SYNGR2 serves as a prognostic biomarker and correlates with immune infiltrates in esophageal squamous cell carcinoma.

BACKGROUND: Synaptogyrin-2 (SYNGR2) plays an important role in regulating membrane traffic in non-neuronal cells. However, the role of SYNGR2 in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: All original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated via R 3.5.3. SYNGR2 expression was explored in the TCGA and GEO databases. The correlations between SYNGR2 and cancer immune characteristics were analyzed via the TIMER and TISIDB databases. RESULTS: In general, SYNGR2 was predominantly overexpressed and had reference values in the diagnosis and prognostic estimation of ESCC. Upregulated SYNGR2 was associated with poorer overall survival, disease-specific survival and T stage in ESCC. Mechanistically, we identified hub genes that included a total of 38 SYNGR2-related genes, which were tightly associated with the protein polyubiquitination pathway in ESCC patients. SYNGR2 expression was negatively related to the infiltrating levels of T helper cells. SYNGR2 methylation was positively correlated with the expression of chemokines (CCL2 and CXCL12), chemokine receptors (CCR1 and CCR2), immunoinhibitors (CXCL12 and TNFRSF4) and immunostimulators (CSF1R and PDCD1LG2) in ESCC. CONCLUSION: SYNGR2 may be used as a biomarker for determining prognosis and immune infiltration in ESCC.

ACT001 inhibits pituitary tumor growth by inducing autophagic cell death via MEK4/MAPK pathway.

ACT001, derived from traditional herbal medicine, is a novel compound with effective anticancer activity in clinical trials. However, little is known regarding its role in pituitary adenomas. Here, we demonstrated that ACT001 suppressed cell proliferation and induced cell death of pituitary tumor cells in vitro and in vivo. ACT001 was also effective in suppressing the growth of different subtypes of human pituitary adenomas. The cytotoxic mechanism ACT001 employed was mainly related to autophagic cell death (ACD), indicated by autophagosome formation and LC3-II accumulation. In addition, ACT001-mediated inhibitory effect decreased when either ATG7 was downregulated or cells were cotreated with autophagy inhibitor 3-methyladenine (3-MA). RNA-seq analysis showed that mitogen-activated protein kinase (MAPK) pathway was a putative target of ACT001. Specifically, ACT001 treatment promoted the phosphorylation of JNK and P38 by binding to mitogen-activated protein kinase kinase 4 (MEK4). Our study indicated that ACT001-induced ACD of pituitary tumor cells via activating JNK and P38 phosphorylation by binding with MEK4, and it might be a novel and effective anticancer drug for pituitary adenomas.

Plasma long non-coding RNA BACE1 as a novel biomarker for diagnosis of Alzheimer disease.

BACKGROUNDS: Long non-coding RNA (LncRNA) have been reported to be involved in the pathogenesis of neurodegenerative diseases, but whether it can serve as a biomarker for Alzheimer disease (AD) is not yet known. METHODS: The present study selected four specific LncRNA (17A, 51A, BACE1 and BC200) as possible AD biomarker. RT-qPCR was performed to validate the LncRNA. Receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were applied to study the potential of LncRNA as a biomarker in a population of 88 AD patients and 72 control individuals. RESULTS: We found that the plasma LncRNA BACE1 level of AD patients was significantly higher than that of healthy controls (p = 0.006). Plasma level of LncRNA 17A, 51A and BC200 did not show a significant difference between two groups (p = 0.098, p = 0.204 and p = 0.232, respectively). ROC curve analysis showed that LncRNA BACE1 was the best candidate of these LncRNA (95% CI: 0.553-0.781, p = 0.003). In addition, no correlation was found for expression of these LncRNA in both control and AD groups with age or MMSE scale (p > 0.05). CONCLUSIONS: Our present study compared the plasma level of four LncRNA between AD and non-AD patients, and found that the level of the BACE1 is increased in the plasma of AD patients and have a high specificity (88%) for AD, indicating BACE1 may be a potential candidate biomarker to predict AD.

Long-Term Clinical Outcomes of Invasive Giant Prolactinomas after a Mean Ten-Year Followup.

Objective. The aim of this study is to observe clinical outcomes after more than ten years of followup in a group of patients with invasive giant prolactinomas (IGPs) treated with dopamine agonists (DAs). Methods. Twenty-five patients met the criteria of IGPs, among which 16 patients primarily received bromocriptine (BRC) and the other nine had undergone unsuccessful microsurgery prior to BRC treatment. Results. After a mean follow-up period of 135.5 ± 4.7 months, the clinical symptoms in all patients improved by different degrees. Tumor volume was decreased by a mean of 98.6%, and the tumors of 19 patients had almost completely disappeared. The mean duration of treatment at maximal doses of BRC was 48.5 months. At the last follow-up visit, nineteen patients had normal PRL levels, and 14 of these patients had received the low-dose BRC treatment (at an average of 2.9 ± 0.3 mg/d). Younger patients < 25 years had a significantly higher rate of persistent hyperprolactinemia after long-term BRC treatment (p = 0.043). Conclusion. DAs are a first-line therapy for IGPs because they can effectively achieve long-term control in both shrinking tumor volume and normalizing the PRL level, and majority of patients need low-dose DA maintenance. Younger patients are prone to persistent hyperprolactinemia despite long-term DA treatment.

Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas.

Dopamine agonists (DAs) are the first-line treatment of prolactinomas. They function through the dopamine 2 receptor (D2R) in the tumor cells. Endocan, also called endothelial cell-specific molecule-1 (ESM1), has been described as a marker of neoangiogenesis. However, whether ESM1 promotes the resistance of prolactinomas to DA therapy is largely unknown. In our study, 25 patients with prolactinomas were divided into resistant- and sensitive- groups according to the clinical response to bromocriptine. We found that ESM1-microvessel density of resistant prolactinomas was significantly higher than that of sensitive prolactinomas (47.9 ± 11.6, n = 8, vs 13.1 ± 2.8, n = 17, p = 0.0006), indicating that ESM1 was a DA resistance-related gene. Immunostaining showed that ESM1 was expressed in tumor vessels and sporadic tumor cells, and ESM1 was overlapped with the Smooth Muscle Actin (SMA) and von Willebrand Factor (VWF) in the tumor vessels. Silencing of ESM1 markedly suppressed the viability of GH3 and MMQ cells in vitro, and furthermore, significantly increased the sensitivity of GH3 and MMQ cells to DA treatment. Additionally, silencing of ESM1 down-regulated the angiogenesis-associated genes, such as VEGFR2, FGF2, CD34, CD31, VWF, and EGFR. Knockdown of ESM1 decreased endothelial tube formation of HUVECs, and significantly increased the sensitivity of HUVECs to Avastin treatment. Therefore, we first demonstrate that DA resistance-related ESM1 promotes the angiogenesis and tumor cells growth of prolactinomas, suggesting that ESM1 may be a novel therapeutic target for prolactinomas.

Antiproliferative and apoptosis-inducing activity of schisandrin B against human glioma cells.

BACKGROUND: Malignant glioma is the most devastating and aggressive tumour in the brain and is characterised by high morbidity, high mortality and extremely poor prognosis. The main purpose of the present study was to investigate the effects of schisandrin B (Sch B) on glioma cells both in vitro and in vivo and to explore the possible anticancer mechanism underlying Sch B-induced apoptosis and cell cycle arrest. METHODS: The anti-proliferative ability of Sch B on glioma cells were assessed by MTT and clony formation assays. Flow cytometric analysis was used to detect cell cycle changes. Apoptosis was determined by Hoechst 33342 staining and annexin V/PI double-staining assays. The mitochondrial membrane potential was detected by Rhodamine 123 staining. The in vivo efficacy of Sch B was measured using a U87 xenograft model in nude mice. The expressions of the apoptosis-related and cell cycle-related proteins were analysed by western blot. Student's t-test was used to compare differences between treated groups and their controls. RESULTS: We found that Sch B inhibited growth in a dose- and time-dependent manner as assessed by MTT assay. In U87 and U251 cells, the number of clones was strongly suppressed by Sch B. Flow cytometric analysis revealed that Sch B induced cell cycle arrest in glioma cells at the G0/G1 phase. In addition, Sch B induced glioma cell apoptosis and reduced mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Mechanically, western blot analysis indicated that Sch B induced apoptosis by caspase-3, caspase-9, PARP, and Bcl-2 activation. Moreover, Sch B significantly inhibited tumour growth in vivo following the subcutaneous inoculation of U87 cells in athymic nude mice. COCLUSIONS: In summary, Sch B can reduce cell proliferation and induce apoptosis in glioma cells and has potential as a novel anti-tumour therapy to treat gliomas.

MicroRNA expression profile of bromocriptine-resistant prolactinomas.

MicroRNAs (miRNA) have been implicated in the resistance of tumors to chemotherapy. However, little is known about miRNA expression in bromocriptine-resistant prolactinomas. In this study, 23 prolactinoma samples were classified as bromocriptine-sensitive or -resistant according to the clinical definition of bromocriptine resistance, and their miRNA expression profiles were determined using Solexa sequencing. We found 41 miRNAs that were differentially expressed between the two groups, and 12 of these were validated by stem-loop qRT-PCR. Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas. Furthermore, silencing of mir-93 significantly increased the sensitivity of MMQ cells to dopamine agonist treatment. Mir-93 directly affected p21 expression in MMQ cells by targeting the 3'-UTR. Our study is the first to identify a miRNA expression profile associated with bromocriptine-resistant prolactinoma.

Natural history of postoperative nonfunctioning pituitary adenomas: a systematic review and meta-analysis.

OBJECTIVE: Previous studies attempting to define the natural history of postoperative nonfunctioning pituitary adenomas (pNFPAs) were somewhat limited by selection bias and/or small numbers and/or lack of consistency among the study findings. The aim of this study was to scrutinize the literature in order to analyze the natural history of pNFPAs. METHODS: Electronic database including MEDLINE, PubMed and Cochrane CENTRAL were searched. The literature relating to the patients with pNFPAs without postoperative radiotherapy and pharmacotherapy was collected. Eligible studies reported on the rate of tumor recurrence, the tumor growth-free survival rate (TGFSR) at 5 and 10 years, and/or the residual tumor volume doubling time (TVDT). RESULTS: 19 studies met the criteria. The pNFPAs were divided into two groups: the pooled recurrence rate of group I without detectable residual tumor (371 patients) was 12% (95% CI 6-19%), the TGFSR at 5 and 10 years were 96% (95% CI 89-99%) and 82% (95% CI 65-94%), respectively. The pooled recurrence rate of group II with residual tumor (600 patients) was 46% (95% CI 36-56%), the TGFSR at 5 and 10 years were 56% (95% CI 41-71%) and 40% (95% CI 27-53%), respectively. The mean TVDT was 3.4 years (95% CI 2.4-4.5 years). CONCLUSIONS: pNFPAs, with or without detectable residual tumor, need stratification of treatment and radiological/endocrinological follow-up strategy. According to the TVDT, residual tumor regrowth is very slow, which permits an extensive and safe follow-up program for most patients.

[Differential expression analysis of prolactinoma-related microRNAs].

OBJECTIVE: To explore the relationship between the prolactinoma-related microRNAs (miRNA) and the development, growth and hormone secretion of prolactinoma. METHODS: The technique of Solexa sequencing was employed to analyze the differential expressions of prolactinoma and normal anterior pituitary gland samples. And the stem-loop real-time polymerase chain reaction (PCR) was utilized for confirmation. RESULTS: According to the differentially expressed profiles of miRNAs, 4 miRNAs were down-regulated (miR-130a, miR-199b-3p, miR-200b, miR-125b, P < 0.05) and 6 miRNAs up-regulated (miR-342-3p, miR-432, miR-23b, miR-493, miR-493(*), miR-664(*), P < 0.05). The expression levels of miR-493(*) and miR-432 had a significant positive correlation with the serum level of prolactin (r = 0.47, P < 0.05; r = 0.528, P < 0.01) while miR-342-3p a significantly positive correlation with the invasiveness (r = 0.402, P < 0.05). CONCLUSION: miRNAs are differentially expressed between normal anterior pituitary gland and prolactinomas, between invasive and localized prolactinomas and among different hormone secretion levels. It suggests that miRNAs may be involved in the physiological process of development, growth and hormone secretion of prolactinoma.

[Inhibitory effect of adenovirus-mediated D2S gene plus bromocriptine therapy on primary cultures of human non-functioning pituitary adenoma cells].

OBJECTIVE: To explore the inhibitory effect of non-functioning pituitary adenoma (NFPA) cells after a combined treatment of adenovirus mediated D2S gene and bromocriptine in vitro. METHODS: Adenovirus containing dopamine 2 receptor short isoform (D2S) gene was used to infect NFPA cells. The transfection of D2S gene into NFPA cells was confirmed by immunofluorescence. And cell apoptosis of infected cells treated by bromocriptine was evaluated with CCK-8 assay in vitro. RESULTS: When D2S gene transfection and bromocriptine was used in combination, the survival rate of NFPA cells significantly decreased (40 ± 5)% versus the control group (97 ± 5)% and the pAd-EGFP transfection combined bromocriptine treatment group (90 ± 9)% (P < 0.05). CONCLUSION: The combined treatment of adenovirus-mediated D2S gene and bromocriptine can effectively induce the apoptosis of NFPA cells on primary culture and increase the sensitivity of NFPA to dopamine agonist.

[Natural history study of postoperative residual non-functioning pituitary adenomas].

OBJECTIVE: To observe the postoperative residual non-functioning pituitary adenomas (PR-NFPAs) without postoperative radiotherapy and to analyze the natural history of PR-NFPAs' growth in order to provide a basis for selecting appropriate strategies of clinical treatment. METHODS: We evaluated the natural history of 20 patients with PR-NFPAs who did not receive postoperative radiotherapy and drug therapy. Through MRI images, the residual tumor volumes of those patients were serially measured. We further calculated the monthly growth rate and the tumor volume doubling time (TVDT) and analyzed the correlations between the patient age, gender, volume of residual tumor, cavernous sinus (CS) invasion and TVDT. RESULTS: All patients received observation alone. Among which, 17 adenomas increased in volume and 3 remained unchanged during a follow-up period of 7 months to 17 years (mean 3.90 yr). The mean patient age was 41.8 years. As to 17 patients with tumor regrowth, the tumor volume at the beginning of MRI observation period was 4.73 cm(3) and tumor volume at the last MRI observation was 16.98 cm(3). During the mean 4-year follow-up period, the average monthly growth rate of PR-NFPAs was 7.87% and the mean TVDT was 724 days. Such factors as patient age, gender, volume of residual tumor and CS invasion did not affect the TVDT of PR-NFPAs. CONCLUSION: The tumor growth rate of PR-NFPAs is not significantly correlated with the patient gender, age, volume of residual tumor and CS invasion. In conjunctions with the volume of PR-NFPAs and the distance between residual adenoma and optic chiasm, we should take the TVDT into consideration and determine the appropriate and safe follow-up period.

Expression of D2RmRNA isoforms and ERmRNA isoforms in prolactinomas: correlation with the response to bromocriptine and with tumor biological behavior.

Invasive prolactinomas are more likely to be resistant to drug therapy but the mechanism of this is still unknown. The objective of this study was to analyze the different expression of ERmRNA and D2RmRNA isoforms in prolactinomas responsive and resistant to dopamine agonist (DA), and to discuss the correlation of such gene expression with tumor biological behavior. A prospective study of 20 consecutive patients who harbored prolactinomas was designed. Patients were classified as responsive (14 cases) or resistant (six cases) according to their clinical and biochemical response to bromocriptine. Tumor tissue samples were examined by means of QRT-PCR analysis. Median D2SmRNA expression in responsive patients was about 2.5-fold that in resistant ones (13.5 +/- 10.4 and 5.4 +/- 2.4, respectively, P = 0.09). No significant difference was found between D2LmRNA expression levels (P = 0.77). However, there was a significant difference between D2S/D2LmRNA ratios for responsive and resistant tumors (P = 0.012). A significant difference was not found between these two groups in levels of ERalphamRNA and ERbetamRNA expression (P = 0.20 and 0.06, respectively). D2SmRNA expression was significantly different for invasive and noninvasive tumors (6.2 +/- 3.6 vs. 17.0 +/- 11.2, respectively, P = 0.02). The D2S/D2L ratio is related to the responsiveness of prolactinomas to DA medication, in which D2SmRNA plays an important role. Lower expression of D2SmRNA in invasive tumor patients suggests that invasive prolactinomas may be more likely to be resistant to DA medication.

Correlation of alternative splicing of the D2 dopamine receptor mRNA and estrogen receptor mRNA in the prolactinomas and gonadotrope tumors.

OBJECTIVE: Estradiol (E2) acts to modulate the ratio of two dopamine D2 receptor isoforms (D2L/D2S) by the nuclear estrogen receptor (ER) and to reduce dopamine's inhibitory action on PRL secretion. Here we demonstrate the correlation between the expression of ER mRNA and D2R mRNA isoforms in pituitary neoplasms cells. METHODS: Twenty-four human pituitary adenomas (14 prolactinomas and 10 gonadotrope tumors) were examined for the expression of both ER mRNA and D2R mRNA by means of semi-quantitative RT-PCR analysis. RESULTS: No significant difference was found in ERbeta mRNA expression levels between prolactinomas and gonadotrope tumors (P = 0.871), but there was a significant difference in the expression of ERalpha mRNA (P = 0.003). The significant difference was found between the two pituitary adenomas types in both levels of D2S and D2L mRNA expression (P = 0.036 and 0.007 respectively). Furthermore, both levels of expression in prolactinomas were significantly higher than that in gonadotrope tumors. Additionally, a negative correlation between D2S and ERalpha mRNA expression and a positive correlation between D2L and ERalpha mRNA expression were found in these tumors. CONCLUSION: This study for the first time shows a good correlation between expression of ER and D2R isoforms in prolactinomas and gonadotrope tumors. Reducing the amount of the ERalpha in neoplasm cells can alter the ratio of D2L/D2S, which may increase the drug sensitivity of pituitary adenomas.

Familial and genetic researches on three Chinese families with von Hippel-Lindau disease.

OBJECTIVE: Hemangioblastoma of the central nervous system (CNS) occur as sporadic tumors or as a part of von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary tumor syndrome caused by germline mutation of the VHL tumor suppressor gene. This study shows the clinical characteristics of three large Chinese families with VHL disease and evaluates the consequence of the genetic test for the diagnosis of VHL disease and clinical screening of the family members. METHODS: DNA is extracted from peripheral blood in 43 members from three large families with VHL disease and amplified by PCR to three exons of the VHL gene. The PCR products were directly sequenced and the mutations compared with the Human Gene Mutation Database. RESULTS: The ages of the patients who are given the initial diagnosis ranged from 16 to 47 years (mean: 31 years), and the mean time was 17.3 months (2-30 months) from the emergence of the symptom to patients' first visit. Furthermore, the gender distribution was 20% female (4) and 80% male (16). Twenty VHL disease patients in the three families have the most common manifestation of CNS hemangioblastoma. The cytosine replaced the 716th guanine on four patients and three carriers of virulence gene from the first family, which made the 168th serine replaced by threonine. And no mutation was found on the 22 members of the second family. Meanwhile, it was also found that the guanine replaced the 559th cytosine on one patient and two carriers from the third family, which made the 116th leucine replaced by valine. CONCLUSION: The DNA analysis of VHL germline mutations is clearly superior to clinical information to diagnose VHL disease. The CNS hemangioblastoma is the early manifestation in VHL disease. It is recommended that every patient with CNS hemangioblastoma should be screened for VHL gene mutation. The test for the VHL gene plays a key role in the discovery of asymptomatic patients and the carriers of virulence gene.

Five years follow-up of invasive prolactinomas with special reference to the control of cavernous sinus invasion.

BACKGROUND: Few data are presently available on the effective control of cavernous sinus (CS) invasion of invasive prolactinomas. The aim of this retrospective study, through a mean period of 5 years follow up, is to observe the tumor shrinkage of CS invasive prolactinomas, as well as PRL normalization with bromocriptine therapy. METHODS: 68 patients met the criteria of invasive prolactinomas (Grade III or IV in the classification scheme of Knosp and colleagues; serum PRL level greater than 200 ng/ml). 33 patients underwent bromocriptine therapy as the initial treatment, and 14 of these 33 had combined treatment with microsurgery and/or radiotherapy. The other 35 patients received microsurgery as the primary treatment, after which two patients had normal PRL without taking bromocriptine and other 33 patients received bromocriptine treatment after microsurgery. RESULTS: Tumor volume on magnetic resonance images had completely disappeared in 50 patients (74%), while all the other 18 patients had residual tumor in the parasellar areas, invading the CS, and 14 patients had a secondary empty sella due to tumor shrinkage. Of those 14 patients, seven still had elevated PRL levels; five had optic chiasmal herniation by different degrees (P < 0.05). There were 49 patients with normal PRL levels (72%); five patients with PRL levels more than 200 ng/ml. After the treatment, 14 patients with tumor volume disappearance on MR images and PRL normalization therefore withdrew from bromocriptine therapy. During a subsequent one-and-a-half-year follow-up, tumor recurrence and PRL increase were not found in those 14 patients. Twenty-seven patients maintained normal PRL levels with low-dose bromocriptine, of which 20 patients had their tumor disappear while seven patients had CS residual tumor. CONCLUSIONS: About three-fourths of prolactinomas with CS invasion can be effectively controlled not only with regard to tumor volume disappearance but also in serum PRL normalization. Residual tumor in the CS areas with PRL normalization and no pressure symptoms can be treated with low-dose of bromocriptine so as to achieve long-term tumor volume control and endocrine control. Great attention should be paid to CS residual tumors accompanying the empty sella, especially in cases with optic chiasmal herniation.

Differential centrifugation in culture and differentiation of rat neural stem cells.

(1) The study of neural stem cells (NSC) has attracted much attention in recent years because of their therapeutic potential. However, the problem in culture and differentiation of NSC was how to obtain single cell suspension that preserves the function of NSC, and remove the debris caused by mechanical dissociation. In the present study, we try to find a simple and effective way to address the problem, i.e. differential centrifugation. (2) After a gentle mechanical dissociation using Pasteur pipette, the suspension was first centrifuged at 100 g for 5 min, and then recentrifuged at 400 g for 6 min. Finally, the two deposits were resuspended and seeded into culture flask respectively. The suspension from the second deposit was allowed for further culture and differentiation. Immunofluorescence technique was used to identify neural stem cell, neuron, astrocyte, and oligodendrocyte. (3) After the second differential centrifugation, single cell suspension was obtained with 2-3 cell clusters, and the cells not only grew to form neurospheres, but also differentiated into neurons, astrocytes, and oligodendrocytes. (4) Differential centrifugation is a simple and effective way to obtain single cell suspension, which will help make large-scale production of neurodifferentiated cells more effective.

Biomechanical evaluation of cranial flap fixation techniques: comparative experimental study of suture, stainless steel wire, and rivetlike titanium clamp.

OBJECTIVE: To study the techniques of cranial flap fixation (suture, stainless steel wire, and rivetlike titanium clamp) on biomechanics. METHODS: Twenty-four cadaver craniotomy flaps were reattached with either suture, stainless steel wire, or rivetlike titanium clamp. Cranial flap fixation was timed and measured for the offset between cranial flap with craniotomy skull for every fixation technique. Load-bearing tests were performed by applying an external force until the failure of the fixation system. RESULTS: Rivetlike titanium clamp required significantly less time to fix (94 +/- 13 seconds) than either suture (172 +/- 14 seconds) or stainless steel wire (399 +/- 45 seconds). The offset of cranial flap after rivetlike titanium clamp fixation (0.20 +/- 0.12 mm) was significantly smaller than either suture (2.20 +/- 0.24 mm) or stainless steel wire (1.32 +/- 0.34 mm). Rivetlike titanium clamp was also stronger than suture and stainless steel wire in the load-bearing test. CONCLUSION: Rivetlike titanium clamp is easy to use, requires less time consumption, and shows accuracy and strength.

Bromocriptine treatment of invasive giant prolactinomas involving the cavernous sinus: results of a long-term follow up.

OBJECT: The aim of this study was to observe long-term clinical outcomes in a group of patients treated with bromocriptine for invasive giant prolactinomas involving the cavernous sinus. METHODS: Data from 20 patients with invasive giant prolactinomas at the authors' institutions between July 1997 and June 2004 were retrospectively reviewed. The criteria to qualify for study participation included: (1) tumor diameter greater than 4 cm, invading the cavernous sinus to an extent corresponding to Grade III or IV in the classification scheme of Knosp and colleagues; (2) serum prolactin (PRL) level greater than 200 ng/ml; and (3) clinical signs of hyperprolactinemia and mass effect. Among the 20 patients who met the criteria, six had undergone unsuccessful transcranial or transsphenoidal microsurgery prior to bromocriptine treatment and 14 patients received bromocriptine as the primary treatment. Eleven of the 20 patients underwent adjuvant radiotherapy. After a mean follow-up period of 37.3 months, the clinical symptoms in all patients improved by different degrees. Tumor volume on magnetic resonance images was decreased by a mean of 93.3%. In 11 patients, the tumor had almost completely disappeared; in the other nine patients, residual tumor invaded the cavernous sinus. Visual symptoms improved in 13 of the patients who had presented with visual loss. Eight patients had normal PRL levels. The postoperative PRL level was more than 200 ng/ml in seven patients. During the course of drug administration, cerebrospinal fluid leakage occurred in one patient, who subsequently underwent transsphenoidal surgery. No case of apoplexy occurred during bromocriptine treatment. CONCLUSIONS: Dopamine agonist medications are effective as a first-line therapy for invasive giant prolactinomas, because they can significantly shrink tumor volume and control the PRL level. Tumor mass vanishes in some patients after bromocriptine treatment; in other patients with localized residual tumor, stereotactic radiosurgery is a viable option so that unnecessary surgery can be avoided. The application of radiotherapy does not reliably shrink tumor volume.

[Detection of transfusion transmitted virus infection of healthy blood donors in Hangzhou region and nucleotide sequence analysis of partial positive samples]

OBJECTIVE: To investigate the frequency of transfusion transmitted virus (TTV) infection in healthy blood donors in Hangzhou area and the mutation of TTV genomic fragment. METHODS DNA in serum samples of 203 healthy donors was extracted by phenol-chloroform method to detect TTV by semi-nested polymerase chain reaction and nucleotide sequences of partial amplification products were determined after T-A cloning. RESULTS TTV infection rate in 203 cases of blood donors in Hangzhou area was 15.3%. The homology of the amplified products of partial TTV positive samples compared with thereported nucleotide and putative amino acid sequences of TTV TA278 were 63.51% approximate, equals 67.12% and 59.46% approximate, equals 66.22% respectively. CONCLUSIONS TTV infection rate in the blood donors in Hangzhou is relatively high. The TTV infecting blood donors in the area may be a kind of novel genotype.