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Mahmoud R Hussein

Publications and source records attributed to Mahmoud R Hussein.

At least 19 recordsLinked to original sources
PubMed2007

Immunohistological analysis of immune cells in blistering skin lesions.

BACKGROUND: Bullous skin lesions are characterised by the presence of intraepidermal or subepidermal bullae. Although inflammatory cell infiltrate is a constant feature in these lesions, their immunophenotypic characterisation is still incomplete. AIM: To determine whether the development of bullous skin diseases is associated with changes in the inflammatory cell infiltrate. MATERIALS AND METHODS: 34 cases representing lesions with both intraepidermal and subepidermal bullae were examined using immunoperoxidase staining methods and antibodies targeting antigens for histiocytes (CD68), B cells (CD20+), T cells (CD3+), T cells with cytotoxic potential (T cell intracellular associated antigen, TIA1+) and activity (granzyme B, GRB+). The adjacent normal skin (lesions) and an additional five cases of normal skin were also examined (controls). RESULTS: The transition from normal skin to lesional skin (lesions with intraepidermal and subepidermal bullae) was associated with a significant increase (p< or =0.05) in the density of total inflammatory cell infiltrate, CD68+ cells, CD3+ T lymphocytes, CD20+ B lymphocytes, TIA1+ -resting cytotoxic T cells and GRB+ T cells with cytotoxic activity. CONCLUSIONS: The increase in inflammatory cell infiltrate during the transition from normal to lesional skin may reflect the presence of an increased antigenicity of the lesional cells or a response to some basement membrane components. CD68+ and CD3+ cells, especially the resting cytotoxic ones, achieved numerical dominance in these lesions. Cell-mediated immunity seems to have critical role in the development of these lesions.

Adolescent↗
PubMed2006

The biochemical changes associated with phytic Acid on induced breast proliferative lesions in rats: preliminary findings.

BACKGROUND: Phytic acid is an anti-neoplastic agent. We hypothesize that during mammary tumorigenesis, the administration of phytic acid is associated with biochemical changes including enhancement of apoptosis and inhibition of oxidative stress. MATERIALS AND METHODS: An animal model formed of 25 rats was established. The animals were divided into three groups: (1) a control group which received the same phytic acid treatment in the right route and amount; (2) a carcinogen group which received a carcinogenic substance DMBA that can induce proliferative changes in the mammary gland; (3) treated group which received phytic acid, 60 days after the intake of DMBA. The animals were sacrificed, serum and tissue were evaluated for markers of tumori-genicity (serum total sialic acid, TSA); apoptotic changes (tissue caspase-3 activity and % DNA Fragmentation) and oxidative stress (tissue level of nitric oxide, NO). RESULTS: Following DMBA administration, benign proliferative breast changes occurred in all animals. However, these changes disappeared following phytic acid treatment. As compared to the control group, the development of these proliferative changes in DMBA group was associated with statistically significantly (p < 0.05) increased levels of TSA and NO and decreased apoptotic activity. When compared to DMBA group, the disappearance of the proliferative changes in phytic acid -treated group was associated with statistically significantly (p < 0.05) decreased levels of TSA and NO and increased apoptotic activity. CONCLUSIONS: Administration of phytic acid reversed the proliferative effects of DMBA, suggesting its protective role.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2006

Cryopreservation of intact human ovary with its vascular pedicle.

BACKGROUND: The aim of this study was to assess the immediate post-thawing injury to the human ovary that was cryopreserved either as a whole with its vascular pedicle or as ovarian cortical strips. MATERIALS AND METHODS: Bilateral oophorectomy was performed in two women (46 and 44 years old) undergoing vaginal hysterectomy and laparoscopic hysterectomy, respectively. Both women agreed to donate their ovaries for experimental research. In both patients, one of the harvested ovaries was sectioned and cryopreserved (by slow freezing) as ovarian cortical strips of 1.0 x 1.0 x 5.0 mm(3) each. The other ovary was cryopreserved intact with its vascular pedicle. After thawing 7 days later, follicular viability, histology, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay (to detect apoptosis) and immunoperoxidase staining (to define Bcl-2 and p53 protein expression profiles) of the ovarian tissue were performed. Tissues from non-cryopreserved ovaries served as control specimens (two cases). RESULTS: The overall viability of the primordial follicles was 75 and 78% in intact cryopreserved-thawed (C-T) ovaries and 81 and 83% in ovarian cortical strips in the 46- and 44-year-old patients, respectively. Comparable primordial follicle counts, absence of features of necrosis, mean values of apoptosis and weak Bcl-2 and p53 protein expressions were observed both in the intact C-T ovary and in the C-T ovarian cortical strips. CONCLUSIONS: Cryoperfusion and cryopreservation of entire human ovary can be achieved with the maintenance of excellent viability of the superficial and the deeper tissues using a slow-freezing protocol. Cryopreservation injury is associated neither with significant alteration in the expression pattern of Bcl-2 and p53 proteins in the ovarian tissues nor with significant follicular damage.

Adult↗
PubMed2006

Melatonin and roentgen irradiation of the testis.

Melatonin is a free-radical scavenger and antioxidant. Roentgen irradiation of testis (animal model formed of albino rats) was associated with destruction and depletion of the germinal epithelial cells. In roentgen-irradiated, melatonin-pretreated animals, these changes were markedly ameliorated. Thus administration of melatonin before irradiation can protect testis from some of the destructive effects of roentgen irradiation.

Animals↗
PubMed2006

Analysis of apoptotic cell death, Bcl-2, and p53 protein expression in freshly fixed and cryopreserved ovarian tissue after exposure to warm ischemia.

OBJECTIVE: To evaluate the effect of ischemia time on the expression of Bcl-2 and p53 proteins on freshly fixed and cryopreserved-thawed ovarian tissue. DESIGN: Experimental study using porcine animal model. SETTING: Biological Resources Unit, Cleveland Clinic Foundation. ANIMAL(S): Eight nonpregnant adult sows. INTERVENTION(S): Bilateral oophorectomy was performed in eight sows and the ovaries were subjected to time-dependent (1, 10, 20, and 30 min) warm ischemia (room temperature). Each specimen was divided into two parts, One was fixed as a fresh tissue (freshly fixed) and the other was subjected to cryopreservation, thawing, and fixation (cryopreserved). MAIN OUTCOME MEASURE(S): Apoptosis (TUNEL assay) and Bcl-2 and p53 protein expression (immunoperoxidase method) were assessed. RESULT(S): At 1, 10, 20, 30 min of warm ischemia the apoptotic indices were: 1) statistically significantly higher in the atretic (1.36 +/- 0.20, 1.59 +/- 0.20, 1.67 +/- 0.22, and 1.67 +/- 0.24, respectively) than in the nonatretic follicles (0.69 +/- 0.06, 0.69 +/- 0.06, 0.76 +/-, and 0.06, 0.71 +/- 0.06, respectively; P<.05); 2) not significantly different between freshly fixed and cryopreserved tissues; and 3) nonsignificantly higher with the increased duration of ischemia. Bcl-2 expression was seen in the granulosa but not in the theca cells of most of the healthy and occasional atretic follicles. p53 expression was seen only in few atretic follicles. Increased duration of ischemia was associated with insignificant incremental rise of the number of follicles with Bcl-2 expression (1.82 +/- 0.30, 2.01 +/- 0.44, 2.02 +/- and 0.35, 2.05 +/- 0.42 for healthy follicles at 1, 10, 20, and 30 min, respectively; P=.99). CONCLUSION(S): (1) Apoptosis is involved in follicular atresia; (2) Bcl-2 is induced by warm ischemia; and (3) cryopreservation insult does not alter the apoptotic signals with short tissue preparation time.

Animals↗
PubMed2006

Expression of the heat shock protein-27 in the adult human scalp skin and hair follicle: hair cycle-dependent changes.

BACKGROUND: Heat shock protein (HSP) is a molecular chaperone involved in protein folding, assembly, and transport and in the regulation of cell growth and differentiation. HSP27 protein is expressed in murine hair follicle (HF) and in human skin during fetal development. In this investigation we hypothesized that HSP27 protein is expressed in the human scalp skin and its expression in HF changes with the transitions form anagen --> catagen --> telogen stages. METHODS: To test this hypothesis, the immunoreactivity of HSP27 protein was examined in human scalp skin by immunofluorescent method. A total of 50 normal human scalp skin biopsy specimens were examined (healthy women, age 53-57 years). In each case, 50 HF were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). RESULTS: HSP27 protein expression was prominent in human scalp anagen, and weak in both catagen and telogen HFs. Within HF, HSP27 protein immunoreactivity was prominent in the outer root sheath, inner root sheath, precorteocytes, and corteocytes of the hair shaft. In addition, HSP27 protein expression was prominent in the epidermis, sebaceous glands, sweat glands, and arrector pili muscles. LIMITATIONS: Only some types of heat shock proteins are known to date. Also, our knowledge about the exact molecular mechanisms involved in the interactions among these protein and other molecular chaperones is still incomplete. CONCLUSIONS: Our investigation reports, for the first time, the expression patterns of HSP27 in human scalp skin and HF. The differential expression of HSP27 during HF cycling suggests its possible roles in human HF biology.

Adult↗
PubMed2006

Clinicopathological features of melanocytic skin lesions in Egypt.

Although melanocytic skin lesions have been recognized since antiquity, their literature was limited to Caucasians. To date, the clinicopathologic features of these lesions in Egyptians are still unknown. To define these features, diagnostic records of the melanocytic skin lesions received at the Pathology Department, Assuit University Hospitals (1989-2004) were reviewed. The lesions examined included 12 benign naevi (BN), 10 dysplastic naevi (DN), and 21 cutaneous malignant melanomas (CMMs). The DN and CMMs were more common in men than in women (2 : 1 and 1.5 : 1, respectively) while BN were more common in women (2 : 1). The average age incidence was 33+/-5, 38+/-7 and 54+/-3 years, for BN, DN and CMM, respectively. The lower limb (13/21, 62%), head and neck (7/21, 33%) were the most common sites for CMMs. The average size (mm) was 2+/-0.3, 4+/-0.6 and 21+/-0.3 for BN, DN and CMMs, respectively. Recurrence occurred in 10% of CMMs. Histologically, CMMs were of nodular type and composed of epithelioid (7/21, 33%), spindle cells (1/21, 5%), or mixed cells (13/21, 62%). The mean tumour thickness (Breslow) was 6+/-0.5 mm. CMMs included two of 21(9%), three of 21(14%), six of 21(38%), and 10 of 21(38%) with Clark level II, III, IV and V. In Egypt, CMM is the third most common cutaneous neoplasm following squamous and basal cell carcinomas. Compared with Western societies, melanoma has a male sex predilection, similar histological features but different topographical distribution and rare incidence. The striking difference from Western series is the incidence of nodular melanoma - in the West this represents 15-30% of melanomas, with superficial spreading being the majority. Another key difference from the West is the 'sun-bed' culture of the West and the desire to have suntans. This is the first study that reports the clinicopathologic features of melanocytic skin lesions in Egypt.

Adult↗
PubMed2006

The effects of glucocorticoid therapy on the inflammatory and dendritic cells in muscular dystrophies.

Various clinical trials have documented the therapeutic benefit of glucocorticoids (GCs) in enhancing muscle strength and slowing disease progression of Duchenne and Becker muscular dystrophies (DMD/BMD). We hypothesized that GCs may have relevance to the differential anti-inflammatory effect on mononuclear inflammatory cells (MICs) and Dendritic cells (DCs) infiltrating the dystrophic muscles. In this prospective study, two muscle biopsies were obtained (before and after 6-month prednisone therapy) from 30 patients with dystrophies (DMD = 18; BMD = 6; and limb girdle muscular dystrophies (LGMD) = 6). MICs and DCs infiltrating the muscles were examined using mouse monoclonal antibodies and immunoperoxidase staining methods. Muscle strength was evaluated monthly by manual testing, motor ability and timed tests. Prednisone therapy was associated with: (i) functional improvement of overall motor disability, in upper limbs of DMD (P < 0.001) and BMD (P < 0.01) and lower limbs of DMD (P < 0.001) and BMD (P < 0.05); (ii) histological improvement such as fibre size variation (DMD, P < 0.01; BMD, P < 0.05), internalization of nuclei (DMD, P < 0.05), degeneration and necrosis (DMD and BMD, P < 0.01), regeneration (DMD, P < 0.001; BMD, P < 0.01) and endomysial connective tissue proliferation (DMD, P < 0.01; BMD, P < 0.05) and (iii) reduction of total MICs (P < 0.01) and DCs (P < 0.01). There was a positive correlation between the degree of improvement in overall motor disability and reduction of DCs numbers (In upper limbs; r = 0.638, P < 0.01 for DMD and r = 0.725, P < 0.01 for BMD, in Lower limbs; r = 0.547, P < 0.05 for DMD and r = 0.576, P < 0.05 for BMD). Such improvements and changes of MICs/DCs were absent in LGMD. In DMD/BMD, prednisone therapeutic effect was associated with reduced MICs and DCs numbers. Whether this therapeutic effect reflects targeting of the deleterious immune response produced by these cells mandates further investigations.

Adolescent↗
PubMed2006

Tumour-associated macrophages and melanoma tumourigenesis: integrating the complexity.

When the body discovers a tumour cell (foreign antigen), several kinds of mechanisms and cells operate in what is called an immune response. The latter has evolved into two mechanisms: non-specific immunity and specific immunity, which are closely linked to and influence each other. The former represents the first line of defence against neoplastic cells. The adaptive (specific) immunity is orchestrated by antigen-specific T and B lymphocytes. The effector cells of innate immunity include granulocytes, macrophages and natural killer cells. Among these cells, macrophages represent the most important part of innate immunity against tumours. Tumour-associated macrophages (TAMs) are important antigen-presenting cells and as such an understanding of their interactions with tumour cells gives insights into novel therapeutic strategies. In tumours, the effect of TAMs is the outcome of their two concomitantly competing interactions: tumour growth reduction and tumour growth promotion. The macrophage (TAMs) content of melanoma ranges from 0 to 30% and their density increases with increasing tumour thickness. The melanoma cells and TAMs seem to interact with each other through the release of soluble factors that either prevent or enhance tumour growth. For instance, syngeneic macrophages from tumour-bearing mice can inhibit melanoma growth in the nude mice more than the control macrophages. Alternatively, metastatic B16 melanoma cells can produce some macrophage cytotoxic substances that help tumour cells not only escape the host immunosurveillance system but also prevent distant metastasis. Together, these observations suggest opposing effects for these soluble factors in melanoma. To date, little is available in the literature about the interactions between TAMs and melanoma cells. This viewpoint not only tries to examine these interactions but also provides relevant speculations.

Animals↗
PubMed2006

Morphological evaluation of the radioprotective effects of melatonin against X-ray-induced early and acute testis damage in Albino rats: an animal model.

Irradiation has profound effects on the reproductive function. Our knowledge about radioprotective effects of melatonin against X-ray-induced testis damage is rudimentary. In this investigation, we hypothesized that melatonin can minimize germ-cell depletion and morphological features of cell damage in testis following X-ray irradiation (XRI). To examine these effects, and to test our hypothesis, an animal model comprised of 60 Albino rats was established. The animals were divided into five groups: Group 1, non-irradiated; Group 2, X-ray irradiated (XRI, 8 Grays); Group 3, XRI pretreated with solvent (ethanol and phosphate-buffered saline); Group 4, non-irradiated group treated with melatonin and Group 5, XRI pretreated with melatonin. The testes were evaluated for both histological (light microscopy) and ultrastructural changes (transmission electron microscopy). Histologically, there were marked depletions (66%) of the germinal epithelial cells, in XRI group (Groups 2 and 3), whereas these changes were almost absent in XRI testis of animals pretreated with melatonin (Group 5). The number of spermatogenic cells in XRI testis of animals pretreated with melatonin (Group 5) was comparable (95%) to that of non-irradiated group (Groups 1 and 4) but significantly (P < 0.05) higher than those in XRI testis (34%, Groups 2 and 3). Ultrastructurally, XRI testis (Groups 2 and 3) showed features of apoptosis (condensation of the nuclei, vacuolization of the cytoplasm, increased cytoplasmic density and apoptotic bodies). These features were absent in XRI testis of animals pretreated with melatonin (Group 5). Also, this Group showed features of an increased metabolic activity (large acrosomal vesicle, prominent Golgi, increased mitotic activity, increased complement of cytoplasmic organelles and appearance of nucleoli-like bodies). There was a minimal depletion of the Sertoli and Leydig cells following XRI. Also, morphological features of apoptosis were infrequent in these cells. Administration of melatonin (MEL) prior to irradiation can protect testis against its destructive effects. The protective effects include amelioration of germ-cell depletion and apoptotic changes. The clinical ramifications of these observations mandate further studies.

Animals↗
PubMed2006

Alterations of p53, BCL-2, and hMSH2 protein expression in the normal brain tissues, gliosis, and gliomas.

Tumorigenesis involves alterations in the tumor suppressor genes (p53), protooncogenes (BCL-2), and housekeeping genes (human MutS homologue-2 (hMSH2). We hypothesized that development of gliomas is associated with alterations of p53, BCL-2, and hMSH2 protein expression. To test our hypothesis and to examine these issues, we immunostained 60 specimens entailing normal brain tissues, gliosis, and gliomas (Grade I, II, III, IV) for p53, BCL-2, and hMSH2 protein expression. As compared with the normal brain and gliosis, examination of the average weighted scores in gliomas (Grade I, II, III, IV, respectively) showed significant up-regulation of: (i) p53 protein (0.0 +/- 0.0; 0.0 +/- 0.0; 0.9 +/- 0.5; 1.6 +/- 0.8; 1.7 +/- 0.5; and 4.1 +/- 0.8, P < 0.0001) (ii) hMSH2 (1.3 +/- 0.3; 1.5 +/- 0.7; 1.9 +/- 1.1; 2.2 +/- 0.5; 4.1 +/- 1.5; and 4.7 +/- 1.1, P < 0.0006), and (iii) BCL-2 (0.8 +/- 0.5; 1.9 +/- 0.5; 1.9 +/- 0.6; 2.0 +/- 0.6; 4.4 +/- 1.2; and 4.6 +/- 0.8, P < 0.001). The expression values (p53, BCL-2, and hMSH2) were statistically significantly higher (P < 0.05) in astrocytomas (Grade III) than in other gliomas. There was an insignificant negative correlation between p53 and BCL-2 (r = -0.07, P > 0.05) and between p53 and hMSH2 (r = -0.08, P > 0.05) protein expression. Alterations of the p53, BCL-2, and hMSH2 proteins occur during the development of these tumors.

Astrocytoma↗
PubMed2006

Analysis of the expression pattern of glial cell line-derived neurotrophic factor, neurturin, their cognate receptors GFRalpha-1 and GFRalpha-2, and a common signal transduction element c-Ret in the human scalp skin.

BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) and a related family member, neurturin (NTN), as well as their cognate receptors (GDNF receptors, GFRalpha-1 and GFRalpha-2, respectively) are involved in nervous system development and murine hair cycle control. To date, their expression in human scalp skin is still unknown. MATERIALS AND METHODS: The expression pattern of these proteins was examined in human scalp skin by immunofluorescence and immunoalkaline phosphatase staining methods as well as RT-PCR (GDNF). A total of 50 normal human scalp skin biopsy specimens were examined (healthy females, 53-57 years). RESULTS: The expression of GDNF protein was strong in the epidermis and sebaceous and sweat glands. In the epidermis, GDNF protein expression was seen in all layers except the stratum corneum. It was strong in the basal layer and decreased gradually towards the granular layer. The results of RT-PCR analysis revealed that GDNF protein is synthesised in the epidermis. The expression of NTN, GFRalpha-1, and GFRalpha-2 proteins was strong in the papillary dermis and sebaceous and sweat glands. In the epidermis, NTN protein expression was absent. The expression of GFRalpha-1 and GFRalpha-2 proteins was moderate in the epidermis. The expression of c-Ret protein was consistently strong in the epidermis and sebaceous and sweat glands. These proteins were strongly expressed in both epithelial and mesenchymal compartments of human anagen VI scalp hair follicles. CONCLUSIONS: Our investigation reports, for the first time, the expression patterns of GDNF, NTN, GFRalpha-1, GFRalpha-2, and c-Ret proteins in human scalp skin. The expression of these proteins in the skin suggests their possible roles in skin homeostasis. The clinical ramifications of these observations mandate further investigations. Adly MA, Assaf HA, Hussein MR, Paus R. Analysis of the expression pattern of glial cell line-derived neurotrophic factor, neurturin, their cognate receptors GFRalpha-1 and GFRalpha-2, and a common signal transduction element c-Ret in the human scalp skin.

Female↗
PubMed2005

Analysis of the mononuclear inflammatory cell infiltrate in the cirrhotic, dysplastic nodules and hepatocellular carcinomas in patients with chronic hepatitis C infection.

BACKGROUND: Hepatocarcinogenesis is a multistep process entailing the transitions from normal liver --> chronic hepatitis and cirrhotic nodules (CH/CNs) --> dysplastic nodules (DNs) --> hepatocellular carcinomas (HCCs). We hypothesized that hepatocarcinogeneis on top of chronic hepatitis C (CH-C) is associated with alterations in the mononuclear inflammatory cell infiltrate (MICs) in response to altered antigenicity of the damaged hepatocytes. MATERIALS AND METHODS: A total of 19 hepatic resection specimens entailing the entire continuum of the lesional steps of the hepatocarcinogenesis (on top of CH-C) were evaluated for MICs using immunohistological methods and mouse monoclonal antibodies (CD3, CD20, CD68 and T-cell intracellular associated antigen, TIA-1). RESULTS: HCCs were: 1) overrepresented in elderly males (56.1 +/- 2.0 years, with male to female ratio of 1.8:1), and 2) more common in the right than in left lobe (1.1:1) The transitions from normal liver to the subsequent lesional steps (CH-C/CNs, DNs and HCCs) was associated with statistically significantly (p < 0.000) increased density of: tumor infiltrating lymphocytes (9.5 +/- 0.2 vs. 87.1 +/- 1.3 vs. 73.6 +/- 1.6 vs. 72.1 +/- 3.5), CD20+ B cells (4.4 +/- 0.2 vs. 35.0 +/- 2.9 vs.11.3 +/- 1.8 vs. 11.3 +/- 1.6), CD68+ macrophages (1.4 +/- 0.1 vs. 9.5 +/- 1.8 vs. 22.3 +/- 1.6 vs. 18.8 +/- 2.0), CD3+ cells (5.4 +/- 0.1 vs. 87.0 +/- 1.3 vs. 62.2 +/- 1.3 vs. 61.0 +/- 3.4) and TIA-1(+) cytototoxic T cells (0.4 +/- 0.1 vs. 11.6 +/- 2.0 vs. 24.9 +/- 1.2 vs. 30.5 +/- 1.6). CONCLUSIONS: Increased MICs during hepatocarcinogeneis (on top of CH-C) may reflect change in the antigenicity of the damaged hepatocytes. Although both B (humoral response) and T (cell mediated immunity) lymphocytes were involved, the later were the most numerous immunocytes. A considerable fraction of these T cells was TIA-1(+) cells suggesting their cytotoxic potential.

Carcinoma, Hepatocellular↗
PubMed2005

High concentrations of retinoids induce differentiation and late apoptosis in pancreatic cancer cells in vitro.

BACKGROUND: Our previous investigations showed that retinoids, at specific concentrations, can inhibit cell proliferation. In this investigation, we hypothesize that high concentrations of retinoids can induce phenotypic changes (differentiation) and late apoptosis in pancreatic cancer cells in vitro. MATERIALS AND METHODS: To test our hypothesis, retinoid-induced differentiation was assessed: (1) phenotypically by light and electron microscopy and (2) biochemically by measuring carbonic anhydrase, aerobic metabolic and mucin producing activities. Modulation of transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) autocrine pathways were utilized as mechanistic and differentiation markers. RESULTS: The extensive differentiation-indicative phenotypic changes correlated with several folds increase in the aerobic metabolism (MTT reduction and Mitochondrial mass), carbonic anhydrase activity and mucin production. There was a marked increase in TGF-beta (Bioassay and ELISA) and TGF-beta (RIA) secretion. EGF receptor density (Receptor binding assay) was reduced by 50% within six hours and was reflected on abolishment of EGFR ligand-induced proliferation. Cotreatment with the RAR-alpha antagonist, Ro41-5253 or pan-TGF-beta neutralizing antibody abolished the phenotypic and antiproliferative effects of all-trans retinoic acid. Apoptosis (TUNEL assay) was undetectable after three days of treatment with the maximum concentration used. However, apoptosis was extensively induced after six days of treatment. CONCLUSIONS: High concentrations of retinoids were able to induce phenotypic changes (differentiation) and late apoptosis in pancreatic cancer cells in vitro. The clinical ramifications of these observations await further investigations.

Apoptosis↗
PubMed2005

Skin cancer in Egypt: a word in your ear.

BACKGROUND AND OBJECTIVES: In Egypt, the clinicopathologic features of skin cancer are still unknown. MATERIALS AND METHODS: To define these features, registries of the Pathology Departments, Assiut and South Valley University Hospitals were reviewed. The lesions included 21 melanomas, 39 squamous cell carcinomas (SCCs), and 202 basal cell carcinomas (BCCs). RESULTS: Skin cancer represented 5% of the malignant tumors of the entire body. BCC (77%) was the most common skin cancer followed by SCC (15%) and melanomas (8%). The mean age was 54 +/- 3 (melanomas), 66 +/- 10 (BCC), and 60 +/- 5.18 (SCC). The most common sites were the face (BCCs), face and extremities (SCCs), and face and lower limbs (melanomas). The average size (mm) was 21 +/- 0.3 (melanomas), 28 +/- 0.3 (BCC) and 30 +/- 1.1 (SCC). Melanomas, BCCs and SCCs were of nodular, keratotic invasive and nodular infiltrative types, respectively. CONCLUSIONS: In Egypt, skin cancer is uncommon malignancy. As compared to Western societies, the incidence rate of melanoma is very low and its topographic distribution is different. Alternatively, the rates for SCCs/BCCs are comparably high and their topographic distribution is similar. This is the first investigation that reports the clinicopathologic features of skin cancer in Egypt and compares it to other parts of Africa and Western societies.

Adult↗
PubMed2005

Dendritic cells and melanoma tumorigenesis: an insight.

Dendritic cells, distinct class of leukocytes, are professional antigen-presenting cells. They are characterized by their ability to migrate through tissues where they can take up, process, and present antigens. They can interact with, stimulate, and direct T-lymphocyte responses. As such, they are capable of triggering a primary T cell response. Evidence suggest that DCs can elicit strong antitumor immunity. Melanoma is an aggressive malignancy with a poor prognosis. In these tumors, there is a reduced density of DCs in the epidermal, intratumoral and peritumoral sites. This seems to share to a defective T-cell response and ultimately to a poor prognosis in these tumors. Since 1975, more than 806 papers appeared in the literature with melanomas and DCs as keywords. However, in spite of these extensive investigations, a lack of side-by-side analysis of these studies has resulted in tentative conclusions that merely offer a first glimpse at the role of DCs in melanoma. To remedy this issue, this review seeks to examine the background information about DCs including their derivation, morphologic features, functional properties, growth characteristics, and differentiation pathways. This review provides insights into DCs status in the skin, and their roles in melanoma. It also sheds light on the possible use of DCs in melanoma therapy.

Animals↗
PubMed2005

Natural retinoids inhibit proliferation and induce apoptosis in pancreatic cancer cells previously reported to be retinoid resistant.

BACKGROUND: The anticancer ability of natural retinoids on pancreatic adenocarcinoma, an aggressive tumor, is still controversial. This investigation tested the hypothesis that all-trans retinoic acid can inhibit proliferation and induce apoptosis in pancreatic cancer cell lines. MATERIALS AND METHODS: Using our previously optimized conditions, the effect of all-trans retinoic acid (atRA, 0.001-10 microM) was tested in ten human pancreatic adenocarcinoma cell lines with various degrees of differentiation. Proliferation was monitored by cell number, [3H]-thymidine incorporation and cell cycle arrest. Apoptosis was investigated morphologically by light and electron microscopy and biochemically by tissue transglutaminase activity (TGase), mitochondrial membrane potential, cell cycle analysis of sub-G1 cells and detection of fragmented DNA (fragmentation of prelabeled DNA, agarose electrophoresis and TUNEL assays). RESULTS: Retinoic acid caused potent concentration- and time-dependent inhibition of proliferation of all cell lines studied. Cell cycle was arrested at G1 or G2 with extensive reduction of number of cells at S-phase after 24 hours of treatment with apoptotic concentration of atRA. Complete inhibition of proliferation was followed by apoptosis as indicated by the progressive accumulation of sub-G1 apoptotic cells which was confirmed by the more specific DNA fragmentation assays. There were extensive apoptosis-indicative light and electron microscopic changes preceded by phenotypic redifferentiation. TGase was induced between 3-5-fold the control level and its inhibition partially reversed the antiproliferative effect of atRA. Cellular viability during the preapoptotic stage was confirmed by normal mitochondrial membrane potential in the first two days of treatment with the maximum atRA concentration used. However, the potential was progressively reduced with time as a preapoptotic change. Caspase 3-like activity was induced by the apoptotic concentrations of atRA at late time points. However, the redifferentiation indicative changes were not prevented by cotreatment with Ac-DEVE-CHO caspase 3 inhibitor. CONCLUSIONS: Together, our results demonstrated the efficient anticancer ability of natural retinoids on human pancreatic cancer cell lines tested, even those previously reported to be retinoid resistant.

Antineoplastic Agents↗