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1.
Eur J Nucl Med Mol Imaging ; 48(5): 1487-1497, 2021 05.
Article in English | MEDLINE | ID: mdl-33099659

ABSTRACT

PURPOSE: The investigation of a semi-quantitative index in the pelvis to assess for diffuse bone marrow (BM) [18F]-FDG uptake and the investigation of PET skeletal patterns in multiple myeloma (MM) patients, in accordance with prognostic markers, clonal plasma cell (cPC) morphology, and response to therapy. METHODS: We prospectively analyzed [18F]-FDG PET/CT in 90 MM patients (newly diagnosed, 60; relapsed/refractory, 30). Among other PET/CT parameters, we calculated the ratio SUVmax pelvis/liver and examined for correlations with known MM prognostic parameters, cPC morphology (good vs. low/intermediate differentiation), and response to therapy. RESULTS: SUVmax pelvis/liver ratio was significantly lower for the group of good differentiation vs. intermediate/low differentiation cPCs (p < 0.001) and showed a positive correlation with BM infiltration rate, ß2 microglobulin, serum ferritin, international staging system (ISS), and revised ISS; no significant correlation was found with hemoglobin. A cutoff value of 1.1 showed an excellent specificity (99%) and high sensitivity (76%) for diffuse BM involvement (AUC 0.94; p < 0.001). Mixed pattern and appendicular involvement correlated with poor prognostic features while normal pattern, found in 30% of patients, correlated with good prognostic features. Presence of ≥ 10 focal lesions negatively predicted for overall response (p < 0.05; OR 4.8). The CT component improved the diagnostic performance of PET. CONCLUSION: This study showed, for the first time, that cPC morphology and markers related with MM biology, correlate with SUVmax pelvis/liver index, which could be used as a surrogate marker for BM assessment and disease prognosis; PET patterns correlate with MM prognostic features and response rates.


Subject(s)
Fluorodeoxyglucose F18 , Multiple Myeloma , Bone Marrow/diagnostic imaging , Humans , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/therapy , Plasma Cells , Positron Emission Tomography Computed Tomography , Prognosis , Radiopharmaceuticals , Retrospective Studies
2.
Eur J Gynaecol Oncol ; 33(3): 312-5, 2012.
Article in English | MEDLINE | ID: mdl-22873108

ABSTRACT

INTRODUCTION: Small cell carcinoma of the ovary of pulmonary type, is a rare, aggressive tumour with poor prognosis and its optimal management is unclear. CASE PRESENTATION: A 55-year-old Caucasian woman presented with abdominal discomfort and left lumbar pain within a three-week period. At exploratory laparotomy, a 8 cm solid cystic mass of the left ovary was found infiltrating the sigmoid colon, and a bulky mass (11 x 7 x 4 cm) in the left paraaortic infrarenal region. Histopathological features resembling small cell carcinoma of the lungs and positive immunohistochemical stains provided a definite diagnosis of IIIC ovarian small cell carcinoma of pulmonary type. After six cycles chemotherapy with carboplatin and etoposide, the patient is still alive at 21 months from initial diagnosis. DISCUSSION: In this case, the absence of peritoneal involvement and the extensive paraaortic adenopathy is suggestive of a different pattern of spread of this rare tumour. Optimal treatment seems to be radical primary debulking surgery resulting in no residual disease, maximizing the effect of adjuvant chemotherapy for this biological aggressive tumour.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Small Cell/pathology , Ovarian Neoplasms/pathology , Antineoplastic Agents, Phytogenic/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/surgery , Chemotherapy, Adjuvant , Etoposide/therapeutic use , Female , Humans , Lymphatic Metastasis , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery
3.
Poult Sci ; 101(10): 102092, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36055025

ABSTRACT

Colibacillosis is a poultry disease that negatively affects welfare and causes economic losses. Treatment with antibiotics raises concerns on antimicrobial resistance. Consequently, alternative approaches to enhance poultry resilience are needed. Access to feed and water directly after hatch (early feeding) may enhance resilience at later ages. Additionally, a high eggshell temperature (EST) during mid incubation may improve chick quality at hatch, supporting potential positive effects of early feeding. Effects of EST [37.8°C (control) or 38.9°C (higher)] during mid-incubation (embryo days 7-14) and feeding strategy (early feeding or 48 h delayed feeding) were tested in a 2 × 2 factorial arrangement. At hatch, Ì´ 1,800 broilers were divided over 36 pens and grown for 6 wk. At d 8 post hatch, avian pathogenic E. coli (APEC) was inoculated intratracheally as model to investigate broiler resilience against respiratory diseases. Incidence and severity of colibacillosis, local infection, and systemic infection were assessed at 6 moments between 3 h and 7 d postinoculation. Broilers were weighed daily during 13 d postinoculation and weekly thereafter. At higher EST, early feeding resulted in higher incidence of systemic infection compared to delayed feeding whereas at control EST, systemic infection was not different between feeding strategies. Regardless of EST, early compared to delayed feeding resulted in lower incidence of local infection, fewer BW deviations, and higher growth until d 35. In conclusion, early feeding could be considered as a strategy to enhance broiler resilience, but only when EST is not too high.


Subject(s)
Anti-Infective Agents , Escherichia coli Infections , Animals , Anti-Bacterial Agents , Chickens , Escherichia coli , Escherichia coli Infections/veterinary , Ovum , Temperature , Water
4.
Neth J Med ; 78(4): 175-182, 2020 07.
Article in English | MEDLINE | ID: mdl-32641542

ABSTRACT

BACKGROUND: Within-visit variability of repeated sequential readings of blood pressure (BP) is an important phenomenon that may affect precision of BP measurement and thus decision making concerning BP-related risk and hypertension management. However, limited data exist concerning predictive ability of within-visit BP variability for clinical outcomes. Therefore, we aimed to investigate the association between the variability of three repeated office BP measurements and the risk of all-cause mortality, independent of BP levels. METHODS: Data collected through the National Health and Nutrition Examination Survey (NHANES) were analysed. NHANES is a program of studies designed to assess health and nutritional status of adults and children in the United States. A complete set of three sequential BP measurements, together with survival status, were available for 24969 individuals (age 46.8±;19.3 years, 49% males). Multivariable logistic regression models were used to determine the prognostic ability of the examined demographic, clinical, and haemodynamic indices. RESULTS: Among various examined indices of variability of systolic (SBP) and diastolic (DBP) blood pressure measurements, the standard deviation of DBP (DBPSD) was the stronger independent predictor of mortality (odds ratio 1.064, 95% Confidence Interval: 1.011-1.12) after adjustment for age, sex, body mass index, smoking, SBP, heart rate, history of hypertension, diabetes mellitus, hypercholesterolaemia, and cardiovascular events. CONCLUSION: Within-visit variability of three sequential office DBP readings may allow for the identification of high-risk patients better than mean SBP and DBP levels. The predictive value of within-visit BP variability and methods to improve its clinical application are worthy of further research.


Subject(s)
Blood Pressure Determination/statistics & numerical data , Cardiovascular Diseases/mortality , Hypertension/diagnosis , Hypertension/mortality , Office Visits/statistics & numerical data , Adult , Blood Pressure , Blood Pressure Determination/methods , Cardiovascular Diseases/etiology , Female , Heart Disease Risk Factors , Humans , Hypertension/complications , Male , Middle Aged , Nutrition Surveys , Odds Ratio , Predictive Value of Tests , Risk Assessment , United States
5.
Sci Rep ; 10(1): 10215, 2020 06 23.
Article in English | MEDLINE | ID: mdl-32576841

ABSTRACT

African swine fever (ASF) entered Georgia in 2007 and the EU in 2014. In the EU, the virus primarily spread in wild boar (Sus scrofa) in the period from 2014-2018. However, from the summer 2018, numerous domestic pig farms in Romania were affected by ASF. In contrast to the existing knowledge on ASF transmission routes, the understanding of risk factors and the importance of different transmission routes is still limited. In the period from May to September 2019, 655 Romanian pig farms were included in a matched case-control study investigating possible risk factors for ASF incursion in commercial and backyard pig farms. The results showed that close proximity to outbreaks in domestic farms was a risk factor in commercial as well as backyard farms. Furthermore, in backyard farms, herd size, wild boar abundance around the farm, number of domestic outbreaks within 2 km around farms, short distance to wild boar cases and visits of professionals working on farms were statistically significant risk factors. Additionally, growing crops around the farm, which could potentially attract wild boar, and feeding forage from ASF affected areas to the pigs were risk factors for ASF incursion in backyard farms.


Subject(s)
African Swine Fever Virus/isolation & purification , African Swine Fever/epidemiology , Animal Husbandry/methods , Disease Outbreaks/veterinary , Farms/statistics & numerical data , Sus scrofa/virology , African Swine Fever/transmission , African Swine Fever/virology , Animals , Case-Control Studies , Risk Factors , Romania/epidemiology , Seasons , Spatio-Temporal Analysis , Swine
6.
Vet Pathol ; 46(4): 736-45, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19276050

ABSTRACT

Prolactin-secreting pituitary adenomas are common spontaneous lesions in aging FVB females. Prolactin-secreting pituitary proliferations play a significant role in mouse mammary tumorigenesis generally producing adenosquamous carcinomas. Since genetically engineered FVB mice are frequently used to study mammary tumor biology, we have examined a cohort of 64 aging wild-type FVB/N females to establish the prevalence and the nature of spontaneous mammary and pituitary tumors. Tissues from mammary and pituitary glands were studied by histopathology and immunohistochemistry. Of the 64 examined mice, 20 had pituitary tumors and 20 had mammary tumors. Mammary and pituitary tumors were associated in 17 mice. All pituitary tumors were prolactin-positive by immunohistochemistry and classified as prolactinomas. Fourteen mammary tumors, including 12 cases with and 2 without concurrent prolactinomas, were adenocarcinomas with different combinations of epithelial growth patterns. Five mice with prolactinomas had mammary tumors characterized by the epithelial-mesenchymal transition (EMT) phenotype. Estrogen receptor alpha (ERalpha)-positivity was observed for 14 of the 18 mammary tumors tested, including both adenocarcinomas with nuclear immunoreactivity and EMT-phenotype tumors with both nuclear and cytoplasmic immunoreactivity. No immunoreactivity for the progesterone receptor was observed. This study confirms that spontaneous prolactinomas and mammary tumors are both common and significantly associated lesions in FVB mice. Parity and age represented risk factors for the development of these tumors. Compared with previous reports, prolactinoma-associated mammary tumors displayed a broader morphologic spectrum, including cases with the EMT phenotype. The elevated number of prolactinoma-associated and ERalpha-positive mammary tumors opens intriguing possibilities concerning the role of ERalpha cytoplasmic localization during EMT tumorigenesis.


Subject(s)
Mammary Neoplasms, Animal/epidemiology , Mammary Neoplasms, Animal/pathology , Mice, Transgenic , Phenotype , Pituitary Neoplasms/epidemiology , Prolactinoma/epidemiology , Age Factors , Analysis of Variance , Animals , Disease Models, Animal , Female , Immunohistochemistry , Mammary Neoplasms, Animal/etiology , Mice , Pituitary Neoplasms/complications , Prevalence , Prolactinoma/complications , Risk Factors
7.
Eur J Gynaecol Oncol ; 30(2): 239-40, 2009.
Article in English | MEDLINE | ID: mdl-19480269

ABSTRACT

Metastatic tumors to the uterine cervix originating from malignancies in other organs are very rare. A case of a 45-year-old white woman presenting with vaginal bleeding, due to renal cell carcinoma metastasizing to the cervix, is reported. The patient had been treated four years and five months earlier due to two primary malignancies: colon adenocarcinoma and renal cell carcinoma. After D&C, microscopic examination and immunohistochemical staining showed that the tumor was metastatic, originating from the renal cell carcinoma. Radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node resection followed, and postoperatively the patient received targeted therapy with sutinib malate. The possibility of metastasis from another primary should be considered in the differential diagnosis of tumors of the uterine cervix in order to plan optimal management.


Subject(s)
Carcinoma, Renal Cell/secondary , Kidney Neoplasms/pathology , Uterine Cervical Neoplasms/secondary , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/therapy , Female , Humans , Middle Aged , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy
8.
Eur J Gynaecol Oncol ; 29(1): 19-25, 2008.
Article in English | MEDLINE | ID: mdl-18386458

ABSTRACT

Immunohistochemical expression of bcl-2, p53, PR and ER in cases with endometrial carcinomas arrayed on a tissue microarray (TMA) was tested and correlated with clinicopathologic features, overall survival (OS), cancer-related survival (CRS) and disease-free survival (DFS). Seventy-seven patients with endometrial cancer were reviewed. Slides were evaluated by two pathologists blinded to patient clinical characteristics and survival data. Mean age of patients was 62.5 years (range 35-80), median follow up 60 months (range 9-120). Seventy-nine percent of patients were FIGO Stage I; 39% of the cases showed bcl-2 cytoplasmic staining and its expression was significantly correlated with low-grade tumor differentiation and age < or = 60 years. Nuclear p53 overexpression was detected in 23.4% of the cases and was significantly correlated with advanced stages (IIB-IV), non-endometrioid histology, nodal metastasis and advanced age (> 60 years). PR and ER were positive in 63.6% and 30% of the cases, respectively. Analysis of p53 overexpression and bcl-2 expression in relationship with PR and ER status showed a direct correlation between bcl-2 expression and PR positivity (p = 0.001). In a multivariate analysis FIGO staging was the only clinicopathologic parameter independently correlated with DFS. In conclusion p53 overexpression was directly associated with unfavorable clinicopathologic factors such as advanced stage, histologic subtype, advanced patient age and nodal metastasis. Bcl-2 expression was related with younger age, favorable grade and PR expression by tumor cells. Patient survival was not related to the tested biomarkers.


Subject(s)
Adenocarcinoma/physiopathology , Endometrial Neoplasms/physiopathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Receptors, Progesterone/metabolism , Tumor Suppressor Protein p53/metabolism , Adenocarcinoma/immunology , Adult , Aged , Aged, 80 and over , Cohort Studies , Disease-Free Survival , Endometrial Neoplasms/immunology , Female , Humans , Middle Aged , Neoplasm Staging , Protein Array Analysis , Receptors, Estrogen/metabolism
9.
J Clin Invest ; 107(9): 1093-102, 2001 May.
Article in English | MEDLINE | ID: mdl-11342573

ABSTRACT

The relationship between abnormal cell proliferation and aberrant control of hormonal secretion is a fundamental and poorly understood issue in endocrine cell neoplasia. Transgenic mice with parathyroid-targeted overexpression of the cyclin D1 oncogene, modeling a gene rearrangement found in human tumors, were created to determine whether a primary defect in this cell-cycle regulator can cause an abnormal relationship between serum calcium and parathyroid hormone response, as is typical of human primary hyperparathyroidism. We also sought to develop an animal model of hyperparathyroidism and to examine directly cyclin D1's role in parathyroid tumorigenesis. Parathyroid hormone gene regulatory region--cyclin D1 (PTH--cyclin D1) mice not only developed abnormal parathyroid cell proliferation, but also developed chronic biochemical hyperparathyroidism with characteristic abnormalities in bone and, notably, a shift in the relationship between serum calcium and PTH. Thus, this animal model of human primary hyperparathyroidism provides direct experimental evidence that overexpression of the cyclin D1 oncogene can drive excessive parathyroid cell proliferation and that this proliferative defect need not occur solely as a downstream consequence of a defect in parathyroid hormone secretory control by serum calcium, as had been hypothesized. Instead, primary deregulation of cell-growth pathways can cause both the hypercellularity and abnormal control of hormonal secretion that are almost inevitably linked together in this common disorder.


Subject(s)
Adenoma/etiology , Cyclin D1/biosynthesis , Hyperparathyroidism/etiology , Parathyroid Hormone/metabolism , Parathyroid Neoplasms/etiology , Animals , Bone and Bones/pathology , Calcium/blood , Calcium-Binding Proteins/isolation & purification , Chromosome Aberrations , Chromosome Disorders , Cyclin D1/genetics , Gene Rearrangement , Humans , Hyperparathyroidism/genetics , Mice , Mice, Transgenic , Parathyroid Hormone/blood , Parathyroid Hormone/genetics
10.
Eur J Gynaecol Oncol ; 27(6): 607-10, 2006.
Article in English | MEDLINE | ID: mdl-17290593

ABSTRACT

The aim of the study is to present our experience in the treatment of uterine cervix cancer over the last decade. This is a retrospective study of 90 patients with cervical cancer treated in a University Department of Obstetrics and Gynecology from 1993 to 2002. After the disease was histologically confirmed and staged the patients were treated according to stage with surgery (S) radiotherapy (RT), RT alone or Chemoradiaton (C-RT). The course of the disease and follow-up was traced from patient notes and after a structured telephone questionnaire. Mean age of patients was 48 +/- 14.3 years (29-84). Nine of 90 patients (10%) were lost to follow-up. FIGO (1994) staging was I in 50% of patients, II in 33.5%, III in 13.5% and IV in 3%. The size of tumor was < or = 4 cm in 75%. Of the tumors 87% were of squamous histology and 13% adenocarcinomas. Patients were treated with cone biopsy (5.5%), type I hysterectomy pelvic RT (10%), radical (type II-III) hysterectomy and pelvic lymphadenectomy +/- radiotherapy (41%), RT alone in 38% and C-RT in 5.5%. Incidence of complications after surgery was 19.5% and after RT 12.5%. Mean follow-up was 41 +/- 19 months (6-110). Five-year survival in Stage I was 84%, Stage II 64% and Stage III 40%. A single patient with Stage IV disease is alive with disease after two years. In conclusion uterine cervical cancer has improved survival because of early diagnosis. Treatment should be individualized according to the status of disease. Surgery and RT had similar rates of complications.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Hysterectomy , Uterine Cervical Neoplasms/surgery , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Combined Modality Therapy , Female , Humans , Lymph Node Excision , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Analysis , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy
11.
Br J Sports Med ; 39(3): e11, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15728679

ABSTRACT

OBJECTIVES: To compare the effects of proprioceptive neuromuscular facilitation (PNF) and isokinetic training on fibre type distribution and cross sectional area of the vastus lateralis muscle. METHODS: Twenty four male university students were divided into two equal groups: PNF training and isokinetic training (ISO). The training regimen for the PNF group consisted of three sets of 30 repetitions against maximal resistance, alternating two patterns of sequential movements of the right lower extremity: (a) toe flexion and ankle plantar flexion and eversion; (b) knee extension and hip extension, abduction, and internal rotation. The ISO group performed three sets of 30 repetitions alternating knee extension and flexion of the right leg at angular velocities of 180 and 90 degrees /s in an isokinetic dynamometer (Cybex). Both groups trained three times a week for a total of eight weeks. Muscle biopsy specimens were obtained from the right vastus lateralis muscle before and after training. RESULTS: The mean percentage area of type IIB fibre was significantly decreased (p<0.01) after eight weeks of PNF training, whereas that of type IIA fibre was significantly (p<0.05) increased. The mean percentage area of ISO trained type IIAB fibres exhibited an augmentative pattern (p<0.01) with a parallel reduction (p<0.05) in type IIA. Percentage fibre type distribution exhibited a similar pattern. CONCLUSIONS: Both PNF and ISO training alter fibre type distribution and mean cross sectional area. These changes occur in the type II fibre subgroup.


Subject(s)
Exercise/physiology , Muscle Fibers, Skeletal , Muscle, Skeletal/anatomy & histology , Proprioception/physiology , Adult , Biopsy, Needle/methods , Humans , Isometric Contraction/physiology , Male , Muscle, Skeletal/physiology , Physical Education and Training/methods
12.
Am J Surg Pathol ; 17(9): 912-9, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8102513

ABSTRACT

We investigated the expression of proliferating cell nuclear antigen (PCNA) and the number of nucleolar organizer regions (NORs) in 82 cases of CNS tumors. PCNA is a nuclear protein maximally elevated in the S phase of the cell cycle and recognized immunohistochemically in paraffin sections by the monoclonal antibody PC-10. On the other hand, NORs are loops of DNA that carry the rRNA genes and can be demonstrated in paraffin sections using an argyrophilic method (AgNORs). The present study shows a significant correlation of PCNA index and of AgNOR number with the histological grade (PCNA: I versus II, p < 0.01; II versus III, p < 0.01; and III versus IV, p < 0.05; AgNORs: I versus II, p < 0.001; II versus III, p < 0.05; and III versus IV, p < 0.001). Higher values of PCNA index (0.01 < p < 0.05) were found in recurrent tumors. Metastatic carcinomas were characterized by high PCNA indices and AgNOR numbers, similar to grade IV tumors, whereas in CNS lymphomas the malignancy grade was reflected in PCNA indices and AgNOR numbers. A wide range of PCNA and AgNOR values has been observed within each histological type and grade, probably reflecting variations in the biological behavior, but little overlap in PCNA values was present between grades II and III. The latter finding might be of importance in distinguishing between low- and high-grade CNS tumors. The linear regression coefficient between PCNA index and AgNOR number was excellent (0.91). We suggest that PCNA and AgNORs may be successfully applied in routine material to assess the growth potential of CNS tumors. Their prognostic value, however, must be validated with clinical studies.


Subject(s)
Antigens, Neoplasm/analysis , Central Nervous System Neoplasms/pathology , Nuclear Proteins/analysis , Nucleolus Organizer Region/pathology , Central Nervous System Neoplasms/immunology , Central Nervous System Neoplasms/ultrastructure , Humans , Prognosis , Proliferating Cell Nuclear Antigen
13.
Cancer Lett ; 130(1-2): 29-34, 1998 Aug 14.
Article in English | MEDLINE | ID: mdl-9751253

ABSTRACT

Azoxymethane (AOM) is an organotropic colon carcinogen that is commonly used to induce colon tumors in rodents. Unlike its parent compound, 1,2-dimethylhydrazine (DMH), a tumor susceptibility phenotype in inbred mice with respect to AOM has not been established. Thus, this study was undertaken to determine whether genetic susceptibility extends to this carcinogen. SWR/J, A/J (both susceptible to DMH carcinogenesis) and AKR/J (resistant) mice were treated with 10 mg/kg AOM i.p. once a week for 8 weeks. Twenty-five weeks after the initial injection, tumor yield was determined. With a single exception, only SWR/J and A/J mice developed tumors, with a distribution that was limited to the distal colon (16.3+/-1.1 and 36.4+/-2.4. respectively). The formation of aberrant crypt foci (ACF), putative preneoplastic lesions, was also assessed in whole-mount colons using Methylene Blue staining. Consistent with tumor multiplicity, the total number of ACF was highest in A/J mice, followed by SWR/J mice. In addition, A/J mice had a significantly greater number of large ACF (five or more crypts per foci) than the other strains. Despite the absence of colon tumors, however, AKR/J mice did develop a significant number of ACF. This finding suggests that ACF in resistant mice are persistent but do not progress to tumors.


Subject(s)
Azoxymethane/toxicity , Carcinogens/toxicity , Colon/drug effects , Colonic Neoplasms/chemically induced , Mice, Inbred Strains , Precancerous Conditions/chemically induced , Animals , Colon/pathology , Disease Susceptibility , Male , Mice , Mice, Inbred A , Mice, Inbred AKR , Phenotype , Species Specificity
14.
Int J Oncol ; 17(3): 551-8, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10938397

ABSTRACT

Alterations in transforming growth factor beta1 (TGF-beta1) and its type II receptor (TbetaR-II) have been implicated in the pathogenesis of a variety of human cancers and animal tumor models. We postulated that TGF-beta1 and TbetaR-II alterations may also be involved in mouse colon tumorigenesis induced by the chemical carcinogen, azoxymethane (AOM). In the present study, normal colon tissues and AOM-induced colon tumors from SWR/J mice were analyzed for mutational changes in the TbetaR-II gene, and the expression and localization of TGF-beta1 and TbetaR-II were examined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemisty. Direct DNA sequencing of the coding sequence of the TbetaR-II gene revealed no mutational changes in tumors induced by AOM when compared with the sequence from normal colon tissue. However, TGF-beta1 and TbetaR-II mRNA levels in tumor samples were increased 1.8-fold (p<0.01) and 1.3-fold (p<0.01), respectively, when compared with control mouse colon tissue. The results of immunohistochemical analysis of TGF-beta1 and TbetaR-II were correlated with mRNA expression data. An increase in staining intensity of both TGF-beta and TbetaR-II were observed in colon tumors. These findings suggest that alterations in the expression of TGF-beta1 and TbetaR-II may be involved in the pathogenesis of colon tumors induced by AOM in mice.


Subject(s)
Adenocarcinoma/metabolism , Azoxymethane/toxicity , Carcinogens/toxicity , Colonic Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Neoplasm Proteins/biosynthesis , Receptors, Transforming Growth Factor beta/biosynthesis , Transforming Growth Factor beta/biosynthesis , Adenocarcinoma/chemically induced , Adenocarcinoma/genetics , Amino Acid Substitution , Animals , Codon/genetics , Colonic Neoplasms/chemically induced , Colonic Neoplasms/genetics , DNA Mutational Analysis , DNA, Neoplasm/genetics , Male , Mice , Neoplasm Proteins/genetics , Point Mutation , Protein Serine-Threonine Kinases , RNA, Messenger/biosynthesis , RNA, Neoplasm/biosynthesis , Receptor, Transforming Growth Factor-beta Type II , Receptors, Transforming Growth Factor beta/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta1
15.
J Cancer Res Clin Oncol ; 119(7): 379-81, 1993.
Article in English | MEDLINE | ID: mdl-8098331

ABSTRACT

We investigated the expression of proliferating cell nuclear antigen (PCNA) in paraffin sections from 20 cases of medullary thyroid carcinoma (MTC). Follow-up data were available in eleven cases. PCNA index positively correlated with the degree of cellular pleomorphism (grade) of the tumor (p < 0.01), the pathologic stage (p < 0.01) and the poor clinical outcome (p < 0.05). These findings suggest that PCNA may be of prognostic significance in MTC.


Subject(s)
Antigens, Neoplasm/analysis , Carcinoma/immunology , Nuclear Proteins/analysis , Thyroid Neoplasms/immunology , Adolescent , Adult , Carcinoma/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Proliferating Cell Nuclear Antigen , Thyroid Neoplasms/pathology
16.
J Cancer Res Clin Oncol ; 120(7): 393-8, 1994.
Article in English | MEDLINE | ID: mdl-7910610

ABSTRACT

The proliferative activity in 70 cases of soft-tissue tumours was estimated immunohistochemically using the monoclonal antibody PC-10, which recognizes proliferating-cell nuclear antigen (PCNA) in paraffin sections. The PCNA index (i.e. the percentage of positive neoplastic nuclei) and to a lesser degree the PCNA count (i.e. the number of positive neoplastic nuclei per ten high-power fields) positively correlated with the malignancy grade (PCNA index: P < 0.001; PCNA count: P < 0.01). However, the range of values of PCNA index and PCNA count was similar between benign and grade I tumours. A statistically significant positive correlation was also established between PCNA index and PCNA count on the one hand and mitotic count on the other, but the correlation coefficient was low (r = 0.351, P < 0.01, and r = 0.290, P < 0.05 respectively). These results indicate that PCNA immunostaining may successfully be used as an adjunct to the conventional histopathological parameters in assessing the malignancy grade in soft-tissue tumours although it is of limited value in distinguishing between benign and grade I tumours.


Subject(s)
Nuclear Proteins/analysis , Soft Tissue Neoplasms/chemistry , Antigens, Neoplasm/analysis , Cell Division , Immunohistochemistry , Proliferating Cell Nuclear Antigen , Soft Tissue Neoplasms/pathology
17.
J Clin Pathol ; 57(5): 463-6, 2004 May.
Article in English | MEDLINE | ID: mdl-15113851

ABSTRACT

BACKGROUND: KIT is a transmembrane tyrosine kinase receptor, expressed in high amounts in various normal cells. In addition, c-kit mutation or activation is a major pathogenetic event in certain tumours (such as gastrointestinal stromal tumours). There are only limited data in the literature on the expression of KIT in normal and neoplastic renal tissues. AIMS: To investigate KIT expression in normal and neoplastic renal tissues. METHODS: KIT expression was evaluated by means of immunohistochemistry in paraffin wax embedded sections from 67 tissue samples. RESULTS: Eight of eight fetal kidneys, and 10 of 10 normal adult kidneys revealed cytoplasmic staining of renal tubules. The three cases of renal dysplasia studied expressed KIT in their normal and aberrant tubules. Two of 13 conventional renal cell carcinomas (RCCs), two of seven papillary type RCCs, four of seven chromophobe type RCCs, none of six nephroblastomas, seven of seven oncocytomas, two of two mesoblastic nephromas, and two of four angiomyolipomas were positive. CONCLUSION: KIT is expressed in normal fetal and adult renal tubules, and in a subset of renal tumours. The expression of KIT in these renal tumours may prove to have diagnostic relevance and/or therapeutic implications.


Subject(s)
Biomarkers, Tumor/metabolism , Kidney Neoplasms/metabolism , Kidney/metabolism , Neoplasm Proteins/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Adenoma, Oxyphilic/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/metabolism , Child , Child, Preschool , Fetus/metabolism , Humans , Infant , Infant, Newborn , Kidney/embryology , Middle Aged , Nephroma, Mesoblastic/metabolism , Wilms Tumor/metabolism
18.
Chem Biol Interact ; 124(3): 149-60, 2000 Feb 01.
Article in English | MEDLINE | ID: mdl-10728775

ABSTRACT

Azoxymethane (AOM) is an indirect-acting colon carcinogen that produces a high incidence of precancerous lesions, referred to as aberrant crypt foci (ACF), in rats. This study was undertaken to determine whether high dose gavage administration of the cytochrome P-450 2E1 (CYP2E1) inhibitor and chemopreventive agent, diallyl sulfide, would reduce the incidence and severity of ACF formation in the distal colons of AOM-treated Fischer 344 rats. Seven-week-old male rats received 150 or 50 mg/kg diallyl sulfide by gavage 24 and 2 h prior to two weekly i.p. injections of AOM (20 mg/kg). Ten weeks after the last injection of AOM the rats were sacrificed and the colons removed and stained with 0.2% methylene blue. ACF were visualized using stereomicroscopy. Rats pretreated with diallyl sulfide exhibited a significant increase in the number of ACF/cm in the distal colon compared with rats receiving AOM alone. This increase in ACF number was seen in ACF of all sizes. To examine the effects of diallyl sulfide on the initiation stage of AOM-induced carcinogenesis, mutations in the K-ras proto-oncogene were also investigated. ACF and normal appearing colonic mucosa (0.2-0.5 mm3) were microdissected for subsequent PCR-RFLP analysis of a codon 12 (GGT-GGA) activating mutation in the K-ras gene. Greater than 90% of ACF from AOM-treated animals, regardless of diallyl sulfide treatment, exhibited activating K-ras mutations. K-ras mutations were also detected in normal appearing mucosa of AOM-treated animals, although at a lesser frequency (15-35%). These studies demonstrate that diallyl sulfide given in large gavage doses enhances AOM-induced preneoplasia in rats and suggests that diallyl sulfide may alter the disposition of AOM intermediates and/or enhance colonic promotional activity in the rat.


Subject(s)
Allyl Compounds/toxicity , Anticarcinogenic Agents/toxicity , Azo Compounds/toxicity , Carcinogens/toxicity , Colonic Neoplasms/chemically induced , Precancerous Conditions/chemically induced , Sulfides/toxicity , Allyl Compounds/therapeutic use , Animals , Anticarcinogenic Agents/therapeutic use , Colonic Neoplasms/enzymology , Colonic Neoplasms/genetics , Colonic Neoplasms/prevention & control , Cytochrome P-450 CYP2E1 Inhibitors , Drug Synergism , Enzyme Inhibitors/toxicity , Genes, ras/drug effects , Genes, ras/genetics , Male , Mutation , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Precancerous Conditions/enzymology , Precancerous Conditions/genetics , Precancerous Conditions/prevention & control , Rats , Rats, Inbred F344 , Sulfides/therapeutic use
19.
Pharmacol Biochem Behav ; 47(3): 579-85, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8208777

ABSTRACT

Previous work has shown that phencyclidine (PCP) and amphetamine decrease social behavior in rats. The purpose of the present study was to determine the effects of the dopamine antagonists clozapine and haloperidol on PCP- and amphetamine-induced changes in rat social behavior. An intruder paradigm was used, in which rats were injected with drug and placed into a stable home colony of three other rats. Social behaviors were recorded for 30 min. Both amphetamine (4.0 mg/kg) and PCP (4.0 mg/kg) substantially reduced social behavior. Haloperidol and clozapine did not produce a general reversal of the effects of amphetamine or PCP on the total number of social behaviors. Nevertheless, 0.025 mg/kg haloperidol did reverse the effects of PCP and amphetamine on some of the specific social behaviors observed (side threats, mounting, crawling under). Clozapine had no effect on reversing the actions of amphetamine on social behavior, but 2.0 mg/kg clozapine did reverse the effect of PCP on side threats and mounting. These results indicate that DA antagonists do not restore normal social behavior in animals treated with PCP or amphetamine, but can reverse some of the effects of PCP or amphetamine on specific social behaviors.


Subject(s)
Amphetamine/antagonists & inhibitors , Clozapine/pharmacology , Haloperidol/pharmacology , Phencyclidine/antagonists & inhibitors , Social Behavior , Aggression/drug effects , Amphetamine/administration & dosage , Amphetamine/pharmacology , Animals , Clozapine/administration & dosage , Haloperidol/administration & dosage , Male , Phencyclidine/administration & dosage , Phencyclidine/pharmacology , Rats , Rats, Sprague-Dawley
20.
Minerva Urol Nefrol ; 46(3): 175-8, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7801215

ABSTRACT

We report a case of renal oncocytoma which was found incidentally during the nephroureterectomy for renal pelvis carcinoma. The coexistence of two tumors on the kidney with absolutely different origin one from the other is extremely rare and interesting. Herein we discuss the clinical, morphological, histological, ultrastructural and angiographical characteristics of oncocytoma.


Subject(s)
Adenoma, Oxyphilic , Carcinoma , Kidney Neoplasms , Kidney Pelvis , Neoplasms, Multiple Primary , Aged , Female , Humans
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