Biomedical subjects

Bernd W Scheithauer

Publications and source records attributed to Bernd W Scheithauer.

At least 55 records · Page 3Linked to original sources

PubMed2005

Galectin-3 Expression in Functioning and Silent ACTH-Producing Adenomas.

Galectin-3 (Gal-3), a beta galactoside-binding protein, has been implicated in a variety of biological functions including cell growth, differentiation, tumor cell adhesion, angiogenesis, tumor progression, and metastasis. We recently reported that Gal-3 was expressed in a subset of normal pituitary cells and tumors including PRL, ACTH, and in folliculo-stellate (FS) cells and tumors and that Gal-3 had an important regulatory role in pituitary cell proliferation. We further investigated the expression of Gal-3 protein in ACTH- and PRL-producing tumors and the expression of various galectin mRNAs by RT-PCR in pituitary adenomas and normal pituitary. Most silent ACTH subtypes 1 and 2 adenomas were negative or only focally positive for Gal-3 expression compared to functioning ACTH tumors from patients with Cushing's disease and Nelson's syndrome. In the normal pituitary, Gal-3 was expressed in less than 1% of the basophil-invading cells (ACTH cells present in the posterior pituitary) and in a subset of the anterior lobe ACTH-positive cells. RT-PCR analyses showed that many members of the galectin family including galectins 1, 2, 3, 4, 5, 6, 7, 8, and 9 were expressed in normal pituitary and in functioning ACTH- and PRL-producing tumors. These results indicate that Gal-3 is associated with functioning ACTH and PRL tumors and is expressed infrequently in silent ACTH adenomas, suggesting that Gal-3 protein and/or gene is altered in non-functioning ACTH tumors. The use of ACTH and Gal-3 immunostaining should help in the diagnosis of silent ACTH adenomas.

ACTH-Secreting Pituitary Adenoma↗

PubMed2005

Angiogenesis and the growth potential of craniopharyngiomas.

The present study was performed to evaluate the role of neovascularization on the behavior of craniopharyngiomas as well as the contribution of endothelial cell proliferation and migration in the remodeling and expansion of the vascular network associated with angiogenesis. Fourteen primary tumors were studied, all of the adamantinomatous type. CD34 immunostaining, an endothelial cell marker, localized vessels within the connective tissue stroma. MIB-1 immunopositivity was apparent in the nuclei of neoplastic cells, few endothelial cells, and stromal elements. MIB-1 counts were higher in epithelial than connective tissue cells. A positive correlation was found between the number of MIB-1 immunopositive cells and microvessel density (MVD). Immunohistochemistry demonstrated that integrin alphavbeta3 expression was restricted to tumor vasculature; the tumor cells were immunonegative. Only 2.5% of vessels detected with CD34 were immunopositive for integrin alphavbeta3. At present, no therapeutic implications can be drawn from our observations. More studies are needed to assess whether integrin alphavbeta3 antagonists or drugs that arrest the cell cycle of endothelial cells can inhibit angiogenesis in craniopharyngiomas.

Adolescent↗

PubMed2005

Pituitary carcinoma: a clinicopathological review.

Pituitary carcinomas are rare tumors; less than 100 well-documented cases have been reported to date. Such tumors are aggressive and associated with a high mortality rate. The molecular events leading to the development of pituitary carcinomas are largely unknown. Recent studies have only begun to shed light on the probable mechanisms of tumor initiation and progression. A review of the clinicopathological and molecular genetic characteristics of pituitary carcinomas is presented.

Adenoma↗

PubMed2004

Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry.

PURPOSE: Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is an extremely rare and aggressive tumor of early childhood. The poor outcome with conventional infant brain tumor therapy has resulted in a lack of clear treatment guidelines. A registry has been established to create an outcomes database and to facilitate biology studies for this tumor. MATERIALS AND METHODS: A standardized data sheet was provided to treating physicians listing the reports that were to be sent to the registry for abstraction. Follow-up information was sought twice yearly. RESULTS: Information was complete for 42 patients. Median age at diagnosis was 24 months. Nine patients (21%) had disseminated disease at diagnosis. Sixteen tumors were infratentorial; 26 were supratentorial. Twenty patients (48%) received a primary complete resection. Primary therapy included chemotherapy in all patients, radiotherapy in 13 patients (31%), stem-cell rescue in 13 patients (31%), and intrathecal chemotherapy in 16 patients (38%). Recurrent or progressive disease was reported in nine and 19 patients, respectively. Twenty-seven patients (64%) are dead of disease (3 to 62 months from diagnosis) and one patient died of toxicity. Fourteen patients (33%) show no evidence of disease (9.5 to 96 months from diagnosis). The median survival is 16.75 months and the median event-free survival is 10 months. CONCLUSION: Aggressive therapy has prolonged the natural history in a subset of children. Prospective multi-institutional and national clinical trials designed specifically for AT/RT are needed. Enrollment onto the AT/RT registry should be continued.

Central Nervous System Neoplasms↗

PubMed2004

Importance of baseline mini-mental state examination as a prognostic factor for patients with low-grade glioma.

PURPOSE: The outcome and cognitive performance data collected in a prospective, intergroup clinical trial were analyzed to assess the prognostic importance of the baseline (before radiotherapy) Mini-Mental State Examination (MMSE) score in patients with low-grade glioma. METHODS AND MATERIALS: The patients studied were 203 adults with a supratentorial low-grade glioma randomly assigned to low-dose (50.4 Gy in 28 fractions) or high-dose (64.8 Gy in 36 fractions) localized radiotherapy. Folstein MMSE scores and neurologic function scores at baseline in combination with multiple other baseline variables were analyzed. The median follow-up was 7.4 years for the 101 patients still alive. RESULTS: Patients (n = 36) with an abnormal baseline MMSE score (< or =26) had a worse 5-year progression-free survival rate (27% vs. 60%; p <0.001) and overall survival rate (31% vs. 76%; p <0.001) compared with those with a normal score. On multivariate analysis, the baseline MMSE score was a statistically significant predictor of survival. Other factors associated with overall survival were age, tumor size, and tumor histologic type. CONCLUSION: The presence of an abnormal baseline MMSE score was a strong predictor of poorer progression-free and overall survival for patients with a low-grade glioma. The baseline MMSE should be considered in future prognostic scoring systems.

Adult↗

PubMed2004

Adult patients with supratentorial pilocytic astrocytomas: a prospective multicenter clinical trial.

PURPOSE: Supratentorial pilocytic astrocytomas in adults are uncommon. A prospective clinical trial was conducted to obtain clinical and outcome data in these patients. METHODS AND MATERIALS: Between 1986 and 1994, 20 eligible adults with supratentorial pilocytic astrocytomas were enrolled in a prospective intergroup trial of radiotherapy (RT) after biopsy (3 patients) or observation after gross (11 patients) or subtotal (6 patients) resection. RESULTS: At the time of analysis (median follow-up, 10 years), 1 patient (5%) had died and 19 patients (95%) were alive. The 5-year progression-free and overall survival rates were 95%. The cause of death in the patient who died (2.1 years after enrollment) was unknown; a radiographic examination obtained shortly before the patient's demise revealed no signs of progression. Progression in 1 patient approximately 1 month after enrollment required injection of (32)P into an enlarging cyst. The patient required RT approximately 18 months later because of further progression. This patient was alive without evidence of progression 9 years after RT. No toxic effects had been recorded at the latest follow-up examinations. CONCLUSION: With follow-up comparable or superior to that in many retrospective studies, the results of this prospective trial confirm that adults with pilocytic astrocytomas have a favorable prognosis with regard to survival and neurologic function. The vast majority of patients remained stable after gross or subtotal resection and no adjuvant therapy. RT need not be offered to adults with supratentorial pilocytic astrocytoma after gross or subtotal resection; instead, close observation is recommended. Because only 3 patients received RT after biopsy, it is difficult to comment on the effect of RT on their outcome as a group.

Adult↗

PubMed2004

Choroid plexus papillomas: a single institutional experience.

OBJECTIVE: To determine the long-term outcome of resected choroid plexus papillomas (CPPs). METHODS: Medical records and histologic specimens were reviewed for 41 patients (19 male, 22 female; median age, 36 years; range, 6 months to 74 years) with CPP seen between 1974 and 2000. Tumor locations were as follows: 76%, fourth ventricle; 17%, lateral ventricle, and 7%, third ventricle. Fifty-six percent had a gross total resection (GTR) and 44% had a subtotal resection (STR). Median follow-up was 6.5 years. RESULTS: Five-year local control, distant brain control, and overall survival were 84%, 92%, and 97%, respectively. Comparison of GTR and STR at 5 years showed a significant increase in local control (100% vs. 68%; P = 0.04) but not in overall survival (100% vs. 94%). Even after STR, only 50% of patients required a subsequent resection for recurrence. Addition of radiation therapy to initial STR did not seem to influence outcomes. At first relapse, GTR was accomplished in 1 patient, and only STR was accomplished in the others. Addition of radiation therapy to STR in our study led to disease control in half the patients treated, and STR alone led to disease control in only a quarter of the patients. Second relapses were treated palliatively with radiation therapy. CONCLUSIONS: Surgical resection is the treatment of choice for CPPs. After initial STR, reoperations for recurrence are required only half the time. Therefore, there seems to be no role for radiation therapy after initial STR. For STRs at first relapse, local control outcome is poor.

Adolescent↗

PubMed2004

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.

Adenoma↗

PubMed2004

Loss of tumor suppressor in lung cancer-1 (TSLC1) expression in meningioma correlates with increased malignancy grade and reduced patient survival.

Meningiomas represent the second most common central nervous system tumor affecting adults. Two of the most frequent early events in meningioma tumorigenesis involve loss of expression of the neurofibromatosis 2 (NF2) and 4.1B genes. Recently, 4.1B was shown to interact with the tumor suppressor in lung cancer-1 (TSLC1) protein, prompting us to examine the expression of TSLC1 in meningiomas. We developed specific anti-TSLC1 antibodies to examine TSLC1 expression in normal human leptomeninges, human meningioma cell lines, and human meningiomas of different pathological grades by Western blot (n = 10) and immunohistochemistry (n = 123). Whereas TSLC1 was expressed in normal human leptomeninges by immunohistochemistry, TSLC1 expression was absent in 3 human malignant meningioma cell lines and markedly reduced or absent in 30% of benign meningiomas by Western blot. Restoration of TSLC1 expression in a TSLC1-deficient human meningioma cell line resulted in reduced cell proliferation. In a series of 123 meningiomas (98 adult and 25 pediatric), TSLC1 expression was absent in 48% of benign (WHO grade I), 69% of atypical (grade II), and 85% of anaplastic (grade III) meningiomas. Moreover, TSLC1 loss was associated with decreased patient survival, within the overall group, and in the atypical meningiomas. Collectively, these results suggest that TSLC1 plays an important role in meningioma pathogenesis.

Animals↗

PubMed2004

Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance.

The purpose of this study was to establish an accurate and accessible immunohistochemical (IHC) method for detecting vIII Egf receptor and to assess the prognostic significance of the method as applied to the detection of vIII in malignant astrocytomas. The accuracy of the method was determined by comparing vIII immunoreactivity in formalin-fixed and paraffin-embedded tumor sections versus RT-PCR results from the analysis of RNA extracted from corresponding frozen specimens. RT-PCR revealed vIII transcript in 18 of 44 cases in this series, and IHC analysis of matched formalin-fixed and paraffin-embedded sections showed EGFRvIII reactivity in each of these 18 tumors, as well as 1 additional tumor that was negative for vIII transcript. EGFR amplification was evident in all tumors expressing vIII; none of the 15 tumors lacking amplified EGFR were positive for vIII transcript or vIII protein. IHC analysis for vill expression was next applied to a large series of anaplastic astrocytomas (AAs) and glioblastoma multiforme (GBMs) from clinical trial patients with complete follow-up and that had been previously examined by FISH for amplified EGFR. Among the GBMs, vIII detection by IHC was determined in 19 of 46 cases (41.3%) with EGFR amplification, and in only 3 of 59 tumors lacking amplified EGFR (5.1%). Among the AAs, vIII expression was observed in 3 of 14 cases with amplified EGFR (21.4%) and in 6 of 49 cases without EGFR amplification (12.2%). GBM and AA patient survival analysis as a function of vIII expression showed contrasting results, with vIII positivity having no association with survival among GBM patients (p = 0.84), but being highly associated with reduced survival among AA patients (p = 0.0016). This latter finding, though quite possibly a result of vIII's association with increasing AA patient age, suggests that vIII IHC will be useful for identifying and/or confirming the identity of malignant astrocytomas whose clinical behavior is consistent with that of GBM.

Adult↗

PubMed2004

Solitary fibrous tumor of the cerebellopontine angle with salivary gland heterotopia: a unique presentation.

We report the unique association of a solitary fibrous tumor of the cerebellopontine angle with ectopic salivary gland tissue in a 53-year-old woman. The patient, diagnosed 21 years earlier with a right cerebellopontine angle fibrous meningioma, presented with a recurrent mass, which, upon surgical removal, showed features of a solitary fibrous tumor. Strong and diffuse immunoreactivity to CD34 and BCL-2 and a negative epithelial membrane antigen immunostain confirmed the diagnosis. Admixed with the spindle cell neoplasm, a bland glandular element composed of small glands and variably dilated tubules was noted. The vague tubuloacinar arrangement of the glands and the presence of acinar cells with a granular, periodic acid-Schiff-positive, basophilic cytoplasm, resembling serous type acini, were features of benign, although ectopic, salivary gland tissue. The presence of a myoepithelial cell layer, surrounding some of the acini and highlighted by the smooth muscle actin immunostain, strengthened this interpretation.

Biomarkers, Tumor↗

PubMed2004

Regulation of VEGF-A, VEGFR-I, thrombospondin-1, -2, and -3 expression in a human pituitary cell line (HP75) by TGFbeta1, bFGF, and EGF.

Pituitary tumors are highly vascular neoplasms, which suggest an important role of angiogenesis in pituitary tumor growth. We used the human pituitary cell line (HP75) to examine the effects of the growth factors TGFbeta1, bFGF, and EGF on cell growth, and on the regulation of the pro-angiogenic growth factor VEGF-A and the VEGFR-I and the anti-angiogenic molecules thrombospondin (TSP) TSP-1 and TSP-2 along with TSP-3. Real-time RT-PCR was used to measure mRNA levels, and Western blot was used to analyze TSP-1 and TSP-2 protein levels. TGFbeta1 treatment (1 x 10(-9) M) increased VEGF-A mRNA levels significantly (p < 0.05) after 4 and 24 h of treatment. TGF beta1 treatment decreased VEGF-R mRNA levels after 96 h of treatment (p < 0.05). After 96 h of treatment, TSP-1 and TSP-2 mRNA levels were significantly increased (p < 0.05) by TGFbeta1 treatment, which also inhibited HP75 cell growth. Basic FGF also increased TSP-1 mRNA levels after 96 h of treatment, but did not regulate growth of the pituitary tumor cells. Basic FGF and EGF did not modulate changes in VEGF-A mRNA levels after 4 and 24 h of treatment, but EGF increased VEGF-A significantly (p < 0.05) after 96 h of treatment. These results indicate that TGFbeta1 treatment may regulate angiogenesis in pituitary cells by initially increasing levels of pro-angiogenic VEGF-A and then stimulating the anti-angiogenic molecules TSP-1 and TSP-2 levels.

Blotting, Western↗

PubMed2004

Analysis of Cox-2 and thromboxane synthase expression in pituitary adenomas and carcinomas.

Recent studies have examined the role of cyclooxygenase-2 (Cox-2) expression in normal pituitaries and pituitary adenomas and have suggested a role for Cox-2 in the regulation of angiogenesis in the pituitary. Thromboxane synthase (TBXAS), which catalyzes the synthesis of thromboxane A2, is one of the downstream enzymes in Cox metabolism and appears to play a role in the regulation of invasiveness and angiogenesis in some neoplasms. To analyze the role of Cox-2 and TBXAS in pituitary tumor progression, we examined normal pituitaries (n = 8), pituitary adenomas (n = 174), and pituitary carcinomas (n = 7) for expression of Cox-2 and TBXAS by immunohistochemistry. Weak Cox-2 and moderate TBXAS expression was present in normal pituitary cells. Most pituitary adenomas showed increased expression of both Cox-2 and TBXAS. Pituitary tumors as a whole, but particularly carcinomas, showed greater Cox-2 expression than did normal pituitaries. Pituitary adenomas and carcinomas also showed greater staining for TBXAS when compared to normal pituitary. Nonfunctional adenomas had significantly higher levels of TBXAS expression compared to functional adenomas (p = 0.017). Adenomas and carcinomas showed similar degrees of staining for TBXAS. In summary, TBXAS appears to be one of the up-regulated downstream enzymes of Cox metabolism in pituitary tumors. Both Cox-2 and TBXAS may play an important role in pituitary tumor development and progression.

Biomarkers, Tumor↗

PubMed2004

Combined sellar fibrosarcoma and prolactinoma with neuronal metaplasia: report of a case unassociated with radiotherapy.

We report the occurrence of a primary pituitary fibrosarcoma causally unrelated to radiotherapy, admixed in association with a prolactin cell pituitary adenoma showing neuronal metaplasia. These unique findings were associated with multiple endocrine neoplasia type 1 (MEN 1). Primary fibrosarcoma involving the sella is a very rare tumor. The majority of cases have been associated with prior irradiation of either a pituitary adenoma or a craniopharyngioma. Pituitary adenoma with neuronal metaplasia is also rare and usually occurs in the setting of acromegaly. Despite the intimate association of both elements in our lesion, no transition of adenoma to sarcoma was demonstrable by immunohistochemistry or in situ hybridization studies.

Adult↗

PubMed2004

Expression of caveolin-1 and caveolin-2 in the human pituitary: an immunohistochemical study.

Caveolins are coat proteins of caveolae, the plasmalemmal transport vesicles. To our knowledge their presence in the human pituitary and various types of hypophysial adenomas has not been investigated. In the present work, expression of caveolin-1 and caveolin-2 was studied by immunohistochemistry using the streptavidin-biotin-peroxidase complex method. The material included 7 autopsy obtained, 5 surgically removed non-tumorous pituitaries, and 97 hypophysial adenomas classified on the basis of histologic immunohistochemical and ultrastructural features. No immunoreactivity was seen for caveolin-1 and caveolin-2 in non-tumorous adenohypophysial and neurohypophysial cells and in the tumor cells, indicating that caveolins are not involved in the initiation and progression of pituitary adenomas. The expression of caveolin-1 and caveolin-2 in the endothelial cells did not depend on age, gender, endocrine status of the patients, morphologic features, and type of pituitary tumors. Scattered endothelial cells were immunopositive for both caveolins showing similar cytoplasmic localization. Evidence that the two caveolins were indeed localized to the same endothelial cell was demonstrated on consecutive sections using Factor-8 and CD-34, two reliable endothelial cell markers. Not every endothelial cell was immunoreactive for the two caveolins, suggesting that the functional status of endothelial cells is not the same within the adenomas, not even in the same capillary.

Adenoma↗

PubMed2003

Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the folstein mini-mental state examination.

PURPOSE: To assess the neurocognitive effects of cranial radiotherapy on patients with low-grade gliomas, we analyzed cognitive performance data collected in a prospective, intergroup clinical trial. METHODS: Patients included 203 adults with supratentorial low-grade gliomas randomly assigned to a lower dose (50.4 Gy in 28 fractions) or a higher dose (64.8 Gy in 36 fractions) of localized radiotherapy. Folstein Mini-Mental State Examination (MMSE) scores and neurologic function scores (NFS) at baseline and key evaluations were analyzed. Median follow-up was 7.4 years in 101 patients still alive. A change of more than three MMSE points was considered clinically significant. RESULTS: In patients without tumor progression, significant deterioration from baseline occurred at years 1, 2, and 5 in 8.2%, 4.6%, and 5.3% of patients, respectively. Most patients with an abnormal baseline MMSE score (< 27) experienced significant increases. Baseline variables such as radiation dose, conformal versus conventional radiotherapy, number of radiation fields, age, sex, tumor size, NFS, seizures, and seizure medications did not predict cognitive function changes. CONCLUSION: In this population, most low-grade glioma patients maintained a stable neurocognitive status after focal radiotherapy as measured by the MMSE. Patients with an abnormal baseline MMSE were more likely to have an improvement in cognitive abilities than deterioration after receiving radiotherapy. Only a small percentage of patients had cognitive deterioration after radiotherapy. However, more discriminating neurocognitive assessment tools may identify cognitive decline not apparent with the use of the MMSE.

Adult↗

PubMed2003

Cyclooxygenase-2 expression in human pituitary tumors.

BACKGROUND: Cyclooxygenase-2 (COX-2) plays a role in progression of colon, breast, pancreas, and lung carcinomas. The authors investigated COX-2 expression in pituitary tumors. METHODS: Expression of COX-2 was evaluated in 164 surgically removed human pituitary tumors. Correlation of COX-2 with MIB-1, a cell proliferation marker, as well as angiogenesis, patient age, gender, tumor type, size, invasiveness, and metastatic potential was investigated. RESULTS: Cyclooxygenase-2 immunoreactivity was confined to the cytoplasm of tumor cells, whereas the nuclei were unlabeled. Few normal peritumoral adenohypophysial cells showed slight COX-2 cytoplasmic immunoreactivity. The staining intensity and the percentage of immunopositive cells were higher in tumors. Most pituitary tumors (96%) were COX-2-immunopositive. Expression was strong in 60 (44%), moderate in 39 (28%), and weak in 32 (24%). Male gonadotroph adenomas and null cell adenomas showed a high level of COX-2 expression. Growth hormone-producing adenomas, prolactin-producing adenomas, thyrotropic hormone-producing adenomas, female gonadotroph adenomas, silent adrenocorticotropic hormone-producing adenomas, and silent subtype 3 adenomas had a low level of COX-2 expression. Significant correlation was demonstrated with patient age, but not with tumor size, invasiveness, and MIB-1 labeling indices. Expression was medium to high in 76% of macroadenomas and in only 45% of microadenomas. Strong correlations were noted with angiogenesis markers, such as microvessel density and surface density. CONCLUSIONS: Correlation with angiogenesis suggests that COX-2 may be involved in the regulation of angiogenesis in pituitary tumors. Phamacologic inhibition of COX-2 activity might suppress angiogenesis in pituitary tumors and may provide a novel approach for medical therapy.

Adenoma↗

PubMed2003

Differential expression of galectin-3 in pituitary tumors.

Galectin-3 (Gal-3), a beta-galactoside-binding protein, has been implicated in a variety of biological functions, including cell proliferation and differentiation, tumor cell adhesion, angiogenesis, apoptosis, tumor progression, and metastasis. We investigated the role of Gal-3 in the development and progression of pituitary tumors. Immunohistochemical and Western blot analysis of normal and neoplastic human pituitaries showed that only lactotroph (PRL) and corticotroph (ACTH) hormone-producing cells and tumors expressed Gal-3. Gal-3 was present in 24 of 38 (63.2%) PRL adenomas, 5 of 6 (83.3%) PRL carcinomas, 19 of 41 (46.3) ACTH adenomas, and 7 of 8 (87.5%) ACTH carcinomas, but not in 112 other pituitary adenomas and carcinomas. Pituitary folliculo-stellate cells, which have macrophage-type functions in the anterior pituitary, also expressed Gal-3. Hyperplastic and neoplastic pituitaries from p27(Kip1) (p27)-null mice, which produce mainly ACTH, showed increased Gal-3 expression levels compared with control mice. Treatment with transforming growth factor beta1, which regulates pituitary cell proliferation, reduced Gal-3 as well as p27 expression levels in cultured HP75 pituitary cells and Gal-3 in cultured pituitary cells from p27-null mice, suggesting that p27 is not necessary for the inhibitory effects of transforming growth factor beta1 on the cell cycle in the pituitary. The role of Gal-3 in pituitary cell function was examined by RNA interference experiments. Inhibition of Gal-3 gene expression by RNA interference decreased HP75 cell proliferation and increased apoptosis. These results indicate that Gal-3 has an important role in pituitary cell proliferation and tumor progression.

Adenoma↗