MUC4 expression and its relation to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage in non-small cell lung cancer (NSCLC)

There is a peptide sequence homology between the gene product of human MUC4 and rat Muc4/sialomucin complex (SMC). Each contains a transmembrane subunit with two epidermal growth factor (EGF)-like domains that act as ligand for ErbB2. MUC4 and ErbB2 mediate intracellular signaling pathways that are linked to repression of apoptosis and either to proliferation or to differentiation of tumor cells. This study investigates the expression of human MUC4 in neoplastic and corresponding non-neoplastic tissues, and the relation of MUC4 expression in neoplastic tissues to ErbB2 expression, apoptosis, proliferation, differentiation, and tumor stage in a series of 100 non-small cell lung carcinomas (NSCLCs). MUC4 and ErbB2 expressions and cell proliferation (PCNA) were shown using immunohistochemistry. Apoptotic index (AI) and tumor differentiation were determined by morphologic criteria. All the non-neoplastic bronchial tissues and 85% of NSCLCs showed MUC4 expression. MUC4 expression was found to be higher in neoplastic than in non-neoplastic tissues (Yates correction p: 0.0006). MUC4 expression was inversely correlated with AI (p=0.0002) and was correlated with ErbB2 expression (p=0.022), but not with PCNA counts and tumor stage. Our results indirectly suggest that MUC4, in association with ErbB-2, might be involved in the repression of apoptosis and differentiation rather than proliferation in tumor cells of NSCLCs.     

In vitro experimental 211At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin

Purpose  

Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair.     

Presence of obestatin in breast milk: relationship among obestatin, ghrelin, and leptin in lactating women

OBJECTIVE: The peptide hormones ghrelin and leptin have been found in blood and breast milk. This study was undertaken to investigate whether breast milk also contains obestatin, which is derived from the same gene as ghrelin but has opposite actions, and to characterize the relations among serum and milk ghrelin, obestatin, and leptin levels in lactating mothers. METHODS: Venous blood, colostrum, and mature milk were obtained from healthy lactating women (n = 31) just before suckling. The ghrelin and obestatin concentrations were determined by radioimmunoassay. Leptin levels were measured by enzyme-amplified sensitivity immunoassay. RESULTS: Obestatin levels in colostrum (538.9 pg/mL) and mature milk (528.5 pg/mL) were more than twice the corresponding blood levels (270.3 and 289.4 pg/mL, respectively). In contrast, leptin levels in colostrum (2.01 ng/mL) and mature milk (2.04 ng/mL) were more than five-fold lower than the corresponding blood levels (11.54 ng/mL). There was no correlation between breast milk ghrelin levels and leptin (r = -0.18, P > 0.05). However, there was a positive correlation between leptin levels in breast milk and blood (r = 0.369, P < 0.05). CONCLUSION: The origin of milk obestatin is not currently known, but it comes from the blood or breast and may drain through the mammary glands into the milk. Ghrelin, obestatin, and leptin in the milk may directly affect appetite and their levels may be related to the regulation of energy balance and the pathogenesis of obesity.     

Role of N-acetyl cysteine and acetyl-l-carnitine combination treatment on DNA-damage-related genes induced by radiation in HEI-OC1 cells

Abstract

Purpose: The aim of the present study was to evaluate the effect of acetyl-l-carnitine (ALC) and N-acetyl cysteine (NAC) on ionizing radiation (IR)-induced cytotoxicity and change in DNA damage-related genes in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells.

Methods: HEI-OC1 cells were irradiated with 5?Gy radiation and treated by eight combinations of NAC and/or ALC: control, NAC, ALC, IR, NAC?+?IR, ALC?+?NAC, ALC?+?IR, and ALC?+?NAC?+?IR. Cell viability, apoptotic cell death, and DNA damage were measured at the 72nd hour. Eighty-four IR-induced DNA-damage-related genes were determined by RT-PCR gene array and >10-fold changes were considered significant.

Results: IR decreased cell viability by about 50% at 72?hours of incubation. In particular, the ALC and/or NAC combination before IR protected the HEI-OC1 cells (p?<?.05). Single and combination treatment prior to IR led to lower apoptotic cell death (p?<?.05). There was a significant lower DNA damage in ALC?+?NAC?+?IR group compared to IR group (p?<?.05). Expressions of Brca2, Xpc, Mlh3, Rad51, Xrcc2, Hus1, Rad9a, Cdkn1a, Gadd45a which are the DNA-repair genes were found to be significantly higher in NAC?+?ALC?+?IR group than those in individual treatment of ALC or NAC.

Conclusions: ALC and/or NAC treatment prior to IR led to higher cell viability and lower apoptotic cell damage compared to the IR group. The results of the study show that the ALC?+?NAC combination treatment inhibits DNA damage and induces DNA-repair genes to repair radiation damage, and this combination treatment is more effective against radiation-induced DNA damage than NAC or ALC therapy individually.     

p53 antibody: is it an indicator of dedifferentiated thyroid cancer?

Aim

Radioiodine is the most effective treatment modality in differentiated thyroid carcinoma, either in metastatic or residual thyroid tissue. However, sometimes dedifferentiation can develop and the effectiveness of radioactive I-131 decreases. The p53 is a tumor suppressor gene which plays an important role in controlling normal cell proliferation regulation. In the serum of healthy individuals, the presence of p53 autoantibodies is extremely rare. Mutations in this gene cause an accumulation of non-functional proteins and may lead to development of anti-p53 antibodies. The aim of the present study was to devise a simple blood test that could lead to early identification of patients with dedifferentiation. In this respect, we investigate whether the serum level of anti-p53 antibody is of diagnostic value in the follow-up of patients with high levels of thyroglobulin (Tg) and negative I-131 scan.

Materials and methods

Patients who were diagnosed with thyroid cancer, treated with total or near total thyroidectomy and referred for I-131 therapy or low dose I-131 whole body scan were included in our study. Blood samples were taken before the administration of I-131 orally in the group of patients. Besides, 28 healthy subjects were included. We quantified the presence of p53 autoantibodies from serums.

Results

In the present study were enrolled 171 patients with a mean age of 47.7 ± 13.5 years (range 16–80 years) and 28 healthy subjects with an age range of 18–52 years (mean 36.0 ± 9.8 years). One hundred and forty-eight patients had papillary (86.5 %), 7 (4.1 %) follicular, 10 (5.8 %) thyroid tumors of uncertain malignant potential, 2 (1.2 %) Hürthle cell carcinoma, 3 (1.8 %) poor differentiated, and 1 (0.6 %) undifferentiated thyroid carcinoma. The p53 antibodies were positive in 16 (9.4 %) patients and negative in 155 (90.6 %). The p53 antibodies were positive in 3 (10.7 %) healthy subjects, and negative in 25 (89.3 %) healthy subjects. In five patients with high Tg level and negative radioiodine scan, who were accepted as dedifferentiated, p53 antibodies were also negative.

Conclusion

The results of the present study suggested that the level of serum p53 antibody seems to be of limited value in the demonstration of dedifferentiation in thyroid cancer patients.     

Water as Source of Francisella tularensis Infection in Humans,Turkey

Francisella tularensis DNA extractions and isolates from the environment and humans were genetically characterized to elucidate environmental sources that cause human tularemia in Turkey. Extensive genetic diversity consistent with genotypes from human outbreaks was identified in environmental samples and confirmed water as a source of human tularemia in Turkey.     

Complicated Giant Pilomatrixoma of the Parotid Region

Objective

Pilomatrixoma (calcifying epithelioma of Malherbe) is a benign soft tissue tumour arising from dermis or subcutaneous tissue which should be considered in differential diagnosis of preauricular lesions especially when skin fixation is present.

Case Report

Twenty-three year old male referred to our clinic with complaint of left preauricular swelling over 18 months which enlarged and became painful in the last 2 months. Because the lesion showed signs of infection, surgery was planned after medical therapy was completed. FNAB suggest pleomorphic adenoma as preliminary diagnosis. US or MRI showed no specific feature.

Treatment and Prognosis

Total excision, superficial parotidectomy with facial nerve sparing was performed after regression of infectious signs. Postoperatively no recurrence was detected.

Conclusion

Pilomatrixomas are benign tumours but have diagnostic difficulties according to clinical and cytologic findings. This rare lesion should be kept in mind to avoid misdiagnosis as malign parotid tumours, particularly in the presence of skin change.

     

The Impact of Mental Health Nursing Module,Clinical Practice and an Anti-Stigma Program on Nursing Students' Attitudes toward Mental Illness: A Quasi-Experimental Study

BackgroundIt is important to support nursing students during their education in developing positive attitudes toward people with mental illness.ObjectivesTo examine the impact of mental health nursing module, clinical practice, and anti-stigma program on the attitudes of nursing students toward mental illness.DesignThe study was a single group pretest and posttest quasi-experimental design.SettingsThis study was conducted in a nursing school in the west of Turkey.ParticipantsThe sample of the study consisted of 64 undergraduate nursing students.MethodsThe data were collected through the Beliefs Toward Mental Illness Scale and Social Distance Scale.ResultsThe mean scores of the dangerousness subscale significantly decreased after mental health nursing module, clinical practice and anti-stigma program. The results revealed significant positive differences in the mean scores of the social distance scale after the theory, clinical practice, and anti-stigma program were completed.ConclusionsThe mental health nursing curriculum should be focused on replacing stereotypes with accurate information. Anti-stigma programs should be included in standard mental health nursing courses.