[Evaluation of the two variants of p63 [d4TAp63 and delta Np73L] expression as molecular markers in the diagnosis and prognosis of breast cancer]

The TP63 gene, as the oldest homologue of TP53, encodes two main N-terminal variants by different promoters: the trans-activating variant, TAp63 with tumor suppressor activity and the amino terminal truncated variant, delta Np63 with oncogenic activity. As the result of the deletion of exon 4 in each of the variants, two further N-terminal variants have been reported for p63 in the last decade: d4TAp63 and delta Np73L, but the exact function of these variants have not been determined in normal and tumoral cells. In this study we evaluated the expression pattern of p63 variants and usefulness of d4TAp63 and delta Np73L as potential diagnostic molecular markers in breast cancer. In this study 30 tumoral and 20 non tumoral samples of marginal tissues were studied by use of Semi-quantitative Reverse Transcriptase-nested PCR [RT-nPCR] method. SPSS16 software was used for data analysis. In all cases with expression of TAp63 and delta Np63 variants, d4TAp63 and delta Np73L variants were always expressed with their long variants simultaneously. In tumoral and marginal samples delta Np73L mean expression level was significantly higher than the mean expression level of d4TAP63 [P = 0.009 and P=0.008 respectively]. delta Np63 expression levels in tumoral and marginal samples were also higher than those of TAp63, which had a statistically significant difference in tumoral samples [P=0.03], but no significant difference was detected in marginal samples [P = 0.11]. The results indicated dominant negative inhibitory activity of delta Np63 and its potential role as an oncogene in breast cancer. delta Np73L variant compared to d4TAp63, in tumoral and non tumoral breast tissues can act as dominant negative variant. Both variants [delta Np73L and d4TAp63] with similar expression patterns to their respective longer variants [delta Np63 and TAp63] and simultaneous expression with their variants are likely to be involved in strengthening the tumor suppressor activity in normal and tumoral breast cells. On the other hand, according to the expression patterns of delta Np73L and d4TAp63 variants, they cannot be considered as molecular markers in the diagnosis of breast tumors

[Evaluation of nucleostemin gene expression as a new molecular marker in breast tumors]

Nucleostemin is one of the stem cell enriched proteins which encodes a novel nucleolar GTP-binding protein found at high levels in the adult and embryonic stem [ES] cells but not in terminally differentiated cells. It is also expressed in tumor cell lines as well as in the several types of human cancers. Due to the increasing rate of breast cancer in recent years, in the present study we evaluate the usefulness of Nucleostemin as a potential diagnostic and therapeutic molecular marker in breast tumors. A total of 41 tumoral and 20 non-tumoral adjacent tissues were studied by Semiquantitative Reverse Transciptase-Polymerase Chain Reaction [RT-PCR]. Beta 2m was used as an internal control. Data were analyzed through SPSS software. According to the obtained results, nucleostemin is a proliferation marker with higher eapression in breast tumors rather than in adjacent normal tissues. Nucleostemin expression level was significantly correlated with profilertion potential of breast benign tumors [p<0.05]. The expression of Nucleostemin was significantly correlated with the advanced stages of breast tumors [p<0.05]. Nucleostemin expression level may be used in estimating tumor size and as a potential prognostic marker for determinig breast tumors stage and future metastases. Moreover, nucleostemin inhibition can be an effective sterategy in decreasing the proliferation of breast tumor cell lines

[Evaluation of the expression of survivin-3b and survivin-3alpha ,the novel splice variants, as diagnostic tumor markers in thyroid cancer]

Survivin is a new member of inhibitor of apoptosis protein family [IAP] that plays an important role in the regulation of cell cycle and inhibition of apoptosis. Distinct expression of this gene in tumoral cells versus normal cells introduces it as the fourth major transcriptome in cancers. Thyroid carcinoma is the most common endocrine malignancy. Considering the highly heterogeneous nature of tumoral and non-tumoral thyroid nodules from the pathological viewpoint and also in regard to the absence of appropriate molecular markers, extensive efforts have been made to find a specific molecular tumor marker for diagnosis of thyroid tumors. Studies have been demonstrated that the expression pattern of survivin and its splice variants was different in cancerous tissues compared to normal tissues. In this study we evaluated expression of survivin-3b and survivin-3alpha, the novel survivin splice variants, as diagnostic markers for thyroid cancer. This was a descriptive study. 77 thyroid specimens; including 49 tumoral, 14 non-tumoral and 14 tumor margin samples were collected and expression of survivin-3b ands-3alpha was investigated by hemi-nested RT-PCR method. Tumoral samples showed the highest expression of survivin-3b and survivin-3alpha and the lowest expression was detected in the specimens of tumor margins. In this study we demonstrated the expression of survivin-3b and survivin-3alpha in thyroid tumors for the first time. In conclusion significant expression of survivin-3b and survivin-3alpha splice variants in tumoral cells shows their roles in thyroid cancer progression and their efficiency as molecular markers for detection and classification of tumoral and nontumoral thyroid nodules

[Detection of P53 gene exons 5 and 6 mutations among east azerbaijani women with breast cancer]

Breast cancer [BC] is the most common invasive malignancy affecting women worldwide. The tumor-suppressor P53 gene [P53] is frequently mutated in breast tumors. To use P53 as a target for therapy, it is important to accurately assess p53 mutation status in tumor samples. A total of 102 tumor samples were collected from breast cancer patients referred to Tabriz hospitals between the 2007-2009 period. DNA was extracted by Proteinase K- Isopropanol method and then performed amplification and sequencing of P53 from exons 5 and 6. Mutations in the P53 gene were detected in 17.6% of the patients. Including 7 polymorphisms [6.68%] and 11 mutations [10.78%]. Overall, 18.2% of the mutations were found in codons 160 [ATG>AAG] and 163 [ATC>AAG] in exon 5. Also 81.8% of the mutations observed in exon 6: codon 193[CAT>AAT], codon195 [ATC>TTC], codon 195 [ATC>AAC], codon 198[GAA>TAA], codon 220 [TAT>TGT], codon 213 [CGA>CTA], and codon 214 [CAT>CG]. No alteration observed in intron5 and all of polymorphism detected in 13399A>G nucleotide of exon 6. The majority of detected mutations are missense that located on DNA-binding domain of P53. This type of mutation usually leads to the production of a mutant protein with a compromised structure and altered DNA-binding capacity. This is the first report of its kind from the East Azarbaijan region. Our results indicate a rather high frequency of exon 6 mutations in P53 among patients with breast cancer. Furthermore, the mutation pattern appears differs from other regions. However, further studies are needed to determine the role of P53 mutations in breast cancer development

[Study of expression pattern of eIF4E gene as a molecular marker in thyroid cancer]

Regulation of protein synthesis in the early stage of translation depends on the function of eIF4E factor especially in the form of eukaryotic initiation factor [eIF4F]. Overexpression of eIF4E in multiple cancer types, including malignancies of the prostate, breast, colon, lung, and the hematopoietic system is indicative of the role of this factor in tumorogenesis and promotion of the cancers. In this study we investigated the expression pattern of eIF4E as a new molecular marker in thyroid tumors and their marginal normal tissues. We used semi-quantitative RT-PCR technique to examine the expression of eIF4E in 21 papillary carcinoma tissue specimens and 14 specimens of corresponding marginal normal tissue adjacent to the malignant lesions. Beta 2m gene was considered as an internal control. Rate of expression of eIF4E in different groups were compared with one another by use of SPSS software and data were analyzed by one way ANOVA and t-test. Our data revealed significant expression of eIF4E in all tumor samples compared to non-tumor lesions and normal tissues [P<0.05]. Moreover the expression level was notably increased in malignant tumor samples compared to marginal tissues of the tumors [P<0.05]. The rate of expression was more in tumor samples than non-malignant samples. The results of this study indicated that the rate of expression of eIF4E gene is associated with kind of tumor and grade of malignancy. Also this study confirmed the role of eIF4E gene in tumor progression and development of thyroid tumors. Therefore eIF4E gene expression can be an appropriate indicator for diagnosis of tumors and can be used as a guide for grading of thyroid tumors. This prognostic and diagnostic factor can be considered as a promising therapeutic target for treatment of cancers

incidence of transient and permanent hypocalcaemia after total thyroidectomy for thyroid cancer

Hypocalcaemia is one of the more acute complications of total thyroidectomy and occurs after parathyroid injury during surgery. The aim of this study is to assess the incidence rate and risk factors of transient and permanent hypocalcaemia in patients who had undergone total thyroidectomy, due to malignant thyroid diseases and to determine the value of parathyroid gland autotranplantation in thyroid cancer surgeries. Sixty-five patients, diagnosed with thyroid malignancy, who were treated by total thyroidectomy with or without radical neck dissection between 2002 and 2006, were studied retrospectively. Of patients 60% were female [mean age 39.59 +/- 10.24 years] and 40% were male [mean age 42.11 +/- 11.93 years]. Complications of total thyroidectomy, permanent and transient hypocalcaemia in particular, were studied. In eleven patients, parathyroids were transplanted within fibers of sternocleidomastoid and deltoid muscles. Transient hypocalcaemia occurred in 18 patients and was treated by intravenous and oral calcium supplements. None of patients progressed to permanent hypocalcaemia. Temporary recurrent laryngeal nerve paresis occurred in 2% of patients but there was no case of paralysis. There was a significant difference in hypocalcaemia occurrence between patients, who had just total thyroidectomy and those who underwent thyroidectomyt with neck dissection [p=0.01]. Hypocalcaemia after total thyroidectomy is a serious and dangerous complication, requiring prompt diagnosis and proper treatment. Parathyroid gland transplantation for an injured or incidentally removed parathyroid, between fibers of sternocleidomastoid or deltoid muscles, can prevent the occurrence of permanent hypocalcaemia

[Evaluation of the expression of Survivin-2 alpha splice variant as a molecular marker in thyroid cancer]

Thyroid carcinoma is the most common endocrine malignancy. Considering highly heterogenous nature of tumoral and non-tumoral thyroid nodules from pathological point of view and also in regard to absence of appropriate molecular markers, extensive efforts have been made to find a molecular tumor marker for specific diagnosis of thyroid tumors. Recent attention has been paid to Survivin, a new member of the Inhibitor of Apoptosis Protein Family [IAP], as a new molecular marker in cancer. Studies have been demonstrated that Survivin and its splice variants have different expressions in cancerous tissues compared to normal tissues. In this study the expression of Survivin-2alpha splice, one of the newest Survivin variants, was evaluated in thyroid cancer as a molecular marker. Tissue samples were collected from 77 thyroid specimens including 49 tumoral, 14 nontumoral and 14 tumor margin samples. The expression of Survivin-2 alpha was studied by Hemi-Nested RT-PCR method. Expression of Survivin-2 alpha splice was the highest in surgical margin samples compared to non-tumoral and tumoral samples. The lowest expression was that of tumoral samples. Our data demonstrated the expression of Survivin-2 alpha in thyroid tumors. Although the expression of surviving-2 alpha splice variant in tumoral cells was lower than that of tumor margins, it did not show a significant difference. Therefore it seems likely that it does not have a special role in the progression of tumor and development of abnormal nature of the cells. According to the results of this study, it can be concluded that the different expressions of 2 alpha in these groups can not be an appropriate criterion for distinguishing tumors from non-tumoral lesions of thyroid gland

[Evaluating the expression of survivin and its splice variants; 2B and AEx3 as new diagnostic molecular markers in thyroid cancer]

Thyroid cancer is the most common endocrine malignancy. Because of the highly heterogeneous nature of tumoral and non-tumoral thyroid nodules and lack of suitable clinico-pathological criteria and absence of appropriate molecular markers, scientists have been trying to find a molecular tumor marker for specific diagnosis of thyroid tumors. Recent attention has been paid to Survivin, a novel member of the Inhibitor of Apoptosis Protein Family [IAP], as a new molecular marker in cancer. Studies have demonstrated that Survivin and its splice variants have different expression in cancerous tissues compared to normal tissues. In this study the expression of Survivin and its splice variants; 2B and [delta] Ex3 were evaluated as new diagnostic molecular markers in thyroid cancer. Tissue samples were collected from 61 thyroid specimens including 14 tumor margins, 11 non-tumoral and 36 tumoral samples. Expression levels of Surviving and its variants were measured by semi quntitative RT-PCR. Expression level of Survivin in tumor samples was significantly higher compared with surgical margins and non tumural tissues. There was also a significant increase in expression level of Survivin-[delta]Ex3 in tumoral tissues compared with surgical margins. The expression of Survivin 2B in tumors was lower than the non-tumoral tissues. Our data indicated the important role of Survivin in production of thyroid tumors and also revealed that high expression of [delta]Ex3 variant is correlated with nature of thyroid tumors. Therefore, evaluating Survivin gene expression and its recently introduced splice variants may be used in diagnosis and classification of thyroid tumors from non-tumoral lesions

Giant thymolipoma mimicking cardiomegaly

A 28-year-old man presented with a chest radiograph strongly suggestive for cardiomegaly. Although he did not consent any hemodynamic studies, cardiomegaly was ruled out on the basis of the clinical course. Computed tomography showed the existence of a large mass in both sides of the heart and in both lower hemitho-races. The tumor was resected by anterior mediastinotomy; it was weighted 2100 g and measured almost 35X25X6cm. Histopa-thologic examination revealed thymolipoma

Organizing lobar penumonia: report of a case

Organizing Lobar Pneumonia is a rare form of Bronchiolitis Obliterans Organizing Pneumonia. Herein, we report a rare case of organizing pneumonia involving lung, mediastinum and esophagus. A 16-year-old girl was referred to our center with clinical signs and symptoms of dysphagia and weight loss. The main abnormal radiologic and endoscopic findings were stricture of the lower third of esophagus and calcified lobar pneumonia of the lung. Pathologic examination of biopsies taken from esophageal stricture and resected lung revealed fibrosis and organizing lobar pneumonia. This combination, to our knowledge, has not been reported previously