8 was 74% in at least one marker. The highest incidence of LOH was recorded for D8S84 (41%) followed by 37% for D8S87, 29% for D8S85, and 25% for D8S88. Deletions at chromosome 8 were shown to be associated with high grade of the tumor and LOH at D8S85 was associated with metastatic lymph nodes. The overall percentage of LOH in chromosome 9 was 54% and its highest incidence was for D9S126 (36%), followed by 26%, 21%, 19% for D9S166, D9S128 and D9S180, respectively. Fifty nine percent (59%) of the cases with LOH at 9q were diagnosed as squamous cell type (SCC), whereas 9% only were transitional cell type (TCC). No significant association was recorded between the presence of schistosomiasis and LOH detected in all markers used in this study.

CONCLUSION: Our data indicate that more than one tumor suppressor gene on chromosomes 8 and 9 are involved in high grades of bladder carcinogenesis, one at 8p12 and another at 8q21.1 regions. Also, a region at 8q23-quarter may harbor tumor suppressor gene that involved in metastasis of bladder cancer. Our study also revealed that 9p21 (p16INK4) region is involved in both types of the tumor (SCC & TCC). PTCH located at 9q22.3, as well as the TSC gene at 9q34 are involved in squamous cell carcinoma rather than transitional carcinoma. Region 9q12-13 is considered to be a critical region of urothelial tumor suppressor genes. Finally, the present study shows no line of demarcation between schistosomiasis-associate and non schistosomiasis-associated bladder cancer in terms of LOH of the tested microsatellite markers on chromosome 8 and 9. This suggests that data obtained from schistosoma-associated bladder cancer can be extrapolated to bladder cancer induced by a schistosomiasis independent mechanism.

Kieler, J., and M. E. Houssini, "Specificity of tumor cell stimulation of DNA inhibitory cytokine production in vitro.", Anticancer research, vol. 1, issue 4, pp. 235-41, 1981. Abstract

ST/a splenocytes and peritoneal macrophages sensitized to tumorigenic, isoimmunizing R+ ST-L cells in vivo are stimulated to produce a DNA inhibitory supernatant in vitro when co-cultured with R+ ST-L cells. Studying the cross-reactions with various uninfected and MuLV infected cells, evidence was obtained for the gp70 specificity of this stimulation. T-cell depletion by thymectomy and whole body irradiation caused a moderate reduction of the DNA inhibitory effect of the splenocyte culture supernatant. However, macrophage depletion by silicate caused an almost complete abolishment of DNA inhibitory cytokine production, which could not be restored by the addition of supplementary non-sensitized spleen cells.

El Agouza, I. M., S. S. Eissa, M. M. El Houseini, D. E. El-Nashar, and O. M. Abd El Hameed, "Taurine: a novel tumor marker for enhanced detection of breast cancer among female patients.", Angiogenesis, vol. 14, issue 3, pp. 321-30, 2011 Sep. Abstract

INTRODUCTION: The antioxidant Taurine found to display antineoplastic effect through down regulation of angiogenesis and enhancement of tumor cell apoptosis. It has been found that progressive inhibition of apoptosis and induction of angiogenesis may contribute to tumor initiation, growth and metastasis in the pathogenesis of breast cancer.

AIM OF THE STUDY: To correlate taurine level with the levels of some bioomolecules operating in both angiogenesis (VEGF, CD31) and apoptosis (TNF-α and Caspas-3) which could help for breast cancer pronostication and to evaluate a possible role of serum taurine level as an early marker for breast cancer in Egyptian patients.

PATIENTS AND METHODS: Four groups of a total 85 female candidates were studied in this work. The first group consists of 50 female patients at National Cancer Institute (NCI), Cairo University were diagnosed and undergoing surgery for breast carcinoma. In the second group 10 having benign breast lesions, were included. The third group consists of five cases, with positive family history. Twenty healthy females were also recruited as control. A preoperative blood sample were taken from each patient to measure serum level of VEGF; Taurine; CA15.3 and TNF- α. Sample of fresh tumor and their corresponding safety margins were obtained from the first and second groups, for determination of caspase-3; histopathological examination and immunohistochemical assay of VEGF and CD31.

RESULT: No significant differences in the serum level of CA15.3 between the breast cancer patients, the high risk and the control group. TNF-α (apoptotic biomolecule) level showed a significant difference only between breast cancer group and control group. The VEGF (angiogenic biomarker) showed a highly significant difference between breast cancer patients, the high risk and the control group. Regarding the antioxidant taurine (antiangiogenic biomolecule) serum level in breast cancer group exhibited a value strongly lower than the high risk and control group. Also the correlative ratio between the angiogenic/apoptotic biomarker (VEGF/TNF-α) showed a highly significant difference between the main previous three groups. Same observation were also noticed in the correlation between angiogenic/antiangiogenic (VEGF/taurine) ratio in the same groups. Moreover the enzymatic activities of Casp-3 in the tissue homogenate were statistically higher in adjacent normal tissues than in malignant tissues. The result of immunohistochemical investigation showed a significant increase in the density of intracellular VEGF and microvessel density expressed as CD31 in cancer cases compared to normal adjacent tissue.

CONCLUSION: It is suggested that assessment of taurine level in sera of patients with high risk for breast cancer are of great value in the early diagnosis of malignant changes in the breast.

Steinman, R. A., B. Hoffman, A. Iro, C. Guillouf, D. A. Liebermann, and M. E. El-Houseini, "Induction of p21 (WAF-1/CIP1) during differentiation.", Oncogene, vol. 9, issue 11, pp. 3389-96, 1994 Nov. Abstract

The recently cloned protein, p21 (WAF1/CIP1) is a downstream effector of p53, and mediates growth arrest by inhibiting the action of G1 cyclin-dependent kinases. Since cellular differentiation is frequently characterized by G1 arrest, we examined whether p21 upregulation occurs in differentiation. We show that p21 expression is triggered by multiple differentiation-inducing agents in hematopoietic and hepatoma cells through a p53-independent pathway. The dramatic rise in p21 levels occurs as an immediate early response to differentiation inducers. The induction of p21 is coupled to the expression of early differentiation markers, and is uncoupled from apoptosis. Finally, evidence is presented that p21 expression is uncoupled from G1 arrest in the presence of deregulated c-myc.

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