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1.
Med Lav ; 115(1): e2024002, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38411979

ABSTRACT

BACKGROUND: The growing concern for the faculty's well-being is allied with the emotionally demanding nature of teaching, which has an adverse effect on physical and mental health. There is abundant evidence that academic medicine faculty are subjected to high rates of dissatisfaction, distress, burnout, and turnover among medical educators. This study is dedicated to the exploration of the association between job satisfaction and psychological distress among academic medicine faculty in Kazakhstan. METHODS: The observational cross-sectional study was conducted among medical educators in Kazakhstan between 1 October and 25 December. The survey was completed by 715 representatives of academic medicine staff. The sample size was calculated by Epi Info Sample Size Calculator, version 7.0. Multinomial logistic regression analysis using the forced entry procedure was applied to identify the factors associated with job satisfaction. RESULTS: The prevalence of job satisfaction, depression, anxiety, and stress was 19.2%, 40.6%, 41.3%, and 53%, respectively. Three variables were significantly associated with job satisfaction: having a partner (AOR=0.79; 95% CI 0.38-1.659), having work experience of 5-10 years (AOR=0.32; 95% CI 0.14-0.74), and holding a Ph.D. degree (AOR=0.40; 95% CI 0.18-0.91). Job satisfaction was significantly associated with depression (p=0.005) and stress (p<0.001). CONCLUSIONS: Compared to previous research in this area, our findings reported a higher prevalence of psychological distress and dissatisfaction. Potential reason for higher rates of dissatisfaction may be the global disruption due to COVID-19 pandemic.


Subject(s)
Job Satisfaction , Psychological Distress , Humans , Cross-Sectional Studies , Faculty, Medical , Kazakhstan/epidemiology , Pandemics
2.
J Prev Med Hyg ; 64(2): E215-E225, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37654854

ABSTRACT

Introduction: Psychological distress refers to a set of painful mental and physical symptoms of anxiety and depression, which often coexist and coincide with common somatic complaints and chronic conditions. In Kazakhstan, mental disorders are the second leading cause of years lived with disability. Currently, medical education in Kazakhstan is undergoing comprehensive reform, which creates an additional burden on faculty, fostering mental health concerns. Methods: A quantitative observational cross-sectional study was conducted in 6 large medical universities in Kazakhstan. Data were obtained from 715 faculty academics by using an online self-reported DASS-21. Statistical analysis was performed using the SPSS version 20.0. Bivariate and multivariate logistic regression analyses were applied to evaluate the relationship between predictor and outcome variables. Results: The total prevalence of depression, anxiety, and stress was 40.6%, 41.3%, and 53.0%, respectively. Younger age (p = 0.002), female gender (p = 0.001), being single (p = 0.044) or in a relationship (p = 0.001), having chronic diseases (p < 0.001), holding Master (p = 0.036) or PhD degree (p = 0.040), employment status (p = 0.034), and being involved in additional activities (p = 0.049) were significantly associated with different dimensions of distress. Conclusions: Nearly half of the study population reported symptoms of depression, anxiety, and stress. Due to the higher prevalence of psychological distress amongst academic medicine faculty, determined risk factors must be taken into consideration in developing policies for mental issues prevention.

3.
Indian J Ophthalmol ; 70(12): 4325-4330, 2022 12.
Article in English | MEDLINE | ID: mdl-36453339

ABSTRACT

Purpose: To study and describe clinical characteristics of congenital and developmental cataract at a tertiary eye care facility. Methods: In this retrospective study, 942 children (1311 eyes) presenting with congenital/developmental cataract over a 10-year study period were included. Gender, age at surgery, main presenting complaint, morphologic type of cataract, laterality, family history, and associated findings were recorded. Results: The overall proportion of boys and girls undergoing cataract surgery was approximately equal (P = 0.110). However, in the cases of bilateral cataract, the proportion of boys was larger than girls (P = 0.028). More than half (62.3%) of the patients underwent surgery at the age of >3 years. The main presenting complaint was white pupils, accounting for 48.1% of cases. Total cataract was the most common morphologic type in all age groups. In total, 133 children out of 942 (14.1%) had a positive family history of congenital/developmental cataract. Strabismus and nystagmus were seen in 27.2% and 19.3% of the eyes, respectively. Additional ocular dysmorphology was found in 97 (10.3%) of patients. Coexisting systemic disease was found in 149 (15.8%) cases. Among syndrome-associated cataracts, Down syndrome accounted for the majority of cases. Conclusion: High prevalence of total cataracts as well as frequent association with strabismus and nystagmus are likely to be the consequences of delayed presentation.


Subject(s)
Cataract , Nystagmus, Pathologic , Strabismus , Male , Child , Female , Humans , Child, Preschool , Kazakhstan , Retrospective Studies , Cataract/epidemiology , Pupil
4.
Ann Med ; 54(1): 1988-1993, 2022 12.
Article in English | MEDLINE | ID: mdl-35833752

ABSTRACT

PURPOSE: To investigate the age at recognition and presentation for surgery for congenital and developmental cataract at Kazakh Eye Research Institute in Kazakhstan. METHODS: A retrospective review of children aged 0-18 years, who presented with congenital and developmental cataract between January 1, 2010 and December 31, 2020. All medical records were reviewed. Gender, age at recognition, age at surgery, laterality, residential location (rural/urban) were recorded. RESULTS: The study population included 897 patients of children presented with congenital and developmental cataract over a 10-year study period, 58% of them were boys and 44.6% were from rural areas. Cataract was bilateral in 621 (69.2%) and unilateral in 276 (30.8%) of patients. Median age at recognition for patients with congenital/developmental cataract was 12 months. Median age at surgery for congenital/developmental cataract was 51 months. Only 14.7% of children underwent surgery within first year of life. The urban citizens underwent surgery earlier than patients from rural areas. The median delay in presentation for surgery was 15 months. CONCLUSION: The average age at cataract surgery in the population of Kazakhstan is much older than in developed countries. It is essential to study barriers that associated with delayed presentation to build strategies to overcome them.Key messagesIt is known that cataract surgery in children early in life provides favourable visual outcome.Children with congenital and developmental cataract in Kazakhstan experience delay in surgical treatment.Children from rural areas undergo cataract surgery later than urban citizens.


Subject(s)
Cataract Extraction , Cataract , Cataract/congenital , Cataract/epidemiology , Child , Female , Follow-Up Studies , Humans , Infant , Kazakhstan/epidemiology , Male , Retrospective Studies , Visual Acuity
6.
Iran J Public Health ; 43(6): 760-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-26110146

ABSTRACT

BACKGROUND: Kazakhstan, a developing middle-income country, has the highest road traffic collision (RTC) mortality in the European Region. The aims of this study were to determine main characteristics of road traffic fatalities in Semey region, Kazakhstan and to compare findings with National data and middle-income European countries. METHODS: This descriptive surveillance study assesses RTC mortality rates and epidemiology in the Semey Region of East Kazakhstan Oblast. Data of all 318 road traffic fatalities form the Semey Regional Center for Forensic Medicine were analyzed for the 5-year period of January 1, 2006 through December 31, 2010. RESULTS: Over the study period, the average road traffic mortality in the Semey Region was 12.1 per 100,000 population with downward trend by 35.1% (p=0.002). The victims mean age was 37.1 (SD=17) years. Males predominated at 74.5%. Vehicle fatality was the most common mode of fatality at 61.3%. The majority of collisions, 53.1%, occurred on highways. Most victims, 67.3%, have died at the scene of collision; in 67.3% of fatalities, autopsies identified multiple injuries as cause of death. The high number of fatal collisions took place in "no snow" season (P<0.001), with an overall 5-years downward dynamic. CONCLUSION: High proportion of males, pedestrians and car occupants among road traffic fatalities; high proportion of death on scene in case of highway collisions are specifics for Semey region, Kazakhstan. These findings can be used to formulate preventive strategies to reduce fatalities and to improve the medical care system for road traffic fatalities.

8.
Cancer ; 112(10): 2143-51, 2008 May 15.
Article in English | MEDLINE | ID: mdl-18348306

ABSTRACT

BACKGROUND: It has been postulated that radiation induces breast cancers in atomic bomb (A-bomb) survivors. Oncogene amplification is an important mechanism during breast carcinogenesis and also serves as an indicator of genomic instability (GIN). The objective of this study was to clarify the association of oncogene amplification in breast cancer in A-bomb survivors with radiation exposure. METHODS: In total, 593 breast cancers were identified in A-bomb survivors from 1968 to 1999, and the association between breast cancer incidence and A-bomb radiation exposure was evaluated. Invasive ductal cancers from 67 survivors and 30 nonsurvivors were analyzed for amplification of the HER2 and C-MYC genes by fluorescence in situ hybridization, and expression levels of hormone receptors were analyzed by immunostaining. RESULTS: The incidence rate increased significantly as exposure distance decreased from the hypocenter (hazard ratio per 1-km decrement, 1.47; 95% confidence interval [95% CI], 1.30-1.66). The incidence of HER2 and C-MYC amplification was increased significantly in the order of the control group, the distal group (P = .0238), and the proximal group (P = .0128). Multivariate analyses revealed that distance was a risk factor for the coamplification of C-MYC and HER2 in breast cancer in survivors (odds ratio per 1-km increment, 0.17; 95% CI, 0.01-0.63). The histologic grade of breast cancers became significantly higher in the order of the control group, the distal group, and the proximal group and was associated with oncogene amplifications. CONCLUSIONS: The current results suggested that A-bomb radiation may affect the development of oncogene amplification by inducing GIN and may be associated with a higher histologic grade in breast cancer among A-bomb survivors.


Subject(s)
Breast Neoplasms/genetics , Gene Amplification , Neoplasms, Radiation-Induced/genetics , Nuclear Warfare , Proto-Oncogene Proteins c-myc/genetics , Receptor, ErbB-2/genetics , Survivors , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Genomic Instability , Humans , Immunoenzyme Techniques , In Situ Hybridization, Fluorescence , Incidence , Middle Aged , Neoplasms, Radiation-Induced/mortality , Nuclear Weapons , Prognosis , Proto-Oncogene Proteins c-myc/metabolism , Radioactive Fallout , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Risk Factors , Survival Rate
9.
Int J Cancer ; 122(5): 1082-8, 2008 Mar 01.
Article in English | MEDLINE | ID: mdl-17985346

ABSTRACT

Defective DNA damage response (DDR) can result in genomic instability (GIN) and lead to the transformation into cancer. P53-binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins. Because 53BP1 molecules localize at the sites of DNA double strand breaks (DSBs) and rapidly form nuclear foci, the presence of 53BP1 foci can be considered as a cytologic marker for endogenous DSBs reflecting GIN. Although it has been proposed that GIN has a crucial role in the progression of thyroid neoplasms, the significance of GIN during thyroid tumorigenesis remains unclear, particularly in patients. We analyzed, therefore, the level of GIN, as detected with immunofluorescence of 53BP1, in 40 cases of resected thyroid tissues. This study demonstrated a number of nuclear 53BP1 foci in thyroid cancers, suggesting a constitutive activation of DDR in thyroid cancer cells. Because follicular adenoma also showed a few 53BP1 nuclear foci, GIN might be induced at a precancerous stage of thyroid tumorigenesis. Furthermore, high-grade thyroid cancers prominently exhibited an intense and heterogeneous nuclear staining of 53BP1 immunoreactivity, which was also observed in radiation-associated cancers and in mouse colonic crypts as a delayed response to a high dose ionizing radiation, suggesting increased GIN with progression of cancer. Thus, the present study demonstrated a difference in the staining pattern of 53BP1 during thyroid carcinogenesis. We propose that immunofluorescence analysis of 53BP1 expression can be a useful tool to estimate the level of GIN and, simultaneously, the malignant potency of human thyroid tumors.


Subject(s)
Adenoma/genetics , Carcinoma/genetics , Genomic Instability , Intracellular Signaling Peptides and Proteins/metabolism , Thyroid Neoplasms/genetics , Adenoma/metabolism , Adenoma/pathology , Adult , Aged , Aged, 80 and over , Animals , Carcinoma/metabolism , Carcinoma/pathology , Cell Nucleus/metabolism , Colon/metabolism , Female , Fluorescent Antibody Technique , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Tumor Suppressor p53-Binding Protein 1
10.
Endocr Pathol ; 18(2): 68-75, 2007.
Article in English | MEDLINE | ID: mdl-17916995

ABSTRACT

This study addressed the immunohistochemical expression of MUC1 in papillary thyroid carcinoma (PTC) of different histotypes, sizes, and morphological features of aggressiveness, and its correlation with the overexpression of cyclin D1, a target molecule of the Wnt pathway. MUC1 expression was examined in a total of 209 PTCs. Cytoplasmic MUC1 expression was elevated in the tall, columnar cell and oncocytic variants (100%), Warthin-like (78%), and conventional PTCs (61%), and in papillary microcarcinoma (PMC) with the conventional growth pattern (52%). On the contrary, it was low in the follicular variant (27%) of PTC and PMCs with follicular architecture (13%). Cytoplasmic MUC1 accumulation did not associate with any clinicopathological features except peritumoral lymphoid infiltration in PTCs and in PMCs with the conventional growth pattern. MUC1 staining correlated with cyclin D1 overexpression in conventional PTCs and PMCs and PMCs with follicular architecture. The results demonstrate that MUC1 expression varies broadly in different histological variants of PTC, being the lowest in tumors with follicular structure. In general, it does not prove to be a prognosticator of PTC aggressiveness. A high correlation between MUC1 and cyclin D1 implies MUC1 involvement in the Wnt cascade functioning in a large subset of human PTCs and PMCs.


Subject(s)
Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Cyclin D1/biosynthesis , Cyclin D1/genetics , Cytoplasm/metabolism , Mucin-1/biosynthesis , Mucin-1/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Adult , Female , Genetic Markers , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Paraffin Embedding , Prognosis
11.
Endocr J ; 54(3): 399-405, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17429154

ABSTRACT

The activating point mutation of the BRAF gene, BRAF(T1799A), is the most common and specific genetic alteration in adult papillary thyroid carcinoma (PTC) and a possible marker of malignant potential of PTC. We have applied the PCR-RFLP method using fine-needle aspiration biopsy samples not only to our clinical practice but also to the international medical assistance effort around the Semipalatinsk Nuclear Testing Site in Kazakhstan. Seventy-seven cases (100 nodules) from Japan and 131 cases (137 nodules) from Kazakhstan were examined. There were 14 Japanese and 76 Kazakhstani cases of cytological malignant tumors from the examined samples. We detected 12 (85.7% of PTC) and 19 (25% of PTC) cases with BRAF(T1799A) among the Japanese and Kazakhstani cases, respectively. Of these cases, we found mutations in one cytologically "suspicious" case and even in two pathologically "benign" cases (after surgery in Kazakhstan). All of the BRAF mutation-positive cases, including those three, were confirmed as PTC by careful pathological examination, including immunohistochemical analysis. In summary, our PCR-RFLP method for BRAF(T1799A) detection using FNAB samples is useful not only for preoperative diagnosis of PTC but also as a complementary diagnostic tool for accurate pathological diagnosis, even after surgery.


Subject(s)
Carcinoma, Papillary/diagnosis , DNA Mutational Analysis , Diagnostic Techniques, Endocrine , Preoperative Care , Proto-Oncogene Proteins B-raf/analysis , Thyroid Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy, Fine-Needle , Carcinoma, Papillary/genetics , Child , DNA, Neoplasm/analysis , Female , Humans , Japan , Kazakhstan , Male , Middle Aged , Polymorphism, Restriction Fragment Length , Proto-Oncogene Proteins B-raf/genetics , Thyroid Neoplasms/genetics
12.
Hum Pathol ; 38(4): 621-8, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17270245

ABSTRACT

A radiation etiology is well known in thyroid carcinogenesis. RET oncogene rearrangement is the most common oncogenic alteration in Chernobyl-related papillary thyroid cancer (PTC). To find the characteristic alteration associated with RET rearrangements in radiation-induced thyroid cancers, we analyzed the RET oncogene by fluorescence in situ hybridization. The fluorescence in situ hybridization technique has the possibility of detecting RET rearrangements at a single-cell level regardless of the specific fusion partner involved and directly reveals RET copy number on a per-cell basis. Our study demonstrated RET amplification in all 3 cases of radiation-associated thyroid cancers but not in sporadic well-differentiated PTC (n = 11). Furthermore, RET amplification was observed in all 6 cases of sporadic anaplastic thyroid cancers (ATCs). The frequency of RET amplification-positive cells was higher in ATC (7.2%-24.1%) than in PTC (1.5%-2.7%). The highest frequency of RET amplification-positive cells was observed among ATC cases with a strong p53 immunoreactivity. In conclusion, we found RET amplification, which is a rare oncogenic aberration, in thyroid cancer. This report is the first one to suggest the presence of RET amplification in PTC and ATC. RET amplification was correlated with radiation-associated, high-grade malignant potency, and p53 accumulation, suggesting genomic instability. RET amplification might be induced by a high level of genomic instability in connection with progression of thyroid carcinogenesis and, subsequently, be associated with radiation-induced and/or high-grade malignant cases.


Subject(s)
Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Gene Amplification , Neoplasms, Radiation-Induced/genetics , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction
13.
Pathol Res Pract ; 201(6): 469-74, 2005.
Article in English | MEDLINE | ID: mdl-16136754

ABSTRACT

Primary pulmonary artery sarcomas (PASs) are rare and lethal tumors. They are easily misdiagnosed as chronic pulmonary embolism, mediastinal mass or tumor emboli, which delay a proper treatment. Although the advanced technologies are now increasingly being used, their diagnosis is usually hard to establish preoperatively at the present time. We report here a case of a 68-year-old female with PAS with lung metastases, who firstly presented with symptoms of common cold and anemia. Although a PAS had been suspected, the final diagnosis of pulmonary intimal sarcoma was made only postoperatively by histological and immunohistochemical examination. The patient died 8 months after the operation because of tumor growth progression, despite adjuvant chemotherapy and radiation therapy. Although pulmonary intimal sarcomas are usually of poorly differentiated mesenchymal malignancy, most reported cases are immunohistochemically positive for vimentin, alpha-smooth muscle actin (SMA), and/or desmin, therefore resembling leiomyosarcomas. However, the diagnosis of leiomyosarcoma should not be made on the basis of immunostains in the absence of typical morphologic features, and PAS, like the present case, should be more appropriately classified as intimal sarcoma according to the new WHO Classification of Tumours of Soft Tissue and Bone published in 2002.


Subject(s)
Lung Neoplasms/secondary , Pulmonary Artery/pathology , Sarcoma/secondary , Tunica Intima/pathology , Vascular Neoplasms/pathology , Aged , Biomarkers, Tumor/metabolism , Endarterectomy , Fatal Outcome , Female , Humans , Neoplasm Recurrence, Local , Pulmonary Artery/metabolism , Pulmonary Artery/surgery , Radiography, Thoracic , Sarcoma/metabolism , Sarcoma/surgery , Tomography, X-Ray Computed , Vascular Neoplasms/metabolism , Vascular Neoplasms/surgery
14.
Thyroid ; 15(4): 306-13, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15876151

ABSTRACT

Premature senescence may play an important role as an acute, drug-, or ionizing radiation (IR)-inducible growth arrest program along with interphase apoptosis and mitotic catastrophe. The aim of the study was to evaluate whether IR can induce senescence-like phenotype (SLP) associated with terminal growth arrest in the thyroid cells, and if so, to evaluate impact of terminal growth arrest associated with SLP in intrinsic radiosensitivity of various thyroid carcinomas. The induction of SLP in thyroid cells were identified by: (1) senescence associated beta-galactosidase (SA-beta-Gal) staining method, (2) dual-flow cytometric analysis of cell proliferation and side light scatter using vital staining with PKH-2 fluorescent dye, (3) double labeling for 5-bromodeoxyuridine and SA- beta-Gal, (4) Staining for SA-beta-Gal with consequent antithyroglobulin immunohistochemistry. IR induced SLP associated with terminal growth arrest in four thyroid cancer cells lines and in primary thyrocytes in time- and dose-dependent manner. Analysis of relationship between induction of SLP and radiosensitivity revealed a trend in which more radioresistant cell lines strongly tended to show lower specific SLP yields (r = -0.93, p = 0.068). We find out that SA-beta-Gal staining is detectable in irradiated ARO xenotransplants, but not in control tumors. We, therefore, conclude that induction of SLP with terminal growth arrest contribute to the elimination of clonogenic populations after IR.


Subject(s)
Cellular Senescence/radiation effects , Thyroid Gland/radiation effects , Animals , Cell Line, Tumor , Cell Proliferation/radiation effects , Humans , Male , Mice , Mice, Inbred BALB C , Mitosis , Radiation Tolerance , beta-Galactosidase/analysis
15.
Int J Oncol ; 25(6): 1729-35, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15547711

ABSTRACT

Mutation in exon 15 of the BRAF gene is a characteristic feature of human thyroid papillary carcinoma (PTC). To determine the role of such mutation(s) in the neoplastic progression of thyroid papillary microcarcinoma (PMC), we analyzed 46 cases from 31 Russian and 15 Japanese patients with PMC. Mutated BRAF (the BRAFT1796A transversion in all cases) was detected in 13/46 (28.2%) of the tumors: 9/31 (29.0%) and 4/15 (26.6%) in Russian and Japanese individuals, respectively, displaying no signs of difference in the mutational rates in the PMCs from patients with diverse genetic background seen in PTCs. Occurrence of the BRAF mutation did not significantly correlate with the patients' gender, age at presentation, metastatic indices or with papillary, mixed papillary and follicular, and solid/trabecular PMC histotype. On the contrary, the tumors of follicular morphology significantly associated with the mutation-free genotype (P=0.018), and in the mixed-type tumors characterized by co-occurrence of well-differentiated and less differentiated components, the BRAF mutational frequency was significantly elevated (P=0.020). The results indicate the BRAFT1796A mutation is prevalent in PMCs, and thus these tumors may have a spectrum of genetic events partly overlapping with that of PTCs.


Subject(s)
Carcinoma, Papillary/genetics , DNA Mutational Analysis , Proto-Oncogene Proteins B-raf/genetics , Thyroid Neoplasms/genetics , Adult , Aged , Carcinoma, Papillary/pathology , Female , Humans , Japan , Male , Middle Aged , Polymerase Chain Reaction , Russia , Thyroid Neoplasms/pathology
16.
J Pathol ; 202(4): 446-55, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15095272

ABSTRACT

Cyclin D1 is a target molecule transcriptionally activated by aberrant beta-catenin in Wnt signalling, while prolyl isomerase Pin1 promotes cyclin D1 overexpression directly or through accumulation of beta-catenin in cancer cells. This study aimed to elucidate whether Pin1 was involved in cyclin D1 overexpression and aberrant beta-catenin in thyroid tumourigenesis by examining 14 follicular adenomas (FAa) and 14 papillary thyroid carcinomas (PTCs). All PTCs displayed cyclin D1 overexpression and strong cytoplasmic beta-catenin and/or decreased membrane beta-catenin expression by immunohistochemistry. Overexpression of cyclin D1 mRNA was observed in 45.5% of FAs and 54.5% of PTCs by TaqMan real-time PCR. Pin1 expression was observed in PTC by immunostaining and was confirmed by reverse transcriptase-PCR. There was a strong correlation between cyclin D1 and Pin1/cytoplasmic/membrane beta-catenin expression (p < 0.001), and between Pin1 and cytoplasmic (p < 0.001)/membrane (p = 0.002) beta-catenin expression in thyroid tumours. Mutation of the beta-catenin gene could not be detected in PTC. Western blot analysis demonstrated high levels of cyclin D1 and beta-catenin as well as Pin1 expression in a human PTC cell line possessing wild-type beta-catenin and APC genes. This study suggests that both cyclin D1 overexpression and aberrant beta-catenin expression are of significance in thyroid tumours. Pin1 expression appears to correlate closely with the level of cyclin D1 and aberrant beta-catenin expression in thyroid tumours such as FA and PTC. Pin1 may be an important factor in regulating cyclin D1 and beta-catenin expression during thyroid carcinogenesis.


Subject(s)
Cyclin D1/metabolism , Neoplasm Proteins/metabolism , Neoplasms, Radiation-Induced/metabolism , Thyroid Neoplasms/metabolism , Adult , Cell Transformation, Neoplastic , Cyclin D1/genetics , Cytoskeletal Proteins/metabolism , DNA Mutational Analysis , DNA, Neoplasm/genetics , Female , Gene Expression , Humans , Male , Middle Aged , NIMA-Interacting Peptidylprolyl Isomerase , Peptidylprolyl Isomerase/metabolism , RNA, Messenger/genetics , Radioactive Hazard Release , Reverse Transcriptase Polymerase Chain Reaction , Thyroid Neoplasms/etiology , Trans-Activators/metabolism , Tumor Cells, Cultured , beta Catenin
17.
Pathol Res Pract ; 199(8): 551-8, 2003.
Article in English | MEDLINE | ID: mdl-14533940

ABSTRACT

Small cell carcinoma of the endometrium (SCCE) is extremely rare. Previous reports indicate that SCCE frequently shows systemic spread and has a poor prognosis. Beta-catenin has been shown to be a key downstream effector of the Wnt signaling pathway, which regulates cell growth and survival. Decreased membranous expression of beta-catenin in cancers correlates with poor prognosis and is associated with dissemination of tumor cells and the formation of metastases. Recently, some different investigators demonstrated aberrant beta-catenin accumulation in neuroendocrine tumors arising in different organs, suggesting a role for the Wnt/beta-catenin signaling pathway during neuroendocrine tumorigenesis. Here, we report a new case of SCCE associated with peritoneal spreading and aggressive course; the patient died one month after surgery. This study also aimed at assessing the involvement of the Wnt signaling pathway in this rare neuroendocrine tumor. Interestingly, both intense nuclear beta-catenin accumulation and cyclin D1 immunoreactivity were restricted to carcinoma cells invading lymphatic vessels. However, mutation analysis failed to demonstrate any mutation in exon 3 of the beta-catenin gene or exon 15 of the APC gene in the present case. Although the mechanism of nuclear accumulation of beta-catenin is still unknown, the heterotopic nuclear localization of beta-catenin may play a role in the tumor invasion process and, subsequently, may be associated with the aggressive behavior of SCCE.


Subject(s)
Carcinoma, Small Cell/metabolism , Cytoskeletal Proteins/metabolism , Endometrial Neoplasms/metabolism , Proto-Oncogene Proteins/metabolism , Trans-Activators/metabolism , Zebrafish Proteins , Biomarkers, Tumor/metabolism , Carcinoma, Small Cell/secondary , Carcinoma, Small Cell/surgery , Cell Nucleus/metabolism , Cell Nucleus/pathology , Cyclin D1/metabolism , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Fatal Outcome , Female , Humans , Immunoenzyme Techniques , Middle Aged , Wnt Proteins , beta Catenin
18.
Thyroid ; 13(6): 537-45, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12930597

ABSTRACT

The Semipalatinsk nuclear test site (SNTS), the Republic of Kazakhstan, has been contaminated by radioactive fallout. The alteration of oncogenic molecules in thyroid cancer around the SNTS was considered worthy of analysis because it presented the potential to elucidate the relationship between radiation exposure and thyroid cancer. This study aimed to analyze both beta-catenin and cyclin D1 expressions in thyroid carcinomas around the SNTS. We examined nine cases of chronic thyroiditis, eight cases of follicular adenomas, and 23 cases of papillary carcinomas. Immunohistochemically, all carcinomas displayed a strong cytosolic beta-catenin expression, while both chronic thyroiditis and follicular adenomas showed a significantly lower cytoplasmic beta-catenin (22.2% and 37.5%, respectively). No cyclin D1 immunoreactivity was evident in chronic thyroiditis. In contrast, 62.5% of follicular adenomas and 87.0% of papillary carcinoma showed cyclin D1 overexpression. Additionally, a strong correlation between cytoplasmic beta-catenin and cyclin D1 expression was suggested in thyroid tumors. This study revealed a higher prevalence of both aberrant beta-catenin expression and cyclin D1 overexpression in papillary thyroid cancers around the SNTS than sporadic cases. The analysis of the alteration of the Wnt signaling-related molecules in thyroid cancer around the SNTS may be important to gain an insight into radiation-induced thyroid tumorigenesis.


Subject(s)
Cyclin D1/biosynthesis , Cytoskeletal Proteins/biosynthesis , Neoplasms, Radiation-Induced/metabolism , Nuclear Warfare , Radioactive Fallout/adverse effects , Thyroid Neoplasms/metabolism , Trans-Activators/biosynthesis , Adolescent , Adult , Aged , Carcinoma, Papillary/metabolism , Cell Membrane/metabolism , Cytoplasm/metabolism , Female , Humans , Immunohistochemistry , Kazakhstan , Male , Middle Aged , Neoplasms, Radiation-Induced/pathology , Prevalence , Thyroid Gland/metabolism , Thyroid Gland/pathology , Thyroid Neoplasms/pathology , beta Catenin
19.
Mutat Res ; 527(1-2): 81-90, 2003 Jun 19.
Article in English | MEDLINE | ID: mdl-12787916

ABSTRACT

Molecular analysis of cDNA derived from a papillary thyroid carcinoma (PTC) (follicular variant of papillary thyroid carcinoma on histology) which developed in an externally irradiated patient 4 years after exposure identified a portion of the 5' region, exons 1-3, of the rfp gene juxtaposed upstream of the fragment encoding the tyrosine kinase (TK) domain of the ret gene. The fusion gene, termed Delta rfp/ret, was the result of a balanced chromosomal translocation t(6;10) (p21.3;q11.2) confirmed by interphase FISH painting, with breakpoints occurring in introns 3 and 11 of the rfp and ret genes, respectively. Both Delta rfp/ret and reciprocal ret/rfp chimeric introns had small deletions around breakpoints consistent with presumed misrepair of a radiation-induced double-strand DNA break underlying the rearrangement. No extensive sequence homology was found between the fragments flanking the breakpoints. The fusion protein retained the propensity to form oligomers likely to be mediated by a coiled-coil of the RFP polypeptide as assessed by a yeast two-hybrid system. NIH 3T3 fibroblasts stably transfected with a mammalian expression vector encoding full-length Delta RFP/RET readily gave rise to the tumors in athymic mice suggestive of high transforming potential of the fusion protein. Thus, the Delta rfp/ret rearrangement may be involved in a causative manner in cancerogenesis and provides additional evidence of the role of activated ret oncogene in the development of a subset of papillary thyroid carcinoma.


Subject(s)
Carcinoma, Papillary/genetics , Gene Rearrangement , Neoplasm Proteins/genetics , Neoplasms, Radiation-Induced/genetics , Proto-Oncogene Proteins/genetics , Thyroid Neoplasms/genetics , 3T3 Cells , Adult , Animals , Carcinoma, Papillary/etiology , Carcinoma, Papillary/pathology , Chromosome Breakage , Chromosomes, Human, Pair 10 , Chromosomes, Human, Pair 6 , Female , Humans , Mice , Oncogene Proteins, Fusion/genetics , Recombinant Fusion Proteins/genetics , Thyroid Neoplasms/etiology , Thyroid Neoplasms/pathology , Translocation, Genetic , Transplantation, Heterologous
20.
Endocr J ; 50(1): 85-9, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12733713

ABSTRACT

To assess thyroid status among the schoolchildren around Semipalatinsk Nuclear Testing Site (SNTS), Kazakhstan, and to evaluate the current status of iodine deficiency in this area, we performed medical screening of schoolchildren in two villages, Kaynar and Karaul villages, East Kazakhstan Region, Republic of Kazakhstan, located within 100 km of SNTS. A total of 196 schoolchildren were chosen at random. Control groups comprised 250 schoolchildren from Nagasaki, an iodine-rich area, and 100 schoolchildren from Gomel, an iodine-deficient area contaminated by the Chernobyl Nuclear Power Plant accident. Ultrasound screening of thyroid revealed three cases of benign thyroid disease (two cases of goiter and one single cyst), but no cases suspicious of malignancy. The urinary iodine (UI) concentrations of subjects in Kaynar and Karaul ranged from 21.8 to 735.8 microg/L, 4.3% of whom showed low UI concentrations (<50 microg/L), compared with 0% in the Nagasaki group and 52% in the Gomel group. The median UI concentration in Kaynar and Karaul was 153.2 microg/L, which was significantly lower than that in Nagasaki (366.3 microg/L, p<0.0001) but higher than that in Gomel (47.3 microg/L, p<0.0001). In conclusion, there was a low incidence of morphological abnormalities in the thyroid, and no evidence for severe iodine deficiency among the Kazakhstani children studied. These results suggest that there is no transgenerational risk for schoolchildren born from parents irradiated as a result of tests carried out in SNTS.


Subject(s)
Neoplasms, Radiation-Induced/epidemiology , Radioactive Pollutants , Risk Assessment , Thyroid Neoplasms/epidemiology , Adolescent , Air Pollutants, Radioactive , Child , Child, Preschool , Environmental Exposure , Female , Humans , Incidence , Iodine/deficiency , Iodine/urine , Kazakhstan/epidemiology , Male , Neoplasms, Radiation-Induced/diagnostic imaging , Parents , Random Allocation , Risk Factors , Thyroid Neoplasms/diagnostic imaging , Ultrasonography
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