Cystic Hyperplasia Research Articles

Histopathological Pattern of Endometrium on Diagnostic D & C in Patients with Abnormal Uterine Bleeding

Aims and Objectives: To determine histopathologi-cal pattern of endometrium in patients with abnormal uterine bleeding. Study Type: Observational, Cross sectional. Place of Study: Obs and Gynae department, Madina teaching hospital, FSD. Duration of Study: One and a half year from Oct 2008 to Apr 2010. Patients and Methods: Patients presenting to Madina teaching hospital OPD with complaint of abnormal uterine bleeding were assessed via inclusion and ex-clusion criteria to be included in this study. A detailed history was followed by general physical, systemic, and gynecological examination. A pelvic ultrasound was performed followed by diagnostic D&C. Endo-metrial biopsy sent for histopathological examination in Pathology department of Madina teaching hospital, FSD. Data was collected over a period of one and a half year, and shifted to computer for analysis. Statisti-cal package of social sciences (SPSS) version 15 was used for statistical analysis of data. Chi-square good-ness of fit was used as test of statistical significance. Results: The most common pathological pattern iden-tified was proliferative phase endometrium (46.4%). Secretary phase endometrium was second most common pathology (37.6%). Cystic (5.2%), adenomatous (3.8%), and atypical (3.6%) hyperplasia constituted 12.6% of bulk. In 1.4%, endometritis was identified as a cause of abnormal uterine bleeding followed by atrophic endometrium (1%). Polyp was identified in 0.6% of cases followed by endometrial carcinoma (0.4%). Conclusion: Histopathological pattern of endomet-rium in patients with abnormal uterine bleeding is qui-te variable regardless of age, parity and ethnicity. Al-though the incidence of endometrial hyperplasia is grossly variable, yet incidence of endometrial carci-noma is small in all sited studies. Key words: D&C, AUB.

Apocrine Gland Hyperplasia in an 11-year-old Rabbit ( Oryctolagus cuniculus)

A 2-kg, 11-year-old neutered male rabbit ( Oryctolagus cuniculus) was presented for examination of a mandibular swelling. On clinical examination, 2 well-defined subcutaneous masses (15 mm and 5 mm in diameter) were identified along the ventral area of the left horizontal ramus of the mandible. An intraoral examination revealed a moderately elongated first premolar located within the left mandibular arcade. The mandibular masses were removed through surgical excision and coronal reduction was performed on the first left lower premolar. The 2 masses were isolated from the underlying tissue and there was no evidence of involvement of the abnormal tissue with structures comprising the oral cavity. The histological examination of the excised tissue revealed unencapsulated cystic, multiloculated and multilobulated masses consisting of numerous, variably sized cystic spaces and tubules supported by a moderately dense fibrovascular stroma. The final disease diagnosis of the mandibular tissue masses was cystic apocrine gland adenomatous hyperplasia, most likely of sweat gland origin. Apocrine gland hyperplasia is a benign, nonneoplastic lesion. The etiology of cystic hyperplasia of the apocrine glands is unknown in domestic species, but it is reported to occur in male dogs and less frequently in cats. This case is believed to be the first description of apocrine gland hyperplasia in the submandibular region of a rabbit.

Early life inorganic lead exposure induces testicular teratoma and renal and urinary bladder preneoplasia in adult metallothionein-knockout mice but not in wild type mice

Inorganic lead compounds are carcinogenic in animals and have carcinogenic potential in humans. In mice, lead (Pb) is a transplacental carcinogen in the kidney. Metallothionein (MT) is a metal-binding protein that can reduce the toxicity of various metals, including Pb, either by direct sequestration or as an antioxidant for metals that generate reactive oxygen species. Although MT appears to reduce Pb carcinogenicity in adult mice it is unknown how MT deficiency may affect Pb carcinogenicity from early life exposure. Thus, groups ( n = 10) of pregnant MT-I/II double knockout (MT-null) or 129/SVJ MT wild type (WT) mice were exposed to Pb acetate in the drinking water (0, 2000, 4000 ppm Pb) from gestation day 8 through birth and during lactation. Maternal drinking water Pb exposure continued to wean at 4 weeks of age and the male offspring were then directly exposed to Pb until 8 weeks of age and observed until 2 years old. High dose (4000 ppm) but not low dose (2000 ppm) Pb reduced survival in the latter part of the study in both MT-null and WT mice. In MT-null mice, but not WT, early life Pb exposure caused a dose-related increase in testicular teratomas, to a maximum incidence of 28% compared to control (4%). Pb-induced renal cystic hyperplasia, considered preneoplastic, was a prominent occurrence in MT-null mice but nearly absent in WT mice. Pb dose-related increases in renal cystic hyperplasia occurred in adult MT-null with early life exposure with maximal incidence of 52%. Pb-treated MT-null mice also showed dose-related increases in urinary bladder hyperplasia with occasional papilloma that were absent in WT mice. Thus, MT deficiency made mice more sensitive to early life Pb exposure with regard to testes tumors, and renal and urinary bladder preneoplastic lesions.

Density of Langerhans cells in the keratocystic odontogenic tumor

INTRODUCTION: Keratocystic odontogenic tumors (KOTs) are distinct odontogenic lesions commonly affecting the mandible bones. Langerhans cells (LCs) are specialized dendritic cells responsible for the presentation of antigens to T lymphocytes in mucosal and cutaneous surfaces. OBJECTIVE: This study analyzed the immunohistochemical expression of LCs in KOTs. MATERIALS AND METHODS: Fifteen cases of KOTs were studied using the anti-CD1a marker. Results: LCs were observed in all 15 cases analyzed. They were found to be concentrated in areas of cystic epithelial hyperplasia, mainly in those areas presenting higher concentration of inflammatory cells. Furthermore, a significant association between the number of LCs and areas of cystic epithelium presenting hyperplasia (Mann-Whitney test, p = 0.0223) was observed. The shape and location of these cells in KOTs epithelium were variable. CONCLUSION: The lower number of LCs observed on atrophic cystic epithelium of KOTs may be due to decreased epithelial immunosurveillance and this may result in locally aggressive invasiveness.

Diagnosis | Cystic mammary gland hyperplasia and neoplasia

Diagnosis | Cystic mammary gland hyperplasia and neoplasia

Behandlung eines Uterusadenokarzinoms eines Minipigs durch Ovariohysterektomie

An 11-year-old, 75-kg, miniature pig was presented because of haemorrhagic vulvar discharge attributable to chronic endometritis. Ovariohysterectomy was carried out with the patient in dorsal recumbency and anaesthetised using total intavenous anaesthesia and positive-pressure ventilation. A ventral midline approach was chosen to remove the ovaries and uterus, which contained brown fluid and multifocal masses in the uterine wall. Histological examination of the uterine masses revealed leiomyoma, cystic hyperplasia and adenocarcinoma. After surgery, the miniature pig recovered without complications and remained healthy at follow-up 4 months later.

β-catenin expression:the role in carcinogenesis and development of human breast cancer

Objective To explore the role of β-catenin expression in breast carcinogenesis. Methods β-cateninin expression of the breast diseases was detected by immunohistochcmical staining. A-mong them, there were cases with intraductal papilloma n=25, DBCH (disease of the breast cystic hyper-plasia) n = 27, DBCH with ADH(atypical ductal hyperplasia) n=26, DCIS(ductal carcnoma in situ) n=29 and IDC(invasive ductal cancinoma)n=58. Results The positive rates of β-catcnin expression in in-traductal papilloma,DBCH, DBCH with ADH, DCIS, and IDC were 4.0%, 3.7%, 23.1%, 72.4% and 79.3%, respectively. The expression of simple membranous β-catenin was statistically related with tumor size, lymph node metastasis and TNM staging (P<0.05), the expression rate was higher in patients with smaller size, no lymph node metastasis and stage Ⅰ or Ⅱ, but not with tumor grading and age of the pa-tient. The co-expression of membranous and cytoplasmic β-catenin was significantly correlated with lymph node metastasis, tbe rate rised higherly only in patients with lymph node metastasis (P<0.05). Further-more, the possibility of lymph node metastasis was higher in membranous and cytoplasmic β-catenin co-ex-pression group than in membranous group. Conclusion Positive expression of β-catcnin occurred early and continued to exist during neoplastic transformation of mammary cells;the co-expression of membranous and cytoplasmic β-catenin was significantly related with lymph node metastasis, which implied they might be a risk factor of poor prognosis, whereas the expression of membranous β-catenin only was negtively cor-related with tumor size,lymph node metastasis, and TNM staging,it might be an indicator of good progno-sis. Key words: β-catenin; Breast cancer

Pituitary Enlargement in Patients with PROP1 Gene Inactivating Mutation Represents Cystic Hyperplasia of the Intermediate Pituitary Lobe. Histopathology and Over 10 Years Follow-up of Two Patients

Patients with a PROP1 inactivating mutation present combined pituitary hormone deficiency (CPHD) and pituitary maldevelopment. A retrospective analysis of 31 CPHD patients with a PROP1 mutation revealed two individuals, aged 18 and 4.5 years, who had undergone subtotal surgery to remove pituitary tumors, 16.8 x 12 mm and 9 x 10 x 12 mm in size. Histological reassessment of tissue samples revealed epithelial cells, partially oxyphilic, forming gland-like microcystic structures, most of them filled with eosinophilic colloid. These structures were directly linked with fragments of the posterior lobe. Neither atypia nor any traces of proliferation activity (Ki-67 LI=0%) were noted. Immunohistochemistry showed the presence of all hormonal phenotypes of cells. These findings corresponded to the intermediate lobe of the pituitary gland. For this type of pathology we propose the term 'cystic hyperplasia of the intermediate pituitary lobe' and suggest PROP1 gene assessment in patients with CPHD in order to avoid unnecessary neurosurgical interventions.

Expression and clinical significance of vascular endothelial growth factor in benign and malignant tissues of breast

ObjectiveTo detect the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) count in breast benign affection, breast atypical hyperplasia and breast carcinoma in situ, and to clarify the relationship between VEGF expression, MVD and the clinicopathological features of these diseases.MethodsThe expression of VEGF and MVD count in 115 cases breast benign diseases (including 40 breast fibroid tumor, 40 breast cystic hyperplasia and 35 intraductal papilloma, 19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining (SP-method).ResultsThe positive rate of VEGF in breast benign diseases, breast atypical hyperplasia and breast carcinoma in situ were 21.74%(25/115)、 31.58.% (6/19)and 53.13%(17/32) respectively. It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The expression of VEGF increased gradually in the three groups (P<0.05). The MVD count of the three groups were 14.41±2.59, 18.89±4.47 and 21.13±4.12 respectively, It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The MVD count of the three groups increased gradually (P<0.05). In VEGF positive group, MVD count was 19.41±4.78; In VEGF negative group, MVD count was 14.91±3.15. The MVD count was higher in VEGF positive group than that in VEGF negative group (P<0.05).ConclusionThe results of this study suggested that VEGF could promote microvessel growth in breast tumors. The occurrence and progression of breast cancer might be related with the expression of VEGF.

Incidental finding of uterine adenomyosis in a bitch with reproductive disorders: a case report

Uterine adenomyosis, a disease not widely addressed in dogs, is characterised by the progressive penetration of endometrial glands and stroma into the myometrium, together with smooth-muscle hyperplasia. This report describes a case of adenomyosis in an 8-year-old German Shepherd bitch with mammary tumours, concomitant with cystic ovarian disease and endometrial cystic hyperplasia. Clinical signs included presence of small nodules and enlargement of mammary glands, and bloody uterine discharge. Ultrasonography confirmed the uterine and ovarian abnormalities, while the diagnosis was later confirmed by histopathological examination. The findings are discussed as possibly related to the reproductive disorders observed, and a hypothetical participation of hormonal factors, as has been described in woman, is suggested. However, further studies must be realized.

CDB-2914 for Uterine Leiomyomata Treatment

To evaluate whether 3-month administration of CDB-2914, a selective progesterone receptor modulator, reduces leiomyoma size and symptoms. Premenopausal women with symptomatic uterine leiomyomata were randomly assigned to CDB-2914 at 10 mg (T1) or 20 mg (T2) daily or to placebo (PLC) for 3 cycles or 90-102 days if no menses occurred. The primary outcome was leiomyoma volume change determined by magnetic resonance imaging at study entry and within 2 weeks of hysterectomy. Secondary outcomes included the proportion of amenorrhea, change in hemoglobin and hematocrit, ovulation inhibition, and quality-of-life assessment. Twenty-two patients were allocated, and 18 completed the trial. Age and body mass index were similar among groups. Leiomyoma volume was significantly reduced with CDB-2914 administration (PLC 6%; CDB-2914 -29%; P=.01), decreasing 36% and 21% in the T1 and T2 groups, respectively. During treatment, hemoglobin was unchanged, and the median estradiol was greater than 50 pg/mL in all groups. CDB-2914 eliminated menstrual bleeding and inhibited ovulation (% ovulatory cycles: CDB-2914, 20%; PLC, 83%; P=.001). CDB-2914 improved the concern scores of the uterine leiomyoma symptom quality-of-life subscale (P=.04). One CDB-2914 woman developed endometrial cystic hyperplasia without evidence of atypia. No serious adverse events were reported. Compared with PLC, CDB-2914 significantly reduced leiomyoma volume after three cycles, or 90-102 days. CDB-2914 treatment resulted in improvements in the concern subscale of the Uterine Fibroid Symptom Quality of Life assessment. In this small study, CDB-2914 was well-tolerated without serious adverse events. Thus, there may be a role for CDB-2914 in the treatment of leiomyomata. ClinicalTrials.gov,www.clinicaltrials.gov, NCT00290251 I.

Expression of vascular endothelial growth factor in different breast tissues and clinical significance thereof

To investigate the differences in the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) count in breast benign affection, breast atypical hyperplasia, and breast carcinoma in situ and to clarify the association of VEGF expression and MVD with the clinicopathological features of these diseases. Immunohistochemistry (SP-method) was used to examine the expression of VEGF and MVD count in 100 samples of breast benign affection (including 35 cases of breast fibroid tumor, 35 cases of breast cystic hyperplasia, and 30 cases of intraductal papilloma), and 15 samples of breast atypical hyperplasia, and 25 samples of breast carcinoma in situ, obtained during operation. The positive rate of VEGF of the breast carcinoma in situ group was 56% , significantly higher than hose of the breast benign affection and breast atypical hyperplasia groups (22% and 33% respectively, P < 0.05). However, there was no significant differences in positive rate of VEGF among breast fibroid tumor, breast cystic hyperplasia, and intraductal papilloma (all P > 0.05). The MVD value of the breast carcinoma in situ group was 20.1 +/- 6.1, significantly higher than those of the breast benign affection group and breast atypical hyperplasia groups (14.3 +/- 3. 5 and 18.5 +/- 3.6 respectively, both P < 0.05). There was no significant differences in MVD value among breast fibroid tumor, breast cystic hyperplasia, and intraductal papilloma (all P > 0.05). In breast tumors, angiogenesis is probably mediated mainly by VEGF. The occurrence and progression of breast cancer may be related with the expression of VEGF.

Correlation of contrast-enhanced MR images with the histopathology of minimally invasive thermal and cryoablation cancer treatments in normal dog prostates.

Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

CCR7 deficiency causes ectopic lymphoid neogenesis and disturbed mucosal tissue integrity

AbstractHomeostatic trafficking of lymphocytes through extralymphoid tissues has been recently observed, and a potential role in immune surveillance and the establishment of peripheral tolerance are considered. However, the mechanisms regulating lymphocyte recirculation through peripheral tissues under noninflammatory conditions are not well understood. Here, we demonstrate that the chemokine receptor CCR7 controls not only lymphocyte trafficking to and within secondary lymphoid organs but also homeostatic migration of T and B lymphocytes through nonlymphoid tissues. Lack of CCR7 results in a massive accumulation of lymphocytes in epithelial tissues. In particular, the gastrointestinal mucosal tissue of CCR7−/− mice is highly permissive for the formation of lymphoid aggregates, which develop into ectopic follicular structures with major topologic characteristics of lymph nodes. Flow cytometry analysis of CD4+ T cells derived from ectopic follicles revealed that CD44hiCD62Llo effector memory T cells predominate in the gastric lymphoid aggregates. In aged mice, lack of CCR7 induced age-dependent histomorphologic changes in the stomach with profound cystic hyperplasia and an increased rate of mucosal proliferation resembling Menetrier disease. Thus, CCR7 regulates the cellular organization of visceral tissue by governing life-long recirculation of naive and memory lymphocytes under homeostatic conditions.

Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1

Branching of ureteric bud-derived epithelial tubes is a key morphogenetic process that shapes development of the kidney. Glial cell line-derived neurotrophic factor (GDNF) initiates ureteric bud formation and promotes subsequent branching morphogenesis. Exactly how GDNF coordinates branching morphogenesis is unclear. Here we show that the absence of the receptor tyrosine kinase antagonist Sprouty1 (Spry1) results in irregular branching morphogenesis characterized by both increased number and size of ureteric bud tips. Deletion of Spry1 specifically in the epithelium is associated with increased epithelial Wnt11 expression as well as increased mesenchymal Gdnf expression. We propose that Spry1 regulates a Gdnf/Ret/Wnt11-positive feedback loop that coordinates mesenchymal–epithelial dialogue during branching morphogenesis. Genetic experiments indicate that the positive (GDNF) and inhibitory (Sprouty1) signals have to be finely balanced throughout renal development to prevent hypoplasia or cystic hyperplasia. Epithelial cysts develop in Spry1-deficient kidneys that share several molecular characteristics with those observed in human disease, suggesting that Spry1 null mice may be useful animal models for cystic hyperplasia.

Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen

Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 microg/pup/day) or tamoxifen (TAM; 10 microg/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-alpha, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES.

Patohistološke promjene u endometrijumu dobijenom dijagnostičkom kiretažom

Pathological bleeding from uterus most often represents a warning sign to serious changes in genital organs of a woman. The study analyses pathohistological findings of endometrium obtained by diagnostic curettage of 486 patients with pathological bleeding from uterus, who were treated at the Gynecology and Obstetric Ward of the Doboj General Hospital in the period of 2003 to 2005. Most of the women with pathological bleeding from uterus belonged to the age group of 41 to 50 years (226 women, 46.50%). Pathohistological examination of the curetted material, cystic hyperplasia of endometrium was most often the cause of uterine bleeding (157 cases, 32.77%), followed by endometritis (156 cases, 32.09%) and hyperplasia simplex (82 cases, 16,87%). Adenocarcinoma of endometrium was diagnosed in 30 cases (6.17%). Pathological bleeding from uterus is most often the case at women in the age group of 41 to 60. The most frequent cause of the pathological bleeding from uterus are endometrial hyperplasia, and endometritis. The diagnostic curettage with pathohistological examination of the obtained endometrium represents a standard in pathological uterine bleeding diagnostics.

Funisitis Associated with Leptospiral Abortion in an Equine Placenta

Funisitis, inflammation of the umbilical cord, is well recognized in human placentas. This report describes a case of funisitis associated with leptospiral infection in the placenta of a Thoroughbred foal born prematurely. The umbilical cord had diffuse superficial yellow discoloration along its entire length. Microscopic evaluation showed an exudate of neutrophils admixed with fibrin on the surface. Warthin-Starry staining showed spirochetes in the Wharton's jelly of the umbilical cord. A locally extensive, severe placentitis not involving the star and allantoic cystic hyperplasia were the other lesions observed in the allantochorion. Leptospira funisitis is similar to the funisitis of congenital syphilis in humans, although there are some major microscopic differences. In Leptospira funisitis, lesions were limited to the cord surface, whereas in lesions in human umbilical cords with Treponema pallidum infection, the changes are observed mostly around the vessels and in the Wharton's jelly.

Disorders in Cytokine Gene Expression in Endometrial Hyperplasia and Effect of Hormone Therapy

We studied local expression of insulin-like growth factor 1, insulin-like growth factor receptor, epithelial growth factor, transforming growth factor beta2, PCNA, TNF-alpha, type I TNF receptor, Fas, FasL, IFN-gamma, IL-1beta, IL-4, IL-6, IL-8, IL-10, and IL-12 genes in intact and hyperplastic endometrium. Endometrial hyperplasia was associated with reduced production of TNF-alpha (p<0.05), PCNA (p<0.05), and epithelial growth factor mRNA and enhanced production of Fas mRNA (p<0.01). The expression of TNF-R1, IL-1beta, and IL-12 genes decreased only in glandular cystic hyperplasia (p<0.05 for all genes), expression of insulin-like growth factor 1 gene decreased only in adenomatous hyperplasia (p<0.05). Dufaston therapy of glandular cystic hyperplasia and zoladex therapy of adenomatous hyperplasia normalized expression of Fas receptor, PCNA, and insulin-like growth factor 1 genes, while the expression of IFN-gamma and IL-6 genes, which was normal in hyperplasia, decreased (p<0.05). Zoladex therapy decreased the production of transforming growth factor beta2 (p<0.05) and IL-1beta (p<0.01) mRNA, dufaston therapy decreased production of TNF-alpha (p<0.05) and IL-4 mRNA (p<0.05). Hence, both apoptosis and proliferative activity were suppressed in endometrial hyperplasia, and hormone therapy created prerequisites for transition of the endometrium into the normal proliferation stage.

Promotion of thyroid tumors in rats by pregnenolone-16alpha-carbonitrile (PCN) and polychlorinated biphenyl (PCB).

Pregnenolone-16alpha-carbonitrile (PCN) and Aroclor 1254 (PCB) both reduce serum thyroid hormone levels in rats, but only PCN consistently produces an increase in serum thyrotropin (TSH). PCN-mediated increases in TSH result in increased thyroid follicular cell proliferation and hyperplasia, which may represent early events on a morphological continuum leading to neoplasia. The purpose of this study was to assess whether PCN, a compound that increases serum TSH, and PCB, which does not increase TSH, promote thyroid tumors in a two-stage carcinogenesis model. Male SD rats were administered the thyroid tumor initiator diisopropanolnitrosamine (2.5 g/kg, sc), and after seven days were fed control diet, diet containing 1000 ppm PCN, or diet containing 100 ppm PCB for 19 weeks. Body weights were unaffected by PCN treatment, but were reduced 21% after 19 weeks of PCB treatment compared to control. PCN treatment significantly reduced serum T4 through week 3 before returning to control concentrations, whereas T4 levels following PCB treatment fell below detection limits by week 3 and remained drastically reduced through week 19. TSH concentrations in PCN-treated rats increased three-fold at week 2, then declined to near control values at week 19. After one week of PCB treatment, TSH concentrations reached nearly twice that of controls, and were sustained until week 6. The incidence of thyroid follicular cell proliferative lesions, including cystic and follicular hyperplasia, cystic and follicular adenoma, and follicular carcinoma, was significantly increased following PCN treatment, but not following PCB treatment. PCB treatment caused an increase in thyroid carcinomas (4 of 22 rats) not associated with the proliferative-type lesions produced by PCN, despite an increase in TSH serum concentrations. In conclusion, PCN appears to promote thyroid tumors in a manner consistent with known effects of excessive TSH stimulation. However, thyroid carcinomas stemming from PCB treatment indicate that separate mechanisms exist for the production of thyroid cancer in rodents by chemicals classically considered microsomal enzyme inducers.